Peroxide dependent and independent lipid peroxidation: site-specific mechanisms of initiation by chelated iron and inhibition by alpha-tocopherol. Peroxidation of linoleic acid (LA) was catalyzed by Fenton reagent (H2O2 and Fe2+) in positively charged tetradecyltrimethylammonium bromide (TTAB) micelles, but not in negatively charged sodium dodecylsulfate (SDS) micelles. However, more hydroxyl radicals formed via the Fenton reaction were trapped by N-t-butyl-alpha-phenyl-nitrone (PBN) in SDS micelles than in TTAB micelles. Generation of linoleic acid alkoxy (LO) radicals by Fe2+ via reductive cleavage of linoleic acid hydroperoxide (LOOH) resulted in peroxidation of LA and formation of PBN-LO. adducts in SDS micelles, but not in TTAB micelles. This LOOH dependent lipid peroxidation could be catalyzed in TTAB micelles in the presence of a negatively charged iron chelator, nitrilotriacetic acid (NTA). LO radicals formed by the LOOH dependent Fenton reaction were also trapped by PBN at the surface of TTAB micelles in the presence of NTA, but not in its absence. The consumption of a spin probe, 16-(N-oxyl-4,4'-dimethyloxazolidin-2-yl)stearic acid (16-NS) during the LOOH dependent Fenton reaction in the presence of NTA was higher in TTAB micelles of LA than in those of lauric acid (LauA), although the rates and amounts of LO radicals formed in the two types of fatty acid micelles were similar. The rates of 5-NS consumption in LA and LauA micelles were almost the same, and were lower than the rate of 16-NS in LA micelles. NTA-Fe2+ initiated peroxidation of LA in TTAB micelles without a lag time in the presence of LOOH, but after a lag period, peroxidation occurred without LOOH.(ABSTRACT TRUNCATED AT 250 WORDS)


Recent developments in the molecular cloning and characterization of hepatitis C and E viruses. The molecular properties of the genomes of both hepatitis C virus (HCV) and hepatitis E virus (HEV), the major etiologic agents of non-A, non-B hepatitis, are briefly described. The organization of the genome of each of these viruses is discussed and compared to those of other related or distantly related viruses that contain single-stranded, positive-sense RNA genomes. In the case of HEV, the reactivity of expressed proteins and genetic divergence of geographically distinct isolates are also described within the context of sequence variation, type-common epitopes and type-specific epitopes.


Chronic prenatal methadone exposure alters central opioid mu-receptor affinity in both fetal and maternal brain. The effects of chronic prenatal methadone exposure (6.3-9.0 mg/kg/day) via osmotic minipumps to pregnant dams on fetal and maternal brain opioid mu-receptors were assessed on gestation day 20 and day 7 postnatally. By using the 3H-DAMGO binding assay, it was shown that chronic methadone treatment (gestation days 7-20) did not affect mu-receptor capacity in both fetal and maternal brains during gestation day 20, nor when tested 7 days after delivery. However, this chronic exposure decreased mu-receptor affinity in both fetal and maternal brain homogenates when determined on day 20 of pregnancy. Scatchard analysis of binding data in both tissues indicated that the methadone-induced increase in KD returned to control values when tested 7 days after delivery. The change in mu-receptor affinity was not due to competition between 3H-DAMGO and residual methadone. Extensive washing of the brain homogenates failed to alter the affinity of the receptor but decreased the concentration of the residual methadone. This decrease in receptor affinity was also observed in extensively washed brain tissue from female adult rats treated acutely with methadone (9.0 mg/kg, IP) or when brain homogenates were exposed to methadone (50 ng/ml) in vitro. Thus, these data suggest that methadone alters mu-receptor affinity by some unknown mechanism.


The Pas2 protein essential for peroxisome biogenesis is related to ubiquitin-conjugating enzymes. In the yeast Saccharomyces cerevisiae, PAS genes are essential for the biogenesis and proliferation of peroxisomes. Recently, the first two genes, PAS1 (ref. 3) and PAS3 (ref. 4), have been characterized. Here we report the cloning and sequencing of the PAS2 gene. It encodes a new member of the ubiquitin-conjugating (UBC) protein family and is the first member associated with peroxisomes. The proposed function of the Pas2 protein as a UBC enzyme (UBC10) is supported by the fact that site-directed mutagenesis of a strictly conserved and functionally essential cysteine residue of UBC proteins leads to mutant Pas2 proteins unable to complement pas2 mutant strains. Ubiquitination of proteins is known to play an important part in DNA repair, sporulation, cell cycle control and degradation of abnormal proteins. We provide evidence for a crucial role of the ubiquitin-conjugation pathway in organelle formation.


Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function. Inositol phospholipid turnover is enhanced during mitogenic stimulation of cells by growth factors and the breakdown of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) may be important in triggering cell proliferation. PtdInsP2 also binds actin-binding proteins to regulate their activity, but it is not yet understood how this control is achieved. The protein alpha-actinin from striated muscle contains large amounts of endogenous PtdInsP2, whereas that from smooth muscle has only a little but will bind exogenously added PtdInsP2. In vitro alpha-actinin binds to F-actin and will crosslink actin filaments, increasing the viscosity of F-actin solutions. We report here that alpha-actinin from striated muscle is an endogenous PtdInsP2-bound protein and that the specific interaction between alpha-actinin and PtdInsP2 regulates the F-actin-gelating activity of alpha-actinin. Although the F-actin-gelating activity of alpha-actinin from smooth muscle is much reduced compared with that from striated muscle, exogenous PtdInsP2 can enhance the activity of smooth muscle alpha-actinin to the level seen in striated muscles. These results show that PtdInsP2 is present in striated muscle alpha-actinin and that it is necessary for alpha-actinin to realize its maximum gelating activity.


[Clinical studies of writer's cramp in 30 patients]. 30 patients with writer's cramp were examined by a neurologist and a psychiatrist. The syndrome was frequently associated with a postural tremor. We found no evidence for a peripheral causation. Electromyographical recordings showed co-contractions of agonists and antagonists as well as individual patterns of increased muscle activity during writing. CT and MRI scans were normal in most patients. The psychiatric examination revealed a history of situational stress at the onset of the disease and also some abnormalities in the biography and personality traits. Since the latter findings were not consistently present we have no evidence that the disease is a neurotic manifestation. We consider it likely that secondary psychoreactive processes may have some significance in the individual patient.


[The value of stereotactic biopsy and percutaneous radiation in therapy of glioblastoma multiforme]. The concept of cytoreductive surgery in the treatment of glioblastoma multiforme is controversial. A retrospective study was carried out between 1986 and 1991 to analyze the results of stereotactic biopsy followed by supportive treatment (n = 49), incomplete radiation therapy (less than 40 Gy, n = 26), and complete radiation therapy (greater than or equal to 40 Gy, n = 58) and to compare with those of resection plus irradiation described in the literature. The patients treated with supportive care and an incomplete course of irradiation had a median survival of less than 8 weeks. For the patients who completed the radiation therapy the median survival was 32 weeks. In patients with midline shift the Karnofsky scores worsened more often during the course of radiation therapy, or therapy had to be terminated prematurely. The most important prognostic determinant was the patient's age. A comparison of survival rates in our series with those reported by other authors for patients who received tumor resection with subsequent irradiation yielded no significant difference. This would appear to cast doubt on the concept of cytoreductive surgery. The treatment of choice for patients with glioblastoma multiforme is at present radiation therapy. There is no question about the necessity of decompressive surgery whenever it is required to perform radiation therapy for severe space-occupying lesions and when it can be performed without causing new neurological deficits.


[New aspects in the diagnosis of herpes simplex virus encephalitis--case reports and virologic findings]. Herpes simplex virus (HSV) is one of the most common causes of severe necrotizing encephalitis in men. Without adequate acyclovir treatment it has a mortality rate of 70%. An early, reliable virological diagnosis is therefore essential. In this study, two newly-introduced diagnostic methods were assessed and compared: Polymerase Chain Reaction (PCR) for detection of HSV-genome in cerebrospinal fluid and HSV-specific isoelectric focusing (IEF) for detection of intrathecal virus specific antibody synthesis in HSV encephalitis (HSVE). PCR proved more effective for the early diagnosis of HSVE and HSVE relapses, whereas HSV-specific IEF was superior for the diagnosis of HSVE in post-acute stages of the disease.


[Turcot syndrome illustrated by two clinical cases]. Turcot syndrome denotes the association between either familial polyposis coli (FPC) or sporadic non-familial polyposis coli, and primary neuroepithelial tumors of the central nervous system (CNS). The clinical and morphological intestinal features in both FPC and Turcot syndrome are the same: the histological picture shows typical (tubular) adenomas, often with adenocarcinomatous transformation. As associated CNS tumors astrocytomas, glioblastomas, spongioblastomas, and medulloblastomas are reported. As a modification of ITOH's classification of 1985 we distinguish between four groups: patients with fewer than 100 polyps (group I); patients with fewer than 10 polyps (group II); patients with FPC or sporadic non-familial polyposis (group III); patients with either CNS tumors or FPC with a direct relative with Turcot syndrome and/or FPC (group IV). In patients belonging to the fourth group the diagnosis of Turcot syndrome should not be made. We report on two patients belonging to group II and group IV respectively, and depict the clinical features as well as the heterogenic appearance of Turcot syndrome as outlined in the literature.


Yohimbine-induced seizures involve NMDA and GABAergic transmission. The alpha 2-antagonist, yohimbine has been shown to dose-dependently induce clonic seizures in mice. The convulsant effects of yohimbine are not due to alpha 2-antagonism, as other alpha 2-antagonists, such as rauwolscine and idazoxan, did not produce seizures at doses up to 100 mg/kg. Since GABAmimetic and excitatory amino acid antagonist agents attenuate yohimbine-induced seizures, the respective contribution of these systems to the production of yohimbine seizures was investigated. The CD50 dose of yohimbine (dose required to produce clonic seizures in 50% of the mice) was determined to be 25.5 mg/kg (s.c.). The CD15 dose of N-methyl-DL-aspartic acid (NMDLA), bicuculline and methyl-6,7-dimethoxy-4 ethyl-beta carboline-3-carboxylate (DMCM) significantly potentiated the convulsant effects of yohimbine, such that the CD50 dose was decreased from 25.5 mg/kg to 1.6, 10.9 and 9.9 mg/kg, respectively. Furthermore, the potentiation in the presence of NMDLA was significantly greater than either bicuculline or DMCM. These results suggest that yohimbine-induced seizures are not only mediated through the impairment of GABAergic transmission but moreover, by a possible endogenous enhancement of excitatory amino acid transmission. In addition, the effects of GABAmimetic agents, competitive and non-competitive NMDA receptor antagonists and strychnine-insensitive glycine receptor antagonists were compared in the yohimbine-, bicuculline- and NMDLA-induced seizure assays.


