Local norepinephrine depletion and learning-related neuronal activity in cingulate cortex and anterior thalamus of rabbits. Multi-unit neuronal activity was recorded in posterior cingulate cortex (area 29) and the anterior ventral (AV) thalamic nucleus during discriminative instrumental avoidance learning wherein a response (stepping in an activity wheel) to a 0.5-s tone (CS+) prevented a foot-shock 5 s after CS+ onset. Presentations of a different tone (CS-) on 50% of the conditioning trials in an irregular sequence with the CS+ did not predict shock and thus required no response. Two groups of rabbits received intracranial micro-injections of 6-hydroxydopamine (6-OHDA) to locally deplete the NE in area 29 or the AV nucleus. Vehicle was injected in the non-depleted area in each group and a third group received vehicle injections in both areas. Dopamine neurons in subjects that received 6-OHDA were protected by pre-treatment with GBR-12909. Neuronal data were collected during two pre-training sessions in response to the tones only and when the tones and shock were presented unpaired. Thalamically depleted rabbits made more, and cortically depleted rabbits made fewer, avoidance responses than controls during the early stages of behavioral acquisition, and cortically depleted rabbits made fewer responses than controls and thalamically depleted rabbits during extinction testing administered after the completion of acquisition. One effect of NE depletion on neuronal activity was entirely local: elimination of neuronal sensitization effects (enhanced discharges elicited by tones during the unpaired tone-shock pre-training treatment relative to pre-training with tones only). Other neuronal effects of NE depletion were system-wide, i.e., they occurred whether the depletion was cortical or thalamic.(ABSTRACT TRUNCATED AT 250 WORDS)


Responses of cat ventroposterolateral thalamic neurons to vibrotactile stimulation of forelimb footpads. Responses of neurons in the ventroposterolateral nucleus of the thalamus to vibration applied to the forelimb footpads were analyzed in anesthetized cats in order to describe the signalling properties of thalamic neurons that received input from the different classes of tactile afferents innervating the glabrous skin of the distal forelimb. Seventy-six thalamic neurons, the majority of which (60 of 76) were positively identified as thalamocortical projection neurons, were classified into two broad groups according to their responses to 1-s step indentations of the skin. A minority (24%) comprised neurons that had slowly adapting (SA) responses, whereas the remainder (76%), the dynamically sensitive neurons, had transient responses to the onset and offset phase of the step and were further classified according to their sensitivity to cutaneous vibrotactile stimuli into those activated by low-frequency vibration (rapidly adapting, RA, neurons) and those activated by high frequencies (Pacinian afferent, PC, neurons). Thalamic RA neurons displayed phaselocked responses to vibration at frequencies up to approximately 100 Hz, while PC neurons displayed phaselocked responses to vibration up to 400-500 Hz. Thalamic SA neurons varied in their responses to vibrotactile stimuli; half were most sensitive to vibration frequencies of 50 Hz or less, while the others responded over a broader range of frequencies. Although three major classes of footpad-related thalamic neurons were identified, there was evidence of convergent input to a small proportion of them. The study demonstrates that thalamic neurons have the capacity for responding to cutaneous vibration with phaselocked, patterned impulse trains, which would enable them to encode information about vibrotactile frequencies up to approximately 300 Hz.


Projections from fetal neocortical transplants placed in the frontal neocortex of newborn rats. A Phaseolus vulgaris-leucoagglutinin tracing study. Fetal rat neocortex grafted into lesion cavities made in the newborn rat neocortex can exchange multiple axonal connections with the host brain. Most previous studies demonstrating efferent transplant-to-host brain connections have used fluorescent retrograde tracers injected into the host brain (Castro et al. 1985, 1987; Floeter and Jones 1984; O'Leary and Stanfield 1989). Other studies have used anterograde axonal tracing with either tritium-labelled amino acids impregnating the transplant and its efferents (Floeter and Jones 1985) or horseradish peroxidase injected into the transplants (Chang et al. 1984, 1986). In the present study we used the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) to examine in detail the course and termination of the efferent neocortical graft fibers. Twenty-six newborn rats had the right frontal cortex forepaw area removed by vacuum aspiration, while anesthetized by hypothermia. A piece of fetal frontal cortex 14-16 embryonic days old (E14-16) was immediately thereafter placed in the lesion, and the recipient rats allowed to survive for 5-7 months. At this time the rats were reoperated under sodium pentobarbital (Nembutal) anesthesia and the transplants iontophoretically injected with PHA-L. Two weeks later the animals were again anesthetized, perfused, and processed for PHA-L immunocytochemistry and routine histology. Analysis of acetylcholinesterase- (AChE) and Nissl-stained sections showed graft survival in 19 of the 26 animals used in this study. When these 19 brains were processed for PHA-L immunocytochemistry, 5 of them were found with certainty to have the PHA-L injection confined to the transplant. Based on these cases PHA-L-reactive fibers arising from labelled transplant neurons were traced into the ipsilateral host neocortex adjacent to the transplant and found to project through the subcortical white matter to the ipsilateral parietal neocortical area 1, and claustrum. Callosal fibers were traced to the contralateral frontal neocortical forelimb and parietal areas. Transplant fibers were also observed to descend through the caudate putamen in the dispersed fiber bundles of the internal capsule to distribute as terminal branches and varicose fibers within the mesencephalic periaqueductal gray, red nucleus, deep mesencephalic nucleus, and intermediate gray of the superior colliculus, as well as in the pontine gray. Similar fibers and terminations were present in the caudate putamen, the reticular, ventrobasal, centrolateral, posterior, and parafascicular thalamic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)


Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the foot in man. Short air-puff stimuli were applied to the sole of the right foot to obtain both psychophysical and neurophysiological responses. The detection threshold (So) was first determined, and six levels of stimulus intensity above threshold were adopted for magnitude estimation. Somatosensory evoked potentials (SEPs) were also recorded over the foot projection area (2 cm posterior to Cz) for the six stimulus intensities. Six components (N40, P45, N55, P70, N80 and P90) were recorded within 100 ms following stimulation. A power function with an exponent of 0.94 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.87; P < 0.001). Similarly, stimulus-amplitude functions of P45-N55, N55-P70 and P70-N80 SEP components were well represented by power functions with exponents of 0.62, 0.63 and 0.78, respectively. The SEP latencies as a function of stimulus intensity had negative power functions. The latency functions of the P45 and N55 components had the largest negative power exponents (-0.17 and -0.15) and showed the highest negative correlations (r = -0.70 and -0.71, respectively) with the stimulus intensity. These results suggest that both the amplitude and the latency information encoded in the SEPs may contribute to the magnitude estimation of the stimulus.


Three-dimensional drawings in isometric conditions: planar segmentation of force trajectory. Normal human subjects grasped an isometric handle with an unrestrained, pronated hand. They were asked to exert forces continuously to draw lemniscates (figure eights) in specified or self-chosen planes and in the presence or absence of a three-dimensional visual feedback cursor and a visual template. In every condition, the mean plane orientation in the force space differed appreciably between the two loops of the figure, as described previously by Soechting and Terzuolo (1987a) for free drawing arm movements. These findings suggest that the planar segmentation of the motor trajectory is not a consequence of joint motion but arises from central constraints related to the production of motor trajectory in space.


Category-related components in visual evoked potentials: photographs of faces, persons, flowers and tools as stimuli. One hundred and sixty black-and-white photographs of faces, persons, tools and flowers constituted the four stimulus categories in the first experimental paradigm. In the second paradigm, 160 black-and-white photographs of persons in a neutral (side view), fighting, greeting and "depressed" postures were used. The same nine female and nine male students volunteered as subjects in both paradigms. EEG responses were recorded through the electrodes F3, F4, Cz, Oz, T5 and T6 and referenced to "linked" mastoid electrodes. Individually averaged EPs and grand averages of the EPs for all 18 subjects were computed as well as bipolar responses for selected pairs of electrodes. Category-related components in the evoked potentials (EPs) were found mainly in the recordings through the midline and the frontal electrodes. These category-specific differences were more prominent, however, in the bipolar recordings between these electrodes and the respective ipsilateral electrodes (T5 or T6) than in the monopolar recordings. Monopolar and bipolar EPs could be divided into those evoked by person stimuli and by non-person stimuli. Category-related differences were demonstrated by computing EP-difference curves related to pairs of stimulus categories. In addition to the statistical analysis of peak amplitudes and peak latencies of the individual curves, a "running" Wilcoxon test was applied and cross-correlation functions between the EPs evoked by different stimulus categories were computed. The "face-related" components of the EPs described in earlier studies could be confirmed. They were prominent in the waves peaking between 130 and 150 ms and between 200 and 230 ms and were stronger when faces rather than full-figure "neutral persons" were used as stimuli. No significant hemispheric differences could be found between any of the EPs. In the second paradigm, EEG responses evoked by person stimuli in a neutral, fighting, greeting or depressed posture exhibited only slight differences, if at all. The "person-responsive" components in the EPs evoked by the photographs of a neutral standing person (side view) were smaller between 120 and 200 ms than in the other three categories in which "expressive" persons were the stimuli.


Identification and characterization of a Giardia lamblia group-specific gene. Giardia lamblia consist of heterogeneous isolates that can be divided into at least three groups. Differential screening of a cDNA library with isolate-specific antisera identified a gene which is expressed and found only in Group 3 isolates. This gene, GLORF-C4, is 597 bp in length and predicts a deduced protein of 198 amino acids that is characterized by a polyserine motif. Giardia can also be grouped by their ability to express certain variant-specific surface proteins (VSPs), expression of which is restricted among groups. In Southern blots, probes specific to two VSPs were used to characterize isolates. Failure to detect VSP genes correlated with inability to express the same VSP. Analysis of isolates with these new probes complements and confirms the groupings previously suggested using other criteria. These genetic differences should allow differentiation of isolates and permit the application of basic epidemiological techniques to determine the manner of spread and the presence of animal reservoirs.


