B lymphocytes secreting IgG linked to latent transforming growth factor- beta prevent primary cytolytic T lymphocyte responses

B lymphocytes secreting IgG linked to latent transforming growth factor (TGF)-beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to unrelated antigens in mixed lymphocyte cultures (MLC) so long as resting resident macrophages and functional Fc receptors are present. This was shown using IgG-secreting plaque-forming cells (PFC) to sheep erythrocytes (SRBC) obtained from popliteal lymph nodes of mice injected repeatedly in foot pads with SRBC. Remarkably, as few as approximately 300 PFC prevented CTL responses of 5 x 10(5) normal syngeneic spleen cells in MLC. Supranatants of short-term cultures of PFC also prevented CTL responses, and suppression was prevented by eliminating or dissociating IgG and TGF-beta present in supranatants or by antibody against active TGF-beta. Furthermore, the latency- associated peptide of latent TGF-beta was detected in approximately 10% of foci of IgG captured from single PFC, indicating that at least some B lymphocytes secrete IgG-TGF-beta as a complex. Resting resident macrophages (which do not produce latent TGF-beta) and functional Fc receptors were required for suppression, consistent with idea that IgG- TGF-beta is taken up through Fc receptors for IgG and that active TGF- beta, cleaved from latent TGF-beta of the complex, is delivered directly to potentially responding CTL. If CTL responses in man are similarly regulated by B lymphocytes, then an ongoing B cell response in patients with chronic viral infections or bearing immunogenic cancers may prevent effective therapeutic vaccination.      

A clinical study of flurazepam

Eleven patients suffering from chronic insomnia were given 30 mg flurazepam for 28 nights. While EEG measures of total sleep time and sleep efficiency were improved, changes in sleep latency and intermittent waking time were small and nonsignificant. Subjective benefits in sleep were confined to the first 2 nights. There was neither increased nor decreased daytime sleepiness. Cognitive functioning was significantly decreased during the first 2 days, and patients were unaware of these changes. Simple motor tasks were relatively unaffected. Desalkylflurazepam concentrations showed significant accumulation over time, but were not predictive of sleep measures or daytime performance in individual subjects. The withdrawal period was characterized by subjectively disturbed sleep and daytime dysphoria.     

Trypanosoma rhodesiense infection in mice: sex dependence of resistance.

There is large variation in the survival of inbred mouse strains infected with Trypanosoma rhodesiense (EATRO 1886). Of those strains that survived for at least 22 days postinfection, female mice were markedly more resistant than male mice. The longer a strain survived, the greater was the difference in survival between male and female mice. Parasite counts were higher in male mice than in females, suggesting that the decreased resistance of males was due to their relative inability to control parasite growth. To determine the possible role of an X-linked resistance gene, resistant (C57BL/6) and susceptible (BALB/c) mice were mated, and their F1 progeny were infected with T. rhodesiense. There was no difference in the resistance between reciprocal F1 male mice (C57BL/6 X BALB/c versus BALB/c X C57BL/6), indicating that an X-linked gene does not account for the difference in resistance between susceptible and resistant mice.     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.      

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.      

Respiratory effects in two-dimensional Fourier transform MR imaging

Respiratory and other regular motions during two-dimensional Fourier transform magnetic resonance imaging produce image artifacts consisting of local blurring and more or less regularly spaced "ghost" images propagating along the direction of the phase-encoding magnetic field gradient. The patterns of these ghost artifacts can be understood in terms of the technique of image production and basic properties of the discrete Fourier transform. This understanding permits, without respiratory gating, production of images of improved quality in body regions in which there is significant respiratory motion. In particular, the ghosts can be maximally separated from the primary image by choosing intervals between phase-encoding gradient pulse increments that are equal to one-half the respiratory period; they can be minimally separated by choosing an interval equal to the respiratory period. Increasing the number of signal averages between each phase-encoding increment decreases the intensity of the ghosts.     

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence.MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA).Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower.ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.     

Dental care access and use among HIV-infected women.

OBJECTIVES: This study sought to identify predictors of dental care use in HIV-infected women. METHODS: In a cross-sectional survey of HIV-infected women enrolled in the northern California site of the Women's Interagency HIV Study, dental care use and unmet need were assessed in relation to selected variables. RESULTS: Among 213 respondents, who were predominantly Black and younger than 45 years, 43% had not seen a dentist and 53% (among dentate women) reported no dental cleaning in more than a year (although 67% had dental insurance coverage, mainly state Medicaid). Nine percent were edentulous. Among nonusers of dental care, 78% reported that they wanted care but failed to get it. Barriers included fear of and discomfort with dentists, not getting around to making an appointment, and not knowing which dentist to visit. Multivariate analysis showed that lack of past-year dental care was associated mainly with unemployment, a perception of poor oral health, and edentulism. CONCLUSIONS: HIV-positive women appear to be underusing dental care services. Fear and lack of information regarding available resources, in addition to unemployment and perception of poor oral health, may be important barriers.     

Propofol hydroxylation by dog liver microsomes: assay development and dog breed differences.

Pharmacokinetic studies indicate that clearance of propofol, an anesthetic agent, is slower in greyhounds compared with other dog breeds. Biotransformation of propofol to 2,6-diisopropyl-1,4-quinol (4-hydroxypropofol) by cytochrome P-450 in the liver is proposed as a critical initial step in the elimination of this drug in dogs. Breed differences in the activity of this enzyme could therefore explain pharmacokinetic differences. An in vitro propofol hydroxylase assay was developed and then used to compare enzyme activities in liver microsomes from male greyhound, beagle, and mixed-breed dogs (five each). HPLC of incubate identified only one NADPH-dependent metabolite, which had a chromatographic retention time and UV absorbance, fluorescence, and mass spectra that were identical with authentic 4-hydroxypropofol standard. HPLC with fluorescence detection provided a highly sensitive quantitation method for 4-hydroxypropofol with a quantitation limit of 8 ng/ml using optimized excitation/emission wavelengths (288 nm/330 nm, respectively). Estimates of apparent K(m) and V(max) for propofol hydroxylation by microsomes from a male beagle dog were 7.3 microM and 3.8 nmol/mg/min, respectively. At a substrate concentration of 20 microM, propofol hydroxylase activity was significantly lower (p =.032) in greyhound microsomes (1.7 +/- 0.4 nmol/mg/min) compared with beagle microsomes (5.1 +/- 1.3 nmol/mg/min) but was not statistically different (p =.42) compared with mixed-breed microsomes (3.1 +/- 1.2 nmol/mg/min). These results indicate that there are breed differences in propofol hydroxylase activity and that deficient hydroxylation of propofol by one or more hepatic cytochrome P-450 isoforms may contribute to slow pharmacokinetic clearance of propofol by greyhounds.