Immunocytochemical localization of the sigma(1) receptor in the adult rat central nervous system

In order to characterize the localization of the sigma(1) receptor in the adult rat central nervous system, a polyclonal antibody was raised against a 20 amino acid peptide, corresponding to the fragment 143-162 of the cloned sigma(1) receptor protein. Throughout the rostrocaudal regions of the central nervous system extending from the olfactory bulb to the spinal cord, intense to moderate immunostaining was found to be associated with: (i) ependymocytes bordering the entire ventricular system, and (ii) neuron-like structures located within the parenchyma. Double fluorescence studies confirmed that, throughout the parenchyma, sigma(1) receptor-immunostaining was essentially associated with neuronal structures immunostained for the neuronal marker betaIII-tubulin. In all rats examined, high levels of immunostaining were always associated with neurons located within specific regions including the granular layer of the olfactory bulb, various hypothalamic nuclei, the septum, the central gray, motor nuclei of the hindbrain and the dorsal horn of the spinal cord. In contrast, only faint immunostaining was associated with neurons located in the caudate-putamen and the cerebellum. Electron microscope studies indicated that sigma(1) receptor immunostaining was mostly associated with neuronal perikarya and dendrites, where it was localized to the limiting plasma membrane, the membrane of mitochondria and of some cisternae of the endoplasmic reticulum. At the level of synaptic contacts, intense immunostaining was associated with postsynaptic structures including the postsynaptic thickening and some polymorphous vesicles, whereas the presynaptic axons were devoid of immunostaining.These data indicate that the sigma(1) receptor antibody prepared here, represents a promising tool for further investigating the role of sigma(1) receptors.     

Study of the protective effects of hyperimmune immunoglobulins G and M against endotoxin in mice and rats

We prepared solutions of human IgM and IgG to various lipopolysaccharide (LPS) species. These were then tested, along with solutions of non-LPS specific human IgG or IgM, for their ability to confer passive immunity against experimental endotoxemia in two animal models. The immunoglobulins were first tested for an effect on the lethality induced by seven different LPSs in actinomycin-D sensitized mice, or by three different bacteria in normal mice. When the immunoglobulins were administered 1 h before challenge, a small protective effect was observed. This protection was dependent upon both the anti-LPS agent, the chemical composition of the LPS, or the strain of Gram-negative bacteria used for injection. The anti-LPS IgM and IgG preparations reduced the mortality induced by Escherichia coli but not by Serratia marcescens or Klebsiella pneumoniae, indicating protection by strain-specific antibodies. When the antibodies were preincubated with LPS or bacteria for 30 min before administration, almost complete protection was seen. The influence of these immunoglobulin preparations or of human albumin (as a control) on the hypotensive and vascular-permeabilizing effects of LPS in rats was then studied. A dose-dependent inhibitory effect was observed with IgG preparations and albumin. At 200 mg/kg, anti-LPS IgG reduced the effects of LPS, while at 400 mg/kg, both anti-LPS and normal IgG preparations showed protection, as did human albumin used at the same dose. The IgM-enriched preparation worsened the initial hypotensive phase after LPS, whereas the anti-LPS IgM significantly reduced the second phase of the hypotension, but only at the largest dose of 400 mg/kg. In this second model using the rat, a clear difference between the activity of IgG and IgM was thus observed. We conclude that pretreatment with human immunoglobulins from large plasma pools modestly, but significantly, attenuated the effects of murine and rat Gram-negative sepsis, but that protection was incomplete. Our results suggest that single regimen intervention strategies may not be sufficient to influence the course of the disease. Received: 12 December 1998     

Analysis through mathematical models of the dynamics of the adrenal cortical response to ACTH in the rat

The distribution and metabolism of ACTH and the dynamics of the adrenal cortical response to this tropic hormone were characterized in the rat, through mathematical models involving data derived from experiments, where plasma corticosterone concentrations were measured following both single injections and infusions of ACTH. The models, which incorporate a previously established model of the dynamics of plasma corticosterone, were statistically validated. The simulated dynamics of the different processes linking ACTH secretion by the adenohypophysis to corticosterone secretion by the adrenal cortex include: (1) a variable MCR for plasma ACTH, modeled as the sum of a constant and a saturable degradation process; (2) the ability of the adrenal gland to secrete at a maximal rate aven after the plasma ACTH concentration has become negligible, modeled as the accumulation of an intermediary productZ directly controlled by the plasma ACTH concentration; (3) a saturable secretion with a small time constant and which, for single injections, always starts in the same fashion, modeled as a “synthesis process” whose input is a saturable function ofZ; (4) an immediate fall of the plasma corticosterone concentration at the end of the ACTH infusions, modeled as a “release process” also controlled byZ. Supported by grants from the Medical Research Council of Canada (MT-1205, MT-1555, and MA-4970), and from INSERM, France (CRL-76-5-020-4).     

