Biomedical subjects

Yoshikazu Mimura

Publications and source records attributed to Yoshikazu Mimura.

5 recordsLinked to original sources

PubMed2003

Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy.

Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5-fluorouracil (5-FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus-amebocyte-lysate test. In the 5-FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNFalpha and IL-6 were seen to increase, peaking at day 6 (IL-6, 350.0 +/- 67.8 pg/ml; TNFalpha, 26.1 +/- 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5-FU group showed dramatic sepsis-like manifestations, whereas the control group did not. Within the 5-FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis-like manifestations after systemic chemotherapy.

Animals↗

PubMed2003

Sublethal endotoxin administration evokes super-resistance to systemic hypoxia in rats.

BACKGROUND: Systemic hypoxia following surgical injury modulates cytokine and catecholamine responses. Endotoxin tolerance develops after pretreatment of animals with sublethal endotoxin doses and is characterized by a reduced inflammatory cytokine response to subsequent endotoxin challenges. The administration of endotoxin also attenuates ischemic injury of rat myocardial tissue following hypoxia, a phenomenon described as cross-tolerance. The objectives of this study were: 1) to determine whether endotoxin evokes a cross-tolerance to systemic hypoxia in rats; and 2) to estimate circulatory and pulmonary performance in rats with systemic hypoxia after endotoxin pretreatment. METHODS: Seventy-two hours before the experiment, Wistar rats were given an intraperitoneal injection of endotoxin at a dose of 10 microg/kg. Polyethylene catheters were inserted into the femoral vein for infusion, and into the femoral artery for blood sampling and blood pressure monitoring. Systemic hypoxia was achieved by continuous inhalation of a modified gas mixture (9% oxygen+ 91% N2) for 4 hours. Plasma TNF-alpha and IL-6 were measured by ELISA, and norepinephrine (NE) by HPLC. RESULTS: The hypoxic rats that were pretreated with saline showed a significant decrease in mean arterial blood and base excess, as compared with the normoxic rats. Endotoxin pretreatment prevented the drop in mean arterial pressure during hypoxia and reduced the decrease in base excess. Hypoxic conditions markedly stimulated TNF-alpha and IL-6 release and increased NE levels, compared to the normoxic rats. Pretreatment with endotoxin suppressed the hypoxia-induced cytokine production as well as attenuating the increase in NE levels CONCLUSIONS: In this rat hypoxia model, endotoxin pretreatment ameliorated the hypoxia-induced inflammatory response as well as suppressing the effects on arterial oxygenation, anaerobic metabolism and NE stimulation.

Adaptation, Physiological↗

PubMed2002

Consistent decrease in telomere length in parathyroid tumors but alteration in telomerase activity limited to malignancies: preliminary report.

Telomerase is known to be activated and telomere length altered in various types of malignant and benign tumors, but whether this is also the case for parathyroid lesions has hitherto been unclear. We therefore investigated telomerase activity and telomere length in 3 parathyroid metastatic cancers, 6 adenomas, 2 cases of parathyroid hyperplasia, and 16 samples of normal parathyroid tissue. Telomerase activity, assayed by the telomeric repeat amplification protocol, was detected in all of the parathyroid cancers (100%), in none of the 8 parathyroid benign lesions, and in only 1 of the 16 normal parathyroid samples (8.3%). Telomere length, determined by the terminal restriction fragment assay, was reduced in the tumor tissues with a mean telomere length of 8.23 +/- 0.86 kbp compared with the 12.61 +/- 0.81 kbp for the 16 age-matched subjects (p = 0.002). The results indicate that telomerase activity and telomere length may reflect the biologic behavior of individual parathyroid lesions.

Adenoma↗

PubMed2002

Telomere shortening with aging in human thyroid and parathyroid tissue.

Progressive telomere shortening with aging was studied using normal thyroid tissue specimens from 46 human subjects aged between 0 and 98 yr and normal parathyroid tissue specimens from 21 human subjects aged between 0 and 83 yrs. There has hitherto been no information documented about telomere length in such thyroid and parathyroid tissues. Age-related shortening at rates of 91 and 92 base pairs (bp) per year, respectively, were observed. Telomere lengths of normal thyroid tissues were 16.53 +/- 1.10 (mean +/- SE), 14.31 +/- 0.80, 11.27 +/- 0.68 and 8.73 +/- 1.08 kbp for age groups less than 2, 20-50, 51-80 and more than 80 yr. Telomere lengths of normal parathyroid tissues were 15.80 +/- 1.46 (mean +/- SE), 15.36 +/- 0.86 and 10.93 +/- 0.78 kbp for age groups less than 4, 20-50 and 51-80 yr. Telomere shortening occurred after 50 yr of age in thyroid and parathyroid tissues. Human thyroid and parathyroid tissues do not seem to show the rapid reduction in telomere length early in life that was reported for some human cell types, suggesting that the rate of telomere shortening has tissue-specific characteristics.

Adult↗

PubMed2001

Inhibition of nitric oxide synthase does not influence urinary nitrite plus nitrate excretion after renal ischemic injury.

BACKGROUND AND AIMS: Whether renal nitric oxide production caused by ischemia/reperfusion (I/R) influences the urinary excretion of nitric oxide (NO) metabolites (nitrite and nitrate) is far from being elucidated. In the present study, we evaluated the role of NO synthase inhibition using N(G)-nitro- L-arginine methyl ester ( L-NAME) in a model of experimental renal I/R injury. METHODS: Male Wistar rats were used in our experiments, and renal I/R injury was achieved after a 30-min occlusion of the bilateral renal artery followed by a 60-min period of reperfusion. Renal function including nitrite plus nitrate excretion and hemodynamics in reperfused kidneys were measured in the presence and absence of L-NAME. RESULTS: Intravenous application of L-NAME (5 mg/kg body weight) resulted in a marked reduction of urine flow, renal plasma flow (0.7 +/- 0.3 ml/min), and the glomerular filtration rate (0.1 +/- 0.01 ml/min), but a significant increase in NO excretion (FENOx, 67.9 +/- 10.5%). In addition we found after L-NAME injection a significant increase of the fractional excretion of sodium (FENa, 49.3 +/- 7.7%) and lithium (FELi, 70.2 +/- 1.6%), as well as the renal vascular resistance compared with animals with renal I/R but non-treated with L-NAME ( P<0.001). Furthermore, we observed a high correlation between FENOx and FELi (r(2)=0.80, P<0.01). CONCLUSION: Our results suggest that renal excretion of NO derivatives is not influenced by NO production during renal I/R injury, although NO contributes to the tubular transport capacity in the ischemia/reperfused kidney.

Animals↗