Postural proprioceptive reflexes in standing human subjects: bandwidth of response and transmission characteristics. 1. This study investigated the reflex control of postural sway during human bipedal stance. The experiments were designed to: (i) find evidence for the operation of 'stretch reflex' pathways during quiet stance, (ii) determine the bandwidth of the reflex response, (iii) describe the reflex transmission characteristics in standing subjects, and (iv) assess the ability of subjects to make a task-dependent change in the reflex. 2. A continuous random perturbation that did not threaten stability was applied at waist level to nine standing subjects. The effects of the perturbation on ankle torque, ankle movement and soleus electromyographic activity (EMG) were identified by cross-correlation. The bandwidth of the reflex response and the transmission characteristics of reflexes that respond to ankle movement were identified by spectral analysis. Changes in these reflex responses were investigated when subjects attempted to stand as still as possible, had their eyes closed, or balanced a load equivalent to their own body in a situation in which neither visual nor vestibular reflexes would be activated. 3. When standing, a reflex response coherent with the perturbation was seen in soleus EMG at frequencies up to 5 Hz, with maximal coherence at 1.0-2.0 Hz. Reflex gain increased with frequency, and there was a frequency-dependent phase advance of soleus EMG on ankle movement reaching 135 deg at 3 Hz. When attempting to minimize sway, subjects produced a more coherent reflex response and significantly increased reflex gain. 4. The response and transmission characteristics of the lower limb proprioceptive reflex in freely standing subjects were similar to those in subjects balancing a load at the ankle, a situation in which vestibular and visual inputs could not contribute. 5. It is concluded that reflex feedback related to ankle movement contributes significantly to maintaining stance, and that much of the reflex response originates from lower limb mechanoreceptors stimulated by ankle rotation. Although reflex gain may be relatively low during quiet stance it can be increased when necessary to maintain stability.


Na+ current densities and voltage dependence in human intercostal muscle fibres. 1. Voltage-clamp Na+ currents (INa) were studied in human intercostal muscle fibres using the loose-patch-clamp technique. 2. The fibres could be divided into two groups based upon the properties of INa. The two groups of fibres were called type 1 and type 2. 3. Both type 1 and type 2 fibres demonstrated fast and slow inactivation of INa. 4. Type 1 fibres had lower INa on the endplate border and extrajunctional membrane than type 2 fibres and required larger membrane depolarizations to inactivate Na+ channels by fast or slow inactivation of INa. 5. Type 2 fibres had a higher ratio of INa at the endplate border compared to extrajunctional membrane than Type 1 fibres. 6. Measurement of membrane capacitance suggested that the increase in INa at the endplate border was due to increased Na+ channel density. 7. Histochemical staining of some fibres suggested that type 1 fibres were slow twitch and type 2 fibres were fast twitch. 8. Differences in the properties of Na+ channels between fast- and slow-twitch fibres may contribute to the ability of fast-twitch fibres to operate at high firing frequencies and slow-twitch fibres to be tonically active.


Mouse hepatitis virus A59 increases steady-state levels of MHC mRNAs in primary glial cell cultures and in the murine central nervous system. Infection of mixed glial cell cultures with mouse hepatitis virus (MHV)-A59 results in an approximately six-fold increase in the level of major histocompatibility complex (MHC) class I mRNA. In situ hybridization of glial cell cultures infected with MHV-A59 again showed enhanced MHC mRNA expression, both in infected and uninfected cells. These results extend our earlier finding that MHC surface antigens are enhanced on astrocytes and oligodendrocytes after MHV-A59 infection and suggest that this enhancement is a result of an increase in the steady-state level of MHC mRNA. We further demonstrate that increases in MHC mRNA occur in the murine central nervous system (CNS) following infection in vivo. Northern blot analysis of RNA from the brains of infected animals showed transient expression of both MHC class I and class II mRNA over the first 14 days of infection. Expression coincided with viral replication and clearance. In situ hybridization of brain sections from infected animals showed that class I and class II expression was widespread throughout all portions of the brain and in uninfected as well as infected cells. Viral RNA, in contrast, was observed in small foci of cells and mostly within the limbic system. Thus enhancement of MHC mRNA was not restricted either to areas of infection or inflammation. The spatial relationship between viral and MHC expression supports our hypothesis that a soluble mediator is involved in the mechanism of the increase in MHC levels. The fact that MHC induction occurs in vivo as well as in vitro suggests MHC may be important in the mechanism of MHV-induced disease.


Soman-induced phosphoinositide hydrolysis in rat hippocampal slices: biochemical characterization. The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman were investigated on different receptors coupled to phosphoinositide (PPI) breakdown on hippocampal slices in vitro. We observed that muscarinic receptor subtypes M1 and M3 are involved in the increase of intracellular inositol phosphate, which is consistent with the procholinergic effect of soman induced by inhibition of AChE. Although the M2 receptor subtypes are known to be coupled to the cAMP second messenger, we demonstrated that in vitro, under soman, they are also involved in the PPI turnover. The other receptor subtypes known to be linked to PPI hydrolysis are not involved in this model of stimulation.


Distribution of transuranic elements in bone. The transport, retention, and excretion of transuranic elements from the body have been widely studied for many years. A summary of the results is given with an emphasis on the distribution of these elements in bone. Implications of these studies for understanding the relationships between lead in blood and lead in bone are presented. The expected distribution of lead at various bone sites is also considered.


[Ambulatory treatment of deep venous thrombosis. From data of a study of 108 patients, an evaluation of its cost and its efficacy]. The study deals with the efficiency and the cost of an ambulatory treatment of deep venous thrombosis by means of Fraxiparine, contention and phlebotonics. 108 patients have been treated. The thrombosis affected the deep veins of the leg in 26 p. cent, the popliteal vein in 9.2 p. cent, the femoropopliteal axis in 19 p. cent as well as superficial thrombosis extended to the depth in 16.6 p. cent. The diagnosis was performed clinically and by ultrasound when phlebography was used in a few cases only (7.4 p. cent). The initial treatment lasted 9.8 days (75 p. cent) 15 days (12 p. cent) and more (12.8 p. cent). Complete re-permeabilization has been noticed in 35.8 p. cent on the 10th day, in 57.5 between the 15th and 30th day. Beside some minor complications 2 recurrences of the thrombosis occurred and 2 patients presented Pulmonary Embolism. They were sent to hospital. The average cost for a treatment was 789 FF for consultation, 1,818 FF for nursing, 1,405 FF for Fraxiparine and 325 FF for contention. hospitalization is sometimes indispensable, sometimes avoidable ... let us make a good choice.


[Klippel-Trenaunay-type syndromes].

[Klippel-Trenaunay-type syndromes]. Seeing the diversity of the clinical look and of the subjacent malformations of the Klippel and Trenaunay Syndrome the following questions can be put forward: must the term KT be kept up? If not how to replace it? The mesoblastic sheet includes angioblastic, lymphoblastic and osteoblastic lineages. Each of them gives rise to malformations. All the malformations and all the signs and symptoms they generate may exist alone or mixed, the diversity of association is unlimited. Hence the syndromes too. They cannot be gathered under the sole term of KT. On the other hand to give each of them an eponym would lead to confusion. Therefore the author proposes to limit himself to the use of the term "type KT" when getting in touch with. Once the syndrome is investigated accurately it must be specified by the causal malformations, the associated malformations and the secondary troubles. It is the only way to be understandable and to allow statistical research.


[Proteus syndrome. Expansion of the phenotype. Apropos of 3 pediatric cases]. In 1979 Cohen et Hayden and in 1983 Wiedemann et al. delineated a syndrome consisting of partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. Hitherto the literature pertaining to this syndrome consists of somewhat more than 100 cases of which some, that have been described previously or subsequently under other headings, were rediagnosed as being Proteus syndromes. Of these, more than half show vascular anomalies closely resembling those observed in the Klippel-Trenaunay syndrome, but in the Proteus syndrome appear to be more haphazardly distributed over the integument. We report 3 pediatric patients with the Proteus syndrome, all showing cutaneous angiodysplasias. These patients were initially diagnosed as suffering from "severe or atypical Klippel-Trenaunay syndrome". In one of these, cardiac tumors were observed soon after birth which subsequently showed spontaneous involution and were therefore considered to be rhabdomyomas. In the Proteus syndrome cardiac pathology is rare, and cardiac tumors have not been described previously. Moreover, we observed umbilical hernia in two of our patients, a feature which has hitherto not been reported in patients with the Proteus syndrome. In all our patients a broad thoracic cage resembling a "body-builders chest", asymmetrical and disproportional macrodactyly and broad, flat feet were conspicuous. These broad, flat feet with macrodactyly and large spaces between the first and second digits were designed by the parents of one of our patient as "chimpanzee's feet". Macrodactyly, "chimp's" feet and a broad thoracic cage are considered by us to be clinical hallmarks of the Proteus syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)


[The biphasic creatine kinase release from isolated rat heart induced by global ischemia and early period of reperfusion]. The present study provided a model with which the kinetics of CK release in the early phase of reperfusion was investigated. By using Langendroff method the isolated rat heart was first perfused for 10 min for establishing equilibrium, then stopped for 10 min to establish global ischemia, and finally followed by reperfusion for sample collection in every 15 s for the measurement of CK activity (U/L) as an index of cellular damage. A characteristic biphasic release of CK was shown under condition of 3 min reperfusion with Krebs-Henseleit (K-H) solution without glucose. The 1st peak of CK release appeared abruptly in the first 15 s of reperfusion and the 2nd one, during 120-180 s of reperfusion. The appearance of the 2nd peak was shifted to 30-75 s by adding glucose (11.1 mmol/L) into the perfusate. The 1st peak mainly reflects ischemic injury while the 2nd represents reperfusion injury. Anoxia (95% N2 + 5% CO2) or glucose addition may delay or decrease both peaks, but low Ca2+ (0.05 mmol/L) only delays the appearance of the 2nd peak to 3 min. The results suggest that the oxygen paradox rather than calcium paradox is involved in both phases of CK release. As for low Ca2+ decreasing the 2nd peak may be attributed to its effect of reducing Ca2+ inflow and overload injury secondary to oxygen paradox.