Experimental Plasmodium falciparum cerebral malaria in the squirrel monkey Saimiri sciureus. Infection of the squirrel monkey, Saimiri sciureus, with several strains of Plasmodium falciparum leads in a proportion of animals to neurological symptoms with a fatal outcome. This first simian model for human cerebral malaria was studied with three strains of parasites, the uncloned Palo Alto(FUP-1) strain, the Palo AltoPLF3 clone MHB11, and the recently monkey-adapted P. falciparum strain IPC/RAY. Cerebral malaria could develop during primo infection of monkeys, whether the animals had been splenectomized or not. It did not occur in all animals and the appearance of neurological symptoms could not be predicted, as it was not related to the degree of parasitemia or duration of parasite infections.


Plasmodium falciparum: chymotryptic-like proteolysis associated with a 101-kDa acidic-basic repeat antigen. Malaria proteinases appear to function in the release of merozoites from infected erythrocytes and the invasion of merozoites into erythrocytes. Chymostatin, an inhibitor of chymotrypsin-like proteinases, inhibits malaria invasion and also inhibits apparent autoproteolysis of a 101-kDa acidic-basic repeat antigen (p101-ABRA) that is found in the vacuolar space surrounding merozoites in Plasmodium falciparum-infected erythrocytes. After purification by a monoclonal antibody (MAb 3D5), p101-ABRA degrades into smaller fragments in the absence of chymostatin. In this study fluorogenic proteinase substrates of the type peptidyl-7-amino-4-trifluoromethyl coumarin with phenylalanine or tyrosine linked to AFC were used to characterize chymotryptic-like activity associated with p101-ABRA. When p101-ABRA from the cell extract of P. falciparum-schizont-infected erythrocytes was affinity purified on MAb 3D5 beads, chymotryptic-like activity bound to the beads. Seventy-four percent to 96% of the activity detected using MeOSuc-KLF-AFC, Suc-LLVY-AFC, or SY-AFC at a pH optimum of 7.0 was removed from the extract and 6 to 33% was detected on the washed beads. Attempts to recover active enzyme eluted from the beads were not successful. Enzymes cleaving two other substrates (MeOSuc-AAPM-AFC and F-AFC) did not significantly bind to mAB 3D5 beads. Chymotryptic-like activity was also associated with p101-ABRA in fractions from sequential DEAE-Sephacel chromatography, Sephacryl S-200 chromatography, and nondenaturing polyacrylamide gel electrophoresis.


The identification of a variant form of cystathionine beta-synthase in nematodes. Characterization of the physical and catalytic properties of the enzyme responsible for nematode "activated L-serine sulfhydrase" activity (L-cysteine + R-SH-->cysteine thioether + H2S) has led to its identification as a novel, variant form (allelozyme) of cystathionine beta-synthase that is distinct from a mammalian-type synthase also present in nematodes. Additional work has demonstrated the ability of live Panagrellus redivivus to produce H2[35S] from exogenous L-[35S]cysteine and 2-mercaptoethanol, thus providing preliminary evidence for the in vivo operation of the activated L-serine sulfhydrase reaction in nematodes.


Schistosoma mansoni: hycanthone/oxamniquine resistance is controlled by a single autosomal recessive gene. Individual schistosomes of an hycanthone/oxamniquine-sensitive strain were crossed with individual schistosomes of the opposite sex and belonging either to the same sensitive population or to a different strain which exhibited high resistance to the two drugs. Schistosome crosses were performed by transfer of single worm pairs into the mesenteric veins of mice and the drug sensitivity/resistance of individual progeny worms was assessed using an in vitro test. Drug resistance behaved as an autosomal recessive trait, as shown by the results of the F1 and F2 generation and of the backcrosses. Drug-resistant worms appeared to be slightly less viable than their sensitive counterpart at all stages of the life cycle. The results are relevant for an interpretation of drug resistance and drug mechanisms and the approach used in this study may be applicable to different genetic markers in schistosomes.


Leishmania tropica infection in hamsters and a review of the animal pathogenicity of this species. Four strains of Leishmania tropica s. st. from Afghanistan were found to be constantly infective to the golden hamster (Mesocricetus auratus), whether inoculated as culture promastigotes from early passages or as amastigotes from the cutaneous lesions. In total, 66 amastigote passages were carried out over 6 passage generations. The footpad lesions were chronic and nonulcerative infiltrates; their evolution is described up to 15 months. No self-healing was observed. Balb/c mice and gerbils were not susceptible. Earlier studies on L. tropica s. st. in laboratory animals, principally by Soviet and French workers, are critically reviewed. This new experimental model of chronic cutaneous leishmaniasis is of special interest for studies on the immunology and chemotherapy of the disease. Some advantages over the commonly used L. major model are discussed.


Leishmania major and Leishmania donovani: effect of LPG-containing and LPG-deficient strains on monocyte chemotaxis and chemiluminescence. Lipophosphoglycan (LPG) is a major glycolipid present on the membrane of Leishmania promastigotes and amastigotes. We have previously shown that preincubation of peripheral blood monocytes with purified LPG inhibits IL-1 production, chemotactic locomotion, and luminol-dependent chemiluminescence (LDCL). In the present study we tested the effect of LPG present on live parasites on monocyte activity. For this purpose, we used two mutant strains deficient in LPG and two LPG-containing strains. One pair was Leishmania major and the other Leishmania donovani. Monocytes in suspension were infected with the different parasite strains and tested for chemotactic locomotion and LDCL at different times between 1 and 72 hr after infection. In parallel, the percentage of infected monocytes was measured in stained cytospin preparations. The results obtained showed that at 1 hr of incubation only the LPG-containing strains inhibited chemotaxis, while the mutant strains showed a normal response. From 4 hr of incubation onwards, the mutant strains also inhibited monocyte chemotactic locomotion. LDCL was only slightly inhibited by the LPG-containing strains after 1 hr, because of a high level of spontaneous stimulation, probably due to phagocytosis. At 24 and 72 hr all strains inhibited LDCL. These results suggest that LPG is responsible for early inhibition of macrophage activity, but that other factors are responsible for inhibition at later stages of in vitro infection. The model described here might represent a useful tool to further analyze the mechanisms involved in immune evasion of Leishmania parasites.


Plasmodium vinckei petteri: identification of the stages sensitive to arteether. Antimalarial activity of arteether, a derivative of artemisinin (qinghaosu) against blood-induced infections of the highly synchronous Plasmodium vinckei petteri rodent species of malaria was evaluated in Swiss mice. A single subcurative dose of arteether of 2.2 mg/kg body weight was injected subcutaneously to mice, either during the prepatent period or during the patent infection, when different stages of the parasitic cycle were present in the blood. It was shown that rings and young trophozoites were the most susceptible stages to arteether. The drug had no effect on merozoites and little effect on mid-term trophozoites which is the stage most sensitive to chloroquine. The alcoholic solution (10% alcohol in sterile water) had an immediate effect while the oily solution (miglyol 840) was active between 3 and 21 hr after injection.


Survey of sulphites determined in a variety of foods by the optimized Monier-Williams method. A survey of sulphite levels in a variety of foods including dried fruit, dried mashed potatoes, shrimp, canned mushrooms and fruit juices has been conducted. The levels found ranged from 0 ppm in orange juice to 3722 ppm as sulphur dioxide in dried fruit. The foods were analysed by the optimized Monier-Williams procedure.


Potential weekly intake of artificial food colours by 3-14-year-old children in Brazil. The Potential Weekly Intake (PWI) of artificial food colours by 3-14-year-old children living in the District of Barão Geraldo, Campinas, São Paulo, Brazil, was estimated on the basis of average consumption data of artificially coloured food and analytically determined colour concentration in foodstuffs ingested. Coloured food consumption data were obtained through dietary recall interviews and collection of the packages and/or labels of the coloured foods consumed during a two-week period. Colours found in the individual types of foods detected through the consumption survey were identified and determined by methods that included wool dyeing and polyamide column extractions, ascending paper chromatography and spectrophotometry. The results showed that all artificial colours used in the composition of 83 commercial food products, including jellies, juices, soft drinks, syrups and 57 different candies, were permitted for use in food in Brazil the year the survey was conducted (1986), in amounts below those prescribed by law. Statistical analysis performed to compare the PWI for different population groups demonstrated that young male children, especially from lower social classes, were most exposed to artificial colours. Comparison of the estimated potential intakes with the toxicologically Acceptable Daily Intake (ADI) showed that consumption of Amaranth, Sunset Yellow, Indigotine and Tartrazine by all children in the study represented approximately 24%, 3%, 0.05% and 0.4%, of the actual ADI values, respectively.


Migration of polyisobutylene from polyethylene/polyisobutylene films into foods during domestic and microwave oven use. Migration of polyisobutylene from polyethylene/polyisobutylene film into foods has been studied in domestic applications such as wrapping of foods and reheating in a microwave oven. The results of these migration studies were obtained by direct measurement using newly developed analytical methods utilizing nuclear magnetic resonance (NMR) and infra-red (IR) spectroscopy as well as predictively from assessment of loss of polyisobutylene from the film. Total levels of polyisobutylene migration into cheese were found to be 8-10 mg/kg, into cake 1-5 mg/kg, and into sandwiches ranged from < 1 to 4 mg/kg. Reheating foods covered with film in the microwave oven, gave migration levels ranging from < 0.01 mg/kg for contact with steam only, up to 0.5 mg/kg for severe splashing of food onto the film and 4 mg/kg for reheated pizza. Migration of polyisobutylene was shown to be skewed towards the low molecular weight fraction of the additive. In typical films, the molecular weight range of polyisobutylene was shown to be 300-6000 daltons (95% limits) centred on 1300 daltons, whereas the additive that had migrated into cheese was found to range from 130-2200 daltons, centred on 520 daltons.


Isolation and determination of zearalenone in rice cultures using liquid chromatography with diode array detection. A rapid method is described for the isolation and determination of zearalenone (ZEN) produced by Fusarium spp., in moist rice culture. Following a simple solvent extraction using acetonitrile:water, the crude extract was defatted with hexane and diluted with methanol. The extract solution containing ZEN was evaporated to dryness, the residue dissolved in acetonitrile and diluted with water. The solution was analysed by liquid chromatography using a UV-diode array detector. The UV spectra and chromatographic data generated from the standard ZEN was stored in a computer and used to identify the toxin in a crude mixture. The purity of the separated peak and the amount of toxin in the crude mixture was determined. The present technique is fast and allows the acquisition of UV spectral information and chromatographic data of ZEN in a single chromatographic operation. Recovery of zearalenone added to the rice was 76-94%.


