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Biomedical subjects

M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 451 records · Page 25Linked to original sources
PubMed1996

Association of myotonic dystrophy and sick sinus syndrome, with special reference to electrophysiological and histological examinations.

Sick sinus syndrome is a rare but potentially important cardiac disorder in patients with myotonic dystrophy. We evaluated 3 patients with myotonic dystrophy complicated with sick sinus syndrome using intracardiac electrocardiography and endomyocardial biopsy. Electrocardiography identified sinus arrest, atrial flutter and right bundle-branch block in 2 cases and marked sinus bradycardia and first-degree atrioventricular block in 1 case. Their sinus node recovery times were significantly prolonged as demonstrated by the overdrive suppression test. Two patients had Adams-Stokes syndrome and one had tachycardia with severe palpitations. Therefore permanent pacemaker implantation was indicated in all 3 cases. Light microscopic analysis of right ventricular endomyocardial biopsies showed vacuolar degeneration and nuclear deformity of cardiomyocytes in all cases and endocardial and interstitial fibrosis in 1 case. These findings indicate that pathological changes may occur in any part of the myocardium in patients with myotonic dystrophy.

Adult↗
PubMed1996

Recovery of Deinococcus radiodurans from radiation damage was enhanced under microgravity.

Effect of microgravity on recovery of bacterial cells from radiation damage was examined on the IML-2 mission in 1994 using extremely radioresistant bacterium Deinococcus radiodurans. The cells were lyophilized and exposed to 60Co gamma-rays with doses 2 to 12 kGy before the space flight. At the end of the mission, the cells were mixed on board with liquid nutrient medium to allow the cells to start recovery process from the radiation damage. Afterwards the cells were stored at 4 degrees C until landing. The influence of cosmic radiation was negligible, because total absorbed dose of space radiation measured during the mission was less than 2 mGy and this bacterium does not decrease its viability after both gamma-rays and high-LET heavy charged particles irradiation with doses up to 5 kGy. The survival of the cells incubated in space increased significantly compared with the ground controls, suggesting that the recovery of this bacterium from radiation damage was enhanced under microgravity.

Colony Count, Microbial↗
PubMed1996

Effect of mitochondrial and/or cytosolic glycerol 3-phosphate dehydrogenase overexpression on glucose-stimulated insulin secretion from MIN6 and HIT cells.

The glycerol phosphate shuttle consists of FAD-linked mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) and its cytosolic NAD-linked isoform (cGPDH). Impaired mGPDH activity has recently been suggested to be one of the primary causes of insulin secretory defects in beta-cells. We found that mGPDH and cGPDH activities in MIN6 cells are comparable to those of isolated islets and higher than those in HIT cells by eightfold and threefold, respectively. Therefore, we selected the MIN6 cell line as a beta-cell model with normally regulated insulin secretion and normal shuttle enzyme activities and the HIT cell line as a beta-cell model with impaired insulin secretion and lower activities of these enzymes. The role of these dehydrogenases in glucose-stimulated insulin secretion was addressed by examining the effects of overexpression of mGPDH and/or cGPDH via recombinant adenoviruses in these cells. Infection with recombinant adenovirus with a cDNA encoding the Escherichia coli beta-galactosidase gene resulted in expression of its gene in 90% of MIN6 and HIT cells. Infection with a recombinant adenovirus with mGPDH cDNA (Adex1CAmGPDH) caused 2.1-fold and 5.7-fold increases in dehydrogenase activity as compared with those of control MIN6 and HIT cells, respectively. Infection with a recombinant adenovirus with cGPDH cDNA (Adex1CAcGPDH) caused a more than 50-fold increase in activity in both cell lines. Glycerol phosphate shuttle flux, as estimated by [2-3H]glycerol conversion to [3H]H2O, was increased to 120-130% by infection with Adex1CAmGPDH, but not with Adex1CAcGPDH infection, in both MIN6 and HIT cells. No further increase in flux through the glycerol phosphate shuttle was detected when the cells were infected with Adex1CAmGPDH together with Adex1CAcGPDH. Furthermore, neither [U-14C]glucose oxidation nor the insulin secretory response to glucose was affected in either cell line. Thus, mGPDH abundance in MIN6 and HIT cells is not directly related to their insulin secretory capacity in response to glucose, and reduced expression of mGPDH is not the primary cause of abnormal insulin secretory responses in HIT cells. The present data indicate that the emerging hypothesis pointing to mGPDH deficiency as a possible cause of NIDDM needs to be carefully evaluated.

