Percutaneous lumbar nucleotomy

The nature of the events whereby the reactive intermediates resulting from the bioactivation of bromobenzene and furosemide induce hepatotoxicity is unknown. To examine a role for disturbances in intracellular calcium homeostasis, secondary to a depletion in cellular reduced glutathione (GSH) and reduced protein thiols (PSHs), isolated mouse hepatocytes were exposed to cytotoxic concentrations of bromobenzene or furosemide. Cytosolic calcium concentration, as well as thiol status, was determined. The incubation of hepatocytes with 3.0 mM bromobenzene, and subsequent additions (1.2 mM) of the agent every hour, resulted in significant GSH depletion. The loss of plasma membrane integrity at 1.5 h preceded both a rise in the cytosolic Ca2+ concentration and depletion of total PSH content. Furosemide (1.0 mM) produced a 70% depletion in cellular GSH content in isolated hepatocytes. The initiation of cell damage occurred concurrently with both a rise in the cytosolic Ca2+ concentration and a depletion of total PSH content 4 h following furosemide addition. Since the increase in cytosolic Ca2+ did not precede cytotoxicity, these results do not support an initiating role for Ca2+ deregulation in bromobenzene and furosemide hepatotoxicities. In addition, depletion of PSH content did not correlate with bromobenzene- or furosemide-induced cytotoxicity.     

Breast-feeding and the nutritional status of nursing children in Chile

4-Pentafluoroethylumbelliferyl-beta-D-glucoside is proposed as an efficient substrate for human leukocyte acid beta-glucosidase. Its synthesis is described. This substrate was compared directly with 4-trifluoromethylumbelliferyl-beta-D-glucoside synthesized by us earlier and with 4-methylumbelliferyl-beta-D-glucoside which is commonly used for acid beta-glucosidase activity assay. The specific activity of acid beta-glucosidase with 4-pentafluoroethylumbelliferyl-beta-D-glucoside was 3- and 8-fold higher than it was with the substrates mentioned above. The kinetic parameters KM and VMAX for human leukocyte acid beta-glucosidase with the three substrates was determined. One possible application of the newly synthesized substrate is its use in the diagnosis of acid beta-glucosidase hereditary deficiency (Gaucher's disease).     

Association with capsid proteins promotes nuclear targeting of simian virus 40 DNA

All animal DNA viruses except pox virus utilize the cell nucleus as the site for virus reproduction. Yet, a critical viral infection process, nuclear targeting of the viral genome, is poorly understood. The role of capsid proteins in nuclear targeting of simian virus 40 (SV40) DNA, which is assessed by the nuclear accumulation of large tumor (T) antigen, the initial sign of the infectious process, was tested by two independent approaches: antibody interception experiments and reconstitution experiments. When antibody against viral capsid protein Vp1 or Vp3 was introduced into the cytoplasm, the nuclear accumulation of T antigen was not observed in cells either infected or cytoplasmically injected with virion. Nuclearly introduced anti-Vp3 IgG also showed the inhibitory effect. In the reconstitution experiments, SV40 DNA was allowed to interact with protein components of the virus, either empty particles or histones, and the resulting complexes were tested for the capability of protein components to target the DNA to the nucleus from cytoplasm as effectively as the targeting of DNA in the mature virion. In cells injected with empty particle-DNA, but not in minichromosome-injected cells, T antigen was observed as effectively as in SV40-injected cells. These results demonstrate that SV40 capsid proteins can facilitate transport of SV40 DNA into the nucleus and indicate that Vp3, one of the capsid proteins, accompanies SV40 DNA as it enters the nucleus during virus infection.     

Cigarette smoking, serum lipids, folate, and vitamin B12 in lung cancer

The purpose of our study was to evaluate the effects of cigarette smoking and serum lipids, folate, and vitamin B12 on the development of lung cancer in the Turkish population. The study group consisted of patients with histologically proven lung cancer and the control group comprised healthy smokers being followed in our smoking cessation outpatient department. Smoking history was obtained from all subjects and serum total cholesterol, HDL cholesterol, triglycerides, vitamin B12, and folate levels were measured. Pack/years of cigarettes smoked were significantly higher in the subjects with lung cancer than in the control group (p < 0.01). Serum total cholesterol, HDL cholesterol, triglyceride, serum folate, and vitamin B12 levels were within normal limits in both groups (p < 0.05), but serum vitamin B12 levels were statistically significantly higher (p < 0.01) in the cancer group than in the controls. In our study, we did not observe low levels of serum cholesterol, vitamin B12, or folate in the lung cancer patients.     

