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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 325 records · Page 18Linked to original sources

[Free/total ratio of prostate-specific antigen (PSA) for prostate cancer detection in patients with gray zone PSA level].

Thirty seven patients complaining of voiding disturbance who showed gray zone total prostate-specific antigen (t-PSA) level (upper limit of normal approximately 10 ng/ml) but did not reveal apparent cancerous findings in the prostate were examined for free PSA (f-PSA) and prostate volume. According to histological diagnosis, 9 were cancer cases and the other 28 were non-cancer cases. The free/total (F/T) ratio was 0.10 and 0.16 in the cancer and non-cancer groups, respectively (t-PSA; DPC kit, p = 0.03). The t-PSA (DPC and Dinabott kits), f-PSA and PSA density alone did not distinguish these two groups. For diagnosis of cancer, the ratio seemed to be F/T, the most reliable followed by PSA density and t-PSA. When using a 13% F/T, the sensitivity and specificity for cancer detection were 88.9 and 70.8%, respectively. t-PSA measured with the Dinabott kit, showed a similar tendency except that the F/T ratio showed a slight variation. Prostate volume and patient age influenced the F/T slightly, but these factors may not impair the usefulness of F/T.

Aged↗

Interleukin-10 gene expression in adult T-cell leukemia.

We studied the serum levels of interleukin-10 (IL-10), in patients with adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) infection. Elevated IL-10 levels were observed in 33 of 45 patients with ATL. Fresh leukemic cells from ATL patients as well as HTLV-I-infected T-cell lines MT-2, SLB-1, and C10/MJ expressed IL-10 mRNA by reverse transcription-polymerase chain reaction analysis, whereas IL-10 mRNA was not detected in normal peripheral mononuclear cells and an uninfected T-cell line Jurkat. IL-10 protein was also detected in the culture medium of leukemic cells from ATL patients as well as these HTLV-I-infected cell lines, and in the extracellular fluids of ATL patients. Interestingly, MT-4 cells, which did not express Tax although transformed by HTLV-I, did not express IL-10 at either the mRNA or protein level. To elucidate the role of the HTLV-I encoded transactivator Tax in IL-10 gene expression, Jurkat cells were transfected with a Tax expression plasmid. In transiently transfected Jurkat cells, endogenous IL-10 mRNA expression was induced by Tax. Stably transfected Jurkat cell lines expressed IL-10 mRNA and secreted IL-10 protein into the culture medium. The nuclear factor (NF)-kappa B pathway is a target for Tax transactivation. We treated MT-2 cells with phosphorothioate antisense oligonucleotides to the p65 subunit of NF-kappa B. A reduction in the expression of p65 was accompanied by a reduction in IL-10 gene expression and IL-10 production. We showed that the IL-10 kappa B-like sites ( kappa B1,-2,034 to -2,025; kappa B2, -1,961 to -1,952; kappa B3, -452 to -443) specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2 cells and that NF-kappa B bound with the highest affinity to the kappa B2 element (kappa B2 > kappa B3 > kappa B1). These data suggest a general role for NF-kappa B activation in the induction of IL-10 gene transcription. Activation of IL-10 in HTLV-I-infected cells may contribute to the pathology associated with HTLV-I infection.

Adult↗

Inhibition of catalase activity in vitro by diesel exhaust particles.

The effect of diesel exhaust particles (DEP) on the activity of catalase, an intracellular antioxidant, was investigated because H2O2 is a cytotoxic oxidant, and catalase released from alveolar cells is an important antioxidant in the epithelial lining fluid in the lung. DEP inhibited the activity of bovine liver catalase dose-dependently, to 25-30% of its original value. The inhibition of catalase by DEP was observed only in the presence of anions such as Cl-,Br-, or thiocyanate. Other anions, such as CH3COO- or SO4-, and cations such as K+, Na+, Mg2+, or Fe2+, did not affect the activity of catalase, even in the presence of DEP extract. Catalase from guinea pig alveolar cells and catalase from red blood cells were also inhibited by DEP extracts, as was catalase from bovine liver. These results suggest that DEP taken up in the lung and located on alveolar spaces might cause cell injury by inhibiting the activity of catalase in epithelial lining fluid, enhancing the toxicity of H2O2 generated from cells in addition to that of O2- generated by the chemical reaction of DEP with oxygen.

