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Biomedical subjects

A Goto

Publications and source records attributed to A Goto.

At least 91 records · Page 5Linked to original sources
PubMed1998

Increase in intracellular hydrogen peroxide and upregulation of a nuclear respiratory gene evoked by impairment of mitochondrial electron transfer in human cells.

We have investigated an interorganelle communication pathway between the nucleus and mitochondria. We loaded a stress specific to mitochondria of human fibroblast cells by antimycin A (AA), an inhibitor of the mitochondrial cytochrome bc1 complex. AA inhibited cellular respiration in a dose-dependent manner. When the respiratory capacity was reduced to 50-70% of the original one, mRNA levels of cytochrome c1 as well as cytochrome b increased at 24 h after AA treatment, resulting in maintenance of the cell viability. In contrast, the cells retaining less than 40% of the original capacity showed no increase in either mRNA level and were targeted for death. Intracellular H2O2 level monitored by the fluorescence of dichlorofluorescein increased within 3 h in both the cases, although this increase was higher in the cells where the mRNA levels increased. An antioxidant N-acetylcysteine repressed the increases of not only H2O2 but also cytochrome c1 mRNA levels. These results suggest that the cells can respond to a limited impairment of electron transfer by promoting expression of nuclear and mitochondrial genes, probably through an H2O2-dependent signaling pathway.

Acetylcysteine↗
PubMed1998

Prostaglandin D2 inhibits inducible nitric oxide synthase expression in rat vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) as well as macrophages have been shown to generate a substantial amount of NO in inflammatory vascular lesions. Prostaglandin (PG) D2 (PGD2) is produced by inflammatory cells, including mast cells and macrophages. We investigated whether PGD2 modulates NO metabolism in rat VSMCs. PGD2 at a concentration of 10(-7) mol/L or greater dose-dependently inhibited nitrite accumulation in the medium of cultured VSMCs stimulated with interleukin 1beta (IL-1beta). In a dose-response analysis of IL-1beta and nitrite accumulation, PGD2 was seen to decrease the maximal ability of VSMCs to generate NO, arguing against competition by PGD2 at cytokine receptors. Northern analysis showed that PGD2 suppresses induction of inducible NO synthase (iNOS) mRNA in IL-1beta-stimulated VSMCs, with consequent inhibition of iNOS protein expression in Western analysis. A thromboxane A2 (TXA2) analogue, U46619 (10(-5) mol/L), produced less inhibition of NO generation than did PGD2. Neither the PGI2 analog carbaprostacyclin nor PGE1 showed any inhibition. PGD2 dose-dependently inhibited NO generation despite the addition of the TXA2 antagonist SQ29548. PGJ2, delta12-PGJ2, and 15-deoxy-delta12,14-PGJ2, all metabolites of PGD2, were as potent as or slightly stronger than PGD2 in the inhibition of NO generation. These data suggest that PGD2 suppresses NO generation in VSMCs by inhibiting iNOS mRNA expression, most likely through the cascade of the PGJ2 series rather than through the TX receptor or cAMP upregulation. Such action makes it likely that PGD2 regulates NO metabolism in vascular lesions.

Animals↗
PubMed1998

Somatosensory homunculus as drawn by MEG.

We studied a detailed somatosensory representation map of the human primary somatosensory cortex using magnetoencephalography. Somatosensory-evoked magnetic fields following tactile stimulation of multiple points in the right hemibody (including the tongue, lips, fingers, arm, trunk, leg, and foot) were analyzed in five normal subjects. We were able to estimate equivalent current dipoles (ECDs) following stimulation of the tongue, lips, fingers, palm, forearm, elbow, upper arm, and toes in most subjects and those following the stimulation of the chest, ankle, and thigh in one subject. The ECDs were located in the postcentral gyrus and generally arranged in order along the central sulcus, which is compatible with the somatosensory "homunculus." Linear distances, averaged in five subjects, from the receptive area of the thumb to that of the tongue, little finger, forearm, upper arm, and toes were estimated to be 2.42 +/- 0.28, 1.25 +/- 0.28, 2.21 +/- 0.72, 2.75 +/- 0.63, and 5.29 +/- 0.48 cm, respectively. The moment of each ECD, which suggested the size of the cortical areas responsive to the stimulation, was also compatible with the bizarre proportion of the homunculus with a large tongue, lips, and fingers. According to these results, we were able to reproduce a large part of the somatosensory homunculus quantitatively on an individual brain MRI.

Brain Mapping↗
PubMed1998

Anti-Fas antibody-induced apoptosis in human colorectal carcinoma cell lines: role of the p53 gene.