Lead intoxication in cattle: a case report. During the autumn of 1989 a feed contamination induced a widespread lead intoxication of cattle in the northern provinces of The Netherlands (Groningen and Friesland). Over 300 farms were involved, affecting about 15,500 animals (mostly dairy cattle). For a period of one to four weeks these animals took up a thousand kg of lead. This resulted in lead levels in milk, livers, and kidneys above the regulatory safety limits. Due to the chelating therapy, which was rapidly applied by the local veterinarians, only about 30 animals died of an acute lead intoxication. A joint action of the governmental and private authorities prevented exposure of consumers to lead-contaminated animal products. Based on observations, measurements and literature data, predictions were made of the lead levels to be expected in animal products and the time needed for depletion of these levels. The appropriate animals were ear-tagged to ensure their identification, and the decline in time of the lead levels in milk and offals was conscientiously monitored. In the second week of 1990 the lead concentrations were decreased to levels well below the regulatory limits, and hence the tags were removed. The present paper reports our observations and conclusions, especially regarding treatment, predictions and outcome of this incident.


Factors affecting the results of T-2 mycotoxin ELISA assay. Certain substances in the sample may increase or decrease the reaction between the enzyme and substrate in ELISA assays. During a survey of T-2 trichothecene in food and animal feed 75% of milled grain samples gave a higher O.D. value in competitive T-2 toxin ELISA than the negative control. In samples spiked with small quantities (10 micrograms/kg) of T-2 toxin this type of reaction resulted in underestimates of toxin content. However, the effect was weak and, owing to the high sensitivity of the assay, it did not result in false negative reactions. The low efficiency of the carrier solvent and natural peroxidases in food and feed were considered to be the cause of the inaccurate reactions. A few fermented and processed foodstuffs and feed gave positive results in the T-2 toxin ELISA assay, but verification of the results by gas chromatography (GC) showed that the reactions were false. Certain substances in the samples destroyed or decreased the enzyme activity. False positive reactions can be distinguished from correct ones by retesting the extracts in different dilutions.


Changes in cassava toxicity during processing into gari and ijapu--two fermented food products. Grated cassava to which tap water was added at levels of 25%, 50% and 75% (v/w) was held at 30 degrees C, 40 degrees C or 50 degrees C and examined over a 6 h period for cyanide content, pH and titratable acidity (TTA). During the come-up time, i.e. the time between addition of water and attainment of desired holding temperature (between 14 and 47 min), reductions in bound cyanide of ca 54-85% occurred, depending on the level of added water and holding temperature. The corresponding losses for the control samples, to which no water was added, were ca 25-33%. The biggest reduction in the bound cyanide of > 99% (from 89.0 to 0.6 ppm) occurred in grated cassava with 75% added water held at 50 degrees C. There was little or no change in pH during the period of study. The reduction of processing time for certain cassava products based on separation into detoxication and flavour development/fermentation stages is discussed.


The cyanobacterium Oscillatoria erythraea--a potential source of toxin in the ciguatera food-chain. A compound lethal to mice (i.p.) was extracted from samples of Oscillatoria erythraea, four species of mollusc and one species of molluscivorous teleost collected from the south-east coast of Queensland, Australia, during and shortly after O. erythraea blooms. The compound was chemically indistinguishable from ciguatoxin (CTX) on the basis of solvent extraction and partitioning and silicic acid chromatography. Residues derived from toxic samples elicited signs of intoxication, death and histopathological changes in mice, consistent with extracts of ciguatoxic material. Stick enzyme immunoassay tests and thin layer chromatography assessment of extracts indicated the presence of ciguatoxin-like polycyclic ether(s). O. erythraea is implicated as a potential elaborator of a CTX-like compound in the tropical marine biota.


[Hepatitis observed during a treatment with a drug or tea containing Wild Germander. Evaluation of 26 cases reported to the Regional Centers of Pharmacovigilance]. Twenty-six patients developed acute hepatitis after taking Germander, an herbal medicine used to facilitate weight loss. Hepatitis occurred within 9 weeks of treatment and was characterized by jaundice and a high level of aminotransferases. Recovery was obtained between 1.5 and 6 months after withdrawal. In 12 cases, readministration was followed by prompt recurrence of hepatitis. The causal relationship is probable but the mechanism remains unclear: there was no relationship with the daily intake and the duration of treatment; there are no toxicological data on Germander compounds; contamination by an unidentified product is possible but has not been demonstrated. It should be emphasized that readministration of Germander produced recurrence of the hepatitis whenever it was performed. As a result, the French Ministry of Health recently decided to prohibit national-wide all Germander containing medicinal products.


[Barrett's esophagus, gastroesophageal acid reflux and duodenogastric reflux during the digestive and postprandial period]. Pathologic gastroesophageal acid reflux appears to be involved in the pathogenicity of Barrett's esophagus. The possible pathogenic role of duodenogastric reflux, however, has been suggested by several studies. The aim of this prospective study was to assess the prevalence of acid or duodenogastric reflux in patients with Barrett's esophagus. Nine patients with histologically proven Barrett's esophagus (mean length: 7.7cm; range: 2-13 cm) were studied by esophageal manometry and 24 hour pHmetry. Duodenogastric reflux was measured in the interdigestive period by aspiration and during the postprandial period using an isotopic method. The results of these different investigations were compared with healthy volunteers (n = 20 to 27). Three patients had complicated Barrett's esophagus (Barrett's ulcer: n = 2, high-grade dysplasia: n = 1). The results of the different investigations showed that a) all patients had abnormal acid exposure and an esophageal motor dysfunction (decrease in lower esophageal sphincter pressure, amplitude and duration of contractions and increase in percentage of peristaltic dysfunction); b) none of the patients had any pathologic duodenogastric reflux neither in the interdigestive nor in the postprandial period. These results a) confirm the high prevalence of acid reflux in patients with Barrett's esophagus, b) show that bile or pancreatic secretions are not involved in the pathogenicity of Barrett's esophagus.


[Medical behaviors and cancer of the exocrine pancreas]. A French national enquiry examined 4,530 cases of cancer of the exocrine pancreas treated from 1982 to 1989. Ultrasonography was performed in 98% of cases. Other radiological or biological investigations varied from one department to another (P < 0.001). Of 769 patients seen in Gastroenterology departments, 47% (range: 0 to 72%) were operated on. Of 3,761 patients undergoing operation, surgical techniques differed significantly from one department to another (P < 0.001). Resections were performed in 21% (range: 2 to 45%) of cases. Causes of unresectability, choice of biliary bypass, indications for gastrojejunostomy, and use of splanchnicectomy varied from one surgical department to another (P < 0.01). Wide variance in therapeutic policies may be explained by differences in local indications or surgical expertise, giving support to the need for a consensus conference to discern the indications of the available therapeutic alternatives for cancer of the exocrine pancreas.


[Changes in gastrointestinal mucins caused by attapulgite. Experimental study in rats]. A histochemical study was carried out to evaluate the changes occurring in mucins secreted by the rat stomach and intestine following a 7 day-treatment with a cytoprotective clay: attapulgite. Staining of gastrointestinal sections was performed with periodic acid-Schiff reagent, alcian blue pH 2.5 and pH 1.0, and with lectin conjugated with horseradish peroxidase for detecting complex carbohydrates. When compared with controls, attapulgite induced an increase in carboxylic mucin content in the cells of the crypts associated with a decrease in sulphated mucins and in binding with soy bean agglutinin in surface epithelial cells in the fundic zone. In the antrum, staining with wheat germ agglutinin was decreased in the crypt cells while Ulex europaeus agglutinin affinity was increased in the glandular cells. The duodenum was characterized by increased binding with Ulex europaeus agglutinin in Brunner's glands. These results show that the polysaccharidic components of the gastrointestinal glycoproteins are modified by attapulgite, and this mechanism may be involved in its cytoprotective effects.


[Transanorectal ultrasonography in the evaluation of extension and the monitoring of epidermoid cancers of the anus treated by radiation or chemotherapy]. Twenty-five consecutive patients (5 men and 20 women) with squamous cell anal carcinoma were evaluated by transanorectal ultrasonography (TRUS). The patients were treated with radiotherapy alone (6 cases) or combined concomitant radiotherapy and chemotherapy (19 cases). The ultrasound findings were compared with clinical stage as assessed by digital examination and with pelvic computed tomography. Four tumors in clinical stage T2 showed evidence of external sphincter involvement at ultrasound (UT3) and one tumor in clinical stage T1 showed an invasion of the internal sphincter at ultrasound examination. Low echogenic, rounded structures, interpreted as enlarged lymph nodes, were identified in 8 cases at ultrasound but were not seen with computed tomography. Ultrasonograms were also obtained one month after the achieved end of radiation. Correct staging was by TRUS and CT in 92% and 72% of cases respectively. When combining clinical stage with TRUS, all tumors classified as T1-T2, UT1, UT2 had a complete response to radiotherapy with or without concomitant chemotherapy. TRUS could be a useful adjunct to digital palpation in initial staging and in follow-up after medical treatment of anal canal carcinoma.


Isolation of a new restriction enzyme, ApaCI, an isoschizomer of BamHI produced by Acetobacter pasteurianus. A new Type II restriction endonuclease ApaCI purified from Acetobacter pasteurianus is an isoschizomer of BamHI that cleaves at the nucleotide sequence 5'-G/GATCC-3' of double-stranded DNA. The single restriction activity present in this strain permits rapidly purified 30,000 units of cleavage activity from 10 g of freshly harvested cells. The resulting ApaCI preparation is free of contaminant nuclease activities that might interfere with in vitro manipulation of DNA.


Permeability factor, cytotoxicity and serotyping of Pseudomonas aeruginosa strains. We analyzed in detail the permeability and cytotoxic activity as well as the serotypes of 127 Pseudomonas aeruginosa strains. Sixty-seven strains were isolated from immunocompromised patients (51 from patients with tumors and 16 from patients after transplantation) and 60 strains were isolated from patient's ears. Culture filtrates of strains isolated from patients after transplantation were responsible for the highest part of permeability reactions corresponding to an intermediate toxin production (68.8%) (categories 2 and 3) and culture filtrates of strains isolated from patients with tumors caused the highest percentage of permeability reactions corresponding to a strong toxin production. Culture filtrates of strains isolated from ears of patients were responsible for the highest percentage of negative permeability reactions (15%). With positive permeability reaction size (categories 2-6) increased also the percentage of cytotoxicity as well as the intensity of morphological changes on Vero cells after 1 and 2 d. We did not observe any relationship between a particular permeability reaction category and the most frequent serotypes (O4, O6) or nontypable strains of the tested groups.


