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A set of new mouse strains were produced that carry the V beta a haplotype of the TCR-alpha/beta and any of a number of different H-2 haplotypes on backgrounds derived from related C57BL, C57L, and C57BR mice. Study of V beta 17a expression in these mice confirms the association between the presence of IE and the deletion of V beta 17a+ T cells. A second H-2 gene causing deletion of V beta 17a+ T cells was mapped in these mice to the K end of H-2k, and H-2 influences on the level of selection of CD4+ V beta 17a+ T cells were indicated.

Since uterine leiomyomata (fibroids) are not found in conditions where oestradiol is either absent or present only in low concentrations, oestradiol is considered to be an important factor in the control of fibroid growth. To investigate whether this is due to a direct effect on the tissue, oestradiol and progestogen receptors were measured in tissue removed at hysterectomy from 12 normally cycling women and 13 women who had received the gonadotrophin-releasing hormone (GnRH) agonist Zoladex (ICI 118630) as a subcutaneous depot given at monthly intervals for 3 months preoperatively and a third group of three women who had received the antioestrogen tamoxifen (20 mg daily) for 3 months before surgery. Both unoccupied oestradiol receptors (measured by separating bound from free hormone with dextran-coated charcoal; DCC) and 'total' receptor populations (as measured by an enzyme immunoassay) were measured in each fibroid and adjoining myometrium. There was significantly more binding of both oestradiol and progestogen to fibroid than to myometrium in both the control (P less than 0.01) and agonist-treated groups (P less than 0.05). Oestradiol binding to fibroids in women treated with Zoladex exceeded that in the normally cycling women (P less than 0.05) which in turn exceeded that in the tamoxifen-treated group (P less than 0.05). However, the binding of progestogen, measured by DCC showed the reverse trend. These results may be explained by the low circulating oestradiol concentration in the GnRH agonist-treated women leading to low receptor occupancy.

The influence of endocrine therapy on the proliferation of estrogen receptor (ER) positive cells and ER negative cells of human breast cancer (MCF-7) serially transplanted into nude mice was analyzed by tumor growth, dextran-coated charcoal (DCC) method, ER-immunocytochemical assay (ER-ICA) and ER-immunocytochemically stained 3H-thymidine autoradiography. In the tamoxifen (TAM) group and the medroxyprogesterone acetate (MPA) group, tumor growth was inhibited, but it was promoted in the 17 beta-estradiol dipropionate (E2) group. The ER level by the DCC method significantly decreased in the TMA, the MPA and the E2 groups. The ER-ICA showed that the ER positive cells rate in the TAM and the MPA group decreased, but it increased in E2 group. However, the ER-immunocytochemically stained 3H-thymidine autoradiography showed that not only the labelling index of ER-positive cells but also that of ER negative cells significantly decreased in the TAM and the MPA groups, but significantly increased in the E2 groups. Therefore it was concluded that endocrine therapy affected the proliferation of both ER positive cells and ER negative cells of ER positive breast cancer.

Two of the major glycoproteins of bovine herpesvirus 1 (BHV-1) are gI, a polypeptide complex with apparent molecular weights of 130,000, 74,000, and 55,000, and gIII (a 91,000-molecular-weight [91K] glycoprotein), which also exists as a 180K dimer. Vaccinia virus (VAC) recombinants were constructed which carry full-length gI (VAC-I) or gIII (VAC-III) genes. The genes for gI and gIII were each placed under the control of the early VAC 7.5K gene promoter and inserted within the VAC gene for thymidine kinase. The recombinant viruses VAC-I and VAC-III retained infectivity and expressed both precursor and mature forms of glycoproteins gI and gIII. The polypeptide backbones, partially glycosylated precursors, and mature gI and gIII glycoproteins were indistinguishable from those produced in BHV-1-infected cells. Consequently, they were apparently cleaved, glycosylated, and transported in a manner similar to that seen during authentic BHV-1 infection, although the processing efficiencies of both gI and gIII were generally higher in recombinant-infected cells than in BHV-1-infected cells. Immunofluorescence studies further demonstrated that the mature gI and gIII glycoproteins were transported to and expressed on the surface of cells infected with the respective recombinants. Immunization of cattle with recombinant viruses VAC-I and VAC-III resulted in the induction of neutralizing antibodies to BHV-1, which were reactive with authentic gI and gIII. These data demonstrate the immunogenicity of VAC-expressed gI and gIII and indicate the potential of these recombinant glycoproteins as a vaccine against BHV-1.