[Role of the central alpha-receptors in the modulation of carotid sinus reflex of rats]. To investigate the effects of the central alpha-receptors on the carotid sinus reflex, phenoxybenzamine (PBZ, 2 micrograms/20 microliters) or yohimbine (Y, 2 micrograms/20 microliters) was injected into the lateral cerebral ventricle (LCV) and intracarotid sinus pressure (ISP)-mean arterial pressure (MAP) relationship curve was constructed and fitted by a Logistic function. The results were as follows: (1) After injection of PBZ into LCV, the ISP-MAP relationship curve shifted upward at a higher ISP level with decreased peak slope and MAP range while the ISP-slope curve shifted downward. (2) After injection of Y into LCV, the ISP-MAP relationship curve shifted upward at a higher ISP level with decreased peak slope and MAP range and increased threshold. The ISP-slope curve shifted downward significantly at 10.64, 15.96 kPa. The peak slope and MAP range of Y group decreased significantly as compared with that of the PBZ group. These results indicated that after blockage of central alpha-receptors the sensitivity of the sinus reflex decreased significantly, and the blockage action of alpha 2-receptor is greater than that of alpha 1-receptor.


[Effects of microiontophoretically applied OMF and U-50488 on spontaneous discharges of respiration related units in the region of nucleus of solitary tract of rat]. It was observed that ohmefentanyl (OMF) and U-50488, when applied microiontophoretically, affected the spontaneous discharges of respiration related units (RRUs) in the nucleus of solitary tract of rat. Of the 44 RRUs recorded, OMF produced depressive effect in 21, excitatory in 7, biphasic effect in 5 while 11 units were not affected. Naloxone administered iontophoretically blocked both the depressive (6 out of 7) and the excitatory units (2 out of 3). Of the 45 RRUs recorded, U-50488 produced depressive effect in 15, excitatory in 5, biphasic effect in 3, while 22 units were not affected. Naloxone blocked both the U-50488 depression (7 out of 9) and excitation (1 out of 2) effect. U-50488 antagonized OMF-induced depression in 4 out of 6 units. The results suggest that depression and excitation produced by OMF and U-50488 may be mediated by different subtypes of opiate receptor.


[Effect of NO-like relaxing factor (NO-LRF) in rat tourniquet shock]. On tourniquet shock (ToS) rat model, it was found that the reactivity of isolated perfused aortic ring to noradrenaline was decreased, while the cGMP content of the aortic tissue was increased. These ToS-induced changes could be potentiated or attenuated respectively by perfusion with NO-precursor, L-arginine, or NO-synthesis inhibitor L-NNA independent of the presence of vascular endothelium. Guanylate cyclase inhibitor, methylene blue, could also attenuate the aortic reactivity. All these results suggest that the aortic musculature can produce a NO-LRF factor capable of lowering the vascular reactivity of the ToS animals. That L-arginine can ameliorate while L-NNA can exacerbate ToS, suggest that NO-LRF do play an adaptive role in the protective mechanism of the organism during ToS.


[The structural-functional organization of G-proteins and their bound receptors]. Recent data on the structure, function and regulation of different types of GTF-binding proteins (G-proteins), playing the key role in transmembrane signalling, and of G-protein-coupled receptors are summarized. Possible mechanisms involved in the receptor-G-protein coupling and G-protein-membrane connection are discussed.


[An electron microscopic study of the behavioral characteristics of human lung tumor cells cultured on soft agar]. The ultrastructure of cells from seven human lung cancers and from the colonies formed by these cells in soft agar was investigated. Tumor cells developed to display the morphofunctional potentials of the initial tumors. Cultured cells of squamous-cell carcinomas contained numerous tonofilaments, those of adenocarcinomas developed microvilli on their apical surfaces and intracellular lumens. On the other hand, cells of squamous-cell carcinomas showed features specific of adenoma epithelium, i.e. well developed microvilli and intracellular lumens. Besides, cells of adenocarcinoma often contained large quantities of tonofilaments considered to be characteristic of epidermoid epithelium. The results obtained suggest a possibility of metaplastic transformation of the lung epithelium.


[The effect of fluorocitrate on oxygen consumption and Ca2+ transport in the mitochondria of liver cells]. The effect of fluorocitrate on oxidative reactions and energy production systems of rat liver mitochondria has been studied. It was shown that oxidation of endogenous substrates and malate with pyruvate as well as the phosphorylation of the added ADP were inhibited by fluorocitrate. Inhibition of oxygen consumption by fluorocitrate induced the efflux of Ca2+ ions from mitochondria and a decrease in the Ca(2+)-accumulating capacity. The effect of fluorocitrate on Ca2+ transport in mitochondria is due to activation of the Ca-efflux pathway in those sensitive to ruthenium red.


[The diagnosis and treatment of hepatopulmonary fistulae of amebic etiology]. The author has analyzed results of treatment of 28 patients with hepato-thoracic complications of amebic abscesses of the liver. Different variations of operative interventions are proposed including the separate (subdiaphragmatic) draining of the cavity of the liver abscess and pleural cavity and in cases of the appearance of bilio-bronchial fistulas--resection of the lung.


[Antioxidants in the combined treatment of acute cholecystitis in middle-aged and elderly patients]. Investigations of the state of processes of lipid peroxidation (PLP) and the antioxidant system (AOS) of the organism performed in 267 elderly and senile patients have shown destabilization of the system "PLP-AOS". The correction of processes of lipid peroxidation with antioxidants improved the course of the postoperative period, decreased the amount of complications and lethality. It allowed a conclusion of the necessity to use antioxidants in the complex treatment of such patients.


[THe role of portal bacteremia and endotoxinemia in the pathogenesis of multiple organ failure in peritonitis]. The indices of portal bacteremia and endotoxinemia, parameters of metabolism, hepatic hemodynamics, the phagocytic function of the liver and leukocyte reaction were studied in 13 patients with diffuse peritonitis of different etiology. Close interconnections of the level of portal toxemia is shown with the degree of activation of the phagocytic function of the liver, changes in hepatic hemodynamics, degree of metabolic disturbances playing an important role in pathogenesis of polyorganic insufficiency as well as the role of leukocytic reaction in microendocrinous regulation of metabolism in peritonitis.


[Antibacterial and detoxification therapy in acute appendicitis]. An analysis of clinical effectiveness of antibacterial therapy, photomodification of autoblood, hemosorption and their combinations was made in 395 patients with acute appendicitis. It was established that no antibacterial and desintoxicating therapy is required in catarrhal appendicitis. The prophylactic application of photomodification of autoblood is thought to be most expedient for phlegmonous appendicitis at the postoperative period, a combination of antibacterial therapy and photomodified autoblood--for gangrenous appendicitis, a combination of antibacterial therapy, photomodification of autoblood and hemosorption--for appendicular diffuse suppurative peritonitis.


[A magnetic field in the combined treatment of suppurative wounds in diabetes mellitus]. Treatment of purulent wounds was carried out in 72 patients against the background of diabetes mellitus. In 42 of them the complex treatment included using magnetic fields. The application of magnetic fields promoted earlier and more pronounced reduction of the intoxication level, stabilization of the antioxidant system of organism and parameters of immune reactivity. The magnetic fields included in the treatment resulted in accelerated necrolysis, appearance of granulations and epithelialization. The duration of treatment became 6.2 days shorter.


[Skin microtransplantation in the surgery of burns (a clinico-experimental study)]. On the basis of experimental and clinical investigations the authors have shown that extensive burns in patients with true deficiency of donor resources might be treated by the method of micro-transplantation of the skin which consists in plasty of the wounds by pieces of auto-skin of small size. The reduction of size of the skin pieces gives the enlargement of the total line of marginal epithelialization and great plasty coefficient as compared with traditional methods of surgical treatment.


[The surgical treatment of severe forms of alkaline reflux gastritis]. An examination of 9 patients with primary and postoperative reflux gastritis has found severe forms subject to surgical correction. When choosing the operative method, not only the intensity of reflux of the duodenal content and the character of alterations of gastric mucosa were taken into consideration but also the cause of chronic disorders of the duodenal patency. In all the patients complete disappearance of preoperative symptoms was noted.


[The treatment of multiple contractures of the fingers]. Under analysis were results of treatment of 93 patients with multiple arthrogenic, dermatogenic and tenogenic contractures of fingers arising after mechanical, thermal and gunshot injuries. The method of distraction with the help of apparatuses developed in the clinic was applied to all the patients. Long-term results were followed-up in 79 patients during 1-12 years. In 73 of them positive results were noted which suggests high efficiency of the method.


[The neurological essence of the "traumatized shin" syndrome]. Fractures of the shin are often accompanied by injuries of muscular and cutaneous branches of the tibial and fibular nerves. In patients with a similar trauma there appears a polyvalent complex of pathological reactions and functional disorders. An experience with treatment of patients with the above pathology allows a conclusion to be made that treatment of neurites should be started from the very first days of admittance of the patients to the hospital.


[The effect of splenectomy on the immune status of children with active liver cirrhosis]. A complex study of parameters of the systemic cell humoral immunity, secretory immune system, functional state and phagocytic activity of neutrophils as well as activity of the complement and its C3, C4 components in 28 children with active cirrhosis of the liver has shown that the disease was accompanied by a generalized disturbance of the immunity mechanisms. Splenectomy in these children was shown to have favorable influence on the immune status, to reduce activity of the immunopathological process in the liver. At the same time, splenectomy results in continuous suppression of neutrophilic phagocytosis which may be a cause of the development of postsplenectomy septic conditions.


[Experience with the use of Soviet interstitial expanders for eliminating soft-tissue defects in the head and neck area]. Extension of the skin with the help of an interstitial expander allows to rationally use local tissues. Soviet models of tissue expanders of different designs were developed and approved in clinic. 46 operations were performed on 23 patients. Effective results of using the expanders were obtained during repairing extensive defects of the hairy part of the head.


[The use of hemoperfusion through a suspension of cryopreserved hepatocytes in acute liver failure]. The present work deals with results of intensive therapy and temporary organ substitution by using hemoperfusion through a suspension of living donor hepatocytes in 71 patients with acute hepatic insufficiency. Hemoperfusion was performed through a suspension of fresh living hepatocytes or through a suspension of cryo-conserved (during 60 days) living hepatocytes. Lethality was 37-42%.