Adenoviridae↗
PubMed1996

An investigation of the psychometric properties of the 26 item Toronto Alexithymia Scale in a Japanese culture.

We investigated the psychometric properties of the Japanese version of the 26 item Toronto Alexithymia Scale in a Japanese culture, testing a sample of 1,008. The validity and reliability of this Japanese version were suggested by significant correlations with the Beth Israel Hospital Psychosomatic Questionnaire and estimates to test-retest and internal consistency. These results suggest that this version may be suitable for Japanese populations. Although alexithymia scores were correlated negatively with increasing age, the result, based on the large sample, seems to be of minimal significance.

Adult↗
PubMed1996

Dose-dependent effect of niceritrol on plasma lipoprotein-a.

Lipoprotein-a, Lp(a), is a variant form of low density lipoprotein (LDL) that contains apolipoprotein-a, whose structure has 75-85% homology with plasminogen. Elevated plasma levels of Lp(a) are considered to be one of the independent risk factors for cardiovascular disease. We studied the effects of niceritrol, a nicotinic acid derivative, on plasma Lp(a) levels in 72 patients with hypercholesterolaemia. The dose of niceritrol was increased every 4 weeks, from 750 to 1500 and then to 2250 mg day-1. The final dose was adjusted to obtain a plasma cholesterol level less than 5.69 mmol l-1. Niceritrol led to significant decreases in plasma levels of median Lp(a), from 16.1 mg dl-1 (interquartile intervals, 8.7 to 32.8) to 11.1 mg dl-1 (interquartile intervals, 6.6 to 21), the mean reduction rate being 17.6%. In the group with pretreatment Lp(a) levels of over 20 mg dl-1, Lp(a) decreased by 10.0, 22.0 and 31.8% at the doses of 750, 1500, and 2250 mg day-1, respectively. In the group with levels less than 20 mg dl-1, only the dose of 2250 mg day-1 was effective in the reduction of Lp(a). The results suggest that the reduction of Lp(a) was dependent on the dose of niceritrol and on the pretreatment level of Lp(a). In conclusion, niceritrol is effective, in a dose-dependent manner, for reducing Lp(a) levels.

Aged↗
PubMed1996

[Anemia in elderly patients with malignant tumors].

Complications, prognosis, and efficacy of treatments were retrospectively studied in elderly patients, some of whom had lung, stomach, colon, pancreatic, and liver cancers. Hemoglobin concentration and characteristics of erythrocytes were measured for up to sixty months. Eighty-eight patients died of cancer, and malignant tumors were detected before death in 57. The average survival periods were 11 months for patients with gastric cancer. 9 months for those with colon cancer, and 7 months for those with lung cancer. Malignancies of the digestive organs and lung were often detected in elderly patients with anemia. In elderly people who were without cancer for more than 78 months the hemoglobin concentration did not change significantly, but in those with a malignancy the hemoglobin concentration continuously decreased. Patients with colon cancer who were given blood transfusions survived longer than those who were not given the transfusions, but the same was not true of patients with gastric or lung cancers. Iron therapy, however, was generally effective in patients with malignant tumors of the gastrointestinal tract. Among those who were near death, the red cell distribution widths differed significantly between patients with different types of carcinomas, but differences in mean corpuscular hemoglobin and in mean corpuscular volume were not statistically significant. In conclusion, hemoglobin concentration and characteristics of erythrocytes should not be neglected in the diagnosis and treatment of cancers in the elderly.

Aged↗
PubMed1996

[Sociomedical study of centenarians in Nagoya City].