Age-related reduction in pituitary corticotropin-releasing hormone receptors in two rat strains. Open field behavior and age-related changes in anterior pituitary corticotropin-releasing hormone (CRH) receptors, as well as plasma ACTH levels, were measured in two inbred rat strains. The strains utilized were Wistar Kyoto (WKY) and Brown-Norway (BN), the former characterized by shorter life-span and hyper-reactivity to stressors as compared to the latter. Behaviorally, WKY rats showed hyper-responsivity to a novel environment as indicated by their delay in entering the open field, increased grooming, reduced rearing, and reduced locomotion. These strain-dependent behavioral differences were not affected by aging. The binding capacity of CRH receptors was similar in both strains and Bmax values were decreased (25-27%) with aging, with no changes in Kd values. In contrast, plasma ACTH levels were 67% higher in WKY than in BN rats but did not change with aging. Thus, despite pituitary CRH receptor down regulation, plasma ACTH levels following decapitation were sustained during aging. This suggests the presence of some compensatory factors in the hypothalamic-pituitary axis regulation which sustain ACTH response during aging. Furthermore, the findings indicate that higher plasma ACTH levels and hyper-reactivity to a novel environment are inversely correlated with longevity in the rat.


Molecular mechanism of the interaction of subendothelial microfibrils with blood platelets. This short review summarizes the present state of our knowledge concerning the mechanisms of the interaction between subendothelial microfibrils and blood platelets. Microfibrils associated with elastin and with basement membranes have been shown to be able to promote platelet adhesion and subsequent activation and aggregation. A 128 kDa thrombospondin (TSP)-like glycoprotein of microfibrils (GP 128) is involved in their reactivity towards platelets, as established from specific inhibition by antibodies against GP 128 and against TSP of the microfibril-platelet interaction. This interaction only occurs in the presence of plasma von Willebrand factor (vWF). VWF effectively binds to microfibrils; this binding does not implicate GP 128, but a 97 kDa protein of microfibrils not yet characterized. In addition, from data based on inhibition of platelet adhesion and aggregation by monoclonal antibodies against platelet membrane glycoprotein Ib (GP Ib), it appears that GP Ib, a platelet membrane receptor for vWF, acts in the vWF dependent microfibril-platelet interaction as a receptor for VWF bound to protein 97 kDa in microfibrils. A tentative model is presented to illustrate the complex mechanism of the microfibril-platelet interactions: recognition of vWF bound to microfibrils by GP Ib would be the first step, which would then allow subsequent binding of GP 128 to its receptor on the platelet membrane.


A rational approach to heparins.

A rational approach to heparins. It is shown why the current practice of expressing heparin activity in International Units is not an adequate way to deal with the situation that arises after injection of low molecular weight heparins. An alternative approach is proposed. It is taken into account that the fraction of a low molecular heparin that binds with high affinity to antithrombin III contains two fundamentally different components: the material above the critical chain-length of 17 sugar units that has both anti-factor Xa activity and antithrombin activity (ACLM) and the material below that length with anti-factor Xa activity only (BCLM). It is shown how the levels of ACLM and BCLM in a plasma sample can be determined and expressed in micrograms/ml.


[The nervous system and the immune system: the role of morphine and opioid peptides in the function of neutrophilic granulocytes]. Inhibition of human granulocyte chemotaxis towards casein was observed in the presence of mu and k receptor agonist, which per se exhibits chemokinetic activity. Naloxone was found to prevent both the opioid and opioid unrelated increase of granulocyte migration. Although opioid agonists with different receptors specificity were capable of strongly modifying human granulocyte migration, no conclusion can be drawn on the role of opioid receptors in regulating migration activity. The effects of morphine and opioid peptide on neutrophil aggregation and ATOP release were studied. Inhibition of human granulocyte aggregation and ATP release was observed in the presence of morphine in a naloxone stereoselective manner, whereas the opioid peptides were ineffective. The effect of DAGO, DADL and dynorphin 1-9 on granulocyte aggregation and ATP release were also evaluated, but these opioid peptides are unable to modify neutrophil function. Our studies confirm the role of mu receptors on modulation of polymorphonuclear granulocyte function and suggest a key role of opioid peptides in the regulation of some immune system functions. In comparative studies Ca++ (A 23,187) and dynorphin 1-9, per se, induced stimulation of arachidonic acid metabolites from granulocytes. In this regard dynorphin 1-9 may function as a mediator between the central nervous system and immunity.


Non specific effects of guanine nucleotides and polyanions on cytosolic platelet phospholipase C. Phospholipase C (PLC) partially purified by electrofocusing from human platelet cytosol was incubated with platelet total lipid vesicles containing [3H] phosphatidylinositol 4,5-bis phosphate ([3H]PIP2). Under optimal assay conditions (pH 4.5), PLC activity was stimulated (1.5 to 7 fold) by GTP gamma S, ATP, ADP, GDP beta S, sodium pyrophosphate and AlF4-. With lipid dispersions containing phosphatidylethanolamine and [3H]PIP2, maximal PLC activity was detected at pH 7.4 and was stimulated by micromolar concentrations of free Ca2+. However, no effect of GTP gamma S could be observed under these conditions. This study demonstrates a possible modulation of cytosolic PLC by polyanionic compounds not involving G-proteins and indicates that in vitro data obtained with guanine nucleotides should be considered with caution.


Effect of chronic cholinergic denervation on the m1 muscarinic receptor mechanism. The first three parts of the transduction mechanism for m1 muscarinic receptors (m1 receptors, receptor-G protein coupling, and the activation of phospholipase C) were studied in the rat hippocampus following unilateral or bilateral surgical lesions of the fimbria/fornix. One nM 3H-pirenzepine was used to label m1 receptors selectively. No changes in m1 receptor numbers were found between age 1.7 and 29 months old during normal aging or one year after cholinergic denervation. The interaction between m1 receptors and their associated G protein was examined by competition between 1 nM 3H-pirenzepine and oxotremorine-M in the presence and absence of a guanine nucleotide. The percentage of guanine nucleotide-sensitive high affinity binding sites for the agonist was similar in rats 1.7-29 months old and in rats 1 year after denervation. The ability of oxotremorine-M to activate phospholipase C, via m1, m3, and m5 receptors was also unchanged more than a year after cholinergic denervation of the hippocampus. We concluded that the initial steps in the m1 receptor transduction mechanism remain remarkably stable after denervation.


[Effect of blockade of opiate receptors by naloxone on lutropin (LH), follitropin (FSH) and testosterone secretion in patients after kidney transplantation]. The influence of opioid receptors blockade by naloxone on lutropin (LH), follitropin (FSH) and testosterone secretion induced by LH-RH was assessed in 12 male kidney transplant patients with stable graft function (KTP) treated by cyclosporine A and prednisone and in 15 healthy subjects. In KTP normal plasma levels of LH in spite of significantly reduced testosteronemia and a reduced response of LH to LH-RH was observed. After blockade of opioid receptors by naloxone normalization of the response of LH secretion to LH-RH was found and a higher increase of the plasma testosterone level was observed in KTP than in healthy subjects. Results obtained in this study suggest abnormal functioning of the hypothalamic-pituitary--gonadal axis in KTP and participation of opioid receptors in its pathogenesis.


[Highly differentiated cancer or adenoma of the liver: diagnostic approach in highly differentiated epithelial tumors of the liver]. High-differentiated hepatocellular carcinoma (h-d HCC) is a not frequent hepatic tumour but its outcome may be beneficial when treated properly. Two cases of h-d HCC recognized on the basis of postoperative histopathology are reported. We have discussed the role of fine needle biopsy in distinguishing h-d HCC from liver adenoma, and we have attempted to outline the diagnostic approach in clinically silent hepatic tumours which are not associated with cirrhosis or elevated alfa-fetoprotein plasma level.


Endogenous viral gene distribution in populations of meat-type chickens. The present study was designed to document the complexity of endogenous viral (ev) genes and seek evidence for their association with production traits in selected and control strains of meat-type chickens. Three populations were studied, each consisting of a control strain and one to three strains selected for various production traits. The ev genes were revealed by digesting genomic DNA with restriction enzymes and detecting DNA fragments on Southern blots using radioactive probes from nucleotide sequences of the avian leukosis virus genome. A total of 31 polymorphic ev loci were identified in these populations from a SacI digest, with an average of 7.3 ev genes per bird. There were no significant differences in ev genes per bird between strains within populations or between selected and control strains overall. Thirty of 62 comparisons in the three populations indicated ev gene frequency differences (P less than .05). Within populations, 13 of 93 comparisons of ev gene frequencies between control and selected strains and 8 of 62 between three selected strains of a sire population showed such differences (P less than .05). Selection for body weight and feed efficiency had been observed to reduce gene frequencies of the slow-feathering gene, which usually contains the ev21 locus; however, these effects were not detected (.05 less than P less than .06) between strains of the dam population in the current study. Such differences suggested possible associations between ev genes and production traits in meat-type chickens.


In vitro tachyphylaxis to isoprenaline in guinea-pig trachea: influence of theophylline? We used frontally opened tracheal rings, contracted with 10 microM of histamine to produce beta-adrenoceptor tachyphylaxis by isoprenaline incubation and to evaluate whether theophylline can prevent this tachyphylaxis. Two concentration-response experiments with isoprenaline were performed in each ring. Between the concentration-response experiments the rings were incubated using four different treatments, isoprenaline (3 microM), theophylline (1 mM), theophylline + isoprenaline or vehicle for 60 min. Tachyphylaxis was evaluated as the difference in pD2 (-log EC50) during the first and second concentration-response experiment. Isoprenaline incubation produced a shift to the right of the concentration-response curve. The shift was small (approximately 0.2 log units) but significantly different from the control group. Theophylline failed to influence the process either alone or in combination with isoprenaline. In conclusion, beta-adrenoceptor tachyphylaxis after isoprenaline incubation in isolated guinea-pig trachea proved to be a very small effect and we observed no influence by theophylline.