[Experience with unilateral portalization of the adrenal and renal blood in chronic hepatitis]. An experience with treatment of 46 patients with chronic hepatitis and liver cirrhosis with the help of left-sided renoportal venous anastomosis is described. Unsuccessful therapeutic treatment is an indication to operation. In remote period after operation from 50 to 100% of clinical symptoms disappeared in 80% of the patients. Positive dynamics of the results of biochemical analyses and scanning of the liver was noted. The operation is not indicated in patients with formed cirrhosis, portal hypertension over 240 mm water column, decompensation of the liver functions.


Leukotriene C4 receptors in cultured smooth muscle cells from bovine anterior cerebral arteries and microcerebrovasculatures. Specific receptors for leukotriene C4 (LTC4) were identified on smooth muscle cells isolated from bovine anterior cerebral arteries (BACASMC) and bovine microcerebrovasculatures (BMSMC). [3H]LTC4 specific bindings to both cells at a fixed input reached the maxima at 60 min and 20 min, respectively. With incremental inputs of radioligand and a constant cell number, [3H]LTC4 specific bindings reached a plateau indicative of a saturable binding site. Analysis of Scatchard plots demonstrated a single population of high-affinity binding sites in both cells. The dissociation constant (Kd) for BACASMC was 39.2 +/- 1.3 nmol.L-1 and its Bmax was 19.3 +/- 2.1 pmol/10(6) cells. For BMSMC, Kd = 2.0 +/- 0.4 nmol.L-1, Bmax = 157 +/- 13 fmol/10(6) cells. The specific [3H]LTC4 bindings was inhibited by unlabeled LTC4, LTD4 and FPL-55712 (an SRS-A antagonist). The inhibitory rates for BACASMC were 70.4% and 35.3% by LTC4 and FPL-55712 at 1 mumol.L-1, respectively. For BMSMC the inhibitory rates were 96.9%, 73.9%, and 44.9% by LTC4, LTD4, and FPL-55712 at 10 mumol.L-1, respectively.


[Alpha adrenoceptor subtypes in smooth muscles of rat pulmonary artery]. The contributions of subtypes of alpha-adrenoceptor to contraction induced by agonists were studied in smooth muscles of isolated rat pulmonary arteries. The results showed that the antagonizing effects of prazosin on the contraction induced by norepinephrine (NE) or phenylephrine (Phe) were more potent than those of yohimbine. The effect of prazosin against Phe was more potent than against NE, and yohimbine was just the reverse. Preincubation of preparations with chlorethylclonidine (CEC) 50 mumol.L-1, after which only alpha 1A adrenoceptors were left, reduced the vascular contraction induced by NE to 36% of the control (P < 0.01). While in the presence of nifedipine 10 mumol.L-1, during which only the responses of alpha 1B adrenoceptors were left, the contraction was weakened to 70% (P < 0.05). The pKA values of alpha 1A subtype (3.37 +/- 0.34) were smaller than those of alpha 1B (6.64 +/- 0.40, P < 0.01). But the values of KA/EC50 were much higher in alpha 1A than those in alpha 1B. The results suggest that in smooth muscle of rat pulmonary artery both alpha 1 and alpha 2 adrenoceptors exist, but alpha 1 is superior functionally. Both subtypes of alpha 1 adrenoceptor are involved in the contraction induced by NE. Compared with alpha 1B subtype, alpha 1A subtype has a lower affinity but a more reserve and a higher efficacy for NE.


[Facilitatory effect of Pinellia ternata lectin on quantal release of acetylcholine from nerve terminals]. Pinellia ternata lectin (PTL) extracted from the rhizome of Pinellia ternata Briet by porcine thyroglobulin-Sepharose 4B column exhibits hemagglutination activity and carbohydrate binding specificity for mannan. Here we reported the effects of PTL on the resting membrane potential of muscle fiber and on the release of acetylcholine (ACh) from the motor nerve terminals in the phrenic nerve diaphragm preparations of mice. The results showed that PTL increased the frequency of miniature end-plate potential (MEPP). In 30 min after the treatment of the preparation with lectin 100 micrograms.ml-1, the frequency of MEPP reached 20 times higher than that of the control. Addition of mannan 1 mg.ml-1 restored the raised discharge of MEPP to its control level immediately. Similar to the effect of PTL on MEPP frequency, the amplitude and mean quantal content of end-plate potential also increased after PTL. At 100 micrograms.ml-1, the lectin depolarized the muscle membrane slightly, while at 10 micrograms.ml-1 no effect on the membrane potential was found. These results were interpreted as the intracellular Ca2+ elevation due to a permeability increase of the nerve terminal to ions after PTL.


[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles]. Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.


[The biochemical aspects of the stimulating action of exogenous RNAse]. A sequence of biochemical reactions in yeast from moment of RNAse interaction with cell membrane to cell division has been studied. RNAse addition in growth medium causes the increase of Ca2+ entering rate in cells in 2.4 times. Under this condition the increase of membrane enzyme adenylate cyclase correlating with the growth of cAMP content in cell and rise of cAMP-dependent protein kinase activity have been observed. A hypothetic scheme of cellular response on the RNAse effect is suggested.


[Antibiotic-resistant mutants of Bacillus intermedius--producers of a number of enzymes]. New antibiotic-resistant strains Bacillus intermedius--producers of phosphohydrolase and protease have been obtained and characterized. Strain S 19 is the more active producer of extracellular enzymes. Autotrophic mutants obtained on its basis possess reduced activity of phosphohydrolase.


[The use of nucleolytic enzymes (ribonucleases, polynucleotide phosphorylases and endonuclease from Serratia marcescens) for producing initial blocks of synthetic endoribonucleases]. The simplest variant of synthetic substrate-ribozyme complex has been proposed. The schemes of potential ribozyme "subunits" synthesis have been worked out: R1--GCUUGAAACAAA; R2--AAAAACUGAUGAAAGC. The macroscale synthesis of dinucleoside monophosphate ApU, GpC, CpU catalyzed by immobilized ribonucleases of different specificity and preparation of oligoadenylates by hydrolysis of poly-A in the presence of endonuclease Serratia marcescens, as well the synthesis of conservative sequences of potential ribozyme such as ApUpG, CpUpG, GpApU, ApApApG and others have been described.


[The effect of the acute and chronic administration of the opiate receptor antagonist naloxone on the development of fatigue during physical loading in rats]. In chronic experiments with rats during the exercises on a treadmill the ECG was registered and duration of the development of exhaustion was determined under control and under acute (1 mg/kg intraperitoneally 1 hour before the experiment) or chronic (1 mg/kg intraperitoneally, twice a day during 5 days) treatment with the opioid receptor antagonist naloxone. Chronic but not acute naloxone action resulted in increase of the fatiguability: the time of achievement of exhaustion decreased by 55.3% (P < 0.05). In this case the exhaustion developed at lower degree of heart rate than in control. Comparison of data obtained with the results of chronic treatment with the opioid antagonist permits to conclude that the chronic blockade increases the fatiguability to a great extent than chronic activation of opioid system. Possible mechanisms causing this difference are under discussion.


[Breast cancer in males: a study of 15 cases of pure ductal carcinoma in situ]. Ductal carcinoma in situ of the breast is very rare in men, representing 0-7% of all male breast cancers. We analysed 15 cases from a retrospective multicentric series of 404 patients (3.7%). It occurs earlier than infiltrating carcinoma (mean age: 55 years), sometimes before 40 years of age. The main symptoms are bloody nipple discharge or retro areolar mass. Modified radical mastectomy constitutes the basic treatment. Lower axillary dissection can eventually be indicated in comedocarcinoma or in tumors larger than 25 mm. The main histologic subgroup is papillary carcinoma, pure or intracystic. As is the case in women, local recurrence, invasive or not, rarely occurs. Theoretically, the cure rate approaches 100%. However, as in all cases of breast cancer in men, an important number of deaths due to secondary cancer or intercurrent disease have been noted. Until now, no clear etiologic factors have been found.


[Effect of preventive and therapeutical function of jian-pi yi-qi li-shui decoction on cisplatin nephrotoxicity in rats]. The effect of preventive and therapeutical function of Chinese herbs compound prescription Jian-Pi Yi-qi Li-Shui decoction (JPYQLSD) on cisplatin (DDP) and nephrotoxicity of rat. It was carried out that the prescription JPYQLSD had notable result in reducing content of serum urea nitrogen, glucosaminidase, beta 2-microglobulin of the rats (P < 0.05). JPYQLSD also could alleviate inhibition on activity of adenosine triphosphatase (ATP-ase). Pathological examination revealed the protective effect of the JPYQLSD on kidneys of rats. It suggested that JPYQLSD has a good effect on preventive and therapeutical function of Cisplatin (DDP) nephrotoxicity. The mechanism of JPYQLSD was to regulate the energy metabolism of rats.


PCR-aided genomic sequencing of 5' subterminal sequences of the maize transposable element Activator (Ac) in transgenic tobacco plants. The maize transposable element Activator (Ac) carries subterminal CpG-rich sequences which are essential for the transposition of the element. It has previously been shown that the methylation of certain sequences contained in this region can alter their ability to interact with the Ac-encoded protein. The novel hypothesis that the methylation of subterminal Ac sequences is required for transposition was tested. Approximately 150 bp of the 5' subterminal region of the Ac element was examined for the presence of 5-methylcytosines by the ligation-mediated polymerase chain reaction (LMPCR)-aided genomic sequencing method. The methylation status of 22 and 39 cytosines on either strand of the DNA were analysed in each of five different transgenic tobacco cultures carrying transposable Ac sequences. Ten micrograms of tobacco DNA were used for each base-specific cleavage reaction before amplification by LMPCR. All but one of the cytosines were unmethylated. Only a minor fraction of the Ac molecules was methylated at one cytosine residue. It is concluded that DNA methylation at the tested Ac sequences is not required for the transposability of Ac or Ds elements in tobacco cells.


A novel G protein-coupled receptor kinase gene cloned from 4p16.3. Within the Huntington's disease (HD) candidate region of 4p16.3, the D4S127 locus displays strong linkage disequilibrium with the defect and anchors a conserved haplotype found on many HD chromosomes. To isolate genes from this region we have applied the exon amplification technique to overlapping cosmids spanning D4S127. Here, we report the discovery of a new gene encoding a novel member of a family of protein kinases that specifically phosphorylate the activated forms of G protein-coupled receptors. Such kinases are thought to participate in desensitization of specific receptors, thereby blocking further signal transduction. This gene must now be carefully scrutinized to determine whether it might be involved in HD.


