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Biomedical subjects

N Yamaguchi

Publications and source records attributed to N Yamaguchi.

At least 91 records · Page 5Linked to original sources

Allelic imbalance on chromosome 18 in neuroblastoma.

We previously demonstrated that chromosome 18 is frequently deleted in neuroblastoma. To further elucidate the role of chromosome 18 deletions in the development of neuroblastomas we examined 82 cases of neuroblastomas for allelic imbalance (AI) at 17 loci on chromosome 18 to define the common region of AI in neuroblastoma. AI at one or more loci on chromosome 18 was detected in 18/82 (22%) cases. AI on 18q was detected in 17/82 (21%) cases, whereas AI on 18p was detected in 4/82 (5%) cases. There was a distinct common region of AI at 18q21.1 between the D18S363 and D18S858 loci. In addition, cases 16 and 53, which did not show AI at 18q21.1, showed AI at 18pter-q12.3 between the D18S52 and D18S36 loci, indicating that another common region of AI may exist on chromosome 18. AI on chromosome 18 did not significantly correlate with any clinicopathological findings of patients with neuroblastoma. The common region of AI at 18q21.1 includes the DCC gene but not the Smad2 and Smad4 genes. However, our previous studies together with the present study indicated that the incidence of DCC mutation is much less than that of AI at 18q21.1 in neuroblastoma. These results indicate that novel tumour suppressor genes involved in the development of neuroblastoma are present at 18q21.1, and possibly at 18pter-q12.3.

Blotting, Southern↗

Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups.

A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substituted A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs from KW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-2189.

Animals↗

Cell membrane changes of structure and function in protein kinase inhibitor-induced polyploid cells.

Exogenous cyclic AMP has been thought to be a chemical without marked pharmacological effect until now, as it is not capable of penetrating the cell membrane in most eucaryotic cells. The present study obtained results consistent with those of most previous studies, showing that exogenous cyclic AMP itself did not interfere with the cell cycle even at the high dose of 100 microM. However, it was found that K252a, a potent inhibitor of protein kinases including protein kinase C, induced DNA re-replication, i.e. DNA synthesis at a elevated DNA ploidy in cells that had not undergone cytokinesis (leading to polyploidization), and that exogenous cyclic AMP markedly potentiated the K252a-induced polyploidization at a very low dose similar to the effective dose of membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP. These findings suggested that the cell membrane changed during the formation of polyploid cells. This supposition was confirmed by scanning electron microscopy to observe structural changes and by determination of cellular attachment to investigate functional changes.

Animals↗

Viability of Escherichia coli O157:H7 in natural river water determined by the use of flow cytometry.

The enzymatic activity and viability of Escherichia coli O157:H7 in natural river water was determined by flow cytometry. River water was collected at two sites (an agricultural area and an industrial area) on the Aigawa River (Osaka, Japan). To facilitate estimation of the physiology of E. coli O157 in natural river water, bacterial cells in the water were stained with 6-carboxyfluorescein diacetate (6CFDA) and propidium iodide (PI). The cells were sorted into two populations, using a flow cytometer, based on their esterase activity. Each population was stained with E. coli O157:H7 fluorescent antibody (FA), and E. coli O157:H7 cells were observed in the esterase-active population. River water samples collected at the same points were incubated with yeast extract containing antibiotics to prevent cell division, and bacterial cells in the incubated samples were stained with PI and FA. Escherichia coli O157:H7 existed in both the viable (elongated and/or fattened) and inactive bacterial population determined by flow cytometry. These results indicate that E. coli O157:H7 may retain metabolic activity and growth potential in the natural aquatic environment.

Colony Count, Microbial↗

The survey of sleeping time of junior high school students: a study on the sleep questionnaire.

We investigated the questionnaire study on sleep of junior high school students to estimate the effect of excessive study hours on their sleep time in 1998. A total of 501 students answered the questionnaire. It was noted that most of the students sleep for 6-8 h on weekdays. The majority of the students of the junior high school felt that their sleep is insufficient on weekdays.

Adolescent↗

Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer's disease and Parkinson's disease.