Diminution in kerosene-mediated induction of drug metabolizing enzymes by asbestos in rat lungs. In order to determine the pulmonary toxicity of kerosene and its ignition product (soot) in asbestos exposed subjects, the activities of phase I and phase II drug metabolizing enzymes in rat lungs after single intratracheal co-exposure to Indian chrysotile asbestos and kerosene or its soot and Indian chrysotile were assayed. Exposure to kerosene or its soot resulted in a significant increase in the level of microsomal cytochrome P-450 and the activity of P-450 dependent monooxygenase, benzo(a)pyrene hydroxylase, as well as in the activities of microsomal epoxide hydrase and cytosolic glutathione-S-transferase (GST). However, in chrysotile exposed animals a reverse pattern in these parameters was recorded. The co-exposure to chrysotile and kerosene or chrysotile and soot led to a significant depletion in cytochrome P-450 level and a decrease in the activities of benzo(a)pyrene hydroxylase, epoxide hydrase and GST when compared to kerosene and soot controls, respectively. These results suggest that asbestos by altering the pulmonary drug metabolizing enzyme system may increase the toxic potential of kerosene and its ignition product in the respiratory system.


Molecular characterization of angiotensin II type II receptors in rat pheochromocytoma cells. The binding sites and biochemical effects of angiotensin (A) II were investigated in rat pheochromocytoma (PC12W) cells. Sarcosine1, [125I]-tyrosine4, isoleucine8-AII ([125I]-SI-AII) bound to a saturable population of sites on membranes with an equilibrium dissociation constant (Kd) of 0.4 nM and a binding site maximum of 254 fmol/mg protein. Competitive displacement of [125I]-SI-AII by agonists and antagonists elucidated a rank order of potency of AIII greater than or equal to AII greater than PD 123177 greater than AI greater than [des-Phe]AII [AII(1-7)] much greater than DuP 753. The stable guanine nucleotide analog 5'-guanylyl imidodiphosphate did not alter the binding affinity or slope of the inhibition curves for AI, AII, AIII, or AII(1-7). Treatment of PC12W cells with AII or AIII did not affect the free intracellular calcium concentration, phosphoinositide metabolism, arachidonate release, cyclic GMP, or cyclic AMP concentrations. [125I]-AII binding sites remained on the cell surface and were not internalized after 2 h at 37 degrees C. Angiotensin II did not stimulate tyrosine, serine, or threonine phosphorylation. Northern analysis of PC12W mRNA with an AT1 receptor gene probe failed to produce an RNA:DNA hybrid at low stringency. These data indicate that PC12W cells express a homogeneous population of AT2 binding sites which differ significantly from AT1 receptors in signal transduction and molecular structure. AT2 sites may act via potentially novel, biochemical pathways or, alternatively, be vestigial receptors.


Effects of central and peripheral type benzodiazepine ligands on growth hormone and gonadotropin secretion in male rats. The action of central and peripheral type benzodiazepine ligands on growth hormone, luteinizing hormone and follicle stimulating hormone levels in serum were studied in male rats. Graded doses of Ro 5-4864, that binds to the peripheral type benzodiazepine receptors, clonazepam, a fairly pure central type agonist and diazepam, a mixed-type agonist, were given intraperitoneally. Also a benzodiazepine partial inverse agonist, FG 7142, was investigated. Clonazepam increased growth hormone levels at 0.2 mg/kg while higher doses were not active. Diazepam (5-25 mg/kg) was not effective. FG 7142 (15 mg/kg) and Ro 5-4864 (25 mg/kg) decreased growth hormone levels. Flumazenil, a central-type antagonist, reversed at least partially the effects of clonazepam and FG 7142, suggesting an effect through GABA-benzodiazepine complex. Elevation of growth hormone could be associated with anxiolysis and decrease of growth hormone with enhanced anxiety. Clonazepam (0.2-5 mg/kg) and diazepam (5-25 mg/kg) increased luteinizing hormone concentrations, but only the effects of 1 mg/kg of clonazepam and 5 mg/kg of diazepam reached statistical significance. Even FG 7142 caused a modest increase of luteinizing hormone at 5 mg/kg, but Ro 5-4864 rather decreased luteinizing hormone, although not significantly. Flumazenil (25 mg/kg) antagonized partially the effects of diazepam and clonazepam. Effects of Ro 5-4864 and FG 7142 were not modified by flumazenil or PK 11195, a peripheral-type mixed antagonist/agonist. Luteinizing hormone stimulation by benzodiazepine ligands may be a pituitary action while inhibition could be caused by the activation of the central GABAergic system. Serum follicle stimulating hormone levels were not significantly altered by central or peripheral type benzodiazepine agonists or antagonists.


CGRP stimulates the adhesion of leukocytes to vascular endothelial cells. Calcitonin gene-related peptide (CGRP) stimulates the adhesiveness of human umbilical vein endothelial cells for U937 cells and human neutrophils in a dose- and time-dependent manner. The onset of CGRP-induced adhesives of HUVEC was rapid (30 min), independent of protein synthesis, and lasted over 24 h in the continuous presence of the peptide. The stimulatory effect of CGRP was completely blocked by the CGRP antagonist, CGRP(8-37). The present study provides evidence in support of the potential role of sensory nerve-derived neuropeptides in the modulation of leukocyte adhesion to vascular endothelial cells.


Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect. Neuropeptide Y (NPY) elicits eating when injected directly into the paraventricular nucleus (PVN) or perifornical hypothalamus (PFH). To identify the essential regions of the NPY molecule and the relative contributions of Y1 and Y2 receptors, the eating stimulatory potency of NPY was compared to that of its fragments, analogues, and agonists when injected into the PVN or PFH of satiated rats. Additionally, antisera to NPY was injected into the cerebral ventricles (ICV) to determine whether passive immunization suppresses the eating produced by mild food deprivation. Tests with NPY fragments revealed that NPY(2-36) was surprisingly potent, nearly three times more so than intact NPY. In contrast, fragments with further N-terminal deletions were progressively less effective or ineffective, as was the free acid form of NPY. Collectively, this suggests that both N- and C-terminal regions of NPY participate in the stimulation of eating. Tests with agonists revealed that the putative Y1 agonist [Pro34]NPY elicited a strong dose-dependent feeding response, while the putative Y2 agonist, C2-NPY, had only a small effect at the highest doses. Although this suggests mediation by Y1 receptors, the uncharacteristically high potency of NPY(2-36) may additionally suggest that the receptor subtype underlying feeding is distinct from that mediating other responses. Additional results revealed that ICV injection of antisera to NPY, which should inactivate endogenous NPY, produced a concentration-dependent suppression of eating induced by mild food deprivation. This finding, along with published work demonstrating enhanced levels of hypothalamic NPY in food-deprived rats, suggests that endogenous NPY mediates the eating produced by deprivation.


[Pneumopathies caused by Chlamydia pneumoniae]. Among the atypical pneumonias observed between March 1990 and March 1991, 6 were diagnosed as being caused by Chlamydia pneumoniae of the TWAR strain. The serological diagnosis was obtained by a microimmunofluorescence test. All 6 patients had anti-TWAR antibody levels higher than 512; they were treated with a macrolide administered by the oral route and were cured without sequelae or recurrences. Four cases received a ten day course of roxithromycin 300 mg/day and one case received erythromycin 2 g/day also for 10 days. The sixth case received a short course of azithromycin 500 mg once daily for three days. In 2 other patients presenting with clinical and radiological signs of pneumonia the diagnosis of C. pneumoniae infection could not be made despite an antibody level equal or higher than 512, since the serological results showed cross-reactions between C. pneumoniae, C. trachomatis and C. psittaci antibody responses.


The MSH/ACTH(4-9) analog Org2766 counteracts isolation-induced enhanced social behavior via the amygdala. MSH/ACTH-like peptides influence social behavior induced by isolation It has been previously demonstrated that changes in locomotor activity as a result of isolation can be counteracted by Org2766 via the amygdala. The present study investigates whether isolation-induced changes in social behavior can also be affected by this peptide via the amygdala. A fully automated observation system was applied for detailed registration and analysis of movements of group-housed and 7-day isolated rats in a social interaction test. Administration of the MSH/ACTH(4-9) analog into the central nucleus of the amygdala elicited decreased locomotion, approach, and avoidance behaviors after isolation as compared to placebo-treated controls. However, general activity and social interest of group-housed rats were not affected by the MSH/ACTH(4-9) fragment. It is hypothesized that the amygdala is a site of action for neuropeptides in modulating social behavior.


Differential effects of ACTH4-10, DG-AVP, and DG-OXT on heart rate and passive avoidance behavior in rats. A computerized telemetry system was used to monitor heart rate (HR), core temperature (CT), and gross locomotor activity in rats treated with saline or neuropeptides during a passive avoidance behavior task. Rats were exposed to a single mild footshock (0.15 mA, for 3 s). Retention tests were conducted at 24 and 48 h after the learning trial. One h prior to the 24-h retention test, each rat received one of the following treatments (SC): saline (SAL), desglycinamide [Arg8]-vasopressin (DG-AVP), ACTH4-10, or desglycinamide-oxytocin (DG-OXT), at a dose of 3 micrograms/rat for DG-AVP and DG-OXT, and 50 micrograms/rat for ACTH4-10. Rats treated with SAL showed a modest increase in avoidance latency accompanied by bradycardia at both retention tests. Rats receiving DG-AVP retained the highest avoidance latency among the experimental groups at both the 24- and 48-h retention test. These rats showed a decrease in HR of the same magnitude as the SAL-treated animals at both retention tests. Rats treated with ACTH4-10 showed an increase in avoidance latency during the 24-h but not during the 48-h retention test. In addition, following ACTH4-10 treatment, a tachycardiac response was found during the 24-h retention test. DG-OXT induced both behavioral and cardiac responses opposite to those found in rats given DG-AVP. CT gradually increased while the rats remained on the platform, irrespective of the treatment. Changes in HR and CT were not influenced by somatomotor activity, as no difference in gross locomotor activity was found among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Intraperitoneally injected cholecystokinin-octapeptide activates pica in rats. Cholecystokinin-octapeptide (CCK-8) was injected intraperitoneally into rats to see if it could cause them to eat kaolin (clay)--a pica behavior which has been shown to indicate gastric distress. In the first study, a single large dose of CCK-8 (20 micrograms/kg) failed to produce pica. In the second study, 4 smaller doses of CCK-8 (8 micrograms/kg), 30 min apart, produced significant ingestion of kaolin compared to the baseline condition of vehicle injections. The pica was comparable to that observed in another group of rats given a toxic dose of LiCl (127 mg/kg, IP). It is concluded that intraperitoneal injections of CCK-8 can induce a state of gastric distress in the rat.