Prognostic value of human papillomavirus in the survival of cervical cancer patients: an overview of the evidence. Some studies have suggested that the presence in tumors of nucleic acids from human papillomavirus (HPV) constitutes a prognostic marker of disease severity in cervical cancer. There are two conflicting lines of evidence in this regard. First, the presence of HPV 18 is equated to rapid progression through early disease stages, possibly resulting in a more aggressive clinical course. Although fragmentary, in terms of the clinical and epidemiological basis, this line of evidence has some experimental support. Second, the absence of HPV from the tumor would confer a worse prognosis than if any viral types were present. Unlike the former, the latter line of evidence is not bolstered by experimental data but emerged from persuasive clinical studies, which had adequate sample sizes, used survival end points, and controlled for confounders. The absence of HPV in some tumors could indicate that they originated through different oncogenic mechanisms, perhaps resulting in different cell proliferation rates and, consequently, distinct clinical behavior. On the other hand, HPV detectability could simply be a correlate of other genuine prognostic characteristics, which would explain its association with survival. Both the nature and the mechanism of the prognostic role for HPV in cervical cancer remain to be elucidated. The paucity of studies can be attributed to the labor-intensive nature of assays for HPV. It is hoped that the advent of the polymerase chain reaction method will facilitate the conduct of retrospective studies of archival histopathology specimens and survival information.(ABSTRACT TRUNCATED AT 250 WORDS)


[The effect of prenatal hyper- and hypoglycemia on liver mitochondrial function and carbohydrate metabolism in rat pups]. Hypoglycemia at the initial stage of the prenatal development decreased the level of glucose in the rat blood, increased glucose-6-phosphatase in the liver. Hyperglycemia increase the glucose content in the blood with relatively minor changes of the glucose-6-phosphatase activity and oxidation of hydrocarbonates.


[The effect of hypothermic stress on Na,K-ATPase activity in rat erythrocytes]. After 3-hr cooling stress, the activity of the erythrocytes' Na,K-ATPase was decreased by 28.9 per cent in rats, its complete restoration occurring within 24 hours after the stress. Possible reasons and factors inducing a disorder in the enzyme activity under conditions of hypothermia, are discussed.


[The postamputation syndrome in rats and its neurochemical characteristics]. Noradrenergic and GABA-ergic systems were correlated and dominated in the processes of spinal cord segmentary apparatus superactivity compensation. An increase in c-GMP content in the spinal cord suggests an intensification of the activation mechanism. An increase in the c-AMP content may suggest an inhibition of the compensatory intensification of noradrenergic or GABA-ergic mechanisms.


Itraconazole in the treatment of histoplasmosis associated with AIDS. Twenty-seven patients suffering AIDS and disseminated histoplasmosis were included in this study, comprising twenty-three males and four females, from 18 to 46 years of age (mean = 32.9). The most frequent clinical manifestations were fever, weight loss, anaemia, skin lesions, pulmonary micronodules, hepatosplenomegaly and adenomegalies. All of them presented other infectious diseases or neoplasias frequently found in AIDS patients. The diagnosis of histoplasmosis was based upon the finding of Histoplasma capsulatum in microscopic examination or in cultures from the following specimens: skin scrapings, bone marrow aspiration, bronchoalveolar lavage, blood cultures, buccal biopsies and lymph node biopsy. Serologic reactions, searching for antibodies, were positive in 11 cases. Itraconazole by oral route, at a daily dose of 200 mg (24 cases) or 400 mg (3 cases), was administered for 6 months. Those patients who were clinically cured after receiving this scheme of treatment were treated with itraconazole 100 mg day-1 as a suppressive therapy. Twenty-three patients were considered responders, 1 as a non-responder and 3 non-assessable. The average survival time was 7.8 months and eleven cases are still alive. Itraconazole proved to be a useful medication in disseminated histoplasmosis associated with AIDS and it was very well tolerated.


Activity of topically applied leukotriene B4 in experimental dermatophytosis. In a pilot study to assess the antimycotic potential of the chemoattractant leukotriene B4 (LTB4), guinea pigs were infected with Trichophyton mentagrophytes var. mentagrophytes and divided into groups of untreated control animals or treated daily with LTB4, isoconazole nitrate or vehicle alone. The animals were assessed clinically, mycologically and histopathologically. Treatment with isoconazole nitrate was the most effective. The LTB4-treated group were clinically worse than the non-treated group and the mycological results remained positive throughout the assessment period.


[Diurnal variations in circulating leukocytes and subsets: relation to plasma cortisol and ACTH]. Surface cellular antigens of leukocytes, lymphocytes and corresponding subpopulations have been analysed by using monoclonal antibodies marked with fluorescein (PITC), parallel to those marked with phycoerythrin (PE). Cortisol and ACTH plasmatics have also been determined through RIA, on two samples at 8am. and 8pm. During this twelve hour evolution, a highly significant dependence of the leukocytes, T, T4 and T8 lymphocytes on the circulating ACTH has also been found. In general during the experiment time leukocytes, lymphocytes and subpopulations, have experimented an increase which is significantly related to the pituitary hormone secretion. The existence of this significant correlation establishes the presence of a possible mechanism that connects the cellular immunity to determined hypothalamus hormones.


Effect of intraduodenal sodium bicarbonate in rat and rabbit exocrine pancreatic secretion. The effect of intraduodenal sodium bicarbonate, 0.1 M, on exocrine pancreatic secretion and the release of two peptides, secretin and VIP, was studied in anesthetized rats and rabbits, two species largely used in the gastroenterology laboratories. In the rabbit, intraduodenal sodium bicarbonate perfusion had no effect either on exocrine pancreatic secretion or on portal plasma levels of secretin and VIP. By contrast, in the rat, intraduodenal sodium bicarbonate perfusion significantly increased hydroelectrolyte exocrine pancreatic secretion and portal plasma secretin levels. A clear interspecific difference reflecting the different gastrointestinal physiology of both species is observed.


[Extensive and combined resections in poorly differentiated lung cancer]. The article generalizes an experience with surgical treatment of lung cancer of low-differentiated structures in 108 patients. Extended and combined resections of the lung in such patients were shown to be expedient. From 83 patients who had had bronchial biopsy in the process of preoperative examination 35 patients (42.2%) had results of histological examinations of the biopsy and operative materials which did not coincide. Extended and combined resections for lung cancer of low-differentiated structure gave 5-year survival in 15.6% of the patients.


[Comparison of various methods for the measurement of the humoral immune response in mice vaccinated with aphthous fever virus]. Kinetics of the humoral immune primary response and seven-day secondary response of adult CF1 mice to FMDV O1 Campos adjuvanted in aluminium hydroxide-saponin (AHS) or in oil emulsion (OE) were evaluated by means of ELISA and passive hemagglutination (PH). Analysis of the response to AHS vaccine showed that ELISA measured maximal titres of primary response at 23 days post-vaccination (dpv), and at day 17 of secondary response, while PH detected maximal titres for primary as well as secondary response around day 60 pv. Mice immunized with OE vaccine studied by ELISA presented a plateau of primary response around 40 dpv, while secondary response was maximal around 80 dpv. The same sera tested by PH showed the highest titres for primary response on day 50 pv and secondary response was maximal on day 40 pv. A criterion for the evaluation of vaccination efficiency in the murine model is proposed based on the methods employed in the determination of antibody level.


Age-related changes in central and peripheral benzodiazepine binding sites. 3H-flunitrazepam binding was studied in membranes from different brain regions and from kidneys and adrenals of young (5-month old) and aged (22-month old) rats. Decreased benzodiazepine receptor density (by 33.7%) was observed only in the cerebellum of aged rats. The number of benzodiazepine receptors was significantly increased in the hypothalamus (by 44.1%). Specific 3H-flunitrazepam binding was also significantly increased in both kidney and adrenal membranes from old rats.


CD43 is expressed normally on Wiskott-Aldrich-derived lymphocytes. The Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by eczema, thrombocytopenia, and profound immunodeficiency in affected males. While the etiology of the syndrome is currently unknown, abnormalities of CD43 have been described as a biochemical marker of the disease. Several investigators have demonstrated alterations in the expression of the CD43 surface antigen on WAS hematopoietic cells, noting either absence, decreased levels or changes in the characteristic molecular weight of the protein on the lymphocytes of affected patients. Biochemical studies have further indicated that glycosylating activity of specific enzymes which may post-translationally modify CD43 is altered in both T cells and Epstein-Barr-virus (EBV)-transformed B cells in WAS patients when compared to unaffected controls. Here we present data on cells derived from two males with a clinical diagnosis of WAS. Analysis of genomic DNA from the mothers of each of these patients (obligate carriers) showed a nonrandom X-chromosome inactivation pattern of nucleated blood cells, confirming the diagnosis of the X-linked syndrome. CD43 was characterized on peripheral blood lymphocytes and long-term EBV-transformed B cell lines, both to further analyze the molecular defects of WAS, as well as to attempt to generate a reproducible method for disease detection. Surprisingly, surface expression, molecular weight and two-dimensional gel analysis failed to demonstrated any reproducible differences in the CD43 expression, whether from disease or normal lymphocytes. Such results suggest possible heterogeneity of this syndrome.


Evidence for abnormally regulated alternative RNA processing of mu chain gene in B-lymphoblastoid cells from Bloom's syndrome. Selective IgM deficiency is commonly found in patients with Bloom's syndrome. In this study, mu mRNA synthesis was investigated in B-lymphoblastoid cells transformed by Epstein-Barr virus (LCL) from a patient with Bloom's syndrome who showed selective IgM deficiency. LCL established from the patient with Bloom's syndrome well expressed IgM molecules in their surface, but scarcely produced secreted IgM, compared with healthy controls. The JH hybridization patterns of digested DNA of LCL from the patient with Bloom's syndrome showed the rearrangement of VDJ as well as those of control LCLs. The mu mRNA was well detected, but mu s C-terminal mRNA was poorly detected compared with control LCLs, indicating that secreted mu mRNA was poorly transcribed though membrane-bound mu mRNA was well transcribed. These results suggest that alternative RNA processing of mu chain gene is abnormally regulated in LCL from patients with Bloom's syndrome.