Neurosin, a novel type of trypsin-like serine protease, has been shown to be preferentially expressed in human brain by northern blotting. We examined neurosin immunolabeling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD) and with Parkinson's disease. We also identified the expression of the mRNA for neurosin by in situ hybridization histochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The neurosin antibody stained all of the nuclei of various cell types. In neurons, there was also staining of neuronal cytoplasm, nucleoli and their processes. In AD, staining of neurons with processes was rare in the damaged areas. Some senile plaques, extracellular tangles and Lewy bodies were also positive for neurosin. Expression of the mRNA for neurosin was seen in neurons in the gray matter, and in microglial cells in the white matter. In AD, the intensity of the signal for neurosin mRNA in the gray matter was decreased compared with normal control brains. The relative levels of neurosin mRNA in AD brains, measured by RT-PCR, were lower than those in controls. These results suggest that in human brain neurosin plays various physiological roles, and that in AD this molecule, like other serine proteases, may have a role in the degradation of such substances as beta-amyloid protein.

Aged↗

Histologic and cell kinetic studies of hair loss and subsequent recovery process of human scalp hair follicles grafted onto severe combined immunodeficient mice.

To establish a model for studying human scalp hair, individually isolated hair follicles were grafted onto back skin of severe combined immunodeficient mice. Histologic changes and cell kinetics in the hair loss and subsequent recovery process were investigated. In the dystrophic stage (from day 7 to 30), all the hair shafts became dystrophic and were shed. Thickening and corrugation of vitreous membrane, apoptosis, and regression of the lower part were observed in the grafted hair follicles. 5-bromo-2'-deoxy-uridine-labeled cells were not detected in the lower end of the follicles, and keratin 19-positive cells appeared there. At the end of this stage their lower part was maximally retracted, secondary germ remained beneath the bulge, and the vitreous membrane disappeared. In the regeneration stage (from day 30 to 50), the same histologic findings as those at the end of the dystrophic stage were observed. The keratin 19-positive cells in the secondary germ, however, were replaced with keratin 19-negative and 5-bromo-2'-deoxy-uridine-labeled cells. Then, differentiation into an inner root sheath and a hair shaft began, and apoptosis was terminated. In the stable growth stage (from day 40 to at least 150), the grafted follicles were immunohistochemically and light microscopically identical with the normal anagen hair follicles except for the presence of melanin incontinence. These findings suggest that the grafted hair follicles entered into dystrophic catagen, subsequently dystrophic telogen, then returned to normal anagen follicles, and that stem cells or their close progeny in the secondary germ play an important part in the recovery process.

Animals↗

Quantitative relationship between cumulative cigarette consumption and lung cancer mortality in Japan.

BACKGROUND: Sufficient evidence has been accumulated to demonstrate the causal relationship between cigarette smoking and lung cancer risk. Therefore, the lung cancer risk of a country is supposedly determined by the amount of cigarettes consumed in the country, but this quantitative relationship has yet to be clarified at a national level. OBJECTIVE: To find the quantitative relationship between cigarette smoking and subsequent lung cancer risk at a national level. METHODS: The quantitative relationship between cigarette smoking and lung cancer mortality is formulated as a function of cumulative cigarette consumption. The formulae for ages 25-29 to 70-74 are estimated by examining the increment of the lung cancer death rate in relation to the unit increase in cumulative cigarette consumption in different birth cohorts. The validity of the quantitative relationships is then examined by comparing lung cancer deaths expected from the formulae with observed deaths in past studies. RESULTS: Cumulative cigarette consumption was found to have increased in later birth cohorts for all ages of males and females. The age-specific lung cancer death rates from 35-39 to 70-74 were found to increase in proportion to cumulative cigarette consumption. Comparison of the results with past studies showed good agreement. CONCLUSION: The change over time in the lung cancer death rate of males and females in Japan can be explained fairly well by the increase in cumulative cigarette consumption at the national level.

Adult↗

Statistical analysis of geographical features of lung cancer mortality in Japan.

BACKGROUND: There is concern about the increase in death rates from lung cancer and that it may become the leading cause of death in the near future. Considerable geographical variations exist in lung cancer mortality in Japan. It seems that the difference cannot be explained by smoking rates, although no data are available to prove this. The evidence implies some unknown risk factors in the development of lung cancer. As an alternative approach, we used geographical or demographic information according to municipality. To explore other factors in lung cancer development, the geographical features of trends in lung cancer mortality in Japan were examined using long-term data. METHODS: We summarized the 20-year municipality-specific standardized mortality ratios (SMRs) by fitting a straight line to the scatter plot of the SMR versus calendar year for each municipality, resulting in an average and a rate of change of SMR. Using the average or rate of change in the SMR as the response variable, we carried out a multiple linear regression analysis for all of Japan and a non-parametric regression analysis for the distance from the municipal office to the nearest coastline, using the ACE algorithm. RESULTS: The average SMR decreased with distance from the coastline and increased with increasing population size of the municipality. The average SMR was high at or near the coastline irrespective of the direction of the nearest coastline. CONCLUSIONS: It was considered that something related to coastline other than population size may be associated with the development of lung cancer.