Animals↗

Bell palsy and herpes simplex virus: identification of viral DNA in endoneurial fluid and muscle.

OBJECTIVE: To determine whether herpes simplex virus type 1 (HSV-1) causes Bell palsy. DESIGN: Prospective study. SETTING: University inpatient service. PATIENTS: 14 patients with Bell palsy, 9 patients with the Ramsay-Hunt syndrome, and 12 other controls. MEASUREMENTS: Viral genomes of HSV-1, varicella-zoster virus, and Epstein-Barr virus were analyzed in clinical samples of facial nerve endoneurial fluid and posterior auricular muscle using polymerase chain reaction (PCR) followed by hybridization with Southern blot analysis. RESULTS: Herpes simplex virus type 1 genomes were detected in 11 of 14 patients (79%) with Bell palsy but not in patients with the Ramsay-Hunt syndrome or in other controls. The nucleotide sequences of the PCR fragments were identical to those of the HSV-1 genome. CONCLUSIONS: Herpes simplex virus type 1 is the major etiologic agent in Bell palsy.

Adult↗

B-cell epitopes in hypervariable region 1 of hepatitis C virus obtained from patients with chronic persistent hepatitis.

The hypervariable domain (HVR1) within the N-terminus of the E2 protein of hepatitis C virus (HCV) is known to be variable antigenically during the course of persistent infection. The aim of the study was to detect B-cell epitopes in HVR1 responsible for neutralizing HCV. The B-cell epitopes were analyzed using two series of synthetic peptides: 25 heptapeptides from the most common amino acids within 73 HVR1 sequences, and 216 heptapeptides, the sequences of which cover more than 65% of the 73 HVR1 sequences. Sera from three patients with chronic hepatitis C were tested for reactivity to the synthetic peptide sequences by enzyme-linked immunosorbent assay (ELISA). The post-interferon (IFN) serum of one patient who had a long-term response to treatment reacted specifically with 13 heptapeptides of 216 variable sequences of HVR1. Some of the amino acid sequences (amino acids 398, 399, 400, 404) of the heptapeptides were also found in those deduced from the nucleotide sequences of HCV genomes in the pre-IFN serum. The sera of the other two patients who did not respond to treatment did not react with the 13 heptapeptides. It is concluded that the B-cell epitopes in HVR1 may be relevant for eliminating viremia in the case of the patient who had a good response to treatment. These results suggest that the analysis of the B-cell epitopes recognized in HVR1 may be important in understanding the mechanism of persistent infection and progression of hepatitis.

Adult↗

Direct isolation of longevity mutants in the nematode Caenorhabditis elegans.

We have isolated several new EMS-induced, long-lived mutants of Caenorhabditis elegans, using a novel screen that eliminates the need for replica plating. Three new alleles of age-1 (z10, z12, and z25) were identified by failure to complement age-1 (hx546) for life span extension; these alleles had life spans ranging from 18.9 to 25.9 days at 25 degrees C, with an average 46% increase in life span. After backcrossing, alleles were examined in a wild-type background for resistance to several environmental stresses: heat (35 degrees C), ultraviolet (UV) light (20 J/m2), and hydrogen peroxide (H2O2) (0.5 M). Two replicates of the test of thermotolerance were completed on each strain, giving mean survivals of 842 min (hx546), 810 min (z10), 862 min (z12), and 860 min (z25), compared to 562 min for wild type. All the age-1 alleles were significantly tolerant, compared with wild type (P < 0.001). Two replicates for UV resistance were also completed with mean survivals of 103, 118, 108, and 89 hr, respectively, compared to 72 hr for wild type. One test of hydrogen peroxide resistance has shown that z12 and N2 had a mean survival of 41 hr, while the other age-1 alleles had mean survival of 54 hr (z10), and 62 hr (z25); H2O2 resistance is the only environmental stress that differentiates among the age-1 alleles.