[Malignant fibrous histiocytoma of the maxillary sinus]. Malignant fibrous histiocytoma is a frequent neoplasm of the soft tissue occurring in patient aged between 5th and 7th decade. Maxillary sinus is an unusual site of origin and few cases have been described in literature. Because of the rarity and its aspecific clinical symptoms, diagnosis is troubled. Moreover, the association of an inflammatory process together with the difficulty to take a representative sample, the histopathological diagnosis is often problematic. The Authors report a case concerning a 30-years-old men treated at National Cancer Institute of Milan. Clinical history, biological behaviour, therapy and prognostic features of the tumor are discussed.


[The electrophysiological properties of the structural polypeptides of the foot-and-mouth-disease virus]. The methodological approaches of isolation of preparations of FMDV structural polypeptides to analyse them by the electrophoresis and electro-focussing methods are presented. The value of isoelectric points of protein coat of FMDV structural polypeptides and corresponding them values of electric potential are determined. The similarity and differences of FMDV serotypes, characterized by the value of relative surface, falling on separate polypeptides, are determined for the virion structure on the basis of superposition principle. FMDV has been shown to possess the summarized negative charge of different values. The charge depends on the virus type and it is a determining condition for viruses resistance in environment. A graphical model of FMDV is suggested on the basis of systemic approach and it reflects the dipole character of electric charge distribution in virion structure and agrees with the virus model, built on the basis of icosahedron symmetry.


Virus-specific T cells in the central nervous system following infection with an avirulent neurotropic mouse hepatitis virus. Intracerebral infection of mice with the neurotropic JHM strain of mouse hepatitis virus usually results in a fatal encephalomyelitis. However, infection with the neutralization resistant mutant, 2.2/7.2-V-2, results in inflammatory cell infiltration of the central nervous system with no apparent clinical symptoms, while conferring resistance to subsequent challenge with a lethal dose of wild type JHMV. The mononuclear cells infiltrating the brains of JHMV variant 2.2/7.2-V-2 infected mice were isolated and characterized. Virus-specific T cells which proliferated in response to JHMV antigen and produced both IL-2 and IFN-g were present among mononuclear cells infiltrating the brain as early as day 5 post-infection. The results suggest that the local immune response within the CNS may be important in dictating the outcome of disease following infections with neurotropic viruses.


Actions of ginsenoside Rb1 on choline uptake in central cholinergic nerve endings. The ginsenoside Rb1 has previously been reported to improve memory deficits induced by anticholinergic drug treatment, and to facilitate acetylcholine (Ach) release from rat brain hippocampal slices. The increase in ACh release was not associated with an increase in calcium uptake into nerve terminals, but was associated with an increase in uptake of the precursor choline. In the present studies, analysis of choline uptake kinetics indicated that Rb1 increased the maximum velocity of choline uptake, while the affinity of the choline uptake carrier for choline (Km) was not significantly altered. Acute treatment with Rb1 did not alter the number of [3H]hemicholinium-3 (HC-3) binding sites in any of three cholinergic brain regions examined, suggesting that the increase in the maximum velocity of choline uptake was not associated with an increase in the number of choline carriers. However, chronic (3 day) administration of Rb1 did increase the number of choline uptake sites in the hippocampus, and to a lesser extent in the cortex.


Changes in gamma-aminobutyric acid release induced by topical administration of drugs affecting its metabolism and receptors: studies in freely moving guinea pigs with epidural cups. The effect of local application of drugs affecting gamma-aminobutyric acid metabolism and receptors on cortical aminoacid release has been investigated in freely-moving guinea pigs equipped with epidural cups. Topical treatment with gamma-aminobutyric acid reuptake and/or metabolism inhibitors (alone and in combination) produced a slow and progressive increase in cortical aminoacid release. The inhibition of gamma-aminobutyric acid-transaminase with ethanolamino-O-sulphate seemed to be a suitable procedure for enhancing the gamma-aminobutyric acid efflux without interfering with its autoreceptor-mediated negative feedback, tested with the gamma-aminobutyric acid agonist (+/-)baclofen and antagonist phaclofen. A substantial part of the gamma-aminobutyric acid outflowing from the cortex was of neuronal origin since tetrodotoxin halved the basal efflux in the presence of gamma-aminobutyric acid reuptake and/or metabolism inhibitors. These results, considered together, indicate that the epidural cup technique may be a useful approach to study changes in cortical gamma-aminobutyric acid release induced by drugs acting on gabaergic transmission and directly applied on the surface of the cortex.


Suppressed mucosal lymphocyte populations by LP-BM5 murine leukemia virus infection producing murine AIDS. LP-BM5 murine leukemia virus (MuLV) infection induces an immunodeficient state in susceptible strains of mice. It has been previously characterized at the level of spleen and peripheral lymph nodes. We recently demonstrated that LP-BM5 MuLV-infected mice lost intestinal host resistance to common opportunistic pathogens. In this article we investigated how murine retroviral infection alters the differentiation of IgA B cell precursors in Peyer's patches (PP), mesenteric lymph nodes (MLN), and the intestinal lamina propria (ILP). After 4 months of LP-BM5 MuLV infection, there was a significant decrease in the absolute numbers of Thy1+, CD4+, and CD8+ cells in PP with a concomitant decrease in the percentage and in the absolute numbers of surface IgA+--(sIgA+) and surface IgM+--bearing (sIgM+) cells. Infection also produced an enlarged MLN with a six-fold increase in cell numbers and a decrease in the relative percentage of sIgA+, cytoplasmic IgA+, and cytoplasmic IgM+ cells. However, murine retrovirus infection caused no significant changes in the percentages of Thyl+, CD4+, CD8+, and CD5+ cells in the MLN. After 4 months of murine retrovirus infection cIgA+ cells from MLN were not able to populate the intestinal lamina propria as the number of IgA plasma cells was significantly decreased. Moreover, there was a concomitant decrease in the number of CD4+ cells per field in the ILP. These results suggest that murine retrovirus infection favors the expansion of IgA B cell precursors at the level of MLN, while simultaneously interfering with the terminal differentiation step and thus preventing IgA plasma cell precursors from seeding the ILP.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain phosphatidic acid and polyphosphoinositide formation in a broken cell preparation: regional distribution and the effect of age. The effect of age on phosphate incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA) was studied. Lysed crude synaptosomal fractions of different brain regions of 3-month-old and 32-month-old Brown Norway rats were used. The brain regions tested were the hippocampus, frontal cortex, occipital/parietal cortex, entorhinal/pyriformal cortex, striatum/septum, thalamus and hypothalamus. The individual specific phosphorylating activities were unevenly distributed within the brain of Brown Norway rats. Strikingly, the distribution of phosphate incorporation into PIP2 was opposite from that of phosphate incorporation into PA. Phosphate incorporation into PA decreased (-15%) with age in almost all brain regions tested, whereas phosphate incorporation into PIP2 decreased with age only in the frontal cortex (-20%) and in the hypothalamus (-8%). The effects of age may reflect a deterioration of phosphoinositide metabolism, with its function in signal transduction coupled to receptors via G-proteins, in the brain regions involved. In addition, there was an age related decrease in protein content and total phospholipid phosphorus content of lysed crude synaptosomal preparations of all brain regions. The high correlation between the changes in these parameters may be indicative of a decrease in the number or size of synaptosomes with age in the brain regions involved.


The association of human papillomavirus antibodies with cervical cancer risk. The association between viral human papillomavirus (HPV) DNA and cervical carcinoma has been well documented. However, less is known about the immune response to HPV infections and its relationship to cervical cancer risk. A higher prevalence of antibodies to HPV16 E7 among women with cervical cancer compared with controls has been reported, but reactivity to other antigens has not been systematically examined. Prevalence of serum IgG antibody reactivities to HPV6-encoded L1 and L2 and to HPV16- and HPV18-encoded E2, E4, E6, E7, L1, and L2 bacterial fusion proteins in a Western immunoblot assay were measured among cases with invasive cervical cancer (n = 69) and control women (n = 81). The intensities of the Western blot bands were graded as +1, +2, or +3 (0 = negative). Antibodies to HPV6 L1 and L2, HPV16 E7 and L2, and HPV18 L2 fusion proteins were observed among 39-62% of cases and 33-71% of controls. After systematic sampling for antibody reactivity to this range of fusion proteins, the sample was expanded to include 150 cases and 145 controls tested exclusively for reaction to HPV6 L1 and L2, HPV16 E7, and HPV16 and HPV18 L2. Relative risk was estimated for > or = +1, +1, and > or = +2 levels of reactivity after adjustment for confounding factors. Except for HPV16 E7, reactivity at the > or = +1 level did not distinguish cases from controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Potentiation by Ca2+ ionophores and inhibition by extracellular KCl of endothelin-induced phosphoinositide turnover in C6 glioma cells. Interactions between endothelin-1 (ET)-induced phosphoinositide (PI) hydrolysis and agents that increase Ca2+ influx (i.e. A23187 and ionomycin) or induce depolarization (i.e. KCl) were investigated using C6 glioma. A23187 dose-dependently potentiated ET (30 nM)- and ATP (100 microM)-induced [3H]inositol phosphate (IP) accumulation. This potentiation was associated with an increase in the maximal stimulation elicited by both ET and ATP but their EC50 values were unchanged. This effect of A23187 occurred at concentrations that did not affect basal PI turnover; i.e. 10 nM-3 microM. Ionomycin within the range of 1 nM-1 microM also significantly enhanced ET-induced PI breakdown and this effect was associated with an increase of [Ca2+]i. KCl in a concentration-dependent manner (14.7-54.7 mM) markedly inhibited PI breakdown elicited by ET and ATP, but had much less inhibition on basal activity and no effect on A23187- and ionomycin-induced responses. In parallel, KCl added before or after ET, sharply attenuated the increase of ET-induced [Ca2+]i but did not affect basal level or ionomycin-induced [Ca2+]i response. Neither the potentiation by A23187 nor the inhibition by KCl of ET-induced PI turnover was observed in cultured cerebellar astrocytes. Our results suggest that the cell type-specific regulation by Ca2+ ionophores and KCl on ET-induced PI metabolism is closely related to perturbation of [Ca2+]i.