Antiaversive action of benzodiazepines on escape behavior induced by electrical stimulation of the inferior colliculus. In the present work, evidence is presented for the involvement of inferior colliculus in the generation and elaboration of aversive responses which suggests that this structure may be part of a brain system that commands aversive states. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the escape response. Afterward these rats were placed inside a shuttle box and submitted to a switch-off paradigm. Electrical stimulation of the inferior colliculus was applied at a current intensity 5% below the escape threshold. This electrical stimulation showed clear aversive properties: the rats quickly learned to interrupt it. Systemic administration (3 and 5.6 mg/kg) as well as inferior colliculus microinjections (10 and 20 nmol) of the anxiolytic compound midazolam caused dose-dependent increases in the latency and reductions in the frequency of switch-off responses to the inferior colliculus electrical stimulation. Similar results were obtained following microinjections into this brainstem structure of the GABA-A agonist muscimol (0.1 and 0.5 nmol). These results suggest that neural substrates commanding defensive behavior in the inferior colliculus may be depressed by benzodiazepines as part of the anxiolytic action of these compounds. This antiaversive action may be produced by the enhancement of GABA-A mechanisms.


Behavioral effects of centrally administered LH-RH agonist in rats. The neuropharmacological actions of the agonist analog D-Trp-6-LH-RH were investigated in several tests after intracerebroventricular (ICV) administrations to male rats. The doses applied were 10, 100 and 1000 ng/animal. In the open field the 1000 ng ICV dose of the peptide D-Trp-6-LH-RH suppressed the ambulation, rearing and grooming. In a combined catalepsy test, the 10 ng and 1000 ng dose of D-Trp-6-LH-RH increased the total duration of immobility. The LH-RH agonist inhibited stereotyped behavior induced by both apomorphine and amphetamine, and the effects of 100 and 1000 ng D-Trp-6-LH-RH were significant. Naloxone in a dose of 0.5 mg/kg IP totally abolished the inhibition of apomorphine-induced stereotypy by 1000 ng D-Trp-6-LH-RH, but the opiate antagonist did not influence amphetamine-induced stereotypy but significantly potentiated the inhibitory effect of 100 ng D-Trp-6-LH-RH. In the tail-flick test the latencies were significantly increased after D-Trp-6-LH-RH ICV, both 20 or 40 min after the injections. The peptide-induced analgesia was totally naloxone reversible. The results indicate that the agonist analog of LH-RH exert potent actions on the central nervous system, and the mechanism of effects may involve dopaminergic transmission and/or endogenous opiates.


Behavioral, neuroendocrine, and immunological outcomes of escapable or inescapable shocks. The present study was designed to evaluate the effects of repeated exposure to escapable or inescapable shocks on subsequent behavior in an activity cage, and on the reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the immune system. We also studied the possible influence of behavioral factors on the behavioral and physiological impact of stress. Although exposure to different stressful situations pointed out marked differential effects in subsequent behavior, it failed to elicit differences in the neuroendocrine and immunological parameters studied. However, interesting results were found in analyzing the influence of behavioral factors. The degree of control exerted over the shock was inversely related to ACTH and corticosterone levels. In addition, individual differences in the exploratory activity to novelty were correlated with poststress lymphoproliferation and antibody formation. These data indicate that the behavioral and physiological outcomes of stress depend on the interrelations between environmental and individual factors (including both preexisting individual differences and the coping responses during stress).


Anorexia induced by toxohormone-L isolated from ascites fluid of patients with hepatoma. To ascertain anorexigenic effect of toxohormone-L, a polypeptide extracted and purified from ascites of patients with hepatoma were infused into the rat third cerebroventricle. Food intake decreased on the first day after infusion of an optimum dose of 10.0 micrograms (p less than 0.05). The suppressive effect on feeding was linearly dose dependent (p less than 0.05). Meal size and latency to the first meal decreased in the 12-h dark period, and the first and the second 4-h cumulative blocks after infusion of a 10.0 micrograms dose (p less than 0.01 for each). The suppressive effects on total food intake and meal size were completely recovered within 24 h after infusion. Neither postprandial intermeal interval nor eating speed was affected. Periprandial drinking, a ratio of water intake to food intake, was not affected after infusion of 5.0 and 10.0 micrograms toxohormone-L. Infusion of a 10.0 micrograms dose showed no effect on ambulation. These findings suggest that anorexia and cachexia produced in cancer patients may essentially be due to the suppressive effect of toxohormone-L on food intake.


Psychological stress and body temperature changes in humans. We investigated the possible changes in body temperature, heart frequency, and blood pressure in 22 residents sitting for the yearly exam at the Specialty School of Psychiatry at Pisa University. All subjects were then evaluated 2 or 3 weeks later, in calm situations. In a subgroup, a specific plasmatic diazepam binding inhibitor (BBIA), previously described, was also measured. The results showed that all subjects underwent significant stress-related changes in the parameters studied, which suggest the involvement of different mechanisms in preexam stress.


Hepatic parenchymal perfusion defects detected with CTAP: imaging-pathologic correlation. To determine whether characteristics of focal hepatic parenchymal perfusion defects detected with computed tomographic arterial portography (CTAP) correlate with underlying pathologic processes, 245 perfusion defects detected with CTAP in 60 patients who subsequently underwent definitive hepatic surgery were characterized by shape, location within the liver, and relative attenuation value and were prospectively correlated with sectioned pathologic specimens. Of 177 round perfusion defects, 102 (58%) were malignant and 75 (42%) were benign. Only one (2%) of 53 peripheral wedge-shaped defects was malignant. All 15 peripheral flat defects were benign. Defects in characteristic locations anterior to the porta hepatis (n = 15) and adjacent to the intersegmental fissure (n = 7) were uniformly benign. While 83 (56%) of 147 soft-tissue attenuation defects were malignant, only four (6%) of 68 intermediate-attenuation defects were malignant. Although these characteristics of parenchymal perfusion defects aid in differentiation of benign from malignant processes, all other types of perfusion defects are nonspecific and may require biopsy.


Case report 749: Primary glomus tumor of bone. We report a case of primary intraosseous glomus tumor in a 30-year-old man who was found to have an expanding, lytic lesion in the distal phalanx of his left thumb. The histological appearance was atypical in that areas of myxoid stroma resembled chondroid material. The unusual location and microscopic appearance caused diagnostic problems. Immunohistochemical studies, including strong positive staining for MSA and negative staining for keratin and S-100 protein, were helpful in establishing the correct diagnosis.


Endocarditis caused by Candida parapsilosis. The authors report a case of endocarditis caused by Candida parapsilosis. To the best of our knowledge, a case has not been described previously in Japan in the English literature. A battery of 8 peroxidase-labeled lectins was tested on sections of paraffin-embedded tissue to determine which lectin could be used in the microscopic diagnosis of C. parapsilosis. One lectin, from Archis hypoaea (PNA) was found to react with C. parapsilosis. On the other hand, C. albicans, Aspergillus, Mucor, and Cryptococcus did not react with A. hypoaea (PNA). On fluorescence microscopic study, C. parapsilosis was not fluorescent, but other fungi were fluorescent when exposed to ultraviolet illumination. Therefore, we propose new procedures for identification of C. parapsilosis in tissue sections using lectin histochemistry and fluorescence microscopy.


Prevalence and outcomes of HBV and anti-HCV seropositive patients with chronic liver disease and hepatocellular carcinoma. The prevalences of serological markers of hepatitis B virus (HBV) and antibody to hepatitis C virus (anti-HCV) were determined in 168 patients (135 males and 33 females), aged 19-79 years (mean = 50.8) in Thailand. Of these, 33 had chronic persistent hepatitis, 35 chronic active hepatitis, 50 cirrhosis and 50 hepatocellular carcinoma (HCC). Seromarkers for either HBV or anti-HCV or both were detected in 140 (83.3%), 3 (1.8%) and 18 (10.7%) patients, respectively, but 7 (4.2%) were sero-negative for both viruses. The overall prevalence of anti-HCV was 12.5% but was significantly lower in HCC (2%) compared to the other 3 groups of liver disease (12-21.5%, p less than or equal to 0.05) and in HBsAg positive (5%) compared to HBsAg negative (30%) patients (p less than 0.001). After 0.5-9 years follow-up of all anti-HCV positive patients, 2 died and another 6 had progressive liver disease. The prevalence of coexistent HBV seromarkers was similar in patients with a progressive (87.5%) and a stable clinical course (92.3%) (p = 0.62). A higher proportion of the anti-HCV-positive patients with a progressive course had a history of blood transfusion [75.0% vs 46.1% (p = 0.20)]. These findings suggest that HBV is the most important etiologic virus associated with chronic liver disease and HCC in Thailand, but HCV may play a role particularly in HBsAg-negative patients.


A comparison of histopathologic diagnosis and the demonstration of human papillomavirus-specific DNA and proteins in penile warts. The extent to which the clinical diagnosis of male condylomata acuminata (CA) will be improved by histopathologic examination, immunohistochemical demonstration of papillomavirus common antigen (BPV), or demonstration of human papillomavirus (HPV)-specific DNA was studied. The relation of nuclear atypia to local cytodestructive therapy and specific HPV types was also analyzed. Altogether, the diagnosis could be histologically verified in 116 of 133 (87%) patients with clinically suspected penile CA. Of these, 69 (59%) had a positive result in in situ DNA hybridization for one or more of HPV types 6/11, 16/18, 31/33/35, or 31/35/51. Atypical cells were observed in 53 CA biopsies (46%), and there was a statistically significant correlation between this finding and the high risk HPV types 16/18, 31/33/35, and 31/35/51. Seventeen patients had neither histologic signs of condyloma acuminatum, nor detectable BPV antigen, and in situ hybridization showed HPV type 31/33/35 DNA in one biopsy, and HPV type 6/11 DNA in another. No correlation between the atypical changes and the type of previous therapy for the warts was found. Our results indicate that histopathologic examination supplemented with new HPV-specific methods is an important tool in diagnosing HPV infections.