Second to fourth digit ratio, body mass index, waist-to-hip ratio, and waist-to-chest ratio: their relationships in heterosexual men and women

BACKGROUND: Prenatal sex steroids have been broadly discussed in terms of their possible effect on brain differentiation, whereas pubertal/adult sex hormones are thought to be the main regulators of sexually dimorphic physical features in males and females. Assessing prenatal steroid exposure has previously been difficult but evidence now suggests that finger length ratio may provide a 'window' into prenatal hormone exposure. The length of the second digit (the index finger) relative to the length of the fourth digit (the ring finger) is sexually dimorphic as males have a lower second to fourth digit ratio (2D:4D). The sexual dimorphism is determined as early as the 14th week of fetal life, and remains unchanged at puberty. There is evidence that sex differences in 2D:4D arise from in utero concentrations of sex steroids, with a low 2D:4D (male typical ratio) being positively related to prenatal testosterone, while a high 2D:4D (female typical ratio) is positively associated with prenatal oestrogen. AIM: The studied aimed to determine whether, and to what extent, adult sexually dimorphic physical traits, which are largely determined at puberty, relate to traits that are largely determined in utero. This work examined the relationship between three sexually dimorphic traits--body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-chest ratio (WCR)--and digit ratio. PARTICIPANTS AND METHODS: BMI, WHR and WCR were assessed in 30 heterosexual male and 50 heterosexual female participants by recording their body height, weight, and measuring their waist, hip and chest circumference. Digit lengths of the second and fourth fingers were measured from photocopies of the ventral surface of the hand and by actual finger measurements. RESULTS: Digit ratio was found to be significantly lower in men than in women. Significant negative correlations were found between female's left and right hand 2D:4D, waist and hip circumference, and WCR. In males, BMI was found to be positively related to digit ratio but remained significant only for left hand 2D:4D. Generally, the relationships were stronger for females than for males. Although not all relationships were found to be significant, they were in accord with our predictions. CONCLUSION: In addition to an activational effect of sex hormones at puberty, the present data suggest an early organizational effect of sex hormones through the association between indices of female body shape, male BMI, and human finger length patterns.     

Peak Identification in Visual Evoked Potentials

Waveform patterns evoked by 4 intensities of flash in normal subjects were studied in relation to intersubject variability. Time-frequency distribution curves of all peaks occurring between 11 and 280 msec after flash onset and meeting minimal criteria were obtained from 46 males. These distributions closely corresponded to similar data reported by others for single intensity stimulation. An algorithm was developed which identified in 67 to 100% of instances a single “peak event’ within the time ranges of each of 6 peak distributions. Many peak events appeared and disappeared within the 4 intensity sets of individuals. Latencies were obtained for these peak events. Application of the algorithm to a replicate sample of 29 Ss, which included 8 females, indicated generalizability. Test-retest data on 15 Ss showed its reliability. The data suggest that methodology significantly contributes to the variability of peak identification among subjects. This may be reduced by employing multiple intensities of stimulation.     

Polymérisation de thiirannes différemment substitués à l'aide du système chiral ZnEt2/(S)-dihydroxy-2,2′ binaphtyl-1,1′, 1. Stéréoélectivité de la polymérisation

Differently substituted thiiranes were polymerized using an atropoisomeric chiral initiator: ZnEt₂/(S)-2,2′-dihydroxy-1,1′-binaphthyl (DHBN) (mole ratio 1/1). It was observed that high stereoelectivities are obtained with monomers bearing small alkyl substituents and that the resolution efficiency of the initiator decreases as the bulkiness of the substituent increases. From the comparison of the results obtained with another initiator system, ZnEt₂/(R)-3,3-dimethyl-1,2-butanediol (DMBD) (mole ratio 1/1), the use of ZnEt₂/(S)-DHBN could be shown to be more suitable for the polymerization of thiiranes with linear alkyl substituents. Contrary to the case of polymerization initiated by the system ZnEt₂/(R)-DMBD, the polymerization reaction of thiiranes with ZnEt₂/(S)-DHBN was usually accompanied by the production of the corresponding olefins in various amounts.     

Bronchitis symptoms in young teenagers who actively or passively smoke cigarettes

This study was undertaken to examine the prevalence of bronchitis (cough with phlegm) symptoms in teenagers who either smoked cigarettes on a regular basis (active smokers) or were non-smokers but who are exposed to passive smoking (passive smokers) in the home. The study was undertaken in 1995 and repeated in 1998. The 1995 study was a cross sectional questionnaire survey of smoking habits in secondary school children aged 13-14 years and was undertaken as part of the ISAAC questionnaire survey. Thirty representative and randomly selected schools from throughout the Republic of Ireland took part in the study. In the 1995 study, 3066 students completed a questionnaire on their current smoking habits and symptoms of cough and phlegm. We found that 634 (20.7%) of these young teenagers actively smoked cigarettes with significantly more females smoking than males with 23.3% of girls compared to 17.6% boys (p = 0.0001). We found that 46.3% of non-smoking children were exposed to smoking in the home (passive smokers) with parental smoking accounting for most of the passive smoking. Bronchitis symptoms were more commonly reported in active smokers compared to non-smokers with an odds ratio of 3.02 (95% CI 2.34-3.88) (p < 0.0001) or in passive smokers compared to those not exposed to smoking with odds ratio of 1.82 (95% CI 1.32-2.52) (p < 0.0001). The 1998 study showed similar results for smoking habits, passive smoking and prevalence of bronchitis symptoms as with the 1995 study. These results document that increased bronchitis symptoms occur in teenagers exposed to active or passive smoking.