Search PubMed⌕ Search

Biomedical subjects

K Iwase

Publications and source records attributed to K Iwase.

At least 19 recordsLinked to original sources

Property of thimerosal-induced decrease in cellular content of glutathione in rat thymocytes: a flow cytometric study with 5-chloromethylfluorescein diacetate.

There is a concern on the part of public health community that adverse health consequences by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the effect of thimerosal on cellular content of glutathione was examined on thymocytes obtained from 4-week-old rats using a flow cytometer and 5-chloromethylfluorescein diacetate. Thimerosal at concentrations ranging from 1 to 10 microM reduced the cellular content of glutathione in a concentration-dependent manner, and the complete depletion of cellular glutathione was observed when the cells were treated with 30 microM thimerosal. L-Cysteine significantly attenuated the actions of thimerosal to reduce the glutathione content and to increase the intracellular Ca2+ concentration. Prolonged incubation (24 h) with 1-3 microM thimerosal induced the apoptosis. The cytotoxic action of thimerosal was greatly augmented when the cells suffered oxidative stress induced by H2O2. It may be unlikely that thimerosal exerts potent cytotoxic action under the in vivo condition because the blood concentration of thimerosal after receiving vaccines does not seem to reach micromolar range and nonprotein thiols at micromolar concentrations are present in the blood.

Animals↗

[Extrapleural pneumonectomy of malignant pleural mesothelioma].

We analyzed 7 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy. Six men and a woman had a mean age of 65 years old. The postoperative mortality rate was 14% (1 death) and morbidity, 43% (3 cases). According to staging of International Mesothelioma Interest Group, 2 patients had stage I disease, 1 did stage II, 3 did stage III and 1 did stage IV. Local recurrences were found in 3 patients and metastasis in 2. In patients with local recurrences, 2 had irradiation with chemotherapy and 1, irradiation. In patients with recurrences of metastasis, 1 had chemotherapy and 1, supportive care. Seven patients with extrapleural pneumonectomy and 10 without surgery had median survivals of 16 months and 10 months, 1-year survival rates of 71% and 40% and 2-year survival rates of 57% and 0% respectively (p=0.071). Extrapleural pneumonectomy with adjuvant therapy could be effective treatment for malignant pleural mesothelioma.

Aged↗

Expression and localization of nm23-H1 in the human placenta.

The involvement of the nm23 gene, initially documented as a putative metastasis-suppressor gene, in normal development and differentiation has been supported by several investigations. To date, however, localization and expression pattern of nm23 in the human placenta has not been determined. In the present study, the expression of nm23-H1 was examined by Northern blot and immunohistochemical analyses in human placentas from various stages of gestation. In first trimester placenta, the villous cytotrophoblast and the extravillous trophoblast exhibited strong cytoplasmic staining for nm23-H1. In second trimester and term placentas, the few cytotrophoblasts present showed less intense staining than those in first trimester placenta. Northern blot analysis demonstrated a progressive decrease in nm23-H1 gene expression with advancing gestational age, which is consistent with the results obtained by immunohistochemistry. These findings suggest that nm23-H1 is involved in the differentiation process of the trophoblast, and high levels of nm23-H1 expression seem to reflect the proliferating, less differentiated state of that reserve.

Blotting, Northern↗

CCAAT/enhancer-binding protein beta is required for activation of genes for ornithine cycle enzymes by glucocorticoids and glucagon in primary-cultured hepatocytes.

Transcription of genes for enzymes of the ornithine cycle is activated by hormones such as glucocorticoids and glucagon. Promoters and enhancers of several genes for the enzymes interact with the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors, and C/EBPbeta has been suggested to mediate glucocorticoid response of the gene for arginase, the last enzyme of the cycle. To determine the contribution of C/EBPbeta to hormonal regulation of genes for ornithine cycle enzymes, we examined mice with targeted disruption of the C/EBPbeta gene. Induction of genes for the enzymes by intraperitoneal injection of dexamethasone and glucagon was almost intact in the liver of C/EBPbeta-deficient mice. On the other hand, in primary-cultured hepatocytes derived from C/EBPbeta-deficient mice, induction of genes for the first enzyme carbamylphosphate synthetase, as well as for arginase, in response to dexamethasone and/or glucagon was severely impaired. Therefore, C/EBPbeta is required for hormonal induction of the genes for ornithine cycle enzymes in primary-cultured hepatocytes, while the deficiency of C/EBPbeta is compensated for in vivo.