Clinical course of cervical human papillomavirus lesions in relation to coexistent cervical infections. A prospective follow-up of 530 women with cervical human papillomavirus (HPV) infection was conducted from 1981 to the present (mean 62.9 months). The patients were examined by PAP smears and colposcopy with or without biopsies every sixth month. Endocervical swabs were taken for culture of cytomegalovirus (CMV), herpes simplex virus (HSV), and Chlamydia trachomatis at each visit. During the follow-up period, 179 of the 530 patients (33.8%) had cervical infection and 351 (66.2%) had no coexistent cervicitis. On average, the patients with coexistent cervicitis were younger than those without cervicitis (32 +/- 7.2 years and 37.1 +/- 11.4 years, respectively; P less than 0.0001). C. Trachomatis was isolated from 95 of the 530 women (17.9%), and 19 of the patients had chlamydial cervicitis twice. Cytomegalovirus was isolated from 27 (5.1%) women, 2 of whom also had HSV, and 12 patients had a chlamydial infection. Herpes simplex virus was isolated from 11 (2.1%) women, including 2 patients with coexistent CMV infection. A total of 60 (1.3%) women had nonspecific cervicitis. Of the HPV lesions without coexistent cervical infection, 56.7% regressed, 24.5% persisted, 16.5% progressed, and recurrence was found in 2.3%. The corresponding figures for HPV lesions with coexistent cervicitis were as follows: 66.5%, 22.9%, 9.5%, and 1.1%, respectively. Coexistent active cervical infections had no influence on the clinical course of HPV lesions.


Ischemia/reperfusion: a new hypothesis for the developmental toxicity of cocaine. It has been shown that multiple exposures of gravid rats to cocaine during late gestation result in significant incidences of severe malformations. Hind limb reduction defects were frequent findings in this study. Other studies have shown that comparable abnormalities can be induced in experimental animals by various procedures including vascular clamping, direct fetal exposure to epinephrine, uterine handling following laparotomy, as well as by exposure to hyperbaric oxygen. This paper reviews these and other studies, and presents a novel mechanistic hypothesis that explains their common findings. It is proposed that in each instance, conceptual hypoxia results from hypoperfusion caused by transient vasoconstriction. Following the resumption of normal perfusion, reactive oxygen species are generated by the ischemia/reperfusion mechanisms thought to underlie many pathobiologic lesions. It is proposed that the conceptus is particularly vulnerable to the toxicity of oxygen radicals because of its low antioxidant activities and the highly reduced state of its undifferentiated cells. Sensitivity to cocaine and uterine handling appears to be enhanced during late gestation and it is hypothesized that this results from changes in oxygenation and iron content that increase both the substrate and catalyst for generation of reactive oxygen species.


Intralesional recombinant alpha 2B interferon in the treatment of human papillomavirus-associated cervical intraepithelial neoplasia. Twenty-four patients with human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN); of whom 13 had CIN 1, 8 had CIN 2, and 3 had CIN 3; were treated with recombinant alpha 2b interferon (IFN) by intraperilesional injections. The dosage given was 3 x 10(6) international units per day, 3 days per week for 3 weeks. In situ hybridization was carried out for HPV types 6/11 and 16/18. One year after treatment, complete response was observed in 8 (33%) cases, partial regression in 14 (58%) cases, persistence in 2 (8%) cases (in which case traditional surgical therapy was performed), and progression in none of the cases. Adverse effects (asthenia, fever, chills, and headache) were observed in 20 (83%) cases. None of the patients had myelodepression. Intraperilesional treatment of HPV-associated CIN with recombinant alpha 2B IFN does not appear to be a valid substitute for traditional treatment, but it could be considered in certain cases when surgery is not advised.


Studies of the role of ischemia/reperfusion and superoxide anion radical production in the teratogenicity of cocaine. The administration of multiple doses of cocaine on a single day during late gestation is teratogenic in rats in which hind limb ectrodactyly is a major finding (Webster and Brown-Woodman, '90). We have previously hypothesized that these limb malformations result from the generation of reactive oxygen species during the process of ischemia/reperfusion in vivo. In order to study the direct effects of cocaine versus the aberrant oxygenation it may induce, we have developed a system for culturing rat embryos between days 14 and 15 of gestation. Growth and development of cultured embryos are comparable to that of in vivo controls. Exposure to normoxia (95% O2) with or without cocaine failed to induce limb malformations and exposure to a single long period of hypoxia (20% O2) only reduced limb growth in the anterior-posterior axis. By contrast, embryos receiving multiple brief exposures to hypoxia developed a significant incidence of hind limb ectrodactyly that appeared indistinguishable from that induced by cocaine in vivo. By incubating day 14 embryos in a nitroblue tetrazolium derivative, 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), it was shown that superoxide anion radical appears in the digital rays following two episodes of reperfusion. Little reaction product was seen under the other conditions. Finally, mitochondrial electron transport particles prepared from teratogenically sensitive limb buds spontaneously "leak" electrons to form superoxide anion radical whereas those from insensitive heart fail to do so. We propose that cocaine and other exposures that can transiently reduce conceptual oxygenation during late gestation are teratogenic by virtue of their capacity to induce ischemia/reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Dose dependent suppression of mineralocorticoid metabolism by different heparin fractions. One neglected side effect of heparin therapy is the inhibition of adrenal aldosterone production leading to occasionally life-threatening hyperkalaemia. This is only reported with (therapeutic) high doses (greater than or equal to 20.000 IU). The complex interplay of mineralocorticoid metabolites was studied in 29 subjects with unfractionated (UFH) and low molecular weight heparin (LMWH). Both heparins altered mineralocorticoid metabolism in a dose dependent manner. Whereas no effect was observed with UFH 2 x 5000 IU sc/day or LMWH 2500 a FXa U sc/day, higher doses significantly suppressed aldosterone and 18-hydroxycorticosterone production in plasma and urine. Three out of seven patients receiving UFH 3 x 7500 IU sc/day developed hyperkalaemia. This study shows the threshold dosage of UFH leading to suppression of mineralocorticoid metabolism in man and provides information that LMWH as well as UFH can suppress mineralocorticoid production. With respect to therapeutic implications it is important that LMWH at 2500 a FXa U sc/d had no effect on mineralocorticoid metabolism in contrast to UFH at a dosage currently used for prevention of thromboembolism (3 x 5000 IU sc/d).


Papillomavirus infection among abortion applicants and patients at a sexually transmitted disease clinic. The base-line prevalence of human papillomavirus (HPV) infection among applicants for first trimester induced abortion and among a sexually transmitted disease (STD) clinic population with macroscopically visible condyloma is investigated. Cervical cells were collected from 505 women applying for induced abortion. Cell scrapes were obtained from the surface of the warts from 81 female and 32 male STD patients. HPV DNA 6/11, 16/18, and 31/33/35 were detected by a dot blot technique (ViraPap and ViraType, Life Technologies, Gaithersburg, MD). Of the 505 abortion applicants, 31 (6.1%) had HPV DNA. In the STD population, 64 (79.0%) patients had positive test results for HPV DNA from cervical, introital cell scrapes, or both. Of the 32 male STD patients from whom preputial, urethral samples, or both were taken, 24 (75%) had HPV DNA. After typing, the relative proportion of HPV 6/11 was 9.7% in abortion applicants, 72.2% in female STD patients, and 91.3% in male STD patients. The relative proportion of high-risk HPV types, such as 16/18 and 31/33/35, was 89.7% among abortion applicants, 38.9% among female STD patients and 13.0% among male STD patients. The majority of abortion applicants infected with HPV were thus infected with a potentially oncogenic HPV type, and the prevalence of HPV type 16/18 and 31/33/35 was also high among female STD patients.


Polymerase chain reaction for producing biotinylated human papillomavirus DNA probes for in situ hybridization. Polymerase chain reaction (PCR) was used to produce biotinylated DNA probes for human papillomavirus (HPV) types 16 and 18. The specificity and sensitivity of the probes were tested with in situ hybridization to detect HPV DNA in cervical biopsies or cell lines (CaSki, SiHa, and HeLa). The Gene Amp DNA Amplification kit (Perkin-Elmer Cetus, Norwalk, CT) was used to perform PCR according to the manufacturer's instructions, except that dTTP was substituted by different concentrations of biotinylated dUTP (bio-11-UTP). As the template DNA, the DNA extracted either from CaSki or HeLa cells was used. The reaction mixture was taken through up to 40 cycles of amplification in a Perkin-Elmer Cetus Thermal Cycler (Perkin-Elmer Cetus, Norwalk, CT). The highest yield was achieved when the concentrations of dTTP and biotinylated dUTP were 150 microM and 50 microM, respectively. In situ hybridization results compatible with those obtained with biotinylated or radioactively labelled whole genomic HPV DNA probes were demonstrated when primers from E6, E7, and L1 ORF of the HPV 18 were used to produce the biotinylated probe by PCR. With HPV 16, the positive signals were always weaker with the PCR probe than with the whole genomic probe. Overall, the PCR probes might have a lower sensitivity than the whole genomic probes. The background stain was always stronger with the PCR probes than with the whole genomic probes, especially with HPV 16 probes. There does not seem to be a clear correlation between the sensitivity of PCR probes and the size or nucleotide content of the probe.


