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N Fukushima

Publications and source records attributed to N Fukushima.

At least 109 records · Page 6Linked to original sources
PubMed1998

Onset age-dependent variations of three islet specific autoantibodies in Japanese IDDM patients.

The age related incidence rate of insulin-dependent diabetes mellitus shows a bimodal distribution, not only in Caucasians but also in Japanese. To evaluate the onset age-related autoimmune profile at presentation in insulin-dependent diabetes mellitus (IDDM), glutamic acid decarboxylase (GAD) autoantibody, islet cell antibody (ICA), and insulin autoantibody (IAA) were measured in 137 newly diagnosed Japanese IDDM patients with onset ages between 0-29 years. The prevalence of GAD autoantibody was significantly increased from the lowest (32%) in the 0-5 years onset age group to 75% in the 13-19 years onset age group (P < 0.05), whereas the IAA prevalence significantly decreased from the peak (48%) in the 6-12 years onset age group to 10% in the 20-29 years onset age group (P < 0.05). The ICA prevalence was increased from the lowest (32%) in the 0-5 years onset age group to the highest (53%) in the 20-29 years onset age group similar to that for the GAD autoantibody. Such results demonstrate that there was age-related autoimmune characteristics at presentation of IDDM in Japanese as well as in Caucasians.

Adolescent↗
PubMed1998

Melittin, a metabostatic peptide inhibiting Gs activity.

Some basic amphiphilic peptides are known to directly stimulate heterotrimeric GTP-binding proteins (G proteins). Mastoparan and melittin are known to stimulate Gi activities. Here, we found melittin inhibited guanine nucleotide-dependent adenylyl cyclase activity in synaptic membranes of the rat cerebral cortex. However, in insect cell membranes overexpressing specific heterotrimeric G proteins using baculovirus expression system, melittin showed unique effects different from those by mastoparan on G protein activities. This peptide markedly stimulated Gi1 and G11 activities, whereas it did inhibit Gs activities. Kinetic studies revealed that the inhibition of Gs activity by melittin is attributed to the inhibition of GDP release in exchange for added guanine nucleotides (or the association of guanine nucleotides). Thus, melittin may be the first metabostatic peptide inhibiting G protein (Gs) activity, and both mechanisms through the stimulation of Gi and inhibition of Gs might be involved in the melittin-induced inhibition of adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1998

Low-density induced apoptosis of cortical neurons is inhibited by serum factors.

1. We investigated the survival of neurons under serum-free conditions without any exogenous signal molecules, using primary cultures of rat cerebral cortex. 2. Survival activity, measured with Alamar Blue, showed a cell density dependency under serum-free conditions. 3. The addition of fetal bovine serum suppressed the apoptotic cell death accompanied by DNA-laddering and fragmentation specific in low-density cultures, resulting in the disappearance of the cell density dependency of survival. 4. These findings suggest that serum factors may substitute for endogenous survival factors from cortical neurons in high-density cultures.

Animals↗
PubMed1998

Localization of nitric oxide synthase in human nasal mucosa with nasal allergy.

Nitric oxide (NO) plays an important role in the regulation of upper respiratory function. In the nasal cavity, the concentration of NO in the air in patients with untreated allergic rhinitis is higher than that in normal individuals. NO is produced by the action of NO synthase (NOS) using L-arginine as a substrate. To investigate the expression of NOS in human nasal mucosa, histochemical staining for NADPH diaphorase and immunohistochemical staining for NOS isoforms were carried out in nasal inferior turbinate mucosa from patients with nasal allergy. Those without nasal allergy served as controls. NADPH diaphorase histochemical study revealed that NOS was expressed in the nasal epithelium, submucosal glands, nerve fibres and the endothelium in specimens of both allergic and control groups. Immunoreactivity to endothelial NOS (eNOS) was localized to epithelial and endothelial cells in both allergic and control groups. In some specimens in both groups, nerve fibres around submucosal glands stained positively for eNOS. Immunoreactivity to eNOS, however, was slightly stronger in the epithelia of the allergic group than in those of the controls. Immunoreactivity to inducible NOS (iNOS) was localized to epithelial cells, endothelial cells, nasal glands and inflammatory cells. The staining of epithelial cells and inflammatory cells was more marked in the allergic group than the controls. These findings may suggest that the greater amounts of NO in the nasal air of patients with allergic rhinitis are mainly induced by iNOS activity.

