Zidovudine (azido dideoxythymidine) inhibits characteristic early alterations of lymphoid cell populations in retrovirus-induced murine AIDS

Using flow cytometry technology and multiparameter analyses, we report early and characteristic alterations in lymphoid cell profile in spleen and lymph nodes due to LP-BM5 retrovirus disease (murine AIDS (MAIDS)) and the effect of azido dideoxythymidine, a nucleoside inhibitor, on these changes. MAIDS has been characterized by rapid and profound lymphoproliferation accompanied by hypergammaglobulinemia and immunosuppression. As early as 2 wk postinfection, there is a selective depletion of CD8+ cells whereas the total number of CD4+ cells increases throughout the first 8 wk of infection although the frequency is relatively stable. These population changes were partially delayed by oral AZT therapy for 6 wk postinfection. Ly-6C (AL-21) is expressed on roughly 50% of CD4+ and CD8+ cells in C57BL/6 mice. In MAIDS, the residual population of CD8+ cells is primarily Ly-6C+. The CD4+ cells have a transient increase in ratio of Ly-6C+/Ly-6C- cells at 2 wk postinfection but by 6 wk are primarily Ly-6C-. There was an increase in both the total number and percentage of Mac 1+ cells and a selective depletion of certain splenic B cell subpopulations. Azido dideoxythymidine delays these early population changes.     

Cross-linkage sites in type I collagen fibrils studied by neutron diffraction

Cross-links in tendon collagen are essential for the biomechanical strength of healthy tissue. The nature and position of these cross-links has long been a subject for conjecture. We have approached this problem in a non-destructive manner, by studying neutron diffraction from collagen fibrils that have been specifically deuterated by reduction at keto-amine and Schiff base groups with sodium borodeuteride (NaB2H4). The intensities of the first 23 meridional reflections were recorded for both native and reduced tendons. These data were used to calculate the neutron-scattering density profile of the 67 nm (D) repeat of type I collagen fibrils in rat tail tendon. This approach not only succeeds in determining the location of the cross-linkage sites with respect to the fibril structure, as projected onto the fibre axis, but also presents a novel form of the isomorphous derivative solution to the phase problem.     

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.     

Reinvestigation of phosphorylation of tRNA in Escherichia coli.

This report shows the results of the reinvestigation of tRNA phosphorylation in E. coli. The phosphorylation did not occur on suppressor seryl-tRNA but occurred on other tRNA species. The activity of tRNA phosphorylation was found in E. coli extracts and partially purified. On DEAE-Sephadex A50 and PAGE gel, the phosphorylated-tRNA showed a pattern different from that the natural suppressor serine tRNA.     

Chemo- and karyotaxonomic studies on some rhizomatous species of the genusSymphytum (Boraginaceae)

InS. tuberosum subspp.tuberosum andnodosum, S. grandiflorum andS. ibericum the presence of the pyrrolizidine alkaloids lycopsamine, echimidine and symphytine could be demonstrated. The taxonS. tuberosum contains an unknown compound that seems to be specific for this taxon. This compound is not the pyrrolizidine alkaloid anadoline which has previously been reported for this species. It is possibly represented by a peak on GC/MS with a molecular ion peak at m/z 623 (as TMS derivative) and can be used as a chemotaxonomic marker for the speciesS. tuberosum. The pyrrolizidine alkaloid pattern of the two subspecies ofS. tuberosum reinforces the close relationship. Fresh material ofS. tuberosum contained the triterpene isobauerenol, but in herbarium material isobauerenol was lacking. InS. grandiflorum, neither fresh nor dried material contains isobauerenol. In herbarium material ofS. ibericum also no isobauerenol could be found. More extensive chemotaxonomical research is necessary to support the view thatS. abchasicum is more closely related toS. ibericum than toS. grandiflorum.     

Comparative study of the changes in microanatomical organization of lymph nodes located and functioning in the area of venous congestion

By the morphometric method the microanatomical organization of the popliteal and kidney lymph nodes of the type Vi was studied in venous congestion. In the first experimental series (lymph nodes localize in venous congestion area) the venous congestion in the popliteal lymph nodes was created by the ligature of caudal vena cava. In the second experimental series (lymph nodes, which clean the venous congestion area--the kidney vena was tied up. The small and short time increase of the marginal sinus volume and hypertrophy of the medullary cords, which seemed about medullary substance B-zone stimulation were characteristically for the lymph nodes, localize in the venous congestion area. The sharp increase of the marginal sinus volume during the long experimental time and paracortical T-zone hyperplasia were characteristically for the lymph nodes, which clean the venous congestion area.     