The purpose of this study was to assess the background to the longevity of 36 centenarians in Nagoya city and to compare 14 institutionalized centenarians out of those 36 with 202 individuals in the 70-99 age group in our special nursing home, particularly with regard to blood chemistry and immunity tests. The reasons for their social longevity in terms of profile appeared to be attention to eating habits, abstention from smoking and drinking, occupations with adequate exercise. The incidence of dementia was 65.6% among them. We evaluated centenarians from the viewpoint of Hasegawa's Dementia Scale (HDS) and comprehensive functional assessment of the elderly consisted of the revised version of Hasegawa's Dementia Scale (HDSR), and examination of activity of daily living (ADL), physical perception, and social life. All were positively associated. Thus centenarians independent of physical assistance demonstrated significantly higher systolic blood pressure, and respective scores for HDS, HDSR, ADL, physical perception and social life than their dependent counterparts, were less likely to be institutionalized and suffered from fewer disorders. In particular none were diagnosed as positive for cerebral hemorrhage, infarction and dementia. Age demonstrated significant positive or negative correlation with the following values in blood chemistry and immunity tests: blood cell counts, hemoglobin concentration, hematocrit value, albumin, total protein, total cholesterol, low density lipoprotein cholesterol, creatinine, blood cell nitrogen, uric acid, helper T cell, and IgA immunoglobulin.

Activities of Daily Living↗
PubMed1996

[Changes in erythrocyte structure and in platelets in elderly patients with disseminated intravascular coagulation].

We measured the platelet distribution width, the mean platelet volume, the volume percentage of platelets, and the platelet-to-large-cell ratio in 15 elderly patients with disseminated intravascular coagulation (DIC). Peripheral venous blood mixed with ehtylenediaminetetraacetic acid was analyzed with a Sysmex E-4000 analyzer. The underlying diseases were sepsis, pneumonia, pyelonephritis, and other inflammatory diseases. The mean duration of survival from the onset of DIC was 16.9 +/- 23.9 days. The distribution of red cell sizes before the onset of DIC did not differ significantly from that in patients without DIC, but fragmentation of erythrocytes on blood films was more common in the early stage of DIC (p < 0.01). Before the onset of DIC, the two groups did not differ significantly in the frequency of giant platelets on blood smears. At the onset of DIC, the platelet distribution width, the mean platelet volume, and the platelet-to-large-cell ratio were significantly higher than in patients without DIC. The concentration of glutamic-oxaloacetic transaminase and those of other serum enzymes did not change significantly, but the serum creatinine concentration and the blood urea nitrogen level increased as the platelet-to-large-cell ratio increased. No significant relation was evident between the levels of serum C-reactive protein and creatinine, between the platelet-to-large-cell ratio and the mean volume of red blood cells, or between the platelet-to-large-cell ratio and the distribution of red cell sizes. These data suggest that studies of platelets are more useful in the diagnosis of DIC at early stages of impaired organ function than are other indicators of inflammation such as the level of C-reactive protein.

Aged↗
PubMed1996

[Acute myocardial infarction with idiopathic thrombocytopenic purpura in an elderly patient].

A 71-year-old woman complained of gingival bleeding and epistaxis, and was given a diagnosis of idiopathic thrombocytopenic purpura. She was successfully treated with orally administered prednisolone and azathioprine. She experienced a relapse when she was 77 years old, and immunosuppressive therapy was not effective. Platelet transfusion was performed. She died because of massive gastrointestinal bleeding. An infarct was found in the left anterior part of the myocardium at autopsy. Disseminated intravascular coagulation was not detected on pathological investigation. Abnormal platelet aggregation may be important in the pathogenesis of thrombotic disease in thrombocytopenia.

Aged↗
PubMed1996

High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia.

We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.

Antigens, CD↗
PubMed1996

[Malignant lymphoma and EBV].

Epstein-Barr virus (EBV), a DNA virus of the herpes virus family can infect and transform resting human B lymphocytes in vitro. EBV was originally considered to be a possible causative agent of African Burkitt's lymphoma and nasopharyngeal lymphoepithelioma. Recently, using highly sensitive methods, such as the polymerase chain reaction (PCR) and in situ hybridization (ISH), EBV has been found to be also present in numerous human lymphoproliferative disorders, including Hodgkin's disease, anaplastic large cell lymphoma, B cell lymphoma in immunocompromised patients, peripheral T cell lymphoma, adult T cell leukemia/lymphoma, nasal lymphoma, AILD-T cell lymphoma, pyothorax-associated pleural lymphoma, and angiocentric T/NK cell lymphoma. However, the EBV infection pattern and the role of EBV in each disease is not the same. We introduce the relationship between EBV and each disease found in our department, using Southern blot analysis, PCR, ISH and immunological staining.