Adult↗

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells, perhaps representing V beta-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS: Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells expressing several TCR V betas, especially V beta 5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION: These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Adult↗

During neonatal mechanical ventilatory support, the delivered nitric oxide concentration is affected by the ventilatory setting.

OBJECTIVE: To assess whether the delivered nitric oxide (NO) concentration is affected by a change in the ventilatory setting during neonatal mechanical ventilatory support. DESIGN: Prospective, experimental study. SETTING: Laboratory at Nagoya City University Medical School. INTERVENTIONS: This study was performed by using a pressure-limited, time-cycled, ventilatory support with a neonatal circuit and a 50-mL silicone test lung. NO in N2 gas was administrated into the inspiratory limb at a distance of 4 cm, 80 cm, or 160 cm from the Y piece connected to the adapter of an endotracheal tube. The NO concentration was measured every 0.5 sec by a chemiluminescence analyzer at the Y piece. MEASUREMENT AND MAIN RESULTS: NO concentrations were compared with each of the ventilatory settings of peak inspiratory pressure (PIP) (10-30 cm H2O), positive end-expiratory pressure (0-10 cm H2O), ventilatory flow (10, 20, 30 L/min), and ventilatory rate (30, 40, 50, 60, 70 breaths/min), respectively. The NO concentration was significantly lower when NO was added at 4 cm than at 80 cm or 160 cm from Y piece at the same ventilatory setting of PIP, positive end-expiratory pressure and ventilatory flow, respectively, (p < .01). Although the NO concentration was increased as the settled PIP level was increased (p < .01 or p < .05), it was not changed when the settled positive end-expiratory pressure level was increased. A decrease was seen in the NO concentration as the settled ventilatory flow was increased (p < .01). Lastly, the NO concentration fluctuated greatly in association with the settled ventilatory rate. CONCLUSION: The NO concentration delivered to patients is influenced by the ventilatory setting during neonatal mechanical ventilatory support.

Female↗

Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against beta1-adrenoceptor.

We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1-peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor.

Amino Acid Sequence↗

Interaction between norepinephrine release and intrarenal angiotensin II formation during renal nerve stimulation in dogs.

We examined possible interactions between intrarenal angiotensin II (ANG II) formation and norepinephrine (NE) release during renal sympathetic nerve stimulation (RNS) in anesthetized dogs. During 10 min of continuous RNS (1.5-2 Hz), the ANG II formation rates (ANG II-FR) and NE secretion rates (NE-SR) were determined at 1 and 10 min. Under control conditions, almost the same extent of increase in the NE-SR was observed at 1 and 10 min of RNS, whereas a significant increase in ANG II-FR was observed at 10 min but not at 1 min. During intrarenal arterial infusion of enalaprilat or losartan, the increase in NE-SR and reduction in renal blood flow at 10 min of RNS were suppressed, whereas the NE release and vasoconstriction responses at 1 min remained unaffected. The RNS-induced increases in ANG II-FR were completely abolished during infusion of enalaprilat. These results suggest that NE release on continuous RNS is enhanced by concomitantly formed ANG II, and this interaction depends on the time-related changes in intrarenal ANG II formation during RNS in the canine kidney.

Angiotensin II↗

Reproducibility of diagnosis and its influence on the distribution of lung cancer by histologic type in Osaka, Japan.

