The effect of physical conditioning on antipyrine clearance

The effects of physical conditioning on antipyrine clearance were studied in two groups of subjects. Healthy men not engaged in the systematic practice of any sport were compared with endurance runners (defined as men running >80 km/week). Studies were carried out at three different periods of the annual plan training at 4-month intervals. Antipyrine was administered orally and pharmacokinetic parameters were obtained from saliva samples by the multiple-sample method. Endurance performance, expressed in terms of the maximal oxygen uptake (V˙O_{2 max}), the ventilatory threshold and the 4-mM · l⁻¹ lactate threshold (OBLA), was higher in trained than in control subjects at each of the three periods. Antipyrine clearance was also significantly elevated and antipyrine half-life reduced in runners during all periods. No significant difference in V˙O_{2 max} or antipyrine clearance was found between the various periods in either trained or control subjects. Both ventilatory threshold and OBLA increased significantly along the training period in conditioned subjects. Significant correlations were found between antipyrine clearance and V˙O_{2 max}, ventilatory threshold and OBLA. In summary, these results indicate an association between aerobic conditioning and increased hepatic oxidative metabolism of low-clearance drugs. Accepted: 15 July 1997     

Pericentric inversions of chromosome 4: report of a new family and review of the literature

A family was cytogenetically studied because of the birth of a male child with a multiple congenital anomaly pattern, in whom a dup (4q) recombinant was found. His phenotypically normal mother's karyotype showed an apparently balanced pericentric inversion in a chromosome 4. So as to analyze the occurrence of recombinants, the cytogenetic data from this family are compared with those of the 18 previously reported familial cases of pericentric inversions (PIs) of chromosome 4. The congenital anomalies observed in the child strongly suggest Wolf-Hirschhorn syndrome but some of his clinical features seem to be pathogenetically related to the presence of lymphedema during the intrauterine period. In the multiple congenital anomaly pattern observed in this patient, the lymphedema could be the consequence of the large 4q duplication. The review of chromosome 4 PIs with 4q duplication suggests that the q3 region should be examined when edema is detected prenatally.     

Auditory corticocortical interconnections in the cat: evidence for parallel and hierarchical arrangement of the auditory cortical areas

Summary The origin and laminar arrangement of the homolateral and callosal projections to the anterior (AAF), primary (AI), posterior (PAF) and secondary (AII) auditory cortical areas were studied in the cat by means of electrophysiological recording and WGA-HRP tracing techniques. The transcallosal projections to AAF, AI, PAF and AII were principally homotypic since the major source of input was their corresponding area in the contralateral cortex. Heterotypic transcallosal projections to AAF and AI were seen, originating from the contralateral AI and AAF, respectively. PAF received heterotypic commissural projections from the opposite ventroposterior auditory cortical field (VPAF). Heterotypic callosal inputs to AII were rare, originating from AAF and AI. The neurons of origin of the transcallosal connections were located mainly in layers II and III (70–92%), and less frequently in deep layers (V and VI, 8–30%). Single unit recordings provided evidence that both homotypic and heterotypic transcallosal projections connect corresponding frequency regions of the two hemispheres. The regional distribution of the anterogradely labeled terminals indicated that the homotypic and heterotypic auditory transcallosal projections are reciprocal. The present data suggest that the transcallosal auditory interconnections are segregated in 3 major parallel components (AAF-AI, PAF-VPAF and AII), maintaining a segregation between parallel functional channels already established for the thalamocortical auditory interconnections. For the intrahemispheric connections, the analysis of the retrograde tracing data revealed that AAF and AI receive projections from the homolateral cortical areas PAF, VPAF and AII, whose neurons of origin were located mainly in their deep (V and VI) cortical layers. The reciprocal interconnections between the homolateral AAF and AI did not show a preferential laminar arrangement since the neurons of origin were distributed almost evenly in both superficial (II and III) and deep (V and VI) cortical layers. On the contrary, PAF received inputs from the homolateral cortical fields AAF, AI, AII and VPAF, originating predominantly from their superficial (II and III) layers. The homolateral projections reaching AII originated mainly from the superficial layers of AAF and AI, but from the deep layers of VPAF and PAF. The laminar distribution of anterogradely labeled terminal fields, when they were dense enough for a confident identification, was systematically related to the laminar arrangement of neurons of origin of the reciprocal projection: a projection originating from deep layers was associated with a reciprocal projection terminating mainly in layer IV, whereas a projection originating from superficial layers was associated with a reciprocal projection terminating predominantly outside layer IV. This laminar distribution indicates that the homolateral auditory cortical interconnections have a feed-forward/feed-back organization, corresponding to a hierarchical arrangement of the auditory cortical areas, according to criteria previously established in the visual system of primates. The principal auditory cortical areas could be ranked into 4 distinct hierarchical levels. The tonotopically organized areas AAF and AI represent the lowest level. The second level corresponds to the non-tonotopically organized area AII. Higher, the tonotopically organized areas VPAF and PAF occupy the third and fourth hierarchical levels, respectively.Abbreviations AAF anterior auditory cortical area - AI primary auditory cortical area - AII secondary auditory cortical area - BF best frequency - C cerebral cortex - CA caudate nucleus - CL claustrum - D dorsal nucleus of the dorsal division of the MGB - ea anterior ectosylvian sulcus - ep posterior ectosylviansulcus - IC internal capsule - LGN lateral geniculate nucleus - LV pars lateralis of the ventral division of the MGB - LVe lateral ventricule - M pars magnocellularis of the medial division of the MGB - MGB medial geniculate body - MGBv ventral division of the MGB - OT optic tract - OV pars ovoidea of the ventral division of the MGB - PAF posterior auditory cortical area - PH parahippocampal cortex - PO lateral part of the posterior group of thalamic nuclei - PU putamen - RE reticular complex of thalamus - rs rhinal sulcus - SG suprageniculate nucleus of the dorsal division of the MGB - ss suprasylvian sulcus - TMB tetrametylbenzidine - VBX ventrobasal complex - VLa ventrolateral complex - VL ventro-lateral nucleus of the ventral division of the MGB - WGA-HRP wheat germ agglutinin conjugated to horse-radish peroxidase - WM white matter - VPAF ventro-posterior auditory cortical area     

Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer.