Animals↗

Adenosine does not mediate renal sodium retention and peripheral vasodilation elicited by partial portal vein ligation in rats.

This study was conducted to assess the role of adenosine in the peripheral vasodilation and sodium retention that occurs after partial portal vein ligation (PVL) in the rat. The experiment was performed on day 1 after surgery when transient maximal sodium retention developed and day 7 when rats returned to sodium balance. Hemodynamic studies were conducted under anesthesia in portal hypertensive rats with sodium retention and in sham-operated controls. Measurements were obtained before and after administration of a nonselective A1 and A2 adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX) (10 mg/kg intravenously followed by 150 micrograms/min). Under baseline conditions, portal hypertensive rats with sodium retention were hypotensive, with decreases in total peripheral resistance and filtration fraction on day 1 in comparison with the control group. Although hyperdynamic circulation was still maintained by day 7, there was a return to sodium balance. The adenosine receptor antagonist had a modest vasoconstrictor effect on systemic and renal vasculature in both groups, but less in portal hypertensive rats. However, no change in glomerular filtration rate was observed. DPSPX induced a natriuresis in control rats (from 0.40 +/- 0.11 to 5.97 +/- 0.61 mEq/min on day 1, from 0.48 +/- 0.20 to 6.34 +/- 0.45 mEq/min on day 7). This response was attenuated in portal hypertensive rats on day 1 (from 0.14 +/- 0.04 to 1.67 +/- 0.57 mEq/min). but not on day 7 (from 0.20 +/- 0.06 to 5.11 +/- 0.55 mEq/min). These results suggest that in portal hypertensive rats (1) adenosine is not responsible for vasodilation and sodium retention, (2) a sodium-retaining factor acting directly on the renal tubule is responsible for sodium retention.

Adenosine↗

Aggressive angiomyxoma occurring in the scrotum: report of a case.

The authors recently treated a case of aggressive angiomyxoma occurring in the left scrotum. A 61-year-old Japanese man was diagnosed as having an inguinal irreducible hernia that descended to the bottom of the scrotum preoperatively. However, during the operation a large tumor was found between the spermatic fascia and the skin pressing the testis upward. The tumor measured 20 x 15 x 15 cm, was yellowish with a smooth surface encapsulated by a membrane similar to the pleura, and the cut surface was gelatinous. The histological findings indicated that the tumor had thick-walled vessels which had prominently increased in size, delicately waved collagen fibers, and stromal cells in a myxoid background. The patient has remained recurrence-free as of 11 months after surgery.

Capillaries↗

Tissue superoxide dismutase (SOD) activity and immunohistochemical staining in acute appendicitis: correlation with degree of inflammation.

The mechanism of progression of appendicitis has not been clarified. We examined tissue superoxide dismutase (SOD) activity, thiobarbituric acid reactive substance (TBARS), and the localization of Cu, Zn-SOD in 56 inflamed appendices in relation to histopathological classification. There was a significant difference in SOD activity between catarrhal appendix and phlegmonous and gangrenous appendix (2.3 +/- 0.1 vs 5.0 +/- 0.2 and 4.6 +/- 0.6 units/mg protein, respectively P < 0.05). TBARS value was highest in gangrenous appendix, being significantly different from the levels in the other two types (0.47 +/- 0.04 vs 0.19 +/- 0.01 n mol/mg protein, in catarrhal and 0.20 +/- 0.02, in phlegmonous appendix P < 0.05). Positive staining for Cu, Zn-SOD was demonstrated in 64% of catarrhal appendices, 96% of phlegmonous appendices, and 75% of gangrenous appendices, and intense positive staining was recognized in 9%, 28%, and 40% of these appendices, respectively. These results indicated that active oxygen influences the degree of inflammation in phlegmonous and gangrenous appendicitis. Gangrenous appendicitis and the other two types of appendicitis seemed to be different entities.

Acute Disease↗

Taurine accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats.