Cytomegalovirus disease accompanied by severe hypoproteinemia in a patient with adult T-cell leukemia-lymphoma

A 62-year-old Japanese man complained of fever, general fatigue, anorexia and watery diarrhea during remission of adult T-cell leukemia-lymphoma. Laboratory examinations showed severe hypoproteinemia (2.9 g/dl). However, neither intestinal lesions associated with ATL nor findings suggesting protein losing gastroenteropathy were observed. Cytomegalovirus (CMV) antigen detection assay using peripheral blood leukocytes revealed that he had an active CMV infection with hemophagocytic syndrome. Treatment with ganciclovir and methylprednisolone led to an improvement of hypoproteinemia. CMV disease and associated hemophagocytic syndrome should be considered as a cause of hypoproteinemia in an immunocompromised host.     

Accurate detection of coronary artery disease by integrated analysis of the ST-segment depression/heart rate patterns during the exercise and recovery phases of the exercise electrocardiography test

In this comparative cross-sectional study, we evaluated whether a novel computerized diagnostic variable, ST-segment depression/heart rate ST/HR analysis during both the exercise and postexercise recovery phases of the exercise electrocardiography (ECG) test, can detect coronary artery disease more accurately than methods using either exercise or recovery phase alone. The study population comprised 347 clinical patients referred for a routine bicycle exercise ECG test at Tampere University Hospital, Finland. Of these, 127 had angiographically proven coronary artery disease, whereas 13 had no coronary artery disease according to angiography, 18 had no perfusion defect according to technetium-99m sestamibi single-photon emission computed tomography, and 189 were clinically normal with respect to cardiac diseases. For each patient, the maximum values of the ST/HR hysteresis, ST/HR index, end-exercise ST depression, and recovery ST depression were determined from the Mason-Likar modification of the standard 12-lead exercise electrocardiogram [aVL, aVR, and V1 excluded]. The diagnostic performance of these continuous diagnostic variables was compared by means of receiver-operating characteristic analysis. The area under the receiver-operating characteristic curve of the ST/HR hysteresis was 89%, which was significantly larger than that of the end-exercise ST depression (76%, p < or = 0.0001), recovery ST depression (84%, p = 0.0063), or ST/HR index (83%, p = 0.0023), indicating superior diagnostic performance of the ST/HR hysteresis independent of the partition value selection. In conclusion, computerized analysis of the HR-adjusted ST depression pattern during the exercise phase, integrated with the HR-adjusted ST depression pattern during the recovery phase after exercise, can significantly improve the diagnostic performance and clinical utility of the exercise ECG test for the detection of coronary artery disease.     

Effects of macrophage colony-stimulating factor (M-CSF) on lipopolysaccharide (LPS)-induced mediator production from monocytes in vitro

M-CSF is a macrophage-lineage-specific growth factor that causes proliferation and differentiation of progenitor cells in the bone marrow. To investigate the effects of M-CSF on more matured cells, human monocytes were cultured in the presence or absence of M-CSF for 6 days. Addition of M-CSF at more than 10(2) U/ml resulted in higher viability and caused morphological differentiation to large macrophage-like cells. LPS-induced mediator production was also compared between M-CSF-treated and control cell. Monocytes were incubated with or without M-CSF for 3 days, and were stimulated with 1 microgram/ml of LPS for 2 days. IL-1 beta was not detected in the both culture supernatants, and PGE2 production was not influenced by M-CSF. However, amounts of G-CSF, GM-CSF, IL-6, and TNF-alpha produced in response to 1 microgram/ml of LPS were 1.5 to 2 times greater from monocytes treated with 10(4) U/ml of M-CSF than from control cells. The priming effect of M-CSF on LPS-induced cytokine production was found to require 3-day preincubation, and reached a maximum at the concentration of 10(4) U/ml. M-CSF-treated cells responded to a 10 times lower concentration of LPS than control cells in terms of cytokine production. M-CSF was also shown by flowcytometric analysis to influence the expression of CD14, a receptor for LPS, which might render monocytes more sensitive to LPS.