1. The effect of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked tritium efflux was studied in guinea-pig caudate nucleus slices preloaded with [3H]-choline. 2. 5-HT, 10-300 mumol l-1, temporarily increased the spontaneous tritium efflux (as well as the endogenous acetylcholine (ACh) release) and, after 15 min perfusion, inhibited it. The facilitatory effect of 5-HT on spontaneous efflux was increased while the inhibitory effect did not occur in slices taken from dopamine-depleted guinea-pigs. 3. The increase in spontaneous tritium efflux by 5-HT was blocked by methiothepin, methysergide (pA2 8.7) and by the selective 5-HT2 antagonist, ritanserin (pA2 6.7). 4. The inhibition of spontaneous tritium efflux by 5-HT was prevented by methysergide and methiothepin but not by ritanserin and (-)-propranolol. 5. 5-HT, 100 mumol l-1, inhibited the electrically-evoked tritium efflux and this effect was unchanged in dopamine-depleted slices. 6. The inhibition of electrically-evoked tritium efflux by 5-HT was blocked by methiothepin and methysergide but not by (-)-propranolol or ritanserin. 7. These results suggest that 5-HT may exert a rapid and transient (excitatory) and a more prolonged (inhibitory) control over striatal cholinergic neurones.

Two distinct regions required for both contact hemolysis and entry into LLC-MK2 cells were cloned into Escherichia coli from the Shigella sonnei form I plasmid, pSS120. The first region was cloned into an E. coli HB101 strain containing noninvasive Tn1 insertion mutants of the form I plasmid, and expression of ipa (invasion plasmid antigen) gene products was restored. The plasmid carrying the first region was then transformed into E. coli lacking the form I plasmid, and additional DNA fragments from the form I plasmid were cloned into the same recipient on compatible vectors. Five of these double transformants were found to be positive for contact hemolysis activity. Restriction analysis of these five clones indicated that the previously reported ipa locus and the invA locus were present on the second plasmid region. Only the strains carrying both of these regions were active in contact hemolysis and cell invasion assays. Several proteins, including the a, b, c, and d proteins encoded by the ipa genes, were detected in the double transformants by Western blot (immunoblot) analysis with serum of a monkey convalescing from shigellosis. A positive regulator was suggested to exist in the first region, since the amounts of most of these proteins were simultaneously increased in the presence of this region. Subcloning and nucleotide sequencing indicated that this positive regulator gene was virF. Product analysis of the virF gene with minicells showed that two peptides (30 and 21 kilodaltons) were synthesized and that at least the 30-kilodalton protein was essential for regulation of the ipa genes.

High iron concentrations have been reported in the brains of multiple sclerosis victims. To determine if there are abnormalities in general iron metabolism indicative of iron overload in MS, measurements of transferrin saturation, serum ferritin and red cell ferritin in 31 female and 18 male patients were compared to the results in 49 age- and sex-matched healthy controls. Compared to controls, mean serum ferritin in MS was high, whereas transferrin saturation and red cell ferritin were similar. High values in one or more individual test results were observed in eleven MS patients. They were prevalent in patients who required bilateral assistance to walk or were confined to a chair, and appeared to be related to the severity of the disease. An investigation was made into the relationship of the high serum ferritin values in MS to the HLA-A3 histocompatibility antigen, a marker of the hemochromatosis gene which is prevalent in MS. A statistically significant interaction was not found between serum ferritin and the presence of HLA-A3.

Gram-negative septicemia/endotoxemia remains a serious clinical disorder that is often complicated by disseminated intravascular coagulation (DIC). Plasma antithrombin-III (AT-III) levels usually decrease during gram-negative septicemia/endotoxemia, and even moderate decreases in this major inhibitor of the coagulation system are associated with serious DIC. We demonstrated in an earlier study that prophylactic treatment of rats with 250 U/kg of AT-III followed by endotoxin challenge markedly attenuates DIC, indices of organ damage, and metabolic dysfunction. The present study was to determine whether treatment with 250 U/kg AT-III 1 hr after endotoxin challenge would be similarly efficacious. Rats treated with 250 U/kg of AT-III inactivated by human sputum elastase (ATX) served as protein controls. Blood samples for analysis were obtained 4 hr after AT-III or ATX treatment (5 hr after endotoxin challenge). Rats in the ATX treatment group exhibited abnormalities characteristic of endotoxemia, i.e., decreased fibrinogen levels and platelet counts, increases in prothrombin time and activated partial thromboplastin time, elevated serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (AKP), and hypoglycemia. Treatment with AT-III markedly and significantly (P less than .05) attenuated all of these abnormalities, although survival was not increased. This study strongly suggests that supplementation of plasma AT-III is efficacious after the development of sepsis, although not as efficacious as prophylactic treatment.