The effects of taurine on the regression of pre-established hypercholesterolemia were examined in stroke-prone spontaneously hypertensive rats (SHRSP). Hypercholesterolemia was induced by feeding a hypercholesterolemic diet to SHRSP for 30 days. Then, the diet was switched to normal chow with or without 3% taurine, and the effects were followed up for another 30 days. During regression serum cholesterol level was rapidly decreased, and was accelerated by taurine. A similar accelerated decrease in cholesterol content by taurine was seen also in tissues including the liver, intestine, and aorta. In the liver, acyl-CoA:cholesterol acyltransferase (ACAT) activity was significantly low in the taurine-supplemented group, parallel with the hepatic cholesteryl ester content. On the other hand, hepatic cholesterol 7 alpha-hydoxylase activity maintained a higher level in the taurine-supplemented group. These results showed that taurine accelerates the regression of hypercholesterolemia, and suggested that this effect is related to the increase in cholesterol catabolism to bile acid through the enhancement of 7 alpha-hydoxylase activity.

Animals↗

Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules.

We investigated binding of p53- and Ras-derived peptides with frequently observed missense mutations, to various L cell transfectants expressing a single species of HLA-DR complex, and found that: (i) all the synthetic peptides bound to various DR complexes with a variable affinity; (ii) some DR allelic products had a high affinity for both p53- and Ras-derived peptides (e.g., DRB1*1502), whereas others almost no affinity (e.g., DRB1*1101); and (iii) DR-binding motifs described in the literature can explain some of the allele-specific interactions between mutated peptides and DR complexes. Therefore, some mutated Ras- and p53-derived peptides could be tumor-specific antigens recognized by CD4+ T cells in an HLA-DR allele-specific manner.

Amino Acid Sequence↗

Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats.

Effect of estrogen on apoptotic cell death was studied in the two sexually dimorphic neuronal groups in the developing rat preoptic area (POA): the anteroventral periventricular nucleus of the POA (AVPvN-POA); and the sexually dimorphic nucleus of the POA (SDN-POA). A specific labelling of nuclear fragmentation was performed by terminal deoxynucleotydyl transferase(TdT)-mediated dUTP-biotin nick end-labeling method (TUNEL method) to demonstrate apoptosis. In the AVPvN-POA whose size is larger in females than in males, the number of TUNEL-positive cells was not significantly different between day 5 control and female pups sacrificed 10 h after 25 micrograms estradiol benzoate (EB) injection. However, TUNEL-positive cells showed a significant increase in the female pups sacrificed 24 h after EB injection, compared to that shown in the control female pups. In the SDN-POA whose size is larger in males than in females, EB injection significantly decreased TUNEL-positive cells in the female pups sacrificed 24 h after EB injection, compared to that in controls. These results suggest that estrogen regulates the neuronal number by facilitating apoptotic cell death in the developing AVPvN-POA or by inhibiting it in the developing SDN-POA.

Animals↗

An artificial CuII complex with intriguing oxygen radical-quenching profile. X-ray structure, cytochrome c assay, and ESR study.

A novel artificial peptide named HPH-Pep, comprising a pyridine and two histidine units, was synthesized. The HPH-Pep-CuII complex had unique pentacoordinated structure as shown by X-ray crystallography and exhibited superoxide-scavenging activity as indicated by ESR spectroscopy. The superoxide-quenching profile of HPH-Pep-CuII was studied in detail by cytochrome c assay and ESR spin trapping and it was found that (1) HPH-Pep-CuII did not scavenge hydrogen peroxide or hydroxyl radical and hence the scavenging activity was specific to superoxide, and (2) HPH-Pep-CuII did not generate hydrogen peroxide upon scavenging superoxide.

Copper↗

Prevention of reperfusion injury by inhaled nitric oxide in lungs harvested from non-heart-beating donors. Paris-Sud University Lung Transplantation Group.