Case-Control Studies↗
PubMed1998

Analysis of K-ras oncogene mutation directly applied to atypical cell clusters on cytologic smear slides of bile and pancreatic juice.

To develop an objective reference for the cytological evaluation of atypical cells in bile and pancreatic juice, we analyzed K-ras oncogene mutation in atypical cell clusters, which were collected directly from cytological smear slides; 50 samples (cell clusters) from 31 smear slides of 21 patients with carcinomas of the pancreatic head region, and nine samples from eight cases of benign disease. These cell clusters (5-1000 cells/cluster) were selectively suspended in buffer containing proteinase K, and subjected to DNA extraction. K-ras codon 12 mutation was determined by polymerase chain reaction amplification, followed by digestion with BstNI. The K-ras gene was amplified in 20 of 21 cases with carcinoma (34/50 samples), and in seven of eight cases with non-neoplastic disease (8/9 samples). Among the cases of which primary tumors showed K-ras mutation, amplification was successful in 10 of 11 cases; mutation was demonstrated in three of seven cases with cytologically atypical cells (4/11 samples), and in three of three cases with cytologically malignant cells (5/7 samples). No mutation was identified in the 10 cases of carcinoma without K-ras mutation (0/15 samples), or in eight cases of non-neoplastic disease (0/8 samples). Cytological details could be comparatively evaluated between atypical cell clusters with or without mutation on the same smear slides in two cases. This type of direct analysis of atypical cell clusters may be useful in the self-assessment of cytological diagnosis of bile and pancreatic juice.

Adenocarcinoma↗
PubMed1998

Differential expression of laminin receptors in human hepatocellular carcinoma.

BACKGROUND: Laminin receptors are involved in cell-extracellular matrix interactions in malignant cells that show invasion and metastasis. Hepatocellular carcinoma frequently shows early invasion into blood vessels, and intrahepatic and extrahepatic metastases. However, the role of laminin receptors in hepatocellular carcinoma is unknown. AIMS: To examine the expression of mRNA for laminin receptors and their isoforms in hepatocellular carcinoma. METHODS: The expression of several laminin receptors, including alpha1 integrin, alpha6 integrin and its isoforms alpha6A and alpha6B, beta1 integrin and its isoforms beta1A and beta1B, and 32kD/67kDa laminin binding protein was examined in human hepatocellular carcinomas and non-cancerous liver tissues using the reverse transcription polymerase chain reaction. RESULTS: Alpha6 Integrin, beta1 integrin, and laminin binding protein showed notably increased expression in hepatocellular carcinoma, compared with non-cancerous liver tissue, although the alpha1 integrin did not show a significant change. Furthermore, beta1B integrin, a splicing variant of beta1 integrin, was overexpressed in hepatocellular carcinoma while the beta1A integrin isoform did not show significant changes between hepatocellular carcinoma and surrounding non-cancerous liver tissue. CONCLUSIONS: The differential upregulation of laminin receptors and their splicing isoforms was shown in hepatocellular carcinoma, suggesting that certain laminin receptors and their isoforms may be involved in the development and progression of hepatocellular carcinoma.

Aged↗
PubMed1998

Descriptive epidemiology of IDDM in Hokkaido, Japan: the Childhood IDDM Hokkaido Registry.