The maintenance of hippocampal long-term potentiation is paralleled by a dopamine-dependent increase in glycoprotein fucosylation. Induction of long-term potentiation (LTP) in hippocampal slices of rats caused an increase in both protein synthesis and glycoprotein fucosylation by 38 and 34%, respectively. The enhanced incorporation of [3H]fucose into glycoproteins observed 1 h after tetanization was abolished in the presence of the dopamine D1 receptor antagonist SCH23390 during stimulation whereas the LTP-induced increase of protein synthesis was not influenced by this drug. The enhanced insertion of [3H]fucose into hippocampal glycoproteins 1 h after tetanization was paralleled by an increase in the activity of the fucose metabolizing enzyme, fucokinase. In contrast no changes in protein and glycoprotein synthesis were detectable 5 h after tetanization of the slices. The results provide evidence that in addition to an enhanced protein synthesis a dopamine (D1) mediated increase in glycoprotein fucosylation is necessary for the maintenance of the late stage of LTP.


Effect of kainic acid administration to prepubescent rats on cholinergic markers in selected brain regions of adult rats. Systemic kainic acid administration to prepubescent rats, in a convulsant dose, results in permanent changes in behaviour, learning and memory in adulthood (Holmes et al., 1988, Epilepsia 29, 721-730). With regard to the hypothesis that cholinergic mechanisms play a crucial role in cognitive processes, M1- and M2-muscarinic acetylcholine receptors, choline acetyltransferase, and high-affinity choline uptake as well as benzodiazepine receptors were studied in selected cortical regions (frontal, temporal, somatosensory, visual, piriform cortex), in amygdala, hippocampus, and in the nucleus basalis of Meynert from adult rats, which received at the age of 25 days a single dosage of 11 mg/kg, s.c. kainic acid. Kainic acid treatment of prepubescent rats resulted in the adult brain in decreased numbers of the total population of muscarinic acetylcholine receptors in frontal (by 27%, P < 0.05, two-tailed Student's t-test), temporal (22%, P < 0.05), and piriform cortex (31%, P < 0.05), in amygdala (24%, P < 0.05), and nucleus basalis of Meynert (39%, P < 0.02). The binding affinity was unchanged in these regions. However, in the hippocampus, the dissociation constant was significantly increased following kainic acid treatment, while the receptor numbers remained unchanged. Analysis of competition experiments with the muscarinic antagonist pirenzepine revealed that the reductions of muscarinic acetylcholine receptors in the cortical regions after kainic acid treatment are mainly due to decreases in the number of the muscarinic M1-receptor subtype. In the amygdala, the numbers of both M1- and M2-receptor subtypes are reduced.(ABSTRACT TRUNCATED AT 250 WORDS)


Maintenance of a low-fat diet: follow-up of the Women's Health Trial. This report examines the maintenance of a low-fat diet 1 year on average after the completion of intervention sessions among participants in the Women's Health Trial (WHT). The WHT was a randomized controlled trial of the feasibility of adoption of a low-fat diet among women of moderate or increased risk of breast cancer, conduced in Seattle, Houston, and Cincinnati in 1985-1988. The women randomized to the low-fat diet attended an intensive dietary intervention program for 5-37 months. Intervention women were highly successful in reducing their dietary fat intake from 40.0% of energy intake at baseline to 26.3% by the end of the trial, based on a food frequency questionnaire (or an estimated 24% adjusted for the inaccuracies of a food frequency questionnaire versus a 4-day diet record). During 1989, 1 year on average after the WHT ended, 448 intervention women and 457 control women (87% of eligibles) completed a follow-up survey to determine the degree of maintenance of the diet. The intervention women maintained the low-fat diet with an increase of only 1.4 percentage points of energy from fat, despite the fact that they had attended no further intervention sessions and had made no commitment to maintain the diet beyond the end of the WHT. Furthermore, the degree of maintenance of the low-fat diet was not dependent on the length of time in the intervention, which suggests that intervention led to a sustained change in eating habits after as little as 5-9 months (8-13 classes).(ABSTRACT TRUNCATED AT 250 WORDS)


Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. We examined somatic mutations of the adenomatous polyposis coli (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.


Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome. The Denys-Drash syndrome is characterised by a typical nephropathy, genital abnormalities and also predisposes to the development of Wilms' tumor. These patients eventually go into end stage renal failure. A candidate Wilms' tumor gene, WT1, from the 11p13 chromosome region has recently been cloned. We have analysed the DNA sequence in constitutional cells from eight patients and have shown heterozygous mutations in six of them. Four of the mutations were in exon 9, all resulting in missense mutations. Three were at nucleotide position 1180 resulting in an arg > trp amino acid change. The other was at position 1186 converting an asp > asn in the predicted resultant protein. One patient had a missense mutation in exon 8, converting an arg > his. A single base pair insertion at nucleotide position 821 in exon 6 resulted in the generation of a premature stop codon in the last patient. We were unable to find a mutation in one patient despite complete sequencing of the genomic sequence of the gene. The last patient carried a constitutional deletion of the 11p13 region and no additional mutation was found. There was no obvious correlation between the type of mutation and phenotypic expression. These results further demonstrate that the WT1 gene is important in both the development of the kidney and the genito-urinary system.


Periodic paralysis in quarter horses: a sodium channel mutation disseminated by selective breeding. We recently reported on a linkage study within a Quarter Horse lineage segregating hyperkalaemic periodic paralysis (HYPP), an autosomal dominant condition showing potassium-induced attacks of skeletal muscle paralysis. HYPP co-segregated with the equine adult skeletal muscle sodium channel alpha subunit gene, the same gene that causes human HYPP. We now describe the Phe to Leu mutation in transmembrane domain IVS3 which courses the horse disease. This represents the first application of molecular genetics to an important horse disease, and the data will provide an opportunity for control or eradication of this condition.


Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.


Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187. Dominantly inherited familial amyloidosis, Finnish type (FAF) is caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin (GSN). FAF is common in Finland but is very rare elsewhere. In Finland and in two American families, the mutation is a G654A transition leading to an Asp to Asn substitution at residue 187. We found the same mutation in a Dutch family but a Danish FAF family had a G654T mutation, predicting Asp to Tyr at residue 187. We also found the G654T transversion in a Czech family. Using GSN polymorphisms, different haplotypes were found in the Danish and Czech families. We conclude that substitution of the uncharged Asn or Tyr for the acidic Asp at residue 187 creates a conformation that may be preferentially amyloidogenic for GSN.


[A case-control study of colorectal cancer in Beijing]. A case-control study was conducted among 250 persons suffering from cancer of the colon and rectum (CRC) in the urban area of Beijing from Jan 1, 1988-June 30, 1989 to explore the risk factors for CRC. 500 neighbour residents were matched as control. The chi-square test and conditional logistic Regression analysis show that high consumption of meat, oil, low occupational physical activity and psychological stress were risk factors of CRC. A trend of increased odds ratio (OR) of CRC with high meat intake and a trend of decreased OR with increased occupational physical activity were found. The high consumption of vegetables and the habit of eating uncooked fresh vegetables showed a protective effect on CRC. The results of the study support the CRC etiological hypotheses of "fat-bile acid action" and "deficiency of dietary fibres".


The relationship between polysaccharide antigen and interleukin-1 beta producing activity in Porphyromonas gingivalis. Strains of Porphyromonas gingivalis were serologically classified into three groups (a, b, and c) by immunodiffusion test using the autoclave extracted antigens. All tested strains had proteolytic activity, but the activity differed from strain to strain, regardless of serogroup. It was found that serogroup a strains had more collagenolytic activity than did serogroup b (p < 0.05), but that the three groups have no remarkable differences in trypsin activity. All autoclave extracted serogroup-specific antigens induced the release of interleukin-1 beta (IL-1 beta) from human peripheral monocytes. Serogroup-specific antigen of an invasive strain designated 16-1 (serogroup b) induced the highest release of IL-1 beta among all samples. The results of immunoblotting tests and IL-1 beta production indicated that there are serogroup-specific polysaccharide other than lipopolysaccharide in P. gingivalis.


[The analysis of prognostic factors of primary hepatocellular carcinoma with Cox model]. This paper reports the application of Cox regression model in prognostic factors analysis of Primary Hepatocellular Carcinoma (PHC), based on the data obtained from 1618 registered of cases PHC and 432 hospitalized patients of PHC in ZhongShan City from 1980 to 1989. The result shows that there is an association between PHC and the following factors: extrahepato metastasis, therapeutic method, clinical stage, alpha-fetoprotein, gamma-glutamyl-transpeptidase, the number of tumors in the liver, the size of the tumor, icteric index and history of cirrhosis. Among these factors, clinical stage III, large liver cancer are unfavorable factors for PHC prognosis, while hepatectomy, hepatic artery catheterization chemotherapy, are favorable prognostic factors.


[A comparative evaluation of the morbidity of workers in the leading jobs in superphosphate manufacture]. The general morbidity and transitory disablement in workers engaged into superphosphate production was assessed in connection with age, sex and length of service. The results proved its possibility to serve as informative criteria for the hazardous occupational conditions evaluation.


Large bowel cancer in a young adult presenting as an acute intussusception--a case report. A 14 year old Malay boy with an adenocarcinoma of the transverse colon is reported. A lesion was discovered early when he presented with an uncommon complication in the form of a bowel intussusception. Emergency segmental colonic resection was performed, followed later by an extended left hemicolectomy following histological confirmation of the disease. Benign adenomatous polyp is believed to be the predisposing condition. Both rarities, colorectal cancer in young adults and adult intussusception, are discussed.