BACKGROUND: In lung transplantation using non-heart-beating donors (NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury. We hypothesized that inhaled nitric oxide (NO) would reduce ischemia-reperfusion injury, and thus ameliorate the viability of the lung graft. METHODS: A blood-perfused, isolated rat lung model was used. Lungs were flushed and harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia. The lung was then stored for 2 hours at 4 degrees C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after 1 hour of reperfusion by measuring pulmonary vascular resistance, coefficient of filtration, wet-to-dry lung weight ratio, and myeloperoxidase activity. RESULTS: A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary vascular resistance (6.83 +/- 0.36 mm Hg. mL-1.min-1), coefficient of filtration (3.02 +/- 0.35 mL.min-1.cm H2O-1 x 100 g-1), and wet-to-dry lung weight ratio (8.07 +/- 0.45). Lower values (respectively, 3.31 +/- 0.44 mm Hg.mL-1.min-1, 1.49 +/- 0.34 mL.min-1.cm H2O-1 x 100 g-1, and 7.44 +/- 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improved when NO was given during reperfusion only. All measured variables, including myeloperoxidase activity were significantly improved when NO was given during both ischemia and reperfusion. Myeloperoxidase activity was significantly correlated with coefficient of filtration (r = 0.465; p < 0.05). CONCLUSIONS: These data suggest that inhaled NO significantly reduces ischemia-reperfusion injury in lungs harvested from non-heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.

Administration, Inhalation↗

Lasting beneficial effect of short-term inhaled nitric oxide on graft function after lung transplantation. Paris-Sud University Lung Transplantation Group.

The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange data, lung neutrophil sequestration, and pulmonary artery endothelial dysfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assigned to nitric oxide and control groups. Harvested lungs were preserved in normal saline solution for 24 hours at 4 degrees C. During transplantation, inflatable cuffs were placed around each pulmonary artery to allow separate evaluation of each lung by occluding flow. Compared with the transplanted lungs in the control group, transplanted lungs in pigs treated with inhaled nitric oxide significantly improved gas exchange, pulmonary vascular resistance, shunt fraction, and oxygen delivery at 4 and 24 hours after reperfusion. Neutrophil sequestration, as measured by the neutrophil-specific enzyme myeloperoxidase and the alveolar leukocyte count per light microscopic field, was significantly lower at 24 hours after reperfusion in the transplanted lungs of the nitric oxide group. The nitric oxide-treated native right lungs exhibited significantly reduced increase in neutrophil accumulation compared with that in control native right lungs. After 24 hours of reperfusion, endothelium-dependent relaxation to acetylcholine was similarly and severely altered in both groups. We conclude that short-term inhaled nitric oxide given during the first 4 hours of reperfusion after lung transplantation significantly attenuates reperfusion injury, improving graft function as long as 24 hours after operation. This effect is probably mediated by a decrease in neutrophil sequestration. A protective effect on the contralateral lung was also observed. Inhaled nitric oxide may be a suitable agent when an acute reperfusion phenomenon is anticipated.

Administration, Inhalation↗

The hypolipidemic action of the ACAT inhibitor HL-004 in hamsters fed normal chow.

1. A novel ACAT (acyl-CoA: cholesterol acyltransferase) inhibitor, HL-004, exhibited a strong inhibitory effect on the hepatic and intestinal ACAT, but was less effective on the adrenal ACAT in vitro. 2. HL-004 selectively decreased serum VLDL cholesterol, and inhibited hepatic ACAT activity in hamsters fed normal chow. 3. These results suggest that the cholesterol-lowering effect of HL-004 can be attributed to a decrease in hepatic VLDL secretion via inhibition of ACAT.

Acetanilides↗

Gigantic dense bone island of the jaw.

The clinical and radiographic features of gigantic dense bone islands of the jaw were reviewed in 21 subjects to better determine the pathogenesis of this condition. Most of the islands were asymptomatic. They showed a striking predilection for occurrence in the premolar to molar region of the mandible. The greatest dimension of gigantic dense bone islands measured on panoramic radiographs ranged from 2.5 to 7.0 cm, and they were most commonly structureless radiopaque areas. None showed bony expansion buccolingually, nor did they displace adjacent teeth or bony anatomic structures. It is concluded that gigantic dense bone island is not a benign bone neoplasm and is perhaps merely a large counterpart of smaller dense bone islands or idiopathic osteosclerosis.

Adolescent↗