Inhibition of neuromuscular transmission in isolated mouse phrenic nerve-diaphragm by the enterotoxin of Clostridium perfringens type A. The enterotoxin of Clostridium perfringens type A, a channel forming protein toxin, inhibited neuromuscular transmission under conditions of low calcium. Twitch tension of isolated phrenic nerve-diaphragm preparations elicited by electrical stimulations to the phrenic nerve was recorded isometrically, and the preparations were exposed to the purified enterotoxin. In Krebs solution containing 0.5 mM calcium, the enterotoxin (20 micrograms/ml) reduced within 10 min the amplitude of the twitch tension to 34 +/- 7% (mean +/- S.D., n = 11) of that recorded before the treatment. The effects of the enterotoxin on the twitch tension were irreversible and proceeded independently of stimulation. The reduction of the twitch tension by the enterotoxin was apparent in Krebs solution containing less than 0.6 mM calcium and the degree of reduction was inversely related to the concentration of calcium. The reduction of the twitch tension by the enterotoxin was also dependent on temperature and concentration of the toxin. At temperatures below 20 degrees C, no obvious reduction of twitch tension was observed with 20 micrograms/ml of the enterotoxin. Enterotoxin at a concentration of 0.4 micrograms/ml caused 16 +/- 2% (mean +/- S.D., n = 4) reduction of twitch tension, and the degree of the reduction in twitch tension increased with toxin concentration, reaching a plateau of 65 +/- 4% (mean +/- S.D., n = 7) at 6.5 micrograms/ml of the enterotoxin. The effects of the enterotoxin were antagonized by 2 microM physostigmine. Unlike curare, pretreatment of the preparation with enterotoxin did not antagonize the neuromuscular block by decamethonium. Neither the tension of muscular twitch elicited by direct electrical stimulation to the muscle nor the resting membrane potentials of muscle fibers recorded intracellularly were affected by the enterotoxin. The enterotoxin (2.2 micrograms/ml) reduced the frequency, but not mean amplitude or amplitude distribution, of miniature end-plate potentials, from 0.91 +/- 0.07/sec to 0.72 +/- 0.07 (mean +/- S.E., n = 5). The results suggest that the enterotoxin will provide a novel tool for the studies on the mechanism of the neuromuscular transmission because of the unique characteristics of the inhibition and of the known mechanism of its action on the cell membrane.


Structurally different members of the okadaic acid class selectively inhibit protein serine/threonine but not tyrosine phosphatase activity. The relative potencies of four main types of okadaic acid class compounds as inhibitors of the catalytic subunits of protein serine/threonine phosphatases 1 and 2A and the protein tyrosine phosphatase 1 were determined. These four types of compounds are okadaic acid, calyculin A, microcystin-LR, and tautomycin, which are isolated from different natural sources, a black sponge Halichondria okadai, a marine sponge Discodermia calyx, a blue-green alga Microcystis aeruginosa, and Streptomyces spirover ticillatus, respectively. While okadaic acid was a more effective inhibitor of protein phosphatase 2A (IC50, 0.07 nM) than protein phosphatase 1 (IC50, 3.4 nM), other compounds of the okadaic acid class were equally effective against the two protein serine/threonine phosphatases. The order of potency was microcystin greater than calyculin A greater than tautomycin, and the IC50S ranged from 0.1 to 0.7 nM. None of the okadaic acid class compounds inhibited protein tyrosine phosphatase 1 activity at concentrations up to 0.01 mM. These results indicate that the compounds of the okadaic acid class are selective inhibitors of protein serine/threonine but not tyrosine phosphatases.


Limited small cell lung cancer of the lung treated with combination chemotherapy and radiotherapy: a retrospective analysis. We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3% (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3%). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.


Numerical chromosome aberrations in fibrothecoma. Cytogenetic analysis on a 7-day-old culture of a fibrothecoma showed only numerical chromosome abnormalities: 57, XX, +4, +5, +6, +10, +12, +12, +14, +17, +18, +19, +20. The finding of an extra copy of chromosome 12 in mesenchymal tumors, mostly benign and originating from the female genital tract, may possibly point towards their common embryonic origin.


Targeting of "T" lymphocytes against human hepatoma cells by a bispecific monoclonal antibody: role of different lymphocyte subsets. In an attempt to construct bispecific monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4-8+ TCR alpha/beta+ and CD3+4-8-TCR gamma/delta+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3 + 4 + 8-TCR alpha/beta+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNF-alpha) by all the different subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.


Role of immune response in the prognosis of carcinoma of the uterine cervix: can in vitro analysis provide a better framework for more effective management? Cancer of the uterine cervix is the single largest female malignancy in India and also remains a major problem facing oncologists in other parts of the world. While advances in radiation therapy and surgical techniques have made the treatment of cervical carcinoma impressive, limitations to successful management still remain. In fact, the 5-year survival rate, stage for stage, has not improved in the United States or world wide in the past 40 years. With an estimated half a million women developing this disease annually, this lack of improved survival poses an international unresolved health problem. Immune response has been shown to be a major factor involved in the course of the disease for this cancer. Immunologic monitoring was also shown to be of effective value in assessing the prognosis for cervical carcinoma. We studied the various immunologic abnormalities in cervical cancer, the effects of radiation therapy on immune function, prospects of an immunologic staging system, the relationship between human papillomavirus infection and the immune response, and the possibility of using in vitro immunologic assessment to provide a better framework for more effective management of cancer of the uterine cervix.


Major core proteins, p24s, of human, simian, and feline immunodeficiency viruses are partly expressed on the surface of the virus-infected cells. We have previously shown the expression of human immunodeficiency virus type 1 (HIV-1) major gag protein, p24, on the surface of persistently HIV-1-infected cells by using murine monoclonal antibodies (mAb). We now report that the cell surface gag p24 antigen expression is a universal phenomenon among HIV-1, simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). The mAbs prepared by immunization with purified HIV-1 particles were used as antibodies cross-reactive to HIV-1 and SIVagmp24 antigens. The mAbs to FIV p24 were raised against the gag precursor 50 kDa protein of FIV, which was expressed by Baculovirus vector. The p24 antigen expression on the cell surface was detectable in certain combinations of virus-host cell systems in all of these viruses. Since these p24 regions of the animal viruses seem to play as important a role in cell-mediated immunity as that of HIV-1, the p24 applicability as a candidate epitope for vaccine development could be evaluated in those animals.


Foot and mouth disease vaccine potency tests in cattle: the interrelationship of antigen dose, serum neutralizing antibody response and protection from challenge. The use of tests in cattle remains the basis for evaluating the potency of foot and mouth disease (FMD) vaccines intended for use in cattle. To be able to compare different types of potency test it is essential to have a good understanding of how measurable responses in cattle to vaccination relate to one another. In this paper the interrelationships were examined of log antigen dose (V50), serum neutralizing antibody response (SN50), and protection from challenge (probit), following a single-dose primary vaccination. Estimates of the slopes for each of the three regressions were obtained and these, together with values described by other authors, were used to evaluate how well some of the potency tests for FMD vaccines matched up to Recommendations of the Office International des Epizooties made in 1975.


A potency test method for foot and mouth disease vaccine based on the serum neutralizing antibody response produced in cattle. A method is described for converting a mean serum neutralizing antibody titre after primary vaccination directly into a percentage protection value using a single regression slope. This has advantages over the indirect method in which a potency value is first estimated on the log antigen dose scale before conversion to a percentage protection value, since to do this requires the use of three separate regression slopes. Test designs for the serological method have been formulated that meet the 1975 Recommendations of the Office International des Epizooties, and which possess minimum potency standards at least as high as those of the European Pharmacopoeia's vaccine dose extinction endpoint method.


[Variability of the gyri and sulci of the temporal lobe of human brain]. A study was made of the relief of the temporal lobes from 204 hemispheres of human brain. The authors examined and compared the typological features of the structure of these lobes gyrus. Established the regularities of the construction of temporal gyrus in both hemispheres together with their complexity and diversity, interhemispheric and intertypic asymmetry. Showed variability and complexity of the typological signs to be most pronounced in the areas of the temporal lobe connected with the acoustic center of speech.


[The potential-dependent incoming ionic currents of myoblasts from the frog Rana temporaria developing in culture]. Voltage-dependent inward ionic currents in 1-6-day cultured skeletal myoblasts have been studied using whole-cell patch clamp technique. Sodium (INa) and two types of calcium (ICa) currents were recorded at all stages. INa did not differ from that described in frog striated muscle fibres. Both types of ICa were found to be DHP-sensitive. They differ in their activation time. It is suggested that two types of ICa correspond to ICa of twitch and tonic muscle fibres.


[Indicators of cellular immunity in patients with multiple sclerosis]. As many as 111 patients with multiple sclerosis were subjected to clinical and functional examinations twice: on admission to the hospital and after immunocorrective therapy. The patients were discovered to have alterations in cellular immunity. During exacerbation, there was a decline of suppressors and a rise of the content of B lymphocytes. The immunocorrective therapy led to immunodeficiency stabilization.


[Clinico-immunological monitoring of the condition of patients with multiple sclerosis]. The clinico-immunologic monitoring of 50 patients suffering from genuine multiple sclerosis by means of the clinical, neurophysiological and immunologic methods and NMR tomography attests to the relationship between changes in the clinical and immunologic characteristics. The changes in the immunologic characteristics were found to anticipate the clinical ones. The authors provide evidence for the possibility and necessity of the clinico-immunologic monitoring of the patients' status for predicting the further course of the disease.


[Results of clinico-immunological testing of myelopid in chronic forms of multiple sclerosis]. Forty patients with a verified diagnosis of multiple sclerosis (MS), the majority of whom had the secondary progressive form of the disease, received a short-term treatment with myelopid (MP). After this 10 patients were given a long-term treatment with MP. The clinical trial was carried out by the double blind method using placebo. The patients' status was estimated by special evaluation scales (clinical), immunoassays (the content of T lymphocyte subpopulations, reaction of blast transformation of leukocytes to mitogens under different conditions of cultivation including that in the presence of 0.3 micrograms/ml MP, by assessment of the production and activity of interleukin-2), by the method of evoked potentials and NMR tomography. 60% of the patients manifested an improvement of the clinical status after the short-term MP treatment, which was accompanied by positive dynamics of evoked potentials and a decrease of the functional activity of the cells in the reaction of blast transformation of leukocytes. In such patients, MS ran a more favourable course during 0.5-1.5 years of observation. In 8 patients with the immunologic signs of the pathological process activation, the clinical status worsened after MP. The correlation and regression analyses allowed one to specify the clinico-immunologic indications and contraindications for MP administration. The clinico-immunologic changes noted were not recorded after placebo. In the patients receiving the long-term treatment, one could see a further decline of the functional activity of the cells in the reaction of blast transformation of leukocytes, a rise of the content of T suppressors/killers in the blood, a favourable clinical course of MS.(ABSTRACT TRUNCATED AT 250 WORDS)


[A variant of amyotrophic lateral sclerosis]. The results of the clinico-morphological studies carried out in 30 patients with the anterior-horn variety of amyotrophic lateral sclerosis (ALS) (CNS morphology was investigated in 6 cases) demonstrate this variety to be characterized by early fading of the tendinous periosteal reflexes, rapid development of amyotrophies, weak intensity of pyramid system lesions. This is supported by morphological studies of the CNS and allows advancing an opinion in favour of the priority of motoneuronal injury.


