Genes for immunodominant protein antigens are highly homologous in Mycobacterium tuberculosis, Mycobacterium africanum, and the vaccine strain Mycobacterium bovis BCG.

The relatedness of immunodominant protein antigens in Mycobacterium tuberculosis, M. africanum, and M. bovis BCG was investigated by comparing the genes that encode major protein antigens in M. tuberculosis with their counterparts in the other two mycobacteria. Genes encoding homologs of M. tuberculosis major protein antigens were isolated from M. africanum and M. bovis BCG by constructing lambda gt11 recombinant DNA expression libraries and screening them with murine monoclonal antibodies and DNA probes. The antibodies were directed against four major protein antigens of M. tuberculosis with molecular masses of 71, 65, 19, and 14 kilodaltons. The isolated M. africanum and M. bovis BCG DNA clones were mapped with restriction endonucleases, and the maps of the mycobacterial genes were confirmed by Southern analysis of mycobacterial genomic DNA. The restriction maps of DNA containing the four genes in M. tuberculosis, M. africanum, and M. bovis BCG are identical, indicating that the immunodominant proteins that they encode are highly homologous in the three mycobacteria. Thus, the immunity against tuberculosis engendered by M. bovis BCG vaccination could be provided, at least in part, by the immune response to these homologous antigens.     

Blood flow velocity in the carotid artery as a measure of myocardial contractility.

An attempt was made to derive a useful noninvasive index to evalute a change in myocardial contractile state using transcutaneous Doppler flow-velocity curve from the carotid artery. In 5 mongrel dogs and in 43 patients with various heart disease, Doppler flow velocity curves were obtained from the ascending aorta intravascularly using a Doppler catheter and/or from carotid artery transcutaneously using a Doppler probe. The first derivative of left ventricular pressure (dp/dt) and electrocardiogram (ECG) were recorded simultaneously. The following 3 indices were measured from the Doppler flow-velocity curves: (1) macimum acceleration of blood flow (dv/dt), (2) time from onset of ejection to peak flow (time-to-peak), (3) time interval between the beginning of Q wave of ECG to the peak of Doppler flow velocity curve (ECG Q-Doppler peak).Among these 3 indices, only ECG Q-Doppler peak demonstrated a significant correlation between the values measured intravascularly and transcutaneously. Also, only ECG Q-Doppler peak showed significant correlation with maximum of dp/dt (max dp/dt). Since ECG Q-Doppler peak showed correlation with heart rate, the difference between observed and predicted ECG Q-Doppler peak (delta ECG Q-Doppler peak) was calculated to exclude the effect of heart rate. Predicted value of ECG Q-Doppler peak was calculated from the regression equation between heart rate and ECG Q-Doppler peak in the separate experiments. There was significant correlation between delta ECG Q-Doppler peak and max dp/dt. In 15 patients with coronary artery disease and in 16 healthy subjects, delta ECG Q-Doppler peak and the other noninvasive method (systolic time intervals) were measured. Delta ECG Q-Doppler peak showed better result in the separation of 2 groups than by systolic timeintervals. It was concluded that delta ECG Q-Doppler peak is a useful index to evaluate the myocardial contractile state since this index is readily obtained noninvasively.     

Mitigative action of monoisoamyl-2,3-dimercaptosuccinate (MiADMS) against cadmium-induced damage in cultured rat normal liver cells

Cadmium is non-essential, carcinogenic and multitarget pollutant in the environment. Monoisoamyl-2,3-dimercaptosuccinate (MiADMS) is an ester of dimercaptosuccinic acid that acts as an antioxidant and chelator. Therefore, the mitigative action of MiADMS on viability, morphology, antioxidative enzymes and cell cycle were studied on rat liver cells treated with cadmium chloride (CdCl₂). The cells were treated with 150 μM CdCl₂ alone or cotreated with 300 μM MiADMS (concurrently, 2 h or 4 h post-CdCl₂ treatment) for 24 h. The viability of cells treated with CdCl₂ alone was decreased in comparison to the control cells. Cotreatment with MiADMS resulted in an increase in cell viability in comparison to the CdCl₂ alone treated cells. The CdCl₂ treatment altered the morphological shape of the cells, while cotreatment with MiADMS restored the shape. Antioxidative enzymes activities were decreased in the cells treated with CdCl₂ alone, while MiADMS cotreatment resulted in an increase in enzyme activities. The CdCl₂ arrested the cells in S phase of the cell cycle. Cotreatment with MiADMS alleviated cell cycle arrest by shifting to G1 phase. These results clearly show the mitigative action of MiADMS on CdCl₂ toxicity and may suggest that MiADMS can be used as an antidote against cadmium.     

Insulin augments GnRH-stimulated LHbeta gene expression by Egr-1

Previous studies have shown that insulin augments GnRH-stimulated LH synthesis and release from primary gonadotrophs. In this study, regulation of LHbeta gene expression by GnRH and insulin was examined in LbetaT2 cells. Endogenous LHbeta mRNA is stimulated 2.4-fold by insulin alone, 2.6-fold by GnRH alone, and 4.7-fold by insulin together with GnRH. This effect of insulin, like GnRH, mapped to sequences -140 to +1 in the mouse LHbeta gene. Insulin together with GnRH stimulates activity of an LHbeta-reporter gene 7.1-fold; whereas, GnRH alone or insulin alone stimulates the reporter activity 2.8- and 3.1-fold, respectively. Blocking the binding of Egr-1 to sequences -51 to -42 in the LHbeta gene inhibits effects of insulin and GnRH. Insulin together with GnRH increases Egr-1 mRNA levels and total Egr-1 binding to LHbeta DNA. These findings indicate that insulin may impact regulation of the reproductive axis at the level of the pituitary.     

Polycystic ovary syndrome in adolescence.

Polycystic ovary syndrome (PCOS) is a syndrome of variable combinations of menstrual irregularity, hirsutism or acne, and obesity. It can be diagnosed in adolescence and has early childhood antecedents. PCOS is the single most common endocrine cause of an ovulatory infertility and a major risk factor for the metabolic syndrome and, in turn, development of type 2 diabetes mellitus in women. Thus, it appears that PCOS increases a woman's risk of developing cardiovascular disease. Therefore, identifying girls at risk for PCOS and implementing treatment early in the development of PCOS may be an effective means of preventing some of the long-term complications associated with this syndrome. This article reviews the definition, clinical features, diagnosis, and treatment of PCOS.