The effect of an antigenic stimulation on proliferative response in athymic mice. The proliferation activity of the main cellular categories of bone marrow after infusion of 3H-thymidine was studied in nu/nu and +/+ 1-month- and 3-month-old BALB/c mice in comparison with lymphoid cells in the spleen and mesenteric lymph nodes. The stem cell defect in nu/nu mouse bone marrow is compensated by an increased proliferation in myeloid series and in agranulocytes. The increase of proliferation activity among lymphoid cells in peripheral lymphoid organs was observed only in the 3-month-old mice with a delay in the nudes.


Pesticidal activity of virginiamycins S1 and M1. Virginiamycins S1 and M1, two major components of the antibacterial antibiotic complex produced by Streptomyces virginiae and used as an animal growth promoter in animal husbandry, exhibited a selective insecticidal activity against Leptinotarsa decemlineata comparable with the effect of the organophosphorus pesticide Metathion. An acaricidal effect of the two compounds on eggs of Tetranychus urticae was also observed.


Age-related distribution of cells in cell cycle phases in dependence on specific rate of growth in chemostat cultures of Candida utilis. Individual cells in chemostat cultures of Candida utilis (D = 0.05, 0.1, 0.2, 0.25, 0.3 and 35/h) were analyzed according to the number of bud scars and according to their position in the cell cycle. The distribution in the cell cycle phases depends both on the genealogical age and the specific rate of growth.


A study of paternal age and sex ratio in sperm chromosome complements. There is conflicting evidence as to whether the secondary sex ratio in humans decreases with paternal age. Such an age effect could be caused by an altered frequency in the production of X-chromosome and Y-chromosome-bearing sperm as a man ages. To study this possibility we analysed 9,225 sperm karyotypes from 143 men aged 21-55 years. Human pronuclear sperm chromosome complements were obtained after fusion with golden hamster oocytes. The percentage of X- and Y-chromosome complements was not significantly related to donor age.


A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. A novel variation of the Haplotype Relative Risk (HRR) of Rubinstein et al. [Hum Immunol 1981;3:384] is proposed, in order to glean increased information about linkage disequilibrium or allelic associations by analyzing haplotype-based data rather than genotypic data. It is shown that statistical tests based on our design give much higher power than those based on the original HRR approach. Several additional nonparametric tests based on the same data are analyzed, and power is computed for each of them. Further, parametric likelihood methods are applied to testing linkage equilibrium, and estimating delta, the coefficient of linkage disequilibrium, from the same data.


Genetic structures in the population of Veneto. The genetic structures of the population residing in the provinces of Venice and Rovigo in the Veneto region at the north of the Po delta in Italy was studied in 1,210 individuals residing in 18 sampling areas, using the phenotype and gene frequencies of 7 red cell enzymes: acid phosphatase (ACP1), esterase D (ESD), glyoxalase I (GLOI), glutamic-pyruvic transaminase (GPT), 6-phosphogluconate dehydrogenase (6-PGD), phosphoglucomutase 1 (PGM1), and phosphoglycollate phosphatase (PGP). For the analysis of the distributions of phenotype and gene frequencies, standardized variance and kinship profiles were used. It was found that the genetic differentiation within each province is low, and that only two systems, GPT and PGP, are significantly different between the two provinces. The samples studied seem to belong to a mainly homogeneous population.


Role of blast cell immunophenotyping for the diagnosis and prognosis of acute myeloid leukemia. Bone marrow blast cell antigen expression from 86 patients with de novo acute myeloid leukemias (AML) was studied and correlated with FAB classification and clinical outcome. Among a panel of 14 monoclonal antibodies routinely used for the diagnosis of acute leukemias we studied the expression of six antibodies (CD13, CD15, VIM2, CD33, CD14, CD34) of the granulomonocytic lineage and found that some of them were useful for diagnosis and/or prognosis. For FAB subclassification of AML, the CD13 or VIM2 antigen expression was of no benefit. Monocytic leukemias (M4 + M5PD + M5WD) more frequently expressed CD34 antigen (28/31) than granulocytic (M1 + M2 + M3) subtypes (33/53) (P < 0.01). Finally, the most striking differences were found with CD14 antigen expression: CD14 antigen was more frequently expressed in M4 + M5 leukemias (21/31) than in M1 + M2 + M3 subtypes (12/33) (P < 0.01). The mean percentage of CD14 positive blast cells was accordingly higher in monocytic leukemias than in granulocytic leukemias and the difference was highly significant (P < 0.0001). The CD15 antigen was more frequently expressed in differentiated leukemias (M2 + M3 + M4 + M5WD) (35/44) than in poorly differentiated forms (M1 + M5PD) (17/37) (P < 0.001). The statistical difference was higher when the mean percentage of CD15 positive blast cells were compared (P < 0.0003). Moreover these latter percentages were different in M1 and M2 subtypes (P < 0.003). The blast cell expression of CD13, CD14, CD15 or CD33 was not predictive of the length of CR or survival. Moreover, our results support previously published findings suggesting a longer overall survival duration for patients whose leukemic cells do not express the CD34 antigen (P < 0.01). We also confirm that patients with the more differentiated subtypes of AML (CD13-, CD34+) tend to survive longer than patients with the less differentiated subtypes of AML (CD13-, CD34+) (P < 0.001).


The management of acute myelogenous leukemia in the elderly: ten-year experience in 118 patients. This retrospective study was undertaken to analyse the survival pattern of 118 consecutive, unselected patients with acute myelogenous leukemia (AML) aged between 60 and 82 years observed at a single centre over a 10-year period (1981-1991). Thirty-two per cent of cases had an antecedent hematological disorder (AHD), and 7 per cent had a secondary AML. Forty patients (39 per cent) were managed with palliative intent with short courses with oral hydroxyurea +/- 6-thioguanine. In contrast to 78 patients (61 per cent) selected for remission-induction treatment, these were significantly older (P < 0.0001), had a greater incidence of AHD (P < 0.039) and of hypoplastic AML (P < 0.017), and an inferior amount of blast cells in the bone marrow (P < 0.003). Patients undergoing remission-induction chemotherapy were managed with DAT-like chemotherapy, high-dose cytosine arabinoside (HD-ara-C), and mitoxantrone-based regimens. The complete response (CR) rate was 29 per cent. Response was higher with the two most intensive HD-araC and mitoxantrone-etoposide-araC programmes (P < 0.026), and correlated favourably with no AHD (P < 0.04) and lower blast cell count in the peripheral blood (P < 0.02). Overall survival of responders was longer than in palliation and nonresponder groups (P < 0.025 and P < 0.001, respectively). In the active treatment group, survival correlated with performance status (P < 0.005) and blast cell count (P < 0.05). Infection was the main cause of morbidity during active treatment, accounting for most induction failures (60 per cent), followed by haemorrhage (12 per cent) and resistant disease (12 per cent). These results from an unselected series represent an improvement over those obtained by us in previous years (1971-1980), and show that intensive treatment programmes are applicable to the elderly with AML and that prolonged disease-free survival is possible for some. Improving further CR rate and duration will depend equally on the optimization of supportive care measures and the introduction of more effective therapeutic modalities.


Triple alpha-genes (alpha alpha alpha anti3.7) in a patient with sickle cell anaemia. This paper reports the case of a 17-year-old male student from the Jaizan area in south-western Saudi Arabia who had sickle cell anaemia and possessed three alpha-genes on one chromosome (alpha alpha alpha anti3.7) and two on the other. The clinical manifestations were severe, with frequent blood transfusion requirements and frequent episodes of painful crises, severe anaemia and tissue involvement. In comparison with age and sex-matched sickle cell anaemia patients with one alpha-gene deletion (-alpha/alpha alpha), or a normal alpha-gene arrangement (alpha alpha/alpha alpha), a more severe disease presentation was obvious in the propositus. It is suggested that with the surplus alpha-globin chains, more severe haematological and clinical abnormalities occur, these influence the phenotypic expression of sickle cell anaemia. However, more patients with this type of gene arrangement must be studied before a definite conclusion can be reached regarding the influence of excess alpha-globin chains on the presentation of sickle cell anaemia.


Large cell lymphoma with initial presentation in the bone marrow. This report describes 14 cases of large cell lymphoma with initial presentation as marrow involvement in the absence of peripheral lymphadenopathy. The disease affected mainly the middle-aged and elderly, with male predominance. Most patients presented with swinging fever and peripheral blood cytopenia. Reactive hemophagocytic syndrome was a common finding, causing significant morbidity and mortality. Peripheral lymphadenopathy was absent (by case selection), but involvement of the liver, spleen and paraaortic lymph nodes could be demonstrated in some cases. However, in some patients, the involvement was apparently restricted to the bone marrow. Involvement of the bone marrow was often subtle, and could be missed on causal examination. Immunohistochemical studies on eight cases showed that four exhibited a B-cell phenotype, three a T-cell phenotype and one a non-T non-B phenotype. The prognosis was poor, with survival being measured in days to weeks in most patients.


Polymorphisms of alpha-1-acid (orosomucoid), alpha-2-HS-glycoproteins and alpha-1-B among the Parsis of India. Genetic polymorphisms of plasma alpha 1-acid glycoprotein (oro-somucoid, ORM), alpha 2-HS-glycoprotein (A2HS) and alpha 1-B-glycoprotein (alpha 1B) were studied in a group of Parsis in Bombay, India. The frequencies of ORM1*1, ORM1*2 and ORM1*3 were found to be 0.636, 0.356 and 0.008, respectively. A2HS*1, A2HS*2 and A2HS*3 frequencies were 0.855, 0.135 and 0.010, while the frequencies of A1B*1 and A1B*2 were 0.881 and 0.119, respectively. The phenotype distribution at all three loci was at Hardy-Weinberg equilibrium. The ORM2 locus was monomorphic in the Parsis.