[Pathogenesis of retrobulbar neuritis].

[Pathogenesis of retrobulbar neuritis]. Biological fluids from 146 patients with retrobulbar neuritis were examined for the biochemical, immunochemical and immunologic characteristics that mirror destructive processes in myelin and changes in the system of the cholinoglycine cycle which is one of the stages of the synthesis of myelin in the oligodendrocyte. In the majority of observations, the changes in these reactions of different directions and of varying intensity were revealed. Based on the data obtained the conclusion is made that part of the patients with retrobulbar neuritis may be attributed to multiple sclerosis since according to the laboratory findings, the demyelinating process occurring in them goes beyond optic nerves. Besides, it has been shown with special reference to retrobulbar neuritis that the primary affect, possibly of the viral nature, is likely to be localized in the oligodendrocyte, with myelin being involved in the process for the second time.


[Mathematical analysis of permeability of the blood-brain barrier in bacterial meningoencephalitis]. Atomic-absorption spectrophotometry was used to measure the concentration of certain metals in the blood and CSF in 70 patients suffering from bacterial meningoencephalitis depending on the gravity and stage of the inflammatory process. Probability statistical and correlation analysis of the content of metals in the blood and CSF made in possible to depict the status of permeability and different transformations that regulate the functions of the blood-brain barrier in patients seen over time.


[Permeability of the blood-brain barrier for metals in bacterial meningoencephalitis]. A study was made of blood-brain barrier permeability for metals in 50 patients depending on the period and gravity of bacterial meningoencephalitis. Selective permeability of the blood-brain barrier for metals is aimed in different periods of the inflammatory process at the retention of the mineral composition of the cerebrospinal fluid within the limits required for normal function of the central nervous system.


[Status of cellular immunity in viral, serous and meningococcal meningitis]. The paper is concerned with the immunological status of 62 patients with meningococcal and viral serous meningitides. A noticeable inhibition of cellular immunity, more pronounced in the CSF was detected. A correlation was shown to exist between the level of humoral factors that block T lymphocyte receptors in the CSF and the disease gravity.


[Serous meningitis in Lyme's borreliosis]. The authors relate the results of clinical, epidemiological, immunological, neurophysiological, EMG, ED and REG studies in patients in the early period of Lyme's disease. The patients with clinical and subclinical signs of nervous system lesions and those with serous meningitis were examined. Different levels of the impairment, multiple neuropathies running a subclinical course, interest of the subcortical brain structures and spinal motoneuronal pool are demonstrated. Cases of the mixed infection (tick-borne encephalitis and borreliosis) were revealed. 91% of the patients (50 cases out of 55) were verified serologically.


[Clinical forms of acute herpetic infections of the central nervous system in adults]. The authors describe the course of herpetic encephalitis in 52 patients aged 16 to 64 years. Five types of the initial manifestations of herpetic infection of the CNS were revealed. In 44.3% of cases the disease started from the general cerebral symptomatology and consciousness disturbance; in 13.6% it started in a brain stroke-like manner followed by the development of the comatose status; in 13.6% of cases from memory disorder and unmotivated actions; in the same percentage of cases, the disease onset was marked by the dominance of dizziness, diplopia, ataxia and central hemiplegia ; in 15.9% the disease started from pains in the stomach, loin and lower limbs. Hemispheric and pseudotumorous stem encephalitides (48.1 and 13.6% respectively) were predominant; in 25% meningoencephalitides and in the remainder, encephalomyelitis running their course in the form of disseminated encephalomyelitis (5.7%), focal myelitis (5.7%) or opticomyelitis (1.9%). The data presented attest to the pleomorphism of the clinical picture of herpetic lesions of the CNS.


[Virolex in the treatment of herpetic diseases of the nervous system]. The authors relate the results of the use of virolex (acyclovir), a new etiotropic agent, for the treatment of some herpetic lesions of the nervous system. The use of the drug for the treatment of herpetic encephalitis, one of the gravest forms of encephalitides, exerts a beneficial effect. In the course of the treatment, it is of paramount importance to adhere to the established time of therapy, since the disease may recur. The treatment with virolex of different forms of herpes zoster in children and adults brings about positive results as well.


[Evaluation of the effectiveness of various methods of the treatment of tick-borne encephalitis in the acute period]. To reveal the dependence of the efficacy of the treatment of tick-borne encephalitis (TBE) on the patient's HLA phenotype and to elaborate recommendations for individual treatment, 98 subjects who suffered TBE and who received different types of therapy in the acute period (isolated or combined use of specific homologous immunoglobulin and RNase) were subjected to immunogenetic examinations. The clinical follow-up and immunological examination of the subjects indicated made it possible to distinguish groups with a favorable and unfavourable outcome due to the treatment carried out in the acute period. Computer processing of the immunogenetic data on the patients with TBE allowed the deriving of individual predictors of the efficacy of the symptomatic and etiotropic therapy of TBE. The final effect due to the application of agents possessing an immunomodulating effect on specific humoral immune response is determined not only by the gravity of viral infection but is also associated with a number of allele variants of HLA complex genes which the patient has.


[Status of the nervous system, bioelectric activity of the brain and regional hemodynamics in early latent forms of syphilis]. Patients with early and early latent forms of syphilis were examined for the status of the nervous system, brain bioelectrical activity, cerebral and peripheral hemodynamics, and microcirculation. The methods of a comprehensive study of the above parameters can be recommended for practical use to neuropathologists and dermatovenereologists, enabling early diagnosis of nervous system lesions, choice of a method of correcting the revealed deviations, and evaluation of the treatment efficacy. The same methods may turn out instrumental in preventing late forms of neurosyphilis.


[Rheoencephalography as an indicator of disorders of cerebral circulation in patients after myocardial infarction]. As many as 103 men who suffered myocardial infarction were examined for the clinical and functional manifestations of cerebral circulatory disorders as well as for the coronary heart disease at rest and during bicycle ergometry. The majority of the patients with postinfarction cardiosclerosis were found to have changes in the rheoencephalograms, augmenting with physical exercise. Those changes were most pronounced in patients with the clinical manifestations of atherosclerosis of cerebral vessels and in the presence of angina pectoris. The simultaneous recording of the rheoencephalogram and electrocardiogram during bicycle ergometry can be used for an all-round estimation of the reserves of cerebral and coronary circulation in patients suffering from coronary heart disease and elaboration of rehabilitation measures.


[Clinical course and treatment of acute inflammatory demyelinating polyradiculoneuropathy (Landry-Guillain-Barré syndrome)]. Motor, sensitive and vegetative disorders were subjected to a clinical analysis in 40 adult patients with Landry-Guillain-Barre syndrome in the acute disease stage and during rehabilitation. Investigation of the cerebrospinal fluid and of the rate of the nervous impulses conduction in the peripheral nerves has demonstrated that in the majority of the patients, the clinical findings did not correlate with the laboratory ones. Early diagnosis and rational therapy with plasmapheresis and glucocorticoids ensured a favourable prognosis.


[The automated system of registration of patients with mental disorders using personal computers]. The authors review problems of the design of an automated system of registration of psychoneurological patients by personal computers intended for the data servicing of the supervisors of the regional psychiatric hospital (head physician, heads of departments) and some other persons from the medical personnel. Describe the main functions and potentialities of the system.


[Anaplastic adenomas of the pituitary gland]. A clinical analysis of 108 cases of anaplastic hypophyseal adenomas (AHA) was performed to formulate the clinical AHA symptom-complex and to study their biological peculiarities. AHA is a transitory type from benign to malignant tumors. It accounts for 2.5-18% of all hypophyseal adenomas. The anamnesis period is surprisingly short even in cases of large and giant neoplasms. It is suggested that the tumor becomes malignant in a certain stage of its development and grows rapidly. Hence the tendency of AHA toward bleeding caused by insufficient blood supply of the rapidly growing tumor. Asymmetric visual function disturbance and vast destructive changes in the bony base of the skull are common to AHA. Cavernous sinus invasion and oculomotor nerve involvement were observed in all the patients in different combinations. The frontal and temporal lobes and oral stem regions were often affected. Having once emerged, the cerebral signs progressed due to tumor influence on the ventricular system. AHA were ectopic in 3 cases, with adenohypophyseal tuberculum origin. Taken as a separate group, AHA may serve more differentiated choice of surgical treatment, radiation and drug therapy of the tumor.


[Characteristics of sleep apnea syndrome in neurological practice]. The authors demonstrate the high prevalence of snoring among patients with different patterns of neurological pathology. It is very essential since snoring is a marker of apnea in sleep (AS). A nocturnal polygraphy study was carried out in 55 patients with AS. In central and mixed apnea, the structure of the sleep was found to be relatively intact whereas in obstructive apnea, the sleep was grossly disordered. In obstructive AS, the index of apnea was higher in the slow sleep phase, in central AS, in the fast sleep phase.


[Mental disorders after amputation of the extremities]. Analysis of the dynamics of the disorders has shown that in the acute period following trauma, the patients' status was "abnormal personality in nature, being determined by affective and shock reaction in the hyperkinetic and hypokinetic forms. The subacute period was characterized by the predominance of posttraumatic stress disorders (PTSD), whereas the long-term posttraumatic period by personality disorders pertaining to the asthenic (type I) and asthenic (type II) sphere. The clinical characteristics of type I patients was determined by a range of asthenic, psychasthenic, autistic, sensitive, subdepressive, and hystero-conversion disorders, whereas from the clinicopsychological standpoint, by a high level of somatization, anxiety, depressive disorders, with the aggressiveness level corresponding with normal. It has been established that social rehabilitation of such patients requires measures aimed at an increase of the activity and improvement of communicative functions. Hypoparanoic, excitable and ++hystero-histrionic disorders were common to type II cases. Clinical and psychological examinations have revealed a high level of aggressiveness and anxiety, depressive disorders; somatization was found to be within normal. Social rehabilitation of such patients is to be reduced to a great measure to the correction of deformed personality lines.


[Psychosomatic interrelations in patients with ischemic heart disease and exercise-induced stable stenocardia]. A comparative analysis of the mean profiles of the clinical scale and MMPI in patients with associated coronary heart disease and stable angina pectoris of effort with and without MI revealed an augmentation of the intensity of mental disorders and changes in the personality psychological traits that deteriorate the coping with the social environment because of MI and aggravation of the function of the cardiovascular system.