The histologic types of lung cancer cases diagnosed in 1979-1980 (n=799) and 1987 (n=587) were independently reviewed by two pathologists in order to investigate the reproducibility of the diagnosis of the histologic type when the WHO classification (1981) was used. The specimens from 354 surgical cases and biopsy or cytology specimens from 1032 non-surgical cases were reviewed. The inter-observer agreement was 87.9% (kappa=0.79) for surgical cases and 81.4% (kappa=0.72) for non-surgical cases. When compared to the original diagnosis, the agreement was 86.8% (kappa=0.78) for surgical and 86.4% (kappa=0.79) for non-surgical cases in 1979-1980 and the agreement was 92.8% (kappa=0.87) for surgical and 89.1% (kappa=0.83) for non-surgical cases in 1987. By histologic type, no difference in the agreement was observed except for large cell carcinoma. The distribution of histologic types after the review differed only slightly (less than 6%) from the original distribution. This suggests that in Osaka, Japan, the diagnosis based on the WHO classification (1981) had only a limited influence on the distribution of histologic types, and is not a major reason for the changing trends in lung cancer incidence by histologic type.

Diagnosis, Differential↗

Significance of soluble TNF receptor-I in acute-type fulminant hepatitis.

OBJECTIVE: Fulminant hepatitis is associated with apoptosis of hepatocytes, which is mediated via Fas and tumor necrosis factor (TNF) receptors. The clinical significance of apoptotic factors and these receptors was investigated in fulminant hepatitis. METHODS: Serum levels of TNF-alpha, soluble TNF receptor-I and -II, soluble Fas antigen, and Fas ligand were measured. Then, the relationships between these parameters and the severity or prognosis of fulminant hepatitis were studied. RESULTS: Serum levels of TNF-alpha, soluble TNF receptor-I, and soluble TNF receptor-II were increased in acute-type fulminant hepatitis. In particular, soluble TNF receptor-I was significantly higher than in patients with subacute-type fulminant hepatitis, severe acute hepatitis, acute hepatitis, or healthy controls. The soluble TNF receptor-I level continued to increase or remained high in patients who died of acute-type fulminant hepatitis, and eight of nine patients had a level >10 ng/ml. In contrast, the soluble TNF receptor-I level remained <10 ng/ml in survivors. Soluble Fas and soluble Fas ligand levels tended to increase in all types of acute liver disease and were not specific to fulminant hepatitis. CONCLUSION: Our findings suggested that monitoring the soluble TNF receptor-I level may help to assess the prognosis of acute-type fulminant hepatitis and that TNF might be associated with massive hepatic necrosis.

Acute Disease↗

Improved direct viable count procedure for quantitative estimation of bacterial viability in freshwater environments.

A direct viable count (DVC) procedure was developed which clearly and easily discriminates the viability of bacterial cells. In this quantitative DVC (qDVC) procedure, viable cells are selectively lysed by spheroplast formation caused by incubation with antibiotics and glycine. This glycine effect leads to swollen cells with a very loose cell wall. The viable cells then are lysed easily by a single freeze-thaw treatment. The number of viable cells was obtained by subtracting the number of remaining cells after the qDVC procedure from the total cell number before the qDVC incubation. This improved procedure should provide useful information about the metabolic potential of natural bacterial communities.

Bacteria↗

Role of serotype-specific polysaccharide in the resistance of Streptococcus mutans to phagocytosis by human polymorphonuclear leukocytes.

To clarify the role of cell surface components of Streptococcus mutans in resistance to phagocytosis by human polymorphonuclear leukocytes (PMNs), several isogenic mutants of S. mutans defective in cell surface components were studied with a luminol-enhanced chemiluminescence (CL) assay, a killing assay, and a transmission electron microscope. The CL responses of human PMNs to mutant Xc11 defective in a major cell surface antigen, PAc, and mutant Xc16 defective in two surface glucosyltransferases (GTF-I and GTF-SI) were the same as the response to the wild-type strain, Xc. In contrast, mutant Xc24R, which was defective in serotype c-specific polysaccharide, induced a markedly higher CL response than the other strains. The killing assay showed that human PMNs killed more Xc24R than the parent strain and the other mutants. The transmission electron microscopic observation indicated that Xc24R cells were more internalized by human PMNs than the parental strain Xc. These results may be reflected by the fact that strain Xc24R was more phagocytosed than strain Xc. The CL response of human PMNs to a mutant defective in polysaccharide serotype e or f was similar to the response to Xc24R. Furthermore, mutants defective in serotype-specific polysaccharide were markedly more hydrophobic than the wild-type strains and the other mutants, suggesting that the hydrophilic nature of polysaccharides may protect the bacterium from phagocytosis. We conclude that the serotype-specific polysaccharide, but not the cell surface proteins on the cell surface of S. mutans, may play an important role in the resistance to phagocytosis.

Antigens, Bacterial↗