Genetic polymorphisms of alpha-2-HS-glycoprotein, group-specific component and orosomucoid in the Han population, Chengdu, China. The Han population in Chengdu, China, was investigated for genetic polymorphisms of alpha-2-HS-glycoprotein (A2HS), group-specific component (GC) and orosomucoid (ORM) using isoelectric focusing followed by immunofixation. The allele frequencies were: A2HS*1 = 0.6958,A2HS*2 = 0.3042, GC*1F = 0.4021, GC*1S = 0.3182, GC*2 = 0.2745, GC*1A = 0.0052, ORM1*F1 = 0.7028, ORM1*S = 0.2762, ORM1*F2 = 0.0210, ORM2*A = 0.9965, ORM2*Var = 0.0035.


Alpha-1-antitrypsin (PI) subtypes in Russians and Poles. alpha-1-antitrypsin (PI) subtypes were studied in Poles and Russians. The frequencies of the PI alleles were similar in the two populations, with the exception of the Z allele, whose frequency was significantly lower in Poles. The M3 allele frequency, which is highly heterogeneous in European populations, has medium frequencies in Poles and Russians.


Polyclonal activation of B lymphocytes by lipopolysaccharide requires macrophage-derived interleukin-1. Lipopolysaccharide (LPS) is a potent murine polyclonal B-cell activator which induces cellular proliferation and IgM secretion. The precise role of activated macrophages in the induction of LPS-dependent, B-cell responses has been unclear. Although early reports concluded that the LPS effect occurs independently of other cell types, other studies have suggested that adherent macrophages exert either potentiating or inhibitory effects. In the present study, B-cell mitogenesis and IgM production were measured in primary spleen cell cultures after removing adherent cells by a variety of experimental procedures. B-cell activation by LPS was found to be strictly dependent on the presence of adherent macrophages. Antibody neutralization and cytokine reconstitution studies demonstrated that macrophage-derived interleukin- (IL-1) is a necessary co-factor for LPS-induced polyclonal activation.


Comparative responses of human and rabbit interleukin-1 in vivo: effect of a recombinant interleukin-1 receptor antagonist. The ability of recombinant human and rabbit interleukin-1 alpha (IL-1 alpha) in inducing inflammatory responses in rabbit skin were compared. Intradermal (i.d.) injections of recombinant human IL-1 alpha and recombinant rabbit IL-1 alpha induced intense accumulation of 111In-labelled neutrophils which was dependent on the dose of the cytokines administered. Both forms of IL-1 alpha induced very small levels of plasma protein leakage. Co-injection of the cytokines with the mRNA synthesis inhibitor actinomycin D (Act D) attenuated the number of neutrophils accumulating in response to both human and rabbit forms of IL-1 alpha. Local injection of a recombinant human IL-1 receptor antagonist (IL-1Ra) caused a dose-dependent inhibition of local inflammatory responses initiated by human and rabbit IL-1 alpha s well as rabbit IL-1 beta indicating the species cross-reactivity of the antagonist. IL-1Ra was selective for IL-1 in rabbit skin, as responses induced by C5ades Arg and formyl-methionyl-leucyl-phenylalanine (FMLP) were not inhibited. IL-1Ra significantly inhibited the IL-1-induced neutrophil accumulation only when co-injected with the cytokine. The local administration of the antagonist 30 min after rabbit IL-1 alpha failed to inhibit the inflammatory response. These results suggest that the in vivo events leading to the accumulation of neutrophils in response to IL-1 alpha are rapidly initiated.


Interleukin-3-induced up-regulation of CR3 expression on human eosinophils is inhibited by dexamethasone. Eosinophil function is regulated by several cytokines, including interleukin-3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Culture of human eosinophils with IL-3 produced a marked, dose-dependent up-regulation of CR3 expression. This was maximal after 1 day in culture and dependent on protein and RNA synthesis, as demonstrated by inhibition with cycloheximide and actinomycin D, respectively. IL-5 and GM-CSF had a similar effect on eosinophil complement receptor type 3 (CR3) expression, but the maximal response to IL-5 was always less than to IL-3 or GM-CSF. Dexamethasone inhibited the Il-3-induced up-regulation of CR3 expression in a dose-dependent manner, with an IC50 of 5 x 10(-8) M. This study demonstrates the effect of IL-3, IL-5 and GM-CSF on eosinophil CR3 expression and confirms the capacity of eosinophils to modify their phenotype through de novo protein synthesis. This process could be inhibited by physiological concentrations of glucocorticoids, thus providing an additional mechanism for their mode of action in allergic disease.


Inhibition of interleukin-5 gene expression by dexamethasone. The effect of glucocorticoids on interleukin-5 (IL-5) gene expression was assessed in human peripheral blood mononuclear cells. IL-5 expression was stimulated by phytohaemagglutinin (PHA), IL-2, phorbol myristate acetate (PMA) or Ionomycin. A semi-quantitative assay for IL-5 gene expression was developed, based on RNA extraction and the polymerase chain reaction. IL-5 expression in response to PHA was profoundly inhibited by 10(-6) M dexamethasone, and significant inhibition was detected at doses of dexamethasone as low as 10(-9) M. When dexamethasone was added to the cells at the same time as PHA, the inhibitory effect could be detected as early as 3 hr. Dexamethasone at 10(-6) M also profoundly inhibited the IL-5 response to PMA and to IL-2, but the IL-5 response to Ionomycin was not significantly affected. These results suggest that dexamethasone may be capable of interfering with a pathway involving protein kinase C. There is increasing evidence that IL-5 may play a pathogenic role in asthma and other manifestations of acute hypersensitivity. The present findings indicate that inhibition of IL-5 expression may be one of the mechanisms whereby glucocorticoids exert their beneficial effects in diseases such as asthma.


Characterization of platelet-activating factor synthesized by normal and granulocyte-macrophage colony-stimulating factor-primed human eosinophils. Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3- phosphocholine) is a mediator involved in the pathogenesis of inflammatory diseases associated with tissue eosinophil infiltration. Previous studies utilizing bioassay or assaying enzymes associated with PAF biosynthesis have suggested that human eosinophils produce PAF. The present study has extended these initial studies by identifying and quantifying the different PAF molecular species and analogues synthesized by human eosinophils in response to A23187 and f-Met-Leu-Phe (FMLP). Gas chromatography-mass spectrometric analysis indicated that A23187-stimulated eosinophils produce at least three molecular species of PAF. The predominant species is 1-hexadecyl-2-acetyl-GPC (16:0) followed by 1-octadecyl-2-acetyl-GPC (18:0) and 1-octadecyl-2-acetyl-GPC (18:1). Eosinophils stimulated with FMLP produce approximately 100-fold smaller quantities of PAF relative to those produced in response to A23187 and only the 16:0 molecular species could be measured. A small percentage (comprising between 2 and 5%) of the 2-acetylated phospholipids produced by eosinophils was the 1-acyl analogue of PAF. Long-term (72 hr) incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in a three- to fourfold increase in PAF synthesis from eosinophils stimulated with FMLP, without changes in the profile of PAF molecular species or in the percentage of the 1-acyl analogue of PAF. These data indicate that human eosinophils can produce various molecular species of PAF and that this process can be quantitatively enhanced by GM-CSF.


The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues. An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system.


Signal-dependent pleiotropic regulation of lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3: potent modulation of the hormonal effects by phorbol esters. The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the proliferation of lymphocytes and on the production of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) was examined in normal human peripheral blood mononuclear cells (PBMC) activated in vitro either by phytohaemagglutinin (PHA) or by the monoclonal antibody to the T-cell receptor OKT3, or by the combination of each of these two stimuli with phorbol myristate acetate (PMA). 1,25(OH)2D3 inhibited the proliferative response of PBMC to PHA; this effect, however, was abrogated by the addition of PMA (1.6 nM), and it was reversed from inhibition to stimulation by higher concentrations of the phorbol ester. In contrast to the PHA-activated cells, 1,25(OH)2D3 had no effect on the proliferative response of PBMC to OKT3. Further, 1,25(OH)2D3 inhibited the release of IL-6 in cultures of PHA-activated PBMC, whereas it stimulated IL-6 with the addition of PMA in these cultures. In contrast to the PHA-activated cells, 1,25(OH)2D3 increased IL-6 release in OKT3-activated cells. IL-1 beta production was not affected in either PHA- or OKT3-activated cells by the presence of the hormone, but it was stimulated by 1,25(OH)2D3 when PMA was used as a co-stimulus with either PHA or OKT3. Finally, 1,25(OH)2D3 inhibited IFN-gamma in both PHA- and OKT3-activated cells, but these effects were attenuated in the presence of PMA. These findings demonstrate that the in vitro effects of 1,25(OH)2D3 on lymphocyte proliferation and cytokine production by PBMC are pleiotropic, and that such pleiotropism depends upon the mode of PBMC activation and presumably the signals that are generated in response to the specific agents used to activate these cells.


Immunoregulatory properties of (+)-pentazocine and sigma ligands. (+)-Pentazocine, phencyclidine, and other sigma ligands including 1,3-di-(o)-tolylguanidine (DTG), (+)-1-propyl-3-(3-hydroxyphenyl) piperidine [(+)-PPP] and haloperidol were investigated for their potential immunoregulatory properties. High concentrations (10(-5) M) of DTG and haloperidol were found to suppress in vitro murine splenocyte natural killer activity while equivalent concentrations of (+)-pentazocine, (-)-pentazocine and (+)-PPP were without effect. In a reciprocal fashion, lower doses (10(-9) M) of DTG enhanced natural killer activity. Sigma ligands were also found to affect in vitro polyclonal immunoglobulin production following mitogen stimulation. Specifically, high concentrations (10(-6) M) of haloperidol significantly (P < 0.001) suppressed pokeweed mitogen (PWM)-stimulated IgG and IgM production, yet enhanced lipopolysaccharide (LPS)-stimulated IgM production by murine splenocytes. Lower concentrations (10(-8) to 10(-10) M) enhanced (two- to fourfold) PWM-induced IgM production and LPS-stimulated IgG and IgM production. At high concentrations (10(-6)), (+)-pentazocine suppressed (P < 0.01) LPS-induced polyclonal IgG and IgM but enhanced (P < 0.01) PWM-induced IgM production. Both DTG and (-)-pentazocine (10(-8) to 10(-10) M) significantly augmented (two- to threefold) LPS-stimulated murine splenocyte production of polyclonal IgM. Intracellularly, (-)-pentazocine (10(-9) M), haloperidol (10(-7) M), DTG (10(-7) M) and (+)-PPP (10(-5) to 10(-9) M) enhanced forskolin (10(-6) M)-induced cAMP production in splenic lymphocytes while (+)-pentazocine was without effect. Collectively, the data suggest functional and biologically relevant sigma receptors on cells of the immune system.