[Use of hyperbaric oxygenation in the treatment of acute cerebrovascular disorders in ischemic heart disease]. Altogether 22 patients with concomitant cardio-cerebral acute pathology underwent all-round examinations during and after sessions of hyperbaric oxygenation (HBO). The highest clinical effect was produced by minor, substituting doses of HBO. The revealed phasic nature of the action of HBO in the treatment of patients with acute large-focal myocardial infarction and acute cerebrovascular disorders was found to be due to changes in the function of diencephalic and brain stem formations, determining the decrease of adaptation potentialities in this patients' group. HBO was found to be clinically effective in the treatment of such patients. In order to raise the treatment efficacy, it is necessary that an individual approach be exercised in the choice of therapeutic HBO sessions.


[Asthenic disorders in the clinical picture of chronic neurosis-like diseases]. Studies into asthenic disorders associated with somato-infectious pathology and neurosis-like schizophrenia made it possible to reveal certain features. They manifest themselves in the prevailing in schizophrenic patients of the endogenous psychopathological signs over the exogenous ones, in essential relation of asthenic manifestations to specific deficiency. The differences found can be used for more effective nosological identification of chronic-progressive neurosis-like disorders, conditions and diseases.


[Effect of small doses of L-dopa on synergic tonic reaction in patients with childhood cerebral palsy]. As many as 8 patients aged 8-19 years suffering from infantile cerebral paralysis (ICP) with torsion dystonia, akinetic, rigid, spastic and hypotonically atactic syndromes were examined for the maximum amplitude of EMG activity of the musculus tibialis anterior in voluntary rear flexion of the foot and in Strümpell's tibial synkinesia before treatment and after intake of small doses of L-DOPA (nakom, 62 mg/day). It has been established that the amplitude of voluntary EMG activity and the rate of impulse transmission in efferents of the tibial nerve remained practically unchanged during treatment; in all the cases, the synergic EMG activity, discharges of EMG and prolonged activity decreased; the scope of active movements in the talocrural joint increased by 10-20 degrees. The greatest decrease of synergic EMG activity (by 40%) was recorded in patients with rigid muscle tone, the mean in patients with spastic and spastic -dystonic (by 25-33%), the least one (17%) in muscle hypotonia. It is assumed that voluntary and synergic automatic movements have varying neuromediator supply. The effect of L-DOPA is realized via changes in the function of suprasegmental brain structures regulating polysynaptic postural reflexes with primary action on extensors. The effects of the subcortical nuclei, stem and cerebellar systems are made possible by dopamine neuromediation to a different measure.


[Functional sensory and motor asymmetry profile in patients with neuroses and those with diseases of the digestive system]. Functional sensorimotor asymmetry (FSMA) was analyzed in 21 healthy volunteers, 19 neurotic patients and 29 patients suffering from alimentary diseases. Among the neurotic patients, there prevailed those with the left profile of FSMA as compared to the group of healthy persons. As to the group of the patients with alimentary diseases, a subgroup of persons with no disturbances of emotional information perception by the neurotic type was distinguished according to the psychophysiological characteristics. Among those persons in the given representative sample, none showed the left and symmetric profiles of FSMA.


[Ethnic factors and their relation to the pathogenesis and geography of multiple sclerosis]. Epidemiological and immunogenetic studies made in patients with multiple sclerosis (MS), carried out for the first time in Uzbekistan, demonstrated the varying disease incidence in 4 populations: Uzbek, Tadjik, Russian and Tatar. In Uzbeks and Russians, a significant relationship was established between MS and antigen HLA-B7 carriership. A correlation was noted between the low incidence of MS among Uzbeks (0.8:100,000) and the higher among Russians (11.5:100,000) and the low prevalence of antigen HLA-B7 in the Uzbek and the higher one in the Russian population. It has been shown that the use of the medico-geographic mapping to specify the nature of MS is ineffective without regard to ethnic factors.


[Clinical variants of neuropsychological disorders during remission in chronic alcoholism]. To study the psychopathological characteristics of remissions in alcoholism, 142 patients aged 32 to 45 years were examined. The anxious hypochondriac, neurasthenia-like, asthenic-depressive, anxious suspicious, anxious depressive, excitable, euphoric, apathetic, dysphoric syndromal variants are described. Correlation of the indicated syndromal variants with the other clinical characteristics of alcoholism made it possible to distinguish a favourable and relatively unfavourable type of remission, providing a possibility of differentiating between the treatment and rehabilitation measures in patients suffering from alcoholism.


[Clinical course of poisoning with volatile substances of "Moment-1" glue]. Clinical and psychopathological methods were employed to examine 30 adolescents aged 13-17 years, who exhibited the liking for inhalation of Moment-1 glue vapours. Adolescents from unhappy and alcoholic families were found to be most prone to the toxicomania type in question. The premorbid condition of the adolescents was characterized by the psychopathological personality traits of the unstable type. The intensity of the psychopathological disorders correlated with the patients' age and residual organic brain injury. Combinations of certain volatile organic solvents contained by Moment-1 glue were found to be highly hallucinogenic and neurotoxic. Neurotoxicity was marked by rapid-growing signs of a decrease of the personality level by the organic type. In some cases, there were acute severe poisonings and lethal outcomes. The adolescents described may be attributed to a group at risk for alcoholism and substance abuse. As a rule, it is necessary to perform multimodality treatment to be given in three stages: detoxication therapy, administration of nootropic agents and correctors of behavior, individual and group psychotherapy.


[Changes in the cellular immunity factors in suppurative complications of penetrating craniocerebral trauma]. The authors examined patients with penetrating cerebrocranial trauma (CCT) and uneventful course of traumatic disease (30) and those with CCT complicated by intracranial purulent process (24 persons). A direct correlation of the marked character and severity of the clinical course of the posttraumatic period and the changes in the immune system was revealed. Increase of the level of neutrophil rosette formation, indices of the NST test, the activity and intensity of neutrophil phagocytosis in penetrating CCT allows the development of an intracranial purulent process to be predicted at an early stage before the appearance of clinical sings. Decrease of the number of spontaneous rosette-forming and formazan-positive neutrophils is an indication of an unfavourable course of an intracranial purulent complication with a fatal outcome.


[The CT-stereotaxic neutron brachytherapy of brain tumors with californium sources on the ANET-B apparatus]. A method for stereotaxic intratissue radiotherapy of brain tumors based on the findings of computed tomography is described. Radiosurgical implantation of sources with increased 252Cf content emitting mixed neutron + gamma-radiation was accomplished by means of an ANET-B apparatus by the afterloading method. Neutron irradiation is particularly effective in patients with malignant tumors possessing a large fraction of cells in a state of deep anoxia. Dosimetric planning was conducted by means of an original computer system. Devices and radiation-technical equipment for adaptation of the ANET-B apparatus for irradiation of neurosurgical patients are described. The indications for the use of this method and its place among the complex of measures for the treatment of patients with new growths of the brain are discussed. The first experience in using CT-stereotaxic neutron brachytherapy with californium sources on the ANET-B apparatus for the treatment of 6 patients with malignant glial tumors of the brain is dwelt on.


[The reinnervation of a skin-fascia autograft after its microsurgical transplantation on neurovascular supports]. The dynamics of the restoration of sensitivity of 40 free dermo-fascial grafts was studied: radial from the forearm, dorsal of the foot, deltoid, periscapular, and lateral graft of the upper arm. Effective degree of reinnervation of neurovascular grafts, a radial graft in particular, 12-18 months after a microsurgical operation was shown. The restoration of nerve connections of 63 grafts was appraised in dog experiments by means of a complex of histological and micromorphometric methods. The sources of nerve fiber growth from the sutured cutaneous nerve of the graft along the distribution of the paravasal nerve plexuses were identified. The rate of reinnervation of the graft from the adjoining tissues is determined by the characteristics of the recipient seat and the size of the graft.


[Phonoangiography in aneurysms of the cerebral vessels]. Phonoangiography was conducted in 113 patients with various diseases of the brain. From comparison of the findings of clinical and angiographic examination the authors defined typical phonoangiographic criteria for the diagnosis of arterial and arteriovenous aneurysms of the brain which can be used in out- and inpatient practice.


[A case of hepatoma patient who showed an abnormally high level of serum IRI with the beads method]. A fifty four years old hepatoma patient admitted to the hospital for a surgical operation. Preoperative laboratory examination demonstrated that his serum IRI level was very high (423 microU/ml) when measured with a beads method, however RIA or a microplate method demonstrated normal values. We studied the mechanism of the discrepancy of IRI values. 1) Both the beads and microplate methods demonstrated the same IRI values when the patient's serum insulin was roughly purified with Sep-Pak. The beads method showed high IRI values in serum which passed through Sep-Pak, therefore contained no insulin. 2) The similar results were observed when the patient's serum fractionated by a gel-chromatography (Biogel P-30). The beads method demonstrated high IRI values in both insulin fractions and the fractions containing serum proteins bigger than 40,000 molecular weight. The microplate method demonstrated only one large peak of insulin. 3) When non-specific IgG of guinea pig was used as a fixed antibody instead of human insulin antibody of guinea pig that was used in the beads method, the patient's serum showed the similar values as that obtained with the beads method. We thereby concluded that the abnormal level of IRI by the beads method was derived from the unknown substance reacting with IgG of guinea pig in the patient's serum. After the surgical resection of hepatoma, the levels of IRI measured by the beads method decreased significantly, suggesting that the substance is related to hepatoma cells.


[Evoked potentials in the diagnosis of traumatic lesions of the brachial plexus]. The level of damage to the brachial plexus in different forms of trauma was appraised in 106 patients with traction trauma of the plexus by means of evoked potentials (EP)--short-latent somatosensory EP and EP of peripheral sensory nerves. Whether the plexus was damaged on the pre- or postganglionic level was the main question. The corresponding changes of the electrophysiological values characterizing pre- or postganglionic level of the damage to the plexus were noted, they were verified during the operation. Correlation of the electrophysiological values and the results of myeloradiculography was revealed. Electrophysiological diagnosis is most informative in damage to the plexus at one level (pre- or postganglionic, total or partial) and in combined damages (when some radices are injured on the pre- and others on the postganglionic level). The diagnosis of multiple injuries to the plexus based only on electrophysiological methods is impossible; only one level of the damage is diagnosed.