Animals↗

Left-hand-assisted laparoscopic resection of hepatocellular carcinoma in an accessory liver.

We report a left-hand-assisted laparoscopic resection of hepatocellular carcinoma that developed in an accessory liver in a 47-year-old man. Preoperative assessment of the location of the tumor and the feeder vessels by combined selective angiography and computed tomography studies predicted the feasibility of laparoscopic procedures for complete removal of the tumor. In an attempt to avoid direct contact of the tumor capsule with rigid instruments during the operation, left-hand-assisted procedures were attempted. The encapsulated mass, 6 x 5 x 3 cm in size, was located on the posterior side of the left diaphragm, and a thin stalk between the tumor and the margin of the left lateral segment of the liver proper was recognized. Hand-assisted procedures ensured the complete mobilization of the lesion with an adequate margin, without any unexpected capsular tear. Left-hand-assisted laparoscopic procedures would be feasible for the easy and safe resection of localized hepatocellular carcinoma developing in an accessory liver.

Carcinoma, Hepatocellular↗

Expression of nm23-H1 in hydatidiform mole and its relationship with the development of postmolar disease.

The aim of the present study was to investigate the expression of nm23-H1 in human placenta, hydatidiform mole and choriocarcinoma cells. Nm23-H1 protein was localized in the cytotrophoblast, but not in the syncytiotrophoblast. In the hydatidiform mole cases with subsequent spontaneous remission, nm23-H1 mRNA levels were significantly lower than those in first-trimester placentas. However, its levels were elevated in the hydatidiform mole cases that progressed to persistent gestational trophoblastic disease and were comparable to those of first-trimester placentas, and they were further elevated in choriocarcinoma cells. The present data suggest an association of nm23-H1 for the proliferation activity of trophoblast, and its increased expression may influence the development of persistent trophoblastic disease.

Blotting, Northern↗

Effect of eicosapentaenoic acid ethyl ester on hypothyroid function.

Thyroid hormones affect reactions in almost all pathways of lipid metabolism. It has been reported that plasma free fatty acid (FFA) concentration in hypothyroidism is generally within the normal range. In this study, however, we show that plasma FFA concentration in some hypothyroid patients is higher than the normal range. Symptoms of thyroid dysfunction in these individuals were less severe than those of patients with lower plasma FFA concentrations. From these findings we hypothesized that the change in FFA concentration must correlate with thyroid function. Using an animal model, we then examined the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E), a n-3 polyunsaturated fatty acid derived from fish oil, on thyroid function in 1-methyl-2-imidazolethiol (MMI)-induced hypothyroid rats. Oral administration of EPA-E inhibited reduction of thyroid hormone levels and the change of thyroid follicles in MMI-induced hypothyroid rats. These findings suggest that FFA may affect thyroid functions and EPA-E may prevent MMI-induced hypothyroidism.

Animals↗

Hand-assisted laparoscopic splenectomy for idiopathic thrombocytopenic purpura during pregnancy.

A successful case of a hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum for autoimmune thrombocytopenic purpura in a patient at 23 weeks' gestation is reported. Preoperative splenic arterial embolization was performed on the same day as the operation using painless contour embolic material and super-absorbent polymer microspheres. The abdominal wall retraction method first was applied to avoid the effects of pneumoperitoneum on systemic hemodynamic alterations. However, a sufficient surgical view could not be obtained, as the intra-abdominal organs were elevated because of the enlarged uterus. A surgical view with 4 to 6-mm Hg pneumoperitoneum was available for the hand-assisted splenectomy. The postoperative course was uneventful, and the patient vaginally delivered a healthy infant. A hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum after splenic arterial embolization would be feasible for patients with autoimmune thrombocytopenic purpura during a relatively advanced pregnancy.

Adult↗

The gene for hepatocyte nuclear factor (HNF)-4alpha is activated by glucocorticoids and glucagon, and repressed by insulin in rat liver.