The indices of antipneumococcal immunity in children with chronic pneumonia

In 76 children with chronic pneumonia the levels of serum antibodies to pneumococcal capsular polysaccharide antigens (serotypes 1, 3, 6B, 8, 9N, 15F, 23F), O-polysaccharide and pneumococcal protein somatic antigens were determined by ELISA techniques. The study showed that in sick children the content of antipneumococcal antibodies in the blood increased with age. No correlation between the content of total immunoglobulins and that of antipneumococcal antibodies in the blood of the patients was established, but a sharp decrease in the concentration of antibodies was registered in a child with hypoglobulinemia. No increase in the level of antibodies to pneumococcal antigens was observed in cases of the exacerbation of Pneumococcus-induced inflammatory process in the lungs.     

Side reaction in peptide synthesis. Formation of oxazolidone derivatives

2-Oxazolidone derivatives formed through an intramolecular reaction in the process of alkaline treatment of urethane-type N-protected peptides of which the N-terminal residues were Ser or Thr having unprotected hydroxyl groups. In oder to avoid this side reaction, the esters of these peptides could be cleaved by enzymatic hydrolyses instead of saponification.     

Thermoregulatory responses to acute body heating in rats acclimated to continuous heat exposure

Thermoregulatory responses to an acute heat load with intraperitoneal heating (IH) or indirect external warming (EW) by increasing ambient temperature (Ta) were investigated with direct and indirect calorimetry in rats acclimated to environments of 24.0 degrees C (Cn), 29.4 degrees C (H1), and 32.8 degrees C (H2) for greater than 15 days. The rats were placed in a direct calorimeter where the air temperature was maintained at 24 degrees C for the initial 3 h. IH was then made for 30 min through an electric heater implanted chronically (6.5 W.kg-1) in the peritoneal cavity, and EW was performed by raising the jacket water temperature surrounding the calorimeter from 24 to 39 degrees C (0.19 degrees C.min-1). Hypothalamic (Thy) and colonic temperature immediately before the start of the heat load tended to be higher as the acclimation temperature increased. During IH, the threshold Thy for the tail skin vasodilation (Tth) was significantly higher in H2 than in Cn rats. During EW, however, there was no difference in Tth between the groups. Metabolic heat production (M) was slightly suppressed during IH and significantly depressed only in H2 rats. During EW, M was suppressed in all the groups. The magnitude and duration of suppression were greater in H2 rats than in the other two groups. The responses in nonevaporative heat loss and thermal conductance (C) to the rise in Thy did not differ among the three groups during IH. According to the rise in Thy, however, there was a greater C increase in H2 than in Cn and H1 rats during EW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Linkage disequilibrium studies in multiple endocrine neoplasia type 1 (MEN1)

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary. The MEN1 gene has been localised to a 2-Mb region of chromosome 11q13 by meiotic mapping studies in MEN1 families. Such studies may have a limited resolution of approximately 1 cM (i.e. 1 Mb) and we have therefore investigated 96 MEN1 families (40 British, 17 French, 12 Finnish, 7 Swedish, 7 Dutch, 7 North American, 2 Australian, 1 New Zealand, 1 German, 1 Spanish and 1 Danish) for linkage disequilibrium, in order to facilitate a finer mapping resolution. We have utilised five microsatellite DNA sequence polymorphisms from the candidate region and have accurately determined their allele sizes, which ranged from 161 bp to 272 bp. The heterozygosity and number of alleles (given in brackets), respectively, at the loci were: D11S1883 (76%, 11), D11S457 (55%, 5), PYGM (94%, 18), D11S1783 (10%, 4) and D11S449 (87%, 16). Allelic association was assessed by Chi-square 2 ×n contingency tables, by Fisher exact 2 ×n contingency tables and by a likelihood-based approach. The results of haplotype analysis revealed 91 different affected haplotypes in the 96 families, an identical affected haplotype being observed in no more than two families. These results indicate the absence of an ancestral affected haplotype. Significant linkage disequilibrium (P < 0.005) could be established amongst the microsatellite loci but not between the loci and MEN1 in either the total population or in any of the geographical sub-populations. The absence of linkage disequilibrium between MEN1 and the polymorphic loci is probably the result of the occurrence of multiple different disease-causing mutations in MEN1. Received: 1 April 1997 / Accepted: 25 June 1997