CYP1B1 expression in human lung.

Cytochrome P450 1B1 is a recently recognized phase I bioactivating enzyme with high affinity for both inhaled tobacco carcinogens and 17beta-estradiol. We evaluated the human lung expression of this multifunctional member of the P450 superfamily across 16 individuals. Expression of CYP1B1 was evaluated by qualitative reverse transcription-polymerase chain reaction and Western immunoblots performed on human tumor and nontumor lung tissue. Expression at both mRNA and protein levels was then correlated with smoking history, plasma biomarkers of tobacco exposure (nicotine and cotinine), gender, and tumor histology. CYP1B1 mRNA and protein were detected in 94 and 100% of individuals, respectively. Multivariate analysis confirmed that there were more subjects displaying CYP1B1 mRNA expression in tumor than nontumor tissue (p = 0.0003). Correlation of CYP1B1 protein with plasma cotinine levels was statistically marginal (p = 0.027). Self-reported smoking history, gender, and tumor histology did not correlate with gene expression in the multivariate model. After multivariate modeling for confounding factors, the expression patterns of 5 of 16 individuals appeared to differ from the group as a whole for mRNA and/or protein. We conclude that CYP1B1 is commonly expressed in human lung and hypothesize that it may be an important phase I enzyme with respect to human lung carcinogen metabolism, warranting an understanding of regulatory control and coding region polymorphisms.

Highly attenuated HIV type 2 recombinant poxviruses, but not HIV-2 recombinant Salmonella vaccines, induce long-lasting protection in rhesus macaques.

Immunization schemes employing priming with vector-based vaccine candidates followed by subunit booster administrations have been explored and shown to have merit in the human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus systems. In this study, we have assessed the priming capacity of highly attenuated poxvirus vector (NYVAC and ALVAC)-based HIV-2 recombinants, as well as Salmonella typhimurium HIV-2 recombinants in rhesus macaques. ALVAC- and NYVAC-based vaccine candidates expressing the HIV-2 gag, pol, and env genes or NYVAC-based recombinants expressing either gp160 or gp120 were used to immunize rhesus macaques in combination protocols with alum-adjuvanted HIV-2 rgp160. Following intravenous challenge exposure with 100 infectious doses of the HIV-2SBL6669 parental virus genotype mixture, seven of eight animals were protected from infection. The seven protected animals were rechallenged 6 months postprimary challenge, without additional booster inoculations, with the same dose of the HIV-2SBL6669 parental virus. Five of the seven animals remained protected against HIV-2 infection at 6 months following the second challenge. In contrast, oral immunization with recombinant Salmonella expressing the HIV-2 gag and the gp120 portion of the envelope either alone or in combination with alum-adjuvanted rgp160 failed to confer protection. These results suggest that the NYVAC- and ALVAC-based recombinants may confer long-lasting protection and that these two highly attenuated poxvirus vaccine vectors may represent promising candidates for developing an acquired immunodeficiency syndrome vaccine.

Isolation of a novel simian T-cell lymphotropic virus from Pan paniscus that is distantly related to the human T-cell leukemia/lymphotropic virus types I and II.

An unusual serological profile against human T-cell leukemia/lymphotropic virus type I and II (HTLV-I and -II) proteins was reported in several human Pygmy tribes in Zaire and Cameroon with serum antibodies reactive with gp21 and p24. Here we describe a similar pattern of serum antibodies in a colony of captive pygmy chimpanzees and the isolation of a novel retrovirus, simian T-cell lymphotropic virus from Pan paniscus (STLVpan-p), from the peripheral blood mononuclear cells of several seropositive animals. Cocultures of peripheral blood mononuclear cells from three seropositive pygmy chimpanzees with human cord blood mononuclear cells led to the expression of an HTLV-I- and HTLV-II-related virus initially demonstrated by electron microscopy. Furthermore, several of these cocultures became immortalized T-cell lines expressing the CD4+ CD8+ DR+ phenotype of mature activated T cells. Southern blotting and DNA sequencing of a PCR fragment of viral DNA from these cell cultures demonstrated a distant evolutionary relationship of these viruses to HTLV-I and -II and distinct from the known STLV isolates. We designated this virus STLVpan-p. A genealogical analysis of the captive pygmy chimpanzees colony, originated from wild-caught animals, revealed a prevalence of seropositive offspring from infected mothers, as also observed with HTLVs. The presence in this old African Great Ape species of a virus which is genetically quite distinct from HTLV-I and -II could provide new insights in the phylogenesis of STLVs and HTLVs and be instrumental in the discovery of related human viruses.

Graphic monitoring of labour.

The parturograph is a composite record designed for the monitoring of fetal and maternal well-being and the progress of labour. It permits the early recognition of abnormalities and pinpoints the patients who would benefit most from intervention. Observations are made from the time of admission of the mother to the caseroom and recorded graphically. Factors assessed include fetal heart rate, maternal vital signs and urine, cervical dilatation, descent of the presenting fetal part, and frequency, duration and intensity of uterine contractions.

Detection of unsuspected ovarian pregnancy by wedge resection.

Five follicular ovarian implantations occurred among 200 ectopic pregnancies encountered during a 14-year period. Abortions from impregnated follicles may cause hemoperitoneum more often than is generally suspected. Wedge resection or cystectomy to ensure hemostasis provides tissue for histological examination, without which ruptured ovarian pregnancy may masquerade as rupture of a corpus luteum with hemorrhage ("ovarian apoplexy"). Including patients reported here, IUCD users have within the past five years accounted for about 10% of all ovarian pregnancies recorded in English.

Compounds interfering with ovum implantation and development. I. Alkaloids and antimetabolites.

PIP: The alkaloids ergocornine, vinblastine, and colcemide, with reported effects interfering with ovum implantation and development were investigated in the white New Zealand rabbit and the macaque monkey. 3 antimetabolites, 5-fluorouracil, 6-azauridine, and BW 57-323H, the 6 mercaptopurine derivative, were also investigated. Ergocornine was ineffective at the dosage employed (1.5-2.5 mg/kg) and vinblastine was teratogenic. Colcemide was administered in single doses ranging from .1-5 mg/kg. From Day 9 until term it was an extremely toxic agent to the developing fetus, death occurring within 2-4 hours after administration. At 5.0 mg/kg, 50% of the animals died from toxicity. Administration in the macaque monkey on Days 24, 45, 66, and 84 of pregnancy was without effect. 2-antimetabolites tested in the rabbit (5-fluorouracil and 6-azauridine) had little effect. BW 57-323H administered interperitoneally to pregnant rabbits resulted in complete litter destruction early in pregnancy, was teratogenic midpregnancy and ineffective in late pregnancy. This compound was without effect in macaques when administered on Days 28-30.^ieng