OBJECTIVE: To identify the incidence of IDDM with regard to sex, age, family history of diabetes, season, and 5-year period of childhood IDDM among children ages 0-14 years from a population-based epidemiological study in Hokkaido, Japan, from 1973 to 1992. RESEARCH DESIGN AND METHODS: Registration of all new IDDM cases in Hokkaido was conducted by the Childhood IDDM Hokkaido Registry Study Group from 1973 to 1992. The cases were selected from among 1) patients who were admitted to the member hospitals of the study group, 2) patients who answered a questionnaire distributed to hospitals and diabetic clinics throughout Hokkaido, and 3) patients whose cases were recorded in free-treatment medical records of urban and rural districts. The case ascertainment rate was estimated to be 100%. Differences in incidence with regard to sex, age, family history of diabetes, season, and year period were analyzed by the Poisson regression analysis by GENMOD. RESULTS: During the 20-year period studied, 396 cases (181 boys, 215 girls) of abrupt-onset IDDM were registered. Statistically significant differences in annual incidence were found according to sex (female), age (8-14 years), history (having no diabetes in family), season (spring), and 5-year period. CONCLUSIONS: This is the first population-based, long-term epidemiological study of childhood IDDM from Japan. We observed a significantly higher annual incidence (per 100,000/year) of IDDM in female subjects (1.81), older age-groups (2.25 for 8-14 years), subjects with no family history of diabetes (1.26), diabetes onset in the spring (2.20), and an increased trend over the 20 years. In addition, the heterogeneity of IDDM among Japanese children needs to be elucidated.

Adolescent↗
PubMed1998

[Decongesting effect of tramazoline on nasal airway patency and nasal symptoms as evaluated by acoustic rhinometry: an objective study in 30 allergic and six non-allergic subjects].

In this prospective clinical study, we investigated the effect of the nasal decongestant tramazoline on nasal airway patency in 30 subjects with perennial nasal allergy to housedust mites and in six non-allergic volunteers who served as controls. The allergic subjects were further subdivided into groups, the severe group and the moderate group, according to the level of specific IgE. We used acoustic rhinometry as an objective method, and the nasal cavity volume (NCV) and the minimum cross-sectional area (MCA) were measured before and 10 minutes after nasal spraying. Before mucosal decongestion, the average NCV in the severe group was 5.94 cm3, which was significantly lower than those in the other two groups: 7 cm3 in the control group and 8.13 cm3 in the moderate group, respectively (P = 0.02). A more significant difference was found when the first 3-cm area of the NCV was evaluated (P = 0.009). Pharmacologic decongestion caused an increase in nasal patency by 54% from the baseline NCV values in the control group, 38% in the moderate group and 48% in the severe group. There was no significant difference among the three groups. Changes in nasal symptoms were also determined by questionnaire. The degree of improvement in subjective nasal congestion was more pronounced in the allergic groups than in the control group.

Acoustics↗
PubMed1998

[Reoperation after the Fontan operation in single ventricle and tricuspid atresia].

The outcome of the Fontan-type operation for complex heart disease has been significantly improved, and low morbidity and mortality rates are reported. However, some problems still occur in late follow-up, including ventricular failure, hepatic congestion, supraventricular arrhythmia, cerebrovascular events, exercise intolerance, and residual or new cardiac lesions. Reinterventions after the Fontan-type operation for complex cardiac defects in 43 patients are reviewed. In addition to catheter interventions, the main reasons for reoperation were subaortic stenosis, pulmonary artery and vein obstructions, and interatrial shunt. Early intervention, particularly for subaortic obstruction, is recommended, and the Damus-Kay--Stansel anastomosis appears to be the procedure of choice. Reoperation was required in 6 of the 43 patients, with one operative death. The total event-free survival rate after 10 years of follow-up was 53%. The need for reoperation appears to be reduced after performing the total cavopulmonary shunt procedure compared to that after atriopulmonary connection. However, late arrhythmia remains a significant problem in this group of patients, and further assessment of the results of reintervention for arrhythmia is required.

Fontan Procedure↗
PubMed1997

Safety and kinetic properties of a humanized antibody to human interleukin-6 receptor in healthy non-human primates.

A monoclonal antibody, hPM-1, was constructed by grafting the complementarity determining regions to human interleukin-6 (IL-6) receptor, raised in mouse, onto a human antibody backbone (humanized antibody). It is expected to be useful as a therapeutic agent for IL-6-related diseases such as multiple myeloma. To investigate the toxicological and kinetic properties of hPM-1 preliminarily, normal cynomolgus monkeys, which showed cross-reactivity with hPM-1, were intravenously administered with hPM-1 at doses of 0 (vehicle), 4 or 40 mg/kg once a week for 13 weeks. Upon toxicological examination, there were no changes in clinical signs, food consumption, body weights, urinalyses, body temperatures, electrocardiograms, hematological and biochemical parameters including blood platelet counts, serum levels of immunoglobulin G and C-reactive protein, and pathological findings. In a kinetic study, serum concentrations of hPM-1 showed a linearity between doses of 4 and 40 mg/kg. The serum concentrations, even at a dose of 4 mg/kg, were maintained at a high enough level to inhibit the IL-6 functions throughout the period of the study. Concentrations of hPM-1 in bone marrow were almost equal to those in serum. The antibodies against hPM-1 were detected only in one of four monkeys receiving hPM-1. This study suggests that blockage of the IL-6 receptor by hPM-1 does not induce any influence on a healthy living body, and hPM-1 is not toxic under the conditions of this investigation.