Gene Expression Regulation, Viral↗
PubMed1996

Beta-cell loss and glucose induced signalling defects in diabetes mellitus caused by mitochondrial tRNALeu(UUR) gene mutation.

Japanese diabetic patients with diabetic mothers were screened, using peripheral leukocytes, for an A to G transition at nucleotide pair 3243, a tRNALeu(UUR) mutation of the mitochondrial gene. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegregated with the mutation, except in one young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder, in affected individuals, is a progressive impairment of insulin secretion. In accordance with this finding, the mutation was found to be highly prevalent in a diabetes mellitus subset termed slowly progressive IDDM; the mutation was identified in 3 out of 27 subjects enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic Japanese patients, who are at high risk of progressing to insulin dependence over several years. The histologic characteristics of slowly progressive insulin-dependent diabetes mellitus include substantial loss, though incomplete, of pancreatic beta-cells. Mitochondrial gene defects in beta-cells could therefore cause glucose-induced signalling defects as well as beta-cell loss. This would explain the wide range of diabetic phenotypes, from NIDDM to IDDM, in patients with this mitochondrial gene mutation.

Adult↗
PubMed1996

Modulation of insulin secretion in non-insulin-dependent diabetes mellitus by two novel oral hypoglycaemic agents, NN623 and A4166.

Two novel oral hypoglycaemic agents, NN623 and A4166, have been developed and are now in phase II clinical trial. Both agents have several common characteristics from sulphonylureas. NN623 is a stereoisomer of derivatives of benzoic acid and A4166 is also a stereoisomer of phenylalanine derivative. The predominant mechanism of the action is thought to be like sulphonylureas. Both NN623 and A4166 occupy, at least partly, a common receptor site with glibenclamide and close the ATP-dependent K+ channel. They are rapidly absorbed from the intestine and are eliminated mainly into the bile. NN623 is about 10 times more potent in hypoglycaemic action than glibenclamide and 100 times more than A4166 in terms of dosage. When 1.0 mg NN623 or 60 mg A4166 was given orally in the post-absorptive state to healthy volunteers, both agents evoked hypoglycaemia by 40 min. The duration of hypoglycaemia after NN623 was longer than after A4166 by about 1 hour. The effect of food on their bioavailability is similar. Food has marked influence on the absorption of both drugs and on their efficacy. When 1 mg of NN623 or 60 mg of A4166 was administered just before the meal, Tmax of NN623 and A4166 was 34 +/- 18 min and 18 +/- 6 min, while T1/2 was 0.64 +/- 0.12 h and 0.98 +/- 0.06 h, respectively. The postprandial rise in plasma glucose was reduced at 45 min and thereafter over 4-h after 1.0 mg NN623 and at 30 min to 90 min after 60 mg A4166. Plasma insulin levels rose more than those after placebo from 30 to 90 min after NN623 and at 20 to 40 min after A4166. Both agents stimulated insulin release much more in the postprandial than in the fasting state. There was no difference in the bioavailability after 5 or 7 days of administration. However, when administered immediately after the meal, the absorption of both drugs was delayed and the rise in plasma absorption was not suppressed until 60 min after the meal. Both fasting and postprandial hyperglycaemia were reduced after 1 to 4 weeks of premeal treatment with 0.5 mg NN623 or 60 mg A4166 in subjects with NIDDM. Plasma glucose levels were decreased over 4 h after NN623 and over 1 h after A4166. The meal-induced insulin response was almost doubled by NN623 over 2 h and 1 h by A4166. There was no difference in the bioavailability after breakfast between the first and last administrations of both drugs. In conclusion, a rapid rise in plasma insulin levels is associated with the suppression of postprandial hyperglycaemia.

Administration, Oral↗
PubMed1996

[Insulin release kinetics and insulin sensitivity in impaired glucose tolerance].

This review describes recent studies which have assessed early metabolic alterations in IGT. Several studies showed decreases in the initial insulin release in response to glucose without significant changes in insulin sensitivity in IGT. Fasting plasma proinsulin-like molecules were higher and the pulsatile insulin secretion was altered too. On the other hand, several studies has proposed that insulin resistance develops first. They have demonstrated that absolute day-long plasma insulin concentrations in response to glucose are not lower than normal and glucose metabolism is impaired. These results are still inconclusive. The physiological role of the initial insulin secretion may be clarified, while the effects of the subtle differences in age, obesity, fat distribution, and ethnic groups between IGT and NGT on insulin resistance may be differentiated.