The cell surface Fas antigen transducts an apoptotic signal by its crosslinking with Fas ligand or anti-Fas antibody in a variety of human cultured cells. In this study, we examined the expression of Fas antigen and its mediation of apoptosis in six human colorectal carcinoma cell lines. A flow cytometric analysis revealed that LoVo, DLD-1, WiDr and SW837 cell lines showed higher expression levels of Fas antigen, in contrast to lower expression in COLO201 and COLO320DM. Interferon-gamma enhanced the expression of Fas antigen in all of the cell lines examined. Both Fas ligand and Fas-associated phosphatase-1 (FAP-1) were expressed only in COLO320DM. Anti-Fas antibody induced apoptosis in LoVo carrying wild-type p53 gene, but not in the other five cell lines carrying mutated p53 gene. The transfection of wild-type p53 gene using an adenovirus vector upregulated P53 protein in WiDr and SW837 cells, both of which showed, however, no increase in apoptotic cells by anti-Fas antibody treatment. These results indicated that (1) Fas antigen was variably expressed, regardless of the p53 gene status and (2) the susceptibility to anti-Fas antibody-mediated apoptosis did not correlate to Fas, Fas ligand or FAP-1 expression levels. Therefore, we conclude that wild-type P53 expression might not necessarily be essential for Fas-mediated apoptosis in human colorectal carcinoma cell lines.

Journal Article↗
PubMed1998

Relevance of periglomerular myofibroblasts in progression of human glomerulonephritis.

To clarify the pathological and clinical significance of periglomerular alpha-smooth muscle actin (alpha-SMA)-positive cells, we examined 51 needle-biopsy specimens from patients with human glomerulonephritis. Immunoelectron microscopy confirmed these cells were myofibroblasts showing characteristic features with abundant alpha-SMA-positive thin myofilaments. Nonsclerotic glomeruli with periglomerular myofibroblasts were larger in the Bowman's capsular planar area than nonsclerotic glomeruli without periglomerular myofibroblasts (24.7 +/- 6.0 x 10(3) microm2 v 19.9 +/- 8.5 x 10(3) microm2; P < 0.01). We studied the correlation between the clinical prognosis and the extent of periglomerular myofibroblasts in 24 patients with IgA nephropathy. Patients were divided into two groups; those with plasma creatinine levels within normal range at biopsy and significantly elevated at follow-up were designated group 1 (poor prognosis), and patients with plasma creatinine levels within normal range at biopsy and not significantly elevated at follow-up were designated group 2 (fair prognosis). In the kidneys of group 1 patients, periglomerular alpha-SMA was expressed more intensively than it was in the kidneys of group 2 patients (alpha-SMA expression score, 1.0 +/- 0.48 v 0.52 +/- 0.54; P < 0.05). These findings indicate that periglomerular myofibroblasts appeared surrounding the nonsclerotic hypertrophic glomeruli, which may lead finally to glomerulosclerosis. This report suggests that interaction between the glomerular cells and the periglomerular myofibroblasts may have a role in the progression of glomerular diseases.

Actin Cytoskeleton↗
PubMed1998

Detection of the ongoing sorting of ancestrally polymorphic SINEs toward fixation or loss in populations of two species of charr during speciation.

The FokI family of short interspersed repetitive elements (SINEs) has been found only in the genomes of charr fishes (genus Salvelinus). In an analysis of the insertion of FokI SINEs using PCR, we characterized six loci at which FokI SINEs have been inserted into the genomes of Salvelinus alpinus (Arctic charr) and/or S. malma (Dolly Varden). An analysis of one locus (Fok-223) suggested that a sister relationship exists between S. alpinus and S. malma and the SINE at this locus might have been inserted in a common ancestor of these two species, being fixed in all extant populations examined. By contrast, SINEs at two other loci (Fok-211 and Fok-206) were present specifically in the genome of S. alpinus, with polymorphism among populations of this species. Moreover, the presence or absence of the SINEs of the other three loci (Fok-214, Fok-217, and Fok-600) varied among populations of these two species. The most plausible interpretation of this result is that SINEs, which were ancestrally polymorphic in the genome of a common ancestor of these two species, are involved in an ongoing process of differential sorting and subsequent fixation in the various populations of each species.

Animals↗
PubMed1998

Ouabain-like factor.

Accumulated evidence has suggested that several sodium pump inhibitors, similar to cardiotonic steroids, are present in the human body. Ouabain-like factor, the most appealing candidate, has been found to be increased with high sodium intake and hypervolaemia, and in essential hypertension, mineralocorticoid hypertension, and pregnancy-induced hypertension. Furthermore, blocking the action of ouabain-like factor with digibind or a novel anti-ouabain agent lowers blood pressure in several models of hypertension. Several important questions remain, however, before it can be concluded that ouabain-like factor is indeed involved in the regulation of sodium homeostasis and blood pressure.

Animals↗
PubMed1998

Association of loss of heterozygosity at the p53 locus with chemoresistance in osteosarcomas.