Regulation of macrophage Fc receptor expression and phagocytosis by histidine-rich glycoprotein. Regulation of macrophage Fc receptor (Fc gamma R)-mediated phagocytic function by histidine-rich glycoprotein (HRG) was investigated. Pretreatment of oil-elicited inflammatory mouse peritoneal macrophages with HRG for 1-3 hr increased their Fc gamma R-mediated binding and phagocytosis of IgG-opsonized sheep erythrocyte conjugates (EA). A significant reduction of Fc gamma R-dependent EA binding and phagocytosis occurred after pretreatment of macrophages with HRG for more than 8 hr. These results indicate that HRG is capable of modulating Fc gamma R expression in a biphasic fashion, which directly affects the overall efficiency of phagocytosis. HRG differentially regulated the functions of Fc gamma R subclasses. For example, HRG reduced the efficiency of Fc gamma RII (Fc gamma 2b/gamma 1R)-dependent phagocytosis of erythrocytes conjugated with monoclonal IgG2b or IgG1 by macrophages pretreated with HRG for 24 hr. However, when similar studies were performed using erythrocytes coated with monoclonal IgG2a, HRG was less effective in inhibiting Fc gamma RI (Fc gamma 2aR)-dependent phagocytosis. As an HRG-binding glycosaminoglycan, heparin failed to block the regulatory function of HRG on macrophages. Similarly, interferon-gamma (IFN-gamma) was not capable of blocking the functional activity of HRG. These studies suggest that HRG regulates macrophage function via a novel pathway different from that of heparin or IFN-gamma.


Constitutive endocytosis and recycling of major histocompatibility complex class II glycoproteins in human B-lymphoblastoid cells. Cleavable cell surface radiolabelling reagents were used to measure the endocytosis and recycling of class II major histocompatibility complex (MHC) glycoproteins in human B-lymphoblastoid cells. It is shown that mature class II alpha beta dimers on the cell surface are constitutively endocytosed and that recycling can be demonstrated even from small endosomal pools. Endocytosis was blocked when cellular ATP levels were depleted or when clathrin polymerization was inhibited, implicating clathrin-coated pits in the endocytic process. Taken together with earlier studies, these results suggest that mature class II MHC molecules are constitutively endocytosed and recycled from acidic peripheral endosomes which may enhance their capacity to bind and present T cell epitopes which do not require processing.


Delayed-type hypersensitivity responses regulate collagen deposition in the lung. A previous report showed that hamsters immunized by epicutaneous application of 2,4,6-trinitrochloro-1-benzene (TNCB) were susceptible to the development of pulmonary interstitial fibrosis (PIF) if challenged in the lung with the water-soluble form of this hapten 2,4,6-trinitrobenzene sulphonic acid (TNBS). In this study, we investigated the immunological mechanisms that contributed to increased collagen content in the lungs of hapten-immune hamsters after receiving a pulmonary challenge of the sensitizing hapten trinitrophenol (TNP). In order to evaluate the concept that delayed-type hypersensitivity (DTH) reaction modulated their response to TNP in the lung such that it eventuated into PIF, we compared the cutaneous DTH response (48 hr after challenge) with lung collagen deposition (14 days after challenge) in several lines (strains) of hamsters. The inbred LSH strain, was a high responder in the DTH assay to TNP and developed non-resolving PIF in the hapten-immune animals. This is called hapten-immune pulmonary interstitial fibrosis or HIPIF. We also observed that female LSH hamsters were more susceptible to HIPIF induced by TNP than males. On the other hand, age factors influenced DTH and PIF in random-bred LVG hamsters since young hamsters (3 months old) were low responders to TNP and did not develop PIF in the HIPIF model but matured LVG hamsters (retired breeders) possessed DTH reactivity to TNP and subsequently developed PIF. These results suggest that lung collagen deposition in hapten-immune hamster is regulated by T-lymphocyte-mediated immune inflammation (DTH) in the lung and both are dependent on the ability to develop a cutaneous DTH reaction to the hapten. The elucidation of possible mechanisms of DTH-mediated non-granulomatous, non-resolving PIF is important for understanding of the role of environmental chemicals similar in action to haptens in the mediation of skin and lung diseases.


Ontogeny and development of extrathymic T cells in mouse liver. We previously demonstrated that the liver may be a major site of extrathymic T-cell differentiation in mice. In the present study, the ontogeny and subsequent development of such T cells in the liver and other organs were investigated. This study was possible because these T cells have T-cell receptors (TcR) of intermediate intensity (i.e. intermediate TcR cells) and constitutively express a high level of interleukin-2 receptor beta chain (IL-2R beta). Therefore the two-colour staining for CD3 (or alpha beta TcR) and IL-2R beta identifies even a small proportion of intermediate TcR cells. The total numbers of mononuclear cells obtained from the liver, thymus and spleen varied from foetal to adult life. Especially in the liver, many haematopoietic cells were present in the parenchymal space at the foetal stage. There were no lymphocytes in the sinusoidal lumen at this period. In contrast, lymphocytes appeared in the hepatic sinusoids after birth and increased with ageing. Phenotypic analysis revealed that intermediate TcR cells appeared in the liver and spleen on Day 4 after birth. Bright TcR cells of thymic origin were also present in the peripheral organs on Day 4. Thereafter, intermediate TcR cells increased in the liver, whereas bright TcR cells increased in the periphery as a function of age. Similarly, thymectomized and congenitally athymic mice had mainly intermediate TcR cells in the liver and, to some extent, periphery. It is concluded that intermediate TcR cells, possibly of extrathymic origin, are generated only after birth and expand with ageing.


Characterization of B-cell phenotypic changes during ileal and jejunal Peyer's patch development in sheep. Changes in B-cell phenotype during development of ileal and jejunal Peyer's patches (PP) of sheep were investigated using flow cytometry and immunoperoxidase-stained cryosections. On Day 104 of gestation (term at 150 days) B-cell clusters were identified in the lamina propria of the ileum. These clusters were composed of cells that expressed surface IgM (sIgM), lambda or kappa light chain, and BAQ44A, a B-cell differentiation molecule. No cells in the clusters stained for terminal deoxynucleotide transferase. On Day 132 gestation, a change was evident in the phenotype of ileal PP B cells. Most B cells expressed a reduced level of sIgM and 20% were BAQ44A-. The B cells in the dome region were BAQ44A+ but few BAQ44A+ cells were present in the follicles. At 6-8 weeks of age BAQ44A+ cells were restricted to the dome region of the ileal PP; flow cytometric analysis confirmed that 25% of B cells isolated from the dome/follicle complex were BAQ44A+. Thus, the primordial PP was populated with B cells that were phenotypically similar to circulating B cells (sIgMhigh, BAQ44A+). After 132 days gestation, the predominant B-cell phenotype in the ileal PP changed to sIgMlow and BAQ44A-. This phenotypic change could be the result of either early immigrant B-cell differentiation or subsequent colonization by sIgMlow BAQ44A- B cells. The phenotypic changes of ileal PP follicular B cells were not complete until after birth and different phenotypic changes were observed in follicles of the jejunal PP of young lambs.


Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice. In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance.


Class and subclass-associated specificity differences of anti-gliadin antibodies from mucosa and serum. The class and subclass distribution of antibodies against gliadin in intestinal lavage fluid, saliva and serum was investigated in individuals with coeliac disease. Serum antibodies against gliadin were mainly or even exclusively of the IgA1 subclass. In intestinal lavage fluid and saliva, antibodies of both IgA1 and IgA2 subclasses were found. In patients with and without IgA deficiency, an IgG response was detected both in serum and intestinal lavage fluid with a predominance of IgG1 in selected patients. Specific IgG2, IgG3 and IgG4 antibodies were also detected in intestinal lavage fluid, while no specific IgG2, IgG3 or IgG4 antibodies were found in serum, suggesting a local production of specific IgG antibodies. In Western blot analysis, intestinal lavage fluid and serum IgA antibodies reacted against gliadin components with a MW between 33,000 and 42,000. Serum IgA1 antibodies directed against a gliadin component with a MW slightly higher than 42,000 were also observed. Specific IgG and IgM antibodies in both the secretion and serum against gliadin components with a MW between 33,000 and 42,000 were also detected. This study shows that mucosa-derived gliadin-specific IgA and IgG antibodies may be produced even when there is an absence of specific antibodies of the corresponding immunoglobulin subclass in serum. Furthermore, the specificity of serum and intestinal lavage fluid anti-gliadin IgA1 antibodies may differ.


Hydrocortisone inhibition of human interleukin-4. Glucocorticoids are known to inhibit mitogen-induced proliferation of T cells by suppressing the production of interleukin-2 (IL-2). These hormones have also been shown to inhibit the production of other cytokines, namely IL-1 and interferon-gamma (IFN-gamma). It is demonstrated here that hydrocortisone is able to inhibit mitogen-induced production of human IL-4, both at the secreted protein, as well as at the mRNA level. This effect may explain, in part, the immunosuppressive effects of glucocorticoids in the treatment of allergic disease.


The concept of dose intensification in the treatment of neoplastic disease. This paper summarizes different theoretical and clinical approaches contributing to the concept of dose intensification. According to this concept, the amount of antineoplastic drug delivered per time predominantly determines the clinical outcome in patients with neoplastic disease. With the availability of recombinant haemopoietic growth factors haematotoxic side effects might be reduced, making this concept more feasible for clinical use. However, more prospective randomized studies, in which dose-intensity is the only treatment variable, are needed to prove that dose intensification will lead to higher survival rates.


Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). The EORTC Leukaemia Group. Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.


The side-effect profile of GM-CSF.