[Cancers of the colon and the rectum: news in 1992]. Five studies presented at the 1992 ASCO meeting are analysed. Kligerman's study was designed to determine if pre-treatment with WR-2721 could protect normal tissues from the toxicities induced by radiation therapy (in 100 patients with advanced rectal cancer). This pre-treatment resulted in a 13% reduction of moderate and severe acute toxicity. No WR-2721 patient experienced moderate or severe late toxicities compared to five in the group without pre-treatment. The complete response rate was higher in the WR-2721 group and there was no major WR-2721 related toxicity. Minski studied the acute toxicity (during treatment and two weeks after) of combined pelvic radiation therapy, 5-FU and leucovorin when delivered pre-operatively (16 patients) versus post-operatively (25 patients) in patients with rectal cancer. The toxicity criteria were fatigue, diarrhea, tenesmus, bowel movements, dysuria and erythema. Grade 3+ toxicity was more important in the post-operative therapy group (48% versus 13%). Given this high incidence of grade 3+ toxicity future randomized trials should explore the pre-operative approach. The final report of the inter group study of 5-FU plus levamisole as adjuvant therapy for stage C colon cancer was made by Moertel. With a median follow-up time of 5.5 years, the 5-FU plus levamisole treatment has reduced the recurrence rate by 39%, the cancer related death rate by 32% and the overall death rate by 31%. Most of the recurrences occurred during the first two years. There was a decrease in the liver, great omentum, peritoneum and lung metastases, but there was no modification in loco-regional recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)


[Contribution of a new nitrosourea compound: fotemustine]. Fotemustine is a new nitrosourea which is active against disseminated malignant melanoma. A global response rate (RR) of 24.2% was obtained in a multicenter trial including 153 patients. The RR was 25% on cerebral metastases. A multivariate analysis of the long term survival considering the main prognostic factors, has been achieved. It confirms the efficacy of fotemustine. As a matter of fact, the best survival of good responders compared to non responders is not correlated to the metastatic site. The combination of fotemustine and dacarbazine led to a global RR of 27.2%, up to 40% in non visceral metastases. As an other way of research the administration of fotemustine by the intraarterial hepatic route in the treatment of hepatic metastases of malignant ocular melanoma seems to give higher response rates than those obtained with chemotherapies administered by intravenous route (near 40% of response rate). Fotemustind alone or associated with cisplatinum allowed also interesting results in the treatment of metastatic non small cell lung cancer (NSCLS).


[Ewing's tumor: current knowledge and ignorance]. The diagnosis of Ewing's malignant tumor in the young still raises major problems, either from a clinical point of view because of its rarity, its pluri-potentiality and various symptoms, or on imaging because of its numerous pitfalls. Accordingly the disease is often misdiagnosed as osteomyelitis. Only a high quality biopsy can determine histological diagnosis of undifferentiated small round cell tumor. The chromosomic study shows a specific (11;22)(q24;q12) translocation, and immunocytochemistry and molecular biology show the tumor's neuroectodermal origin. For 20 years, therapy tended toward first line tumor chemoreduction, followed, when appropriate, by complete resection and orthopedic reconstruction of the bone. Radiotherapy, which is responsible for long-term sequelae is now increasingly restricted to inaccessible or incompletely excised tumors. More intensive chemotherapy is being examined in patients with poor prognosis factors such as a negative response to induction chemotherapy, a significant mass or metastases. As a result of new strategies, disease-free survival rate is now between 60-70%. The management of this disease is highly multidisciplinary and patients will now be included in multicentric controlled therapeutic trials. Long term follow-up has to be carried out following completion of treatment.


[A rare cause of neonatal hyperphenylalaninemia: tyrosinemia type I]. Phenylalanine, the direct precursor of tyrosine, is rarely increased in tyrosinemia I. We report on a case of tyrosinemia type I diagnosed through neonatal hyperphenylalaninemia. This case report points out the need for a biological evaluation of the hepatic function in cases of neonatal hyperphenylalaninemia.


[Spinal cord tumor with meningeal invasiveness revealed by intracranial hypertension syndrome]. The association of hydrocephalus and intramedullary spinal-cord tumor with leptomeningeal spread is described in a 20 month-old boy. The pathogenesis of increased intracranial pressure in spinal cord tumor is discussed. Meningeal gliomatosis is rare and is more often observed in the follow-up of cerebral gliomas. It exceptionally occurs in patients without known cerebral or spinal tumor. Such a tumor often occurs in young patients and has a poor prognosis.


[Vitamin D-resistant rickets type II: apropos of 2 cases]. We present two cases of vitamin D-dependent rickets type II, a rare disease caused by a hereditary disorder of the receptor for 1,25 dihydroxyvitamin D (1,25 (OH) 2 D). The first patient was seen for the first time at the age of 2 years with florid rickets, almost complete alopecia, and an elevated plasma level of 1,25 (OH) 2 D; there was no improvement following treatment with 1 alpha-hydroxy-vitamin D3). The second patient, a boy whose parents are first cousins, was seen at the age of 7 years with severe rickets, partial alopecia and an elevated serum level of 1,25 (OH) 2 D; the rickets disappeared after administering high doses of 1 alpha hydroxyvitamin D3 and vitamin D.


[Slow inactivation and blockade of sodium channels of excitable membranes by chemical compounds]. Inactivation of sodium channels during membrane depolarization is accompanied by a dramatic increase in the affinity or accessibility of the channel receptors to local anesthetics (LAs) and related drugs, including a number of antiarrhythmics and anticonvulsants. When bound to inactivated Na channels this drugs induced channels transition to a new slowly reactive state conventionally called as a state of "drug-induced slow inactivation" (DSI). This leads to deepening of the LAs-induced tonic block and to a development of the phasic, "use dependent" block (UDB) during repetitive membrane stimulation. The UDB caused by drugs interacting preferentially with inactivated Na channels (UDB-1) differs from the UDB caused by open-channel blockers (UDB-II) by a number of properties: 1) it depends not only on a frequency of membrane stimulation but also on pulse duration; 2) it can be attenuated by raising the external Ca concentration and practically fully abolished by chemicals eliminating fast Na inactivation (e. g. chloramine T); 3) UDB-I, in contrast to UDB-II, cannot be enhanced by a strong membrane depolarization. In many respects DSI is similar to the normal slow Na inactivation (SI) developing in untreated membrane during 1-3-s membrane depolarization. A detailed comparative analysis of this two processes suggests that DSI results from modulation of the physiological SI. The molecular mechanism of interaction of drugs with inactivated Na channels remains to be solved. We believe that transition of the Na channels to the inactivated conformation leads to exposure of a high affinity "receptor" for LAs (and related drugs) located at the protein: lipid interface of the channel wall.(ABSTRACT TRUNCATED AT 250 WORDS)


[Molecular biology in genetic counseling of Duchenne and Becker myopathy]. From 1985-1991, molecular biology studies were carried out in 115 families affected with X-linked muscular dystrophy (DMD/BMD), including 59 prenatal diagnoses. The approach has changed over the last 6 years when new intragenic markers and cDNA probes became available. The polymerase chain reaction technique allows a rapid detection of dystrophin deletions, but classical Southern blot technique remains useful for restriction length polymorphism analysis. Fifty percent (42/85) of patients with DMD/BMD exhibited deletions of the dystrophin gene. In affected families with a detectable deletion, carrier detection is possible by gene dosage analysis and prenatal diagnosis is reliable. When no deletion is found, carrier detection and prenatal diagnosis depends on linkage analysis using polymorphic probes. Due to the high recombination rate, several markers need to be used. The information provided by linkage analysis must be interpreted given the proper family structure.


[Clinical development of beta-thalassemia-sickle cell anemia apropos of 36 cases]. Hematological and clinical features of 36 mainly Algerian patients with S-beta thalassemia are reported. These data, compared with those reported in the literature, showed a higher prevalence of aseptic necrosis and gall stones, probably related to the large predominance of S-beta zero-thalassemia (30 cases) and a long (14 years) median follow-up period.


[Imipramine withdrawal syndrome during a treatment for enuresis]. The authors report on an observation of imipramine withdrawal syndrome which appeared when tapering the treatment of a case of bed-wetting. Symptoms included vomiting, digestive intolerance and dehydration. Such a presentation can mislead diagnosis towards abdominal or neurosurgical pathology. All symptoms disappeared after a symptomatic treatment or in combination with the return of imipramine. It is therefore important to be aware of this complication before prescribing imipramine treatment for enuresis. The discontinuation of this drug must be very progressive.


[Endoscopic bronchial exploration under local anesthesia in children]. One hundred and forty-two flexible fiberoptic bronchoscopies were carried out in 1 year, under local anaesthesia, in 123 children aged between 15 days and 17 years. Indications were tuberculosis (n = 26), persistent pneumonia (n = 20), suspected foreign body or control after extraction (n = 18), asthma (n = 17), atelectasis (n = 14), recurrent pneumonia (n = 13), opportunistic pneumonia (n = 11), permanent bronchial obstruction (n = 10), miscellaneous disease (n = 13). Fiberoptic bronchoscopy was abnormal in 101 patients (80%) and led to a change in the treatment in 84 cases (68%). True complications (n = 5) were all transient and were followed by complete recovery. Flexible fiberoptic bronchoscopy under local anaesthesia is a simple and safe procedure. It is an essential diagnostic and therapeutic tool in the management of pediatric respiratory disorders.


[Ubiquitin and degenerative diseases of the central nervous system]. Ubiquitin is an ubiquitous 76 aminoacids protein that is present in all cellular compartments. It intervenes in numerous functions of cell metabolism, and in particular in non-lysosomal (but also lysosomal) lysis of altered or short-lived proteins. Immunohistochemical studies have shown that it is present in many inclusions characteristic of neurodegenerative diseases, notably in Lewy bodies, neurofibrillary tangles of Alzheimer's disease, Pick bodies and also in inclusions characteristic of certain motor neuron diseases. The presence of ubiquitin in these inclusions raises 2 questions: (1) the nature of the target proteins, probably altered proteins of the cytoskeleton; (2) the significance of ubiquination: it might reflect the degeneration process or participate in the protection of cells against degeneration or be an active factor in programmed cell death.


[Demonstration of genetic mutation in most of the amyloid neuropathies with sporadic occurrence]. The Portuguese type of familial amyloid polyneuropathy (FAP type I) is a disabling autosomic dominant disorder, which is caused by a point mutation in the transthyretin (TTR) gene. Other TTR gene mutations have been reported recently in other FAP. In the absence of monoclonal gammopathy, sporadic amyloid neuropathies raise a problem for their pathogenicity. In this study, we have looked for TTR gene mutations in apparently sporadic cases of amyloid polyneuropathy by Southern's technique. All the patients were of french origin. None had monoclonal gammopathy. The mean age at onset was 64 (50 to 79 years). Most of the patients (9/1) were male. Five patients were found to carry FAP type 1 mutation, and 2 the tyr 77 (German) mutation. This study suggests that investigations in amyloid polyneuropathy with no overt family history should include systematic DNA analysis.


