Nitric oxide-related vasoconstriction in lungs perfused with red cell lysate

The present study in isolated rat lungs demonstrates that nitric oxide gas (.NO, 70 nM) added to the perfusate containing a small amount of hemolysate [175 microliters of lysed red blood cells (RBC) per 50 ml of Earle's balanced salt solution (EBSS)] triggered profound and sustained vasoconstriction. Vasoconstriction was not observed when .NO was added to lungs perfused with washed intact rat or human RBC or with oxyhemoglobin (Hgb 20 microM). The presence of hemolysate in the perfusate also caused vasoconstriction in response to n-acetylcysteine (50 microM), glutathione (10(-4) M), or ascorbic acid (10(-4) M) and potentiated greatly the vasoconstrictor response to 5 mM KCl. Not only .NO, but also nitroprusside (SNP) or L-arginine and paradoxically three .NO synthesis inhibitors, including N-monomethyl L-arginine, L-NAME, and nitroblue tetrazolium, which have different mechanisms of action, each caused in the presence of hemolysate large vasoconstrictive responses. Hemolysate itself enhanced O2 consumption by slices of lung; no effects of this dose of .NO on lung slice respiration were seen in the absence of hemolysate. Both Hgb and hemolysate lowered perfusate cGMP levels to the same degree suggesting that the vasoconstrictive response was not due to unique effects of hemolysate on guanylyl cyclase. Addition of superoxide dismutase (SOD) and catalase (CAT) to the hemolysate containing perfusate, or addition of a cyclooxygenase or 5-lipoxygenase inhibitor, virtually abolished the .NO induced vasoconstriction. The latter data are consistent with the concept that exposure of the vasculature to hemolysate may result in the formation of peroxynitrite. However, SOD and CAT did not abolish the pulmonary vasoconstriction induced by L-arginine or by NAC. Our data indicate that hemolysate has profound effects on lung vessel tone regulation and on lung tissue mitochondrial function, yet the precise molecular mechanisms responsible for the action of hemolysate are likely to be very complex.     

The pharmacokinetics and metabolism of heptapeptide--a prospective synthetic analog of tuftsin with psychostimulating action in rats

The lymphocyte blast transformation test (LBTT) with three tuberculin dilutions was used to examine 190 patients with varying pulmonary tuberculosis activity, of them 63 patients received chemotherapy. According to the blast formation in the patients' cultured peripheral blood cells by three tuberculin dilutions, a correlation was found between the clinical manifestations of the process and the functional activity of T lymphocytes. Thus, the greatest percentage (500 TU) of blasts in LBTT per mean PPD dose was detectable in patients with low LBTT results by three tuberculin dilutions with positive dynamics during chemotherapy. With further positive dynamics, the proportion of blasts in the cultured peripheral blood cells was highest per high PPD doses (5000 TU). On the contrary, patients with progressive tuberculosis displayed a oppositely directed phasic pattern.     

Characterization and growth regulation of a rat intrahepatic bile duct epithelial cell line under hormonally defined, serum-free conditions

Bile duct epithelial cells, or cholangiocytes, proliferate in vivo under a number of pathologic (i.e., partial hepatectomy) and pathophysiologic (i.e., bile duct ligation, malignant transformation) conditions. However, little is known about the possible growth factors that modulate these proliferative responses, in part because an in vitro model to study proliferation of nontransformed, normal cholangiocytes is not available. We report here the development of a rat cholangiocyte cell line (MMRC, minimal media-requiring rat cholangiocytes) that grows under hormonally defined, serum-free conditions on plastic and maintains a cholangiocyte phenotype. Morphologic as well as functional studies indicate that the cell line is polarized and actively transports fluid and electrolytes in an apical to basolateral direction. MMRC, when cultured for 24 mo. and passaged 80 times, have not undergone malignant transformation, because the cell line failed to grow under anchorage-independent conditions or in nude mice. Cellular proliferation is accelerated 2-8-fold by insulin, insulin-like growth factor 1, epidermal growth factor, and hepatocyte growth factor, growth factors known to stimulate tyrosine kinase receptors, and inhibited 2-10-fold by TGFbeta and IL-2. Glyco-conjugates of primary (i.e., cholic and chenodeoxycholic acid) and secondary bile acids (i.e., deoxycholic and lithocholic acid) do not alter proliferation at low concentration (1 microM), but are toxic at higher concentration (10 microM). In summary, we have developed and characterized a cholangiocyte cell line derived from normal rat liver, which grows under hormonally defined, serum-free conditions, maintains a nonmalignant, cholangiocyte phenotype, displays morphologic and functional features of polarity, and alters its proliferation rate in response to a variety of growth factors.     

Predicting performance during clinical years from the new Medical College Admission Test

The results of a predictive validity study of the new Medical College Admission Test (MCAT) using criteria from the clinical years of undergraduate medical education are presented and discussed. The criteria included course grades and faculty ratings of clerks in internal medicine, surgery, obstetrics and gynecology, pediatrics, and psychiatry; scores on a comprehensive test of clinical knowledge (including patient management type examinations); and scores on Part II of the examinations of the National Board of Medical Examiners (NBME). While the validity coefficients of the MCAT with the Part II examinations ranged from .03 to .47, they were higher than those of undergraduate grade-point averages with the same criteria. The implications of the small-to-medium size validity coefficients for admissions are discussed.     

Thrombocyte lactate dehydrogenase isoenzymes in patients with ischemic stroke

It was established that in the acute period of the ischemic stroke in the maiority of cases a change of isoenzyme structure of LDG thrombocytes was due to a decrease of LDG3 activity. In a number of patients the dominant change in the spectrum was determined by LDG and LDG4 fractions. The changes were of a stable character up to 10 weeks. LDG4 increase was characteristic of the isoenzymes spectrum in the patients with a severe development of the disease and in the patients in the remote period of the stroke. The obtained data can serve as a criterion for evaluating the adaptive changes in acute brain ischemia.     

Diagnosis and treatment of penetrating thoraco-abdominal peace-time wounds

A formula describing weight losses in the first approximation during space mission was derived assuming that humans may adapt to space flight effects. The process depended on two parameters one of which characterized maximum body losses and another--time of adaptation. Weight estimates of Skylab crewmembers obtained with the aid of the formula were in good agreement with actual results. The typical time of adaptation was two days. Possible ways of constructing a more precise model of weight changes and its use to diagnose the status of crewmembers are discussed.