The side-effect profile of GM-CSF. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic molecule which displays a broad range of haematopoietic activities, has become available for clinical evaluation in various patient groups. It has been shown to be effective in preventing or reversing neutropenia. Adverse effects of GM-CSF, however, are dose related. Appropriate dose, route and schedules for GM-CSF in various clinical settings have recently been defined, the usual range being 5-10 micrograms/kg/day either by 4-6 h intravenous infusion or by subcutaneous injection. At such doses, adverse effects are predominantly mild-to-moderate in nature, occur in 20-30% of patients and usually comprise fever, myalgia, malaise, rash and injection site reaction. Early trials using very high doses of GM-CSF were often associated with marked adverse effects, which in rare cases proved severe (pericarditis and thrombosis). Similarly, a so-called "first-dose reaction", defined as a syndrome of hypoxia and hypotension after the initial but not subsequent doses of GM-CSF, was observed in certain predisposed patients following doses above 10 micrograms/kg/day. Subsequent trials have established that intravenous bolus or short infusions of GM-CSF are more likely to promote adverse effects. Certain patient groups, for example those with myelodysplastic syndrome, acute myeloid leukaemia, inflammatory disease, autoimmune thrombocytopenia or malfunctional immunological responsiveness, require careful clinical monitoring in order to avoid potential complications following the administration of GM-CSF. With the current appropriate administration and doses of GM-CSF, the benefit:risk ratio has been greatly improved.


The role of GM-CSF in infection.

The role of GM-CSF in infection. GM-CSF is a hemopoietic growth factor with substantial effects on the proliferation of neutrophils, eosinophils and monocytes/macrophages. Its physiologic role in infection is still poorly understood. The gene for GM-CSF is constitutively transcribed in cells substantial for antiinfectious response. Various cells are activated and induced by TNF and IL-1 to synthesize GM-CSF. No systemic GM-CSF levels can be detected in patients with infection. It is likely that GM-CSF plays its physiological role in the immediate vicinity of the cells by which it is secreted. GM-CSF functionally activates neutrophils, monocytes/macrophages and eosinophils. It may augment T-cell proliferation and function. GM-CSF is effective in mice infected with Staphylococcus aureus or Salmonella typhimurium. Its effect in infectious disease in man should be explored.


Granulocyte-macrophage colony-stimulating factor (GM-CSF): what role in bone marrow transplantation? Infection during the period of bone marrow aplasia remains one of the major risks associated with high-dose chemotherapy and transplantation. Over the past several years, a number of investigators in Europe and North America have evaluated the use of GM-CSF in the setting of autologous bone marrow transplantation. These studies have almost all shown a hastening of myeloid engraftment. This, for the most part, has led to fewer serious infections and a decreased hospital stay for the GM-CSF treated patients. An overall survival advantage has not been noted. There has also not been any consistent multi-lineage effect. Future trials with combinations of sequentially used cytokines may lead to more rapid recovery of red blood cells and platelets in addition to granulocytes.


Increasing plasma phosphorus values by enriching with phosphorus the "acid concentrate" of a bicarbonate-buffered dialysate delivery system. Each of seven hypophosphatemic hemodialysis patients was dialyzed with a phosphorus-enriched, bicarbonate-buffered dialysate. The latter was prepared by the introduction of sodium phosphate salts to the "acid concentrate" of a bicarbonate-buffered dialysate delivery system. The patients tolerated the procedure well and their hypophosphatemia improved.


Effects of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis patients. The aim of this study was to evaluate the effect of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis (HD) patients. Thirty-one HD patients who had never been treated with vitamin D nor related drugs and 12 healthy subjects with normal renal functions were studied. Uremic HD patients were randomly divided into two groups. Sixteen uremic HD patients were treated with oral calcitriol (0.5 micrograms/day) for 8 weeks. 13 uremic HD patients and 12 healthy subjects were given placebo. In all these cases before and after 8 weeks of treatments; serum total lipid, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels were determined. After calcitriol treatment, triglyceride levels were significantly decreased. But total lipid, cholesterol, HDL-cholesterol and LDL-cholesterol levels did not significantly change. In the other two groups there were no significant changes. These results show that calcitriol treatment has a positive effect on triglyceride levels in uremic HD patients. This effect of mechanism of calcitriol treatment has not been known yet. But it could be due to regulation carbohydrates metabolism and normalization of parathormone (PTH) levels.


Dietary protein loading and the oral adsorbent AST-120 in the progression of chronic renal failure in the rat. Excess protein intake enhances the progression of renal failure. The oral carbonaceous adsorbent, AST-120, was found experimentally and clinically to retard the progression of renal failure. This study was designed to determine whether deterioration of renal function by dietary protein loading can be prevented or mitigated by this oral adsorbent. Rats with uremia induced by partial renal infarction were fed a normal or high-protein diet for 70 days with or without AST-120, in which the inorganic phosphate content was adjusted to the same level. The survival rate deteriorated with the high dietary protein, but was improved from 30% to 100% with AST-120. Dietary protein loading reduced renal function, based on creatinine clearance. AST-120 improved renal function and renal histopathology not only in the normal diet group but in the high-protein group as well. The progression of renal failure induced by protein loading is thus shown to be prevented by oral AST-120. The mechanism for its action remains to be clarified.


Improvement of survival rate in patients with cardiogenic shock by using nonpulsatile and pulsatile ventricular assist device. Between January 1988 and January 1992, 65 patients (pts) had a ventricle assist device (VAD) inserted in our clinic. In 24 pts a VAD was applied because of primarily unsuccessful weaning from cardiopulmonary bypass (Group A). In a further 24 pts (Group B) a VAD was installed for the therapy of refractive cardiogenic shock (CS) after initially successful cardiac surgery (n = 21) and after acute myocardial infarction (n = 3). Twelve pts were bridged to heart transplantation (Group C) and five had a VAD inserted for various other reasons (Group D). In 36 (55.4%) of the total 65 pts a nonpulsatile VAD (Biomedicus 540) was used: 10 in Group A; 20 in B, 3 in C and 3 in D. In 29 pts (44.6%) a pulsatile VAD (Abiomed BVS 5000) was used: 14 in Group A, 4 in B, 9 in C and 2 in D. Weaning rate and long-term survival rates were 50% and 46% respectively in Group A and 38% and 42% in Group B. Seven pts from Group C were transplanted and six are long-term survivors. Two pts (40%) in Group D were discharged from hospital. Major postoperative complications were bleeding (46%), thromboembolism (14%), multiple organ failure (11%), renal failure (11%), arterial embolism (4.6%), sepsis (3%). The results indicate that application of a VAD can be recommended in pts with postcardiotomy CS to allow recovery of cardiac function and in pts with irreversible ventricular damage as bridging to HTX.


Extracellular matrix covered biomaterials for human endothelial cell growth. The aim of this study is to optimize conditions for growing endothelial cells on vascular biomaterials. Bovine cornea endothelial cells (BCEC), stimulated by basic Fibroblast Growth Factor (bFGF) secrete an extracellular matrix (ECM) similar to the Descemet membrane produced in vivo by these cells. This ECM, obtained by removing BCEC with an hypotonic shock can be used as a substratum for other endothelial cell growth. Human endothelial cells (HEC) were purified from omentum that was digested with a solution of collagenase-dispase, then filtered through nylon meshes. The cells were further purified by centrifugation onto a Percoll gradient. A comparative study on the attachment and growth of HEC on various coatings (laminin, poly-L-lysine, fibronectin or ECM) indicates that ECM is the most performing substratum. The quality of this endothelium was confirmed by the presence of factor VIII, and MHC class I and the absence of class II antigens.


Peptidyl antithrombogenic agents for extracorporeal blood circulation. The reduction of platelet aggregation and adhesion is essential for preventing thrombus formation during extracorporeal circulation. This report addresses some performances of peptidyl antithrombogenic agents which bind to the adhesive site of fibrinogen. This was based on the recent finding that the sequence of the binding domain of the platelet membrane receptor to fibrinogen was identified as TDVNGDGRHDL (one-letter amino acid code; Thr-Asp-Val-Asn-Gly-Asp-Gly-Arg-His-Asp-Leu), entitled B12. The addition of B12 and shorter-chain analogue peptides dose-dependently suppressed platelet aggregation and adhesion onto a fibrinogen-coated surface. The shorter the amino acid sequence, the less effective was inhibition. The inhibitory effect on platelet adhesion in vivo was significant under continuous infusion of B12. These inhibitory effects were compared with those by a receptor-binding RGD (Arg-Gly-Asp) peptide, which is the common active site to adhesive proteins.


Modelling the optimal control of cyclical leg movements induced by functional electrical stimulation. An optimal control strategy for FES-induced cyclical leg movements in paraplegics is proposed. The control of the cyclical movement of a freely swinging leg is considered as an example. Quadriceps and the flexion withdrawal reflex are stimulated in order to generate a cyclical movement, of which the forward swing resembles the swing phase of gait. Optimal stimulation patterns are determined on the basis of an optimization criterion and a dynamic model of the system. The criterion is based on desired movement parameters and a minimal duration of the stimulation bursts. The movement parameters should ensure the generation of the desired cyclical movement: a desired hip angle range, sufficient foot clearance during the forward swing and knee extension at the beginning of the backward swing. Minimal duration of the stimulation bursts is assumed to yield minimal fatigue. A dynamic model, describing the dynamics of the neural system, the muscles and the leg, was constructed and its parameters identified on the basis of preliminary experiments and literature. Optimal timing of the quadriceps and flexion reflex stimulation bursts was determined by means of computer simulation. These simulations predicted that the flexion reflex should be stimulated in a short burst approximately 150 ms before the start of the forward swing. The quadriceps should be stimulated approximately starting 200 ms before the end of the forward swing in order to ensure knee extension at the beginning of the backward swing. The duration of one cycle of the movement was between 1300 and 1500 ms in these simulations. These results predict that the movement specified by the functional objectives can be realised using only two channels of stimulation. On the basis of the optimal timing, an adaptive control strategy can be designed, which varies the stimulation burst width when muscles fatigue.