Animals↗
PubMed1997

Myocardial histological changes in dilated cardiomyopathy during a long-term left ventricular assist device support.

As the myocardium in patients with dilated cardiomyopathy (DCM) is deteriorating progressively, resulting in a decrease in left ventricular function, patients with end-stage DCM may require implantation of a left ventricular assist device (LVAD) unless they undergo heart transplantation. Although LVAD has been reported to provide excellent hemodynamic support, no data are currently available about the effects of long-term LVAD support on the myocardium in patients with DCM. We describe two patients with end-stage DCM who underwent LVAD implantation and were supported with LVAD for 524 and 245 days, respectively. Serial myocardial biopsies showed increases in myocardial cell diameter and intercellular fibrosis, despite excellent hemodynamic support by LVAD. These data suggest that the myocardium in patients with end-stage DCM deteriorates progressively, even if the pre-load of the left ventricle is reduced by LVAD.

Adult↗
PubMed1997

A case of inflammatory pseudotumour of the common bile duct.

Inflammatory pseudotumour of the common bile duct (CBD) is extremely rare. A 58-year-old Japanese female without choledocolithiasis underwent pancreatico-duodenectomy for constriction of the middle lower region of the CBD. A submucosal tumour protruding into the CBD, was histologically inflammatory consisting of fibroblastic cells, collagen fibres and myxoid stroma with chronic inflammatory cells. This lesion was surrounded by an irregular fibrosclerosing lesion with obliterative phlebitis which involved the neighbouring pancreas and lymph nodes. Clonal analysis of the tumour by polymerase chain reaction analysis of X chromosome inactivation patterns, confirmed the polyclonal nature of the lesion. Immunohistochemically, the fibroblastic cells in both lesions had the same phenotype [vimentin (+), desmin (-), muscle-specific actin (-) and CD34 (+)] suggesting that these lesions with different histological features represent zonation of the same inflammatory process. The outer lesion extended irregularly into adjacent pancreatic tissue and lymph nodes. This fact made it difficult to differentiate this from a malignant lesion, even if frozen sections contained no atypical cells.

Antigens, CD34↗
PubMed1997

The contribution of Na+/H+ exchange to ischemia-reperfusion injury after hypothermic cardioplegic arrest.

BACKGROUND: Na+/H+ exchange has been reported to be one of the key mechanisms in myocardial ischemia-reperfusion injury. However, the effect of temperature on Na+/H+ exchange is not fully understood. METHODS: Sodium-propionate-induced cell swelling, an indicator of the function of the Na+/H+ exchanger, was measured in rat thymic lymphocytes. A Langendorff perfused rat heart model was also employed to investigate the effect of the pharmacologic inhibition of Na+/H+ exchange on the recovery of cardiac function after hypothermic ischemia. This was done using FR168888, an inhibitor of Na+/H+ exchange. RESULTS: In the in vitro study, rat lymphocytes were observed to swell at 17 degrees, 22 degrees, and 27 degrees C, indicating that the Na+/H+ exchanger remains functional even under hypothermic conditions. FR168888 was found to significantly inhibit Na+/H+ exchange-induced cell swelling, even at 17 degrees C. In the in vivo study, pretreatment with FR168888 was found to prevent the deterioration of ventricular function, even after 5 hours of hypothermic cardioplegic arrest. This was associated with a decrease in the reperfusion-induced elevation in resting tension. CONCLUSIONS: These results suggest that Na+/H+ exchange in the heart still occurs, even under hypothermic conditions, and contributes to reperfusion injury, even after hypothermic cardioplegic arrest.

Animals↗
PubMed1997

Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases.