[Value of mediastinoscopy in the preoperative evaluation of non-small cell lung cancer]. Mediastinoscopy is the most reliable examination to determine the presence or absence of lymph node metastases in the preoperative evaluation of lung cancer extension. It is performed either by the cervical route to explore the peritracheobronchial spaces, or by the anterior route to explore the subaortic and anterior mediastinal spaces. It is carried out immediately before thoracotomy, and the rapid frozen section examination of the lymph nodes is accurate enough to decide whether or not resection should be attempted. When mediastinoscopy detects lymph node metastases that are contralateral to the tumour, resection is contra-indicated in view of its poor prognosis. When the metastases are ipsilateral to the tumour, lie low in the mediastinum and are contained in the lymph node capsule, resection is justified since a 5-year old survival can be obtained in almost 10% of the cases. Mediastinoscopy avoids many exploratory thoracotomies. Patients whose cancer is resectable but in whom resection is contra-indicated by this examination have statistically no chance of surviving.


[Adjuvant therapy of surgically treated non-small cell lung cancer]. Adjuvant treatments of non-small cell lung cancers consist of radiotherapy and chemotherapy administered jointly or separately before or after surgery. These treatments have been tested in numerous trials, notably as regards postoperative chemotherapy. For a long time the results were disappointing, and in a randomized study none of the therapeutic regimens prescribed could improve the patients' survival. New hopes of advances in this matter were raised by Goldie and Coldman whose mathematical concept recommended a systemic treatment applied as early as possible in cases with localized tumour. The advent of platinum, the results obtained in metastatic tumours by including this agent in a variety of combinations, and those obtained in localized tumours by chemotherapy and radiotherapy combined have been the second promising element. Multicentre randomized trials have been set up after the encouraging results of a feasibility study on preoperative chemotherapy.


Comparison of two ultrasonic cleaning units for deterioration of cutting edges and debris removal on dental burs. The effects of two ultrasonic cleaning units on surface deterioration and cleaning effectiveness of dental burs were compared in this study. The units tested were the Dextrex Model L 503B (Dextrex Chemical Industries, Inc., Bowling Green, KY) industrial ultrasonic unit and a conventional dental ultrasonic unit L & R T-21 B (L & R Manufacturing Co., Kearny, NJ). SEM photomicrographs of the burs were made before cleaning; and burs were processed for 10 min in each unit. Forty-eight new burs (24 #1/2A diamond and 24 #330 carbide) contaminated with human blood and 48 burs contaminated with tooth debris following cavity preparation were used to evaluate cleanliness. To assess deterioration, 48 new burs were evaluated for changes in the number of diamond chips or pits (carbide burs) and color changes following ultrasonic cleaning. Neither unit sufficiently cleaned the burs, as evidenced by remnants of remaining blood and debris on the burs. The loss of diamond chips was statistically significant for the burs processed in the Dextrex unit (P < 0.001) as well as for burs processed in the L & RT 21-B unit (P < 0.01). The mean number of pits was significant in carbide burs processed in both units as well (Dextrex unit: P < 0.01; L & RT-21 B unit: P < 0.001). No differences were noted in color changes for any of the burs in either unit. These data showed that the industrial-type unit was no more effective in cleaning dental burs than the conventional unit, though both units caused significant amounts of deterioration in the cutting surfaces.


[Biochemical regulations in the dimorphism and virulence of pathogenic fungi for humans]. Some biochemical mechanisms involved in the processes of virulence and dimorphism in fungi pathogenic for humans are reviewed. Among them, the participation of sulphydryl and disulfide groups, hormone receptors and intra- and extracellular proteinases in Histoplasma capsulatum, Paracoccidioides brasiliensis and Coccidioides immitis.


[Extrarenal nephroblastoma. Apropos of a case]. The case of a three year old boy with a rare extra-renal nephroblastoma is presented. The possible origins of these tumors will be considered as well as the prognosis and differential evaluation by CT.


[Use of anti-D (Rh) IgG or intramuscular polyvalent human immunoglobulin in the treatment of chronic autoimmune thrombocytopenic purpura]. The present study compares the effect of the intramuscular injection of low doses of IgG anti-D or human polyvalent immunoglobulin (Ig) on the platelet count of patients with CATP. Forty patients (14 children, 26 adults), 11 who had undergone splenectomy, were divided in the following groups of treatment: 20 patients received a single injection of 300 micrograms of IgG anti-D, 6 patients received the same dose as above plus 0.5 mg/kg daily of prednisone v.o and 14 patients received 640 mg of polyvalent Ig. Each patient was sequentially studied by measuring peripheral blood parameters, reticulocyte index, direct Coombs' test and C3-C4 determinations. Their blood group and Rh factor had been previously determined. The platelet response was evaluated as refractory (no response) and favorable (platelet increment over 50,000/microliters compared with initial platelet count). Patients with a favorable response over a month were considered as a prolonged remission. The results showed a favorable platelet response in 74% of the patients that received a single injection of IgG anti-D alone (one of the patients was Rh negative) or associated to prednisone, and 42.8% of the cases when polyvalent Ig was used. The patients who had not undergone splenectomy obtained better results than the group with splenectomy (62% vs 45%) and children showed a better response than adults (78.5% vs 46.1%). Forty five percent of prolonged remissions (including the Rh negative patient) were obtained with both schemes of IgG anti-D administration and only 28.5% when polyvalent Ig was used. The remissions were significantly longer with IgG anti-D (p < 0.01). The hematological and serological parameters did not show any significant modifications in all the cases and there was no adverse effects with the treatment. In conclusion, the intramuscular injection of immunoglobulins, especially IgG anti-D, produce an increase in the platelet count in some patients with CATP, several of them can obtain prolonged remissions, particularly children and patients that had not received immunoglobulins previously. This treatment is safe, ambulatory, easy to administer, and relatively inexpensive.


The occurrence of high-level streptothricin resistance in thermotolerant campylobacters isolated from the slurry of swine and the environment. This is the first report on the occurrence of streptothricin resistance (MIC > 400 micrograms/ml) in Campylobacter spp. The majority of resistant strains has been typed as C. coli by biotyping and SDS disc electrophoresis of bacterial whole cell proteins. The resistance to streptothricin was strongly connected with resistance to kanamycin (100%) and tetracycline (80%). As an important source of streptothricin-resistant Campylobacter strains we localized slurry of swine previously fed with feed containing streptothricins. Additionally, such strains could also be isolated from river water.


Adjuvant properties of propionibacterium avidum KP-40 in vaccination against endemic viral and bacterial infections. I. Swine immunized with live attenuated Aujeszky's disease virus vaccine and experimentally infected with virulent viruses. Forty 5-month old swine were treated with immunomodulating Propionibacterium avidum KP-40 (PA) and/or immunized with live attenuated Aujeszky's disease (AD) virus vaccine (SuivacA); 8 weeks later all animals were infected with virulent AD viruses (NIA-3). Seven of 10 swine vaccinated without PA developed mild/moderate symptoms of infection with 3- to 5-day fever and a temporary halt in weight gain. Application of PA together with the vaccine lowered the morbidity rate, shortened the period of fever and speeded recovery. Only low levels of virus-neutralizing IgG antibodies were found in vaccinated swine and application of PA did not influence antibody titers.


Regulation and role of brain calcium/calmodulin-dependent protein kinase II. Ca2+/calmodulin-dependent protein kinase II (CaMKII) exhibits a broad substrate specificity and regulates diverse responses to physiological changes of intracellular Ca2+ concentrations. Five isozymic subunits of the highly abundant brain kinase are encoded by four distinct genes. Expression of each gene is tightly regulated in a cell-specific and developmental manner. CaMKII immunoreactivity is broadly distributed within neurons but is discretely associated with a number of subcellular structures. The unique regulatory properties of CaMKII have attracted a lot of attention. Ca2+/calmodulin-dependent autophosphorylation of a specific threonine residue (alpha-Thr286) within the autoinhibitory domain generates partially Ca(2+)-independent CaMKII activity. Phosphorylation of this threonine in CaMKII is modulated by changes in intracellular Ca2+ concentrations in a variety of cells, and may prolong physiological responses to transient increases in Ca2+. Additional residues within the calmodulin-binding domain are autophosphorylated in the presence of Ca2+ chelators and block activation by Ca2+/calmodulin. This Ca(2+)-independent autophosphorylation is very rapid following prior Ca2+/calmodulin-dependent autophosphorylation at alpha-Thr286 and generates constitutively active, Ca2+/calmodulin-insensitive CaMKII activity. Ca(2+)-independent autophosphorylation of CaMKII also occurs at a slower rate when alpha-Thr286 is not autophosphorylated and results in inactivation of CaMKII. Thus, Ca(2+)-independent autophosphorylation of CaMKII generates a form of the kinase that is refractory to activation by Ca2+/calmodulin. CaMKII phosphorylates a wide range of neuronal proteins in vitro, presumably reflecting its involvement in the regulation of diverse functions such as postsynaptic responses (e.g. long-term potentiation), neurotransmitter synthesis and exocytosis, cytoskeletal interactions and gene transcription. Recent evidence indicates that the levels of CaMKII are altered in pathological states such as Alzheimer's disease and also following ischemia.


Regulation of bradykinin-induced phosphoinositide turnover in cultured cerebellar astrocytes: possible role of protein kinase C. Phosphoinositide hydrolysis was studied in primary cultures of rat cerebellar astrocytes prelabeled with [3H]myo-inositol. Among the agonists examined, the rank order of efficacies in causing phosphoinositide hydrolysis was bradykinin > endothelin-1 > ATP > norepinephrine. The bradykinin response was robust (24-fold increase) with EC50 value of 30 nM and saturating concentration of 1 microM. Preincubation of cells with pertussis toxin did not affect the activation of phosphoinositide turnover by bradykinin. Although short-term (within 90 min) treatment of cells with phorbol dibutyrate attenuated bradykinin-induced phosphoinositide breakdown, the inhibitory effect was lost after 3-6 h of phorbol dibutyrate treatment. Extended (24 h) preincubation resulted in a potentiation of bradykinin response. Homologous desensitization of bradykinin response was observed in cells prestimulated with bradykinin for up to 6 h. However, similar to the effect of phorbol dibutyrate, 24-h pretreatment with bradykinin selectively sensitized the response to bradykinin. Up-regulation of the bradykinin response was also observed in cells prestimulated with endothelin-1 or norepinephrine for 24 h, although these treatments resulted in only homologous desensitization to their own response. Our results suggest that cultured cerebellar astrocytes express bradykinin receptors coupled to phospholipase C and in these cells protein kinase C plays a more prominent role in the negative-feedback regulation of bradykinin-evoked phosphoinositide response.