Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity

Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal- reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.      

Clinical importance of Campylobacter pyloridis and associated serum IgG and IgA antibody responses in patients undergoing upper gastrointestinal endoscopy.

Campylobacter pyloridis was isolated from 77% of 220 (35%) unselected adults undergoing gastroscopy. Isolation was significantly associated with histological gastritis (p less than 0.0001), duodenal ulcer (p less than 0.0001), and to a much lesser extent, with gastric ulcer (p less than 0.05). The relation between the isolation of C pyloridis and peptic ulcer seemed to be independent of coexisting gastritis. In those with no endoscopic or histological evidence of disease there was no relation between isolation and increasing age. Antibody responses to a whole cell sonicate of a strain of C pyloridis were measured by means of an enzyme linked immunosorbent assay (ELISA). Increased IgA (p less than 0.0001) and IgG (p less than 0.0001) antibody titres were found in patients with C pyloridis. Peptic ulceration or gastritis were present in 78% and 100% of patients with a high concentration of IgG and IgA, respectively, but in only 9% and 18% of those with low titres. These results provide further evidence for a possible pathogenic role of these organisms in gastric disease and suggest that immunological markers of their presence might be useful non-invasive indicators of disease.     

Immunological characterization of an early cytomegalovirus single-strand DNA-binding protein with similarities to the HSV major DNA-binding protein

Monospecific polyclonal antisera were prepared against the 129-kDa, early, single-strand DNA-binding protein (DB129) of strain Colburn cytomegalovirus (CMV), and used to study its distribution in infected cells and its relatedness to a proposed human CMV (HCMV) counterpart (DB140). Indirect immunofluorescence of fixed, infected human fibroblasts showed DB129 to be localized within the intranuclear inclusions characteristic of replicating CMV. Treatment of infected cells with 50 to 100 micrograms phosphonoformic acid per milliliter resulted in the overproduction of DB129 and its accumulation within nuclei, both inside the inclusions and in surrounding areas of the nucleoplasm, whereas treatment with 500 micrograms/ml prevented inclusion formation, and DB129 was localized at discrete points throughout the infected-cell nuclei. The sera cross-reacted an estimated 10% with HCMV DB140 in an indirect immunoassay, and their use in immunofluorescence localized DB140 to the nuclear inclusions of HCMV-infected cells. Their immunological cross-reactivity, as well as their similar biochemical properties and intracellular distribution, support the likelihood that DB129 and DB140 are the protein products of homologous genes. The relationship of these proteins to the herpes simplex major DNA-binding protein is discussed.     

Effect of age on behavioral and enzymatic changes during thiamin deficiency

Open field behavior and whole brain enzymatic activities were determined during thiamin deficiency in two strains of young, as well as in aged mice. In young CD-1 mice, thiamin deficiency reduced total distance traveled and vertical movements after 7 days and the decline was more than 50% by day 9. The behavioral deficit was highly correlated to decreases in 2-oxoglutarate dehydrogenase activity (KGDH). The open field behavior of Balb/c mice was about 40% less than in CD-1 mice and responded in a qualitatively different manner to thiamin deficiency. The activity of the Balb/c mice increased and then decreased with thiamin deficiency. The activity of 3 month old mice peaked on day 6 (126% of initial score), whereas 10 and 30 month mice showed a much greater increase (about 175% of initial scores), but on day 7. Although the activity of the thiamin dependent enzyme transketolase (TK) was affected similarly at all ages, the activity of KGDH in the aged brain was more sensitive to thiamin deficiency than in the young; KGDH activity declined 41%, 57% or 74% at 3, 10, or 30 months, respectively. Thus, the current mouse model is an attractive one to study the interaction of thiamin deficiency with aging.     

Human papillomavirus types in anogenital warts of children

Tissue from anogenital warts of 25 children, 10 of whom were suspected of being victims of sexual abuse, was investigated by dot blot and Southern blot techniques for human papillomavirus (HPV) types. HPV DNA was detected in 22 children, two of whom had double infections. The genital HPV types 6 and/or 11 were detected in 20 children, and in three children other HPV types were found. One had HPV 18 (as well as 11); in a second child a possible skin type, HPV 2, was detected; and the third child was infected with an unidentified type. In three cases genital wart material was available from one of the parents, and in all three the HPV type was the same as that of the child. For nine other children one or both parents were reported to have genital warts. The source of infection appeared to be the adult genital tract, but sexual contact might not be the only means of transmission.     

Primate cytomegalovirus assembly: evidence that DNA packaging occurs subsequent to B capsid assembly

Results presented here show that when cytomegalovirus (strain Colburn)-infected cells are treated with the DNA synthesis inhibitor hydroxyurea or phosphonoformate, one type of intranuclear capsid accumulates. These particles appeared to contain symmetrically organized internal material, and had a protein composition and sedimentation rate characteristic of B capsids. Radiolabeling experiments provided evidence that a population of B capsids lacking DNA is present during the course of a normal infection. These capsids sedimented slightly slower than the peak of viral DNA in the same region of the gradient, and had a ratio of DNA/protein that was estimated to be sevenfold lower than that of the faster sedimenting C capsids. DNA in both the B and C capsid regions of such gradients was found to be relatively resistant to digestion with DNase. The possibility is considered that herpesvirus B capsids lacking DNA may be counterparts of unexpanded proheads in the bacteriophage assembly pathway.     

Setting characteristics and mechanical behaviour of a calcium phosphate bone cement containing tetracycline

Calcium phosphate cements are used for bone defect filling and they may also be used as delivery systems for active agents. The physicochemical behaviour of an ionic cement, with a final composition of hydroxyapatite, containing tetracycline hydrochloride was investigated. Chemical characterisation, X-ray diffraction analysis, compressive strength and tensile strength were performed. It is known that the antibiotic can be adsorbed on calcium phosphate compounds and the presence of chloride ions can strongly influence the behaviour of the cement. Adding more than 1% (w/w) of 95% pure tetracycline hydrochloride in the solid phase led to a cement with poor mechanical properties, but which, in addition to hydroxyapatite, contained residual starting reagents. For this reason, experiments were also performed with tetracycline previously treated with a calcium sulphate solution. Using a treated tetracycline, it was possible to introduce at least 7% (w/w) of active ingredient whilst still allowing the reaction to proceed to completion i.e. the formation of hydroxyapatite with good mechanical properties. Therefore, treating the tetracycline HCI with calcium sulphate solution prior to reaction conserved the activity of the antibiotic, limited the influence of the antibiotic on the cement evolution and retained the physical properties of the cement.