The gene for a transcription factor hepatocyte nuclear factor-4alpha (HNF-4alpha) is responsible for maturity-onset diabetes of the young, type 1. We examined hormonal regulation of the HNF-4alpha gene in the liver. Stimulation of primary-cultured rat hepatocytes with dexamethasone or glucagon led to induction of HNF-4alpha mRNA, being antagonized by insulin. In the liver of streptozotocin-induced diabetic rat, mRNA and protein levels for HNF-4alpha were elevated, and were normalized by insulin treatment. Therefore, HNF-4alpha in the liver is likely to be involved in the regulation of glucose metabolism in response to these hormones.

Animals↗

Induction of endothelial nitric-oxide synthase in rat brain astrocytes by systemic lipopolysaccharide treatment.

In the brain, three isoforms of nitric oxide (NO) synthase (NOS), namely neuronal NOS (nNOS, NOS1), inducible NOS (iNOS, NOS2), and endothelial NOS (eNOS, NOS3), have been implicated in biological roles such as neurotransmission, neurotoxicity, immune function, and blood vessel regulation, each isoform exhibiting in part overlapping roles. Previous studies showed that iNOS is induced in the brain by systemic treatment with lipopolysaccharide (LPS), a Gram-negative bacteria-derived stimulant of the innate immune system. Here we found that eNOS mRNA is induced in the rat brain by intraperitoneal injection of LPS of a smaller amount than that required for induction of iNOS mRNA. The induction of eNOS mRNA was followed by an increase in eNOS protein. Immunohistochemical analysis revealed that eNOS is located in astrocytes of both gray and white matters as well as in blood vessels. Induction of eNOS in response to a low dose of LPS, together with its localization in major components of the blood-brain barrier, suggests that brain eNOS is involved in early pathophysiologic response against systemic infection before iNOS is induced with progression of the infection.

Animals↗

Quantitative analysis of matrix metalloproteinases-2 and -9, and their tissue inhibitors-1 and -2 in human placenta throughout gestation.

To elucidate the implication of type IV collagenases(MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) for placental development, we quantified their levels in the conditioned media of placental organ culture and primary culture of the trophoblast as well as in the tissue extracts of placentas from different stages of gestation using specific enzyme-linked immunosorbent assays. First trimester villous tissue secreted about 10 times more pro-MMP-2 than pro-MMP-9, and pro-MMP-2 levels dramatically decreased in the second trimester. On the other hand, pro-MMP-9 levels were more than 10 times higher than those of pro-MMP-2 in the primary culture of the first trimester trophoblast, indicating the involvement of stromal cells for prominent pro-MMP-2 secretion from first trimester villous tissue described above. Levels of TIMPs, especially those of TIMP-2, remained constant throughout gestation both in the culture media and tissue extracts. Gelatin zymography revealed abundant secretion of the active form of MMP-2 as well as pro-MMP-2 from first trimester villous tissue. Western immunoblot analysis confirmed the presence of both TIMP-1 and TIMP-2 in placental tissue. These results suggest that active secretion of MMP-2 from villous tissue in the first trimester and constant production of TIMPs throughout gestation are characteristic of placental development.

Blotting, Western↗

Ileal perforation due to a Richter hernia at the drain insertion site following an operation for idiopathic rectal perforation: report of a case.

A case of a Richter hernia at the insertion site of the drainage tube following open abdominal surgery is reported. A 54-year-old man underwent an emergency operation for an idiopathic rectal perforation. A partial resection of the rectum and drainage using four 10-mm (outer diameter) drainage tubes with round cross sections was performed. Despite an uneventful early postoperative course, an emergency reoperation was required for peritonitis due to a bowel perforation 14 days after removing the drain inserted into the rectosacral space. A laparotomy revealed an incarcerated Richter hernia with ileal perforation through the 10-mm drainage site. The postoperative course after a partial resection of the ileum and drainage with Penrose drains was uneventful. This is the first report of a Richter hernia through the insertion site of a drainage tube in abdominal surgery. The possible occurrence of a Richter hernia in cases with postoperative drainage using large-size round drainage tubes should thus be considered in such patients.

Drainage↗

Reverse transcriptase is elevated in the thyroid tissue from Graves' disease patients.