This cross-sectional study was undertaken to determine whether serum hormones (free testosterone, androstenedione, luteinizing hormone, or prolactin) have any influence on serum prostate specific antigen (PSA) levels in patients with stage A-C prostate cancer. Blood samples were collected prior to any treatment in 36 patients; in 19 (group 1), three blood samples were collected 10 minutes apart between 9:00 AM and 9:30 AM for each patient and pooled together to avoid diurnal and episodic variation in serum testosterone values. In the remaining patients, only one sample could be collected (group 2). Free testosterone, androstenedione, luteinizing hormone, prolactin, and PSA levels were determined with appropriate radioimmunoassay techniques. Statistical analyses were performed separately for groups 1 and 2, and then with pooled data. None of the hormones in any of the analyses showed any association to serum PSA values except for prolactin for the pooled data and for group 2. This statistical significance for prolactin disappeared on multivariate analysis. There were 21 African-American men and 15 whites in the study; no racial differences in hormonal levels were found except for lower luteinizing hormone levels in African Americans in group 2 and pooled data. No differences were found between group 1 and group 2 in the mean serum prolactin and luteinizing hormone values. Serum free testosterone, androstenedione, and luteinizing hormone appeared to have no influence on serum PSA values in nonmetastatic cancer patients. Serum prolactin values were inversely associated with PSA values in univariate analysis for the pooled data; this disappeared in multivariate analysis. Unlike other studies that found higher serum testosterone levels in African-American college students than whites, no such differences were seen in this age group. Luteinizing hormone was lower in African-American men than in whites in the pooled study population. Further studies are needed to clarify our findings.     

Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin-2 pathway

Injection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB-reactive T cells bearing T cell receptor (TcR) V_β8 gene products. Given that interleukin 2 (IL-2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro, we tested whether the IL-2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL-2 modulate SEB responses in vivo. Surprisingly, neither IL-2 nor CsA were able to change the in vivo kinetics and magnitude of SEB-induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB-reactive TcR V_β8 gene family. In accord with these in vivo observations, IL-2 is incapable of reversing “anergy” and apoptotic cell death of V_β8⁺ SEB-reactive T cells isolated from SEB-primed mice in vitro. Accordingly, upon SEB injection V_β8⁺ T cells expand rapidly, without expressing IL-2 receptor (IL-2R)α chains in vivo, although SEB induces IL-2R α in vitro. Altogether, these results indicate that the IL-2/IL-2R-mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens. Moreover, the data suggest that unresponsiveness of V_β8⁺ T cells from SEB-primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death. Absence or presence of IL-2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.     

Specific IgE determination to Ani s 1, a major allergen from Anisakis simplex, is a useful tool for diagnosis.

BACKGROUND: The most serious limitation of the serodiagnosis of parasitoses is the occurrence of cross-reactions. OBJECTIVE: The possible use of Anisakis simplex major allergen Ani s 1 for diagnosis. PATIENTS AND METHODS: Forty-nine non-fish-allergic patients with Anisakis simplex hypersensitivity, 21 patients without allergic episodes suffering intestinal anisakiasis with obstruction of the intestinal lumen, and 10 unrelated sera as a control were included in this study to determine specific immunoglobulin (Ig)E and IgG to Anisakis simplex major allergen Ani s 1 by immunoblotting. RESULTS: Eighty-six percent of patients with Anisakis simplex hypersensitivity showed specific IgE directed to Ani s 1. Identical result was obtained for IgG detection in this group. Among patients with intestinal anisakiasis, 86% showed specific IgE, but only 29% had specific IgG (P < 0.001, two-tailed Fisher exact test). One of the 10 control subjects was positive both for IgE and IgG (P < 0.001). CONCLUSIONS: Determination of specific IgE directed to Anisakis simplex major allergen Ani s 1 is a useful tool for the diagnosis of hypersensitivity and intestinal anisakiasis. Further, measurement of specific IgG directed to Anisakis simplex major allergen Ani s 1 is only valid for Anisakis simplex allergy.     

Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.     

Genetic control of in vitro natural cell-mediated activity against Salmonella typhimurium by intestinal and splenic lymphoid cells in mice.

In vitro natural anti-bacterial activity against Salmonella typhimurium by lymphocytes from Peyer's patches and spleens was assessed in several mouse strains. C3H/HeN and CBA/J mice, which are resistant to S. typhimurium infections, showed a natural anti-bacterial activity significantly higher than BALB/c, C57BL/10, C57BL/6 and C3H/HeJ mice, i.e. strains susceptible to the in vivo bacterial infection. In these susceptible strains and also in A/J mice, a significantly higher natural activity was observed in females compared to males. The sex control of natural anti-bacterial activity was further stressed by the fact that orchidectomy could induce a strong activity in low responder C57BL/10 male mice. With the exception of Beige mice, a low natural killer (NK) strain also with no natural activity against S. typhimurium in both sexes, the genetic distribution of natural anti-bacterial activity was extremely different from that of the NK activity. Thus, these results further stress the difference between natural anti-bacterial activity and NK cytotoxicity. Furthermore, our data establish a possible link, although with some exceptions, between in vivo susceptibility to S. typhimurium infections and in vitro natural activity against these bacteria.