Aging↗
PubMed1996

Primary cutaneous T-cell lymphoma with an angiocentric growth pattern: association with Epstein-Barr virus.

We report a case of primary cutaneous T-cell lymphoma with an angiocentric growth pattern. The lesions had been confined for about 2.5 years to the skin, but there had been a gradual progression of the disease both clinically and histologically. We assessed the neoplastic clonality and the presence of Epstein-Barr (EB) virus genome in this case using immunohistochemistry, Southern blot analysis and RNA in situ hybridization. Clonal proliferation of a CD4+ alpha beta T-cell phenotype was demonstrated. In addition, the clonal population harboured the EB virus genome, which suggested that the virus was involved in the pathogenesis of the disease. The patient has remained in remission for 10 months, and has received treatment with cyclophosphamide and prednisone.

Adult↗
PubMed1996

Detection of human T-cell lymphotrophic virus type I in archival tissue specimens.

OBJECTIVE AND DESIGN: To develop a method for the detection of human T-cell lymphotropic virus type I (HTLV-I) in archival biopsy specimens. A polymerase chain reaction-based gene amplification method was developed to detect HTLV-I proviral DNA in paraffin-embedded specimens. The specificity of the polymerase chain reaction products was controlled by Southern blot analysis using a nested oligonucleotide probe and by nucleotide sequencing. The nucleophosmin gene and the T-cell receptor-gamma gene were used as controls for the integrity and adequacy of total DNA and T-cell DNA, respectively. This study was conducted with patients referred to an academic medical center. Biopsy specimens were obtained from lesional skin or lymph node from Japanese patients with HTLV-I seropositive adult T-cell leukemia/lymphoma. The main outcome measure was the ability to detect HTLV-I pX region proviral DNA. RESULTS: Comparative analysis of DNA extracted from fresh samples of the HTLV-I infected MT4T-cell line demonstrated that formalin fixation and paraffin embedding resulted in a 100-fold reduction in sensitivity of the assay. Nevertheless, HTLV-I pX sequences were still readily detectable in paraffin-embedded samples of MT4 T cells and adult T-cell leukemia/lymphoma specimens. Both formalin and B5 fixation were suitable for the assay that was 100% specific for HTLV-I-infected tissues. CONCLUSIONS: The use of this method should greatly facilitate investigation of the role of HTLV-I in human diseases by allowing analysis of a wide variety of archival tissue specimens. In addition, the controls designed for the current study can be used in a variety of other polymerase chain reaction-based studies of T cells to ensure against false-negative results caused by DNA degradation or inadequate T-cell density.

Adult↗
PubMed1996

[Development variations of the R. anastomoticus cum a. lacrimali in Japanese].

This report describes the developmental variations of the R. anastomoticus cum a. lacrimali in 150 Japanese cadavers (300 orbits). The orbits were classified into seven types on the basis of the diameters, directions and anastomoses of the ophthalmic artery (OA), lacrimal artery (LA) and R. anastomoticus cum a. lacrimali (RAL). The definitions and frequencies of the seven types were as follows. 1) Normal type: The diameter of the RAL was smaller than that of the LA (240 orbits, 80.0%). 2) Thin type: The diameter of the RAL was comparable to or larger than that of the LA, but smaller than that of the OA (19 orbits, 6.3%). 3) Thick type: The diameter of the RAL was comparable to or larger than that of the OA (5 orbits, 1.7%). 4) OA type: The OA was absent or vestigial, and the blood of the orbital contents was supplied mainly by the RAL instead of the OA (1 orbit, 0.3%). 5) LA type: The LA arose from the RAL instead of the OA (23 orbits, 7.7%). 6) MMA type: The middle meningeal artery (MMA) was absent or vestigial, and the blood of the dura mater was supplied mainly by the RAL instead of the MMA (1 orbit, 0.3%). 7) Absent type: The RAL could not be found (12 orbits, 4.0%). The OA, MMA and LA types are established anomalies of the RAL that have been described anatomically and clinically. However, few studies have investigated the developmental variations of the RAL in detail. The results of this study suggest that the developmental variations of the RAL are more remarkable than reported previously.

Asian People↗