Clinicopathological features of 28 patients with intraductal papillary tumor (IDPT) and 10 patients with mucinous cystic tumor (MCT) of the pancreas were studied. Both IDPT and MCT showed papillary projections of the epithelium with abundant mucus secretion in the ectatic ducts or cystic spaces. The patients with IDPT comprised 19 men and 9 women with a mean age of 64.9 years. Three fourths of the IDPTs were located in the pancreatic head, and the mean tumor size was 3.5 cm. Local recurrence was observed in one patient, but none died of IDPT. In contrast, all patients with MCT were women, with a mean age of 49.4 years. None of the MCTs arose in the head, and the mean tumor size was 7.1 cm. One patient died of MCT, but all of the others survived without recurrence. Eight IDPTs and three MCTs showed invasion into the surrounding pancreatic tissue. Muconodular infiltration was mainly observed in five IDPTs and one MCTs and tubular infiltration in three IDPTs and two MCTs. A characteristic histological finding associated with the muconodular infiltration in IDPT was subepithelial "mucin droplets" that appeared to represent a change in polarity of mucus secretion. The formation of such subepithelial "mucin droplets" may be the initial step of muconodular infiltration in IDPT. Muconodular infiltration in IDPT appears different morphologically and biologically from the mucinous carcinoma subtype of conventional invasive ductal carcinoma.

Adenocarcinoma, Papillary↗
PubMed1997

Saccular aneurysm in the right-sided aortic arch: a successfully corrected case.

We report the surgical treatment of a rare case of true aortic aneurysm in a right-sided aortic arch. A 49-year-old female patient with obstructive respiratory problems demonstrated a true aneurysm with a diameter of 58 mm located at the right-sided aortic arch between the right carotid artery and right subclavian artery. Surgery was successfully performed by replacing the arch including the aneurysm with a prosthetic graft. The positions of true aneurysms in the right-sided aortic arch can be divided into two subtypes: first, the transverse arch between the right carotid artery and right subclavian artery, and second, the base of the subclavian artery, the Kommerell's diverticulum. The region is informative for consideration of the surgical approach toward aneurysms of this entity.

Angiography, Digital Subtraction↗
PubMed1997

Application of image analysis and neural networks to the pathology diagnosis of intraductal proliferative lesions of the breast.

We studied whether a computer-assisted system using a combination of data collection by image analysis and analysis by neural networks can differentiate benign and malignant breast lesions. Forty-six intraductal lesions of the breast were studied by pathologists and by the computer-assisted system. Histological evaluation was performed independently by three pathologists, and the lesions were classified into pathologically malignant (n = 12), undetermined (n = 13), and benign (n = 21). Computerized nuclear image analysis was performed using the CAS200 (Cell Analysis Systems, Elmhurst, IL) system to obtain data on nuclear morphometric and textural features. A neural network was constructed using the morphometric and texture data obtained from teaching cases of malignant and benign lesions. Then data for unknown cases were classified by the constructed neural network into neural network-malignant (n = 11), -undetermined (n = 5), and -benign (n = 30). The agreement rate between the diagnosis by pathologists and judgment by the computer-assisted system was 75%, excluding pathologically undetermined lesions. There were four false-negative but no false-positive results. False-negative cases had nuclei that were quite different from those of the teaching cases. The agreement rate obtained using either morphometric data or texture data only was lower than that using a combination of both. Selection of appropriate teaching data and incorporation of both morphometric and textural parameters seemed important for obtaining more accurate results. The present data suggest that development of a computer-assisted histopathological diagnosis system for practical use may be possible.

Breast↗
PubMed1997

'Ovarian-type' stroma of pancreatic mucinous cystic tumor expresses smooth muscle phenotype.

'Ovarian-type' stroma of nine mucinous cystic tumors (MCT) of the pancreas, six cystadenomas and three cystadenocarcinomas, were studied immunohistochemically. Most of the spindle cells of the 'ovarian-type' stroma were positive for smooth muscle actin and desmin, but were negative for S-100 protein, cytochrome P450 19 and CD34. Similar stroma with smooth muscle differentiation has been described in hepatobiliary MCT. Embryologic similarity between the pancreas and liver suggests a closely related origin of MCT in both organs.

Actins↗