Therapeutic community treatment for personality disordered adults: changes in neurotic symptomatology on follow-up. Personality disordered patients are important as they place high continuing demands on services and are often refractory to traditional treatments. Often personality disorders may co-exist with neurotic symptomatology, worsening prognosis of the latter. This paper reports change in neurotic symptomatology following intensive, long term, therapeutic community treatment for such patients. Sixty two subjects with personality disorder were followed up for eight months after discharge (response rate 65%). Results showed a highly significant reduction in symptomatic distress as measured by the SCL-90R questionnaire. Investigation of the reliability and clinical importance of the change in individual subjects demonstrated that 55% of subjects had improved reliably, and in 32% this change was also clinically significant, whilst only 6.5% of subjects had deteriorated reliably.


Japanese Type A behavior pattern is associated with "typus melancholicus": a study from the sociocultural viewpoint. An examination of the relationship between Type A behavior pattern (TABP) and "Typus Melancholicus" (TM) in 212 coronary heart disease (CHD) patients in Japan revealed that: CHD patients with TABP were significantly more likely to have a depression-prone personality, what Tellenbach calls "Typus Melancholicus"; this tendency was observed not only in CHD patients but also among healthy Type A subjects; and TM is positively correlated with Type A. The results of our studies from a comparative sociocultural viewpoint indicate that TM may be involved in Japanese TABP, suggesting the possibility that driving, self-sacrificing and obsessional traits are related to Type A behavior in a variety of different cultural contexts.


Perceived self in educated employed and educated unemployed women. The purpose of this study was to compare the perceived self-concept of employed and unemployed educated women. The study also examined the relationship of perceived self-concept with the type of employment and period of service of the employed women. The sample consisted of 150 employed and 150 unemployed educated married women residing in an urban area of Patna. The self-concept scale of Deo (1985) was used in the study. The findings showed that the perceived self of the employed women scored relatively higher in each of the five attributes of the perceived self; ie. Aesthetic, Emotional, Character, Intellectual and Social. It was concluded, from this study, that employment leads to a higher self-concept among educated women, which however varied with different types of employment.


Letters to the Rebbe. Millenium, messianism and medicine among the Lubavitch of Stamford Hill, London. The Lubavitch are a group of Hasidic Jews living in Stamford Hill, London N16. After a description of their lifestyle and the importance of the Rebbe in the community, this paper examines their concepts of the body, health and healing based on Kabbalistic teachings. For this group healing involves both control of sickness and the correction of spiritual disorder associated with it: the Rebbe plays a key role in the latter. The paper ends by discussing the extent to which conversion of religious groups results in any form of healing. (See Glossary for translation of Jewish words.)


Nurses' views of parasuicide in a developing country. This study examines the knowledge, beliefs, attitudes, intentions and experiences of nurses at various stages of their careers with regard to patients who have made suicide attempts. It focuses particularly on the relationship of traditional Shona beliefs about suicide and considers how they interact with western medical beliefs. A detailed questionnaire covering these elements was administered to three groups of nurses. They were sampled at either the beginning or end of their training or after approximately ten years experience. Knowledge of suicide was found to be poor and attitudes towards parasuicide were negative. Traditional beliefs were held strongly by all groups of nurses; western beliefs were strongest amongst experienced nurses. Practical implications of these attitudes and beliefs for training are considered.


Opinions about and reactions to suicide, and the social acceptance of a suicidal classmate among Turkish high school students. The present study investigated the opinions about suicide and reactions to a suicidal peer among 89 female and 78 male Turkish high school students. Females more than males believed that suicide should be discussed among friends. More males than females perceived suicidal persons to be mentally ill and to be punished in the other world. Females showed greater acceptance for a suicidal classmate than males. An attitude for openly discussing suicide was associated with higher acceptance of a suicidal classmate. Perceiving suicidal individuals to be mentally ill was associated with lower acceptance of a suicidal peer.


Psychiatric morbidity of foreign students in Yugoslavia: a 25 year retrospective analysis. Psychiatric morbidity of hospitalized foreign students in Yugoslavia was analyzed in a 25-year retrospective study and was compared to the psychiatric morbidity of a group of Yugoslav students hospitalized in the same psychiatric institutions, over the same time period. Results showed significantly higher rates of paranoid and depressive reactions amongst foreign students, and suggested correlation between their psychiatric morbidity and maladaptation to the new living conditions.


Factors related to psychiatric hospitalisation for first contact patients. In a consecutive series of 178 first contact patients hospitalisation was significantly related to greater distance travelled, low income, acute onset, short duration, past history of illness and history of substance abuse compared to those receiving outpatient disposition. Hospitalised manics and paranoid schizophrenics had higher BPRS scores while hospitalised non-paranoid schizophrenics had lower scores. There was a significant positive correlation between hospitalisation and BPRS items: grandiosity, excitement, elated mood, motor-hyperactivity and distractibility and negative correlation with somatic concern, anxiety, depressive mood and social incompetence. Stepwise multiple regression analysis found the combination of loss of functioning, social incompetence and grandiosity to best predict disposition decision.


Non-attendances at a marital and sexual difficulties clinic: a controlled intervention study. Clients referred to a marital and sexual difficulties clinic were given an information sheet and a questionnaire in a controlled study. This led to a significant reduction in non-attendance at the assessment interview (p < 0.01) and in a significantly higher number of clients attending for therapy (p < 0.05).


Stealing in bulimia nervosa.

Stealing in bulimia nervosa. This clinical study examines the prevalence of stealing and the personal and behavioural factors which distinguish stealing and non-stealing behaviour in a population of 312 female normal-weight bulimics. Bulimic patients who stole had poorer early interpersonal relationships, earlier onset of sexual feelings with greater subsequent sexual activity and increased illicit drug use. The suggestion is made that stealing is a marker of severity. In addition, bulimics who stole appeared to exhibit more obsessional qualities with increased ritualisation.


The impact of the economy on suicide and homicide rates in Japan and the United States. A time series study of socioeconomic correlates of suicide and homicide in Japan and the USA from 1953 to 1982 revealed cross-national differences. Divorce rates were positively associated with rates of personal violence in the USA but negatively associated with these rates in Japan. Unemployment and female labor force participation also correlated differently with rates of personal violence in the two nations suggesting that different theories may be necessary to account for the variation in rates of personal violence in different societies.


[Current understanding of mucociliary transport]. This review article deals with current understanding of mucociliary transport and its significance for clinical practice. The ultrastructure of cilia and principles of mucociliary clearance in the upper respiratory tract are outlined. Practicable diagnostic measures described are the saccharine test, vital cytological sampling of the nasal mucosa and electron microscopy for ultrastructural studies. Special pathologies such as the immotile cilia syndrome and mucoviscidosis are outlined in their relation to mucociliary transport. Recommendations are given as to how mucociliary transport might be influenced therapeutically.


[Diagnostic aspects of isolated sphenoid sinusitis]. The clinical occurrence of isolated sphenoid sinusitis is rare. Due to a long history and few initial symptoms, diagnosis of this potentially fatal infections can be difficult. Radiological aspects in 10 patients are presented (e.g. type and design of examination and whether inflammatory or destructive changes could be shown), as well as clinical aspects (cranial nerve palsy, concurrent inflammation, duration of disease and therapy). CT proved to be superior in diagnosing the extent of any bony changes, while MRI was more useful in detecting inflammation.


[Holmium:YAG laser surgery. Possibilities for use in inflammatory paranasal sinus diseases]. A pulsed Holmium: YAG laser (lambda = 2120 nm) was used during functional endoscopic endonasal surgery in ten patients with recurrent chronic inflammation of the paranasal sinuses. The Holmium: YAG laser energy was coupled to a 600 microns core diameter nylon fiber. Power settings of 950 mJ per 2.5 microseconds pulse at 5 pulses per second were used. Tissue responses to treatment were examined by light microscopy. The photoablative mechanism of the laser-tissue interaction led to bone and soft tissue ablation with only a minor thermal component in the target zone. In comparison with other laser types available clinically, there was no carbonization zone after use of the Holmium-YAG laser. The area of tissue damage produced was significantly smaller (370-520 microns only) and wound healing proceeded without complication. The physical settings of the laser equipment are described with regard to their significance in photoablation when using flexible light-conducting fibers. The possible role of the Holmium: YAG laser in clinical surgery is discussed on the basis of the present experience.


[Decreased aspiration after extensive tumor surgical interventions in the area of the mouth cavity and pharynx by laryngeal suspension]. Lateral laryngeal suspension in combination with a cricopharyngeal myotomy represents a simple technique for prevention and/or treatment of chronic aspiration in patients during or after surgery for head and neck cancer. At the Department of Otolaryngology/Head and Neck Surgery of the University of Heidelberg this technique has been employed with satisfying results in 6 patients with large carcinomas of the oral cavity and pharynx. Lateral laryngeal suspension was not able to prevent--or if used secondarily--to eliminate aspiration completely in all patients. However, none of our patients experienced aspiration of saliva postoperatively. All were able to use a speech canula and some could even be fed orally.


[Immunohistochemical findings in otosclerotic lesions]. Despite numerous scientific efforts, the etiology of otosclerosis still remains unknown. Pathogenically, there are several signs of a chronic inflammatory process of the bony otic capsule. In this study, we tried to characterize the components of chronic inflammation by immunohistochemical techniques. Within otosclerotic lesions a mixed cellular infiltrate can be observed, consisting of lymphocytes, macrophages and plasma cells. Macrophages which are capable of presenting antigen in association with major histocompatibility antigens (MHC) class I and class II to CD8(+)-, and CD4(+)-T cells, respectively, were found in otosclerotic lesions based on their expression of the MAC387 antigen. Furthermore, HLA-DR positive cells and complement C3 have been found in resorption lacunae of otosclerotic lesions. Several osteoblasts and chondrocytes in active otosclerotic lesions reveal a strong surface expression of beta-2-microglobulin, indicating an increased MHC class I antigen expression in active otosclerotic lesions. In agreement with recently published data we found that a large fraction of the lymphoid cells are antigen-primed T-cells expressing an alpha/beta T-cell receptor in association with CD3 molecules on their surfaces. CD4+ lymphocytes which functionally represent lymphokine-secreting cells are activated through the specific recognition of antigen, presented in context with MHC class II molecules such as HLA-DR. Therefore, the presence of MHC class II positive cells are crucial for the initiation of a local immune response. Thus, our observation of HLA-DR positive cells in otosclerotic lesions is of particular interest.(ABSTRACT TRUNCATED AT 250 WORDS)