OBJECTIVE: Hypertrophy of the thyroid gland in Graves' disease is related to an autoimmune response directed against TSH receptors found in thyroid cells. Recently, investigators have suggested that autoimmune diseases, including thyroid diseases may, at least in part, correlate with the expression of proteins encoded by the retroviral genome. In the present study, to confirm the correlation between thyroid autoimmune disorders and retroviral infections, we examined reverse transcriptase (RT) activity in thyroid tissues as a marker of retroviral infection. PATIENTS AND MEASUREMENTS: Thyroid tissues obtained at surgery from patients with various thyroid disorders (normal thyroid adjacent to adenoma, six cases; Graves' disease thyroid tissue, 25 cases; adenoma, eight cases; papillary carcinoma, 12 cases; Graves' disease peripheral blood lymphocytes, 11 cases) were used for RT assay, using a specific, improved assay system. RESULTS: Thyroid tissue extracts from patients with Graves' disease contained high RT activity which resembled that demonstrated in retroviruses. The RT existed in the thyroid tissue as a complex, with endogenous template RNA, and the activity was confirmed not to be due to other DNA polymerases. CONCLUSION: Retroviral RT distinguished from known cellular DNA polymerases is expressed in the thyroids of patients with Graves' disease. In a permissive genetice and immunological environment, retroviral DNA integrated into genomic DNA could precipitate the onset of Graves' disease.

Adenoma↗

Hyperintense basal ganglia on T1-weighted magnetic resonance images following postoperative parenteral nutrition in a pancreatoduodenectomized patient.

The authors reported the magnetic resonance imaging (MRI) detection of manganese (Mn) deposition in the basal ganglia of a pancreatoduodenectomized patient following 30-day parenteral nutrition. A multi-trace element supplement solution including 20 micromol Mn/day was parenterally administered for 30 days postoperatively. The serum level of total bilirubin normalized on the 3rd postoperative day, while the level of alkaline phosphatase continued to exceed the higher limit of normal controls even 2 months after operation. T1-weighted MRI on the 49th postoperative day demonstrated bilateral and symmetrical hyperintense lesions in the globus pallidus. The whole-blood Mn level on the 67th postoperative day was 3.1 (normal range 0.8-2.5) microg/l. T1-weighted MRI on the 103rd postoperative day revealed improvement in the hyperintense lesions, and MRI on the 225th postoperative day revealed no abnormality. The blood Mn level normalized on the 194th postoperative day. Even short-term postoperative parenteral nutrition may result in Mn deposition in the brain, especially in patients with cholestasis following pancreatoduodenectomy.

Aged↗

Lipid peroxidation levels in rat cardiac muscle are affected by age and thyroid status.

Free radicals, hydroxyperoxides and H(2)O(2) are all known to damage cell components. This study was designed to compare the concentrations of hydroxyperoxide and free radical scavengers in the cardiac muscles of old rats in the hyper- or hypothyroid condition, to determine whether rates of peroxidation would differ with age, thyroid status, or both. Rats were rendered hyper- or hypothyroid by administration of l-thyroxine or methimazole for 4 weeks. Among the old rats, the lipid peroxide (LPO) concentrations, measured as thiobarbituric acid (TBA) reactants, were significantly greater in the hyperthyroid than in the euthyroid state and the LPO concentrations measured as TBA+Fe(3+) reactants, which may be precursors of LPO, were significantly greater in the hyperthyroid state, whereas in young rats, the LPO concentrations measured by TBA or TBA+Fe(3+) methods did not differ significantly in the hyperthyroid state. In the euthyroid state, the concentration of LPO measured as TBA+Fe(3+) reactants was significantly reduced with age. Xanthine oxidase (XOD) activity also was markedly increased with age, being more pronounced in the hyperthyroid than in the euthyroid state. The Mn and Cu/Zn superoxide dismutase activities were greater in the hyperthyroid than in the euthyroid state. Glutathione peroxidase activity decreased with age in the euthyroid and, particularly, in the hyperthyroid state. Catalase activity was not affected in the old rats. Concentrations of alpha-tocopherol in the old rats were high in the hyperthyroid state and low in the hypothyroid state, whereas the levels of beta- and gamma-tocopherols in these rats were unchanged in both conditions as compared with the euthyroid state findings. Data suggest that the site of free radical generation differs in older rats, with additional shifts in the location of intracellular lipid peroxidation being noted during hyperthyroidism. Thus, as rats age, the reduction of the free radical scavenger system and the increase in LPO and XOD activities might induce myocardial dysfunction.

Aging↗

[Clinical features of essential thrombocythemia in three children].

Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900 x 10(9)/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea.

Aspirin↗