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite sensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 (p53) and 13q14 (Rb) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss (P < 0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.

Adolescent↗
PubMed1998

Apoptosis and cellular proliferation in human epidermal squamous cell neoplasia.

We examined cell loss (apoptosis) and proliferation in a histopathological spectrum of epidermal squamous cell neoplasia, including 11 cases of solar keratosis (SK), 18 Bowen's diseases (BD) and 19 invasive squamous cell carcinomas (SCC). Apoptotic and proliferative cells were determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) and by the detection of nuclear antigen Ki-67, respectively. Few apoptotic cells were observed in normal epidermis, while TUNEL index (TI; percentage of TUNEL-positive cells) was highest for SCCs, followed by BDs and SKs, in the order given. Although the mean Ki-67 index did not differ between SCCs and BDs, both disease types showed a significantly higher index than the SKs. Of SCCs, both TI and Ki-67 index values were significantly higher in poorly than in well differentiated carcinomas. TI was significantly higher in SCCs without P53 immunohistochemical expression than in SCCs with P53 expression, while TI and Ki-67 indices did not correlate with P53 expression in the SKs and BDs. These results suggest that apoptosis reflects not only cell loss, but also proliferative activity in the epidermal neoplastic lesions.

Apoptosis↗
PubMed1998

Mesangial expression of a nonmuscle myosin heavy chain, SMemb, is associated with glomerular sclerosis and renal prognosis in IgA nephropathy.

To characterize the phenotypic alteration in mesangial cells in human glomerulonephritis, we investigated the expression of nonmuscle-type myosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in IgA nephropathy. The expression of SMemb and alpha-SM actin was examined by immunohistochemistry in biopsy specimens from 45 patients with IgA nephropathy. We examined a total of 489 glomeruli representing all patients enrolled, and found that mesangial expression of SMemb and alpha-SM actin was associated with mesangial proliferation. Only mesangial expression of SMemb showed a significant relationship with mesangial matrix accumulation. Semiquantitative evaluation using composite expression scores showed that the expression of SMemb was elevated in the patients with poor renal prognosis. The expression of alpha-SM actin showed no significant relationship with renal prognosis. These results suggest that mesangial expression of SMemb is an important factor in the progression of IgA nephropathy, and that SMemb and alpha-SM actin are associated with the activation of mesangial cells by different mechanisms.

Adolescent↗
PubMed1998

Angiotensin-Converting Enzyme Inhibition Delays Onset of Glucosuria With Regression of Renal Injuries in Genetic Rat Model of Non-Insulin-Dependent Diabetes Mellitus.

BACKGROUND: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether angiotensin inhibition influences the onset of NIDDM and brings about a regression of renal injury in diabetes mellitus. METHODS AND RESULTS: Six-week-old OLETF rats were treated with the angiotensin-converting enzyme (ACE) inhibitors imidapril or enalapril for 16 weeks. Systolic blood pressure is increased in an age-dependent manner in OLETF rats. In this study, the elevation in systolic blood pressure was dose-dependently reduced by ACE inhibitor treatment. In OLETF rats, plasma concentrations of insulin and glucose increased and the glucosuria occurred at the age of 22 weeks. Simultaneously, OLETF rats exhibited proteinuria and nodular lesions in glomeruli. The ACE inhibitor treatment almost completely reduced glucosuria, and also decreased plasma concentrations of insulin and glucose in OLETF rats. ACE inhibitor treatment lessened the proteinuria and attenuated morphologically the severity of nodular lesions in OLETF rats. Moreover, increases in plasminogen activator inhibitor 1 (PAI-1) in OLETF rats were reduced by the ACE inhibitor treatment, and the improvement of glomerular lesions was related to decreases of PAI-1 and angiotensin II levels in plasma but not to improvement of glucose metabolism. CONCLUSIONS: ACE inhibitors delay onset of NIDDM with attenuation of kidney injury. The regression of kidney lesions is probably due to angiotensin reductions but not to glucose metabolism per se. ACE inhibitor drug therapy may be useful in preventing NIDDM and the subsequent renal injury in patients with NIDDM.

Journal Article↗
PubMed1998

Adenoviral transduction efficiency partly correlates with expression levels of integrin alphavbeta5, but not alphavbeta3 in human gastric carcinoma cells.

Adenovirus has attracted much attention as a vector for gene therapy. Integrin alphavbeta3 and alphavbeta5 mediate adenovirus internalization into cells. We examined adenoviral transduction efficiency and expression of integrin alphavbeta3 alphavbeta5 in 9 human gastric carcinoma cell lines. The percentage of -gal-positive cells was more than 85% 3 days after infection with recombinant adenovirus carrying the bacterial LacZ gene (AxCALacZ) at a dose of 25 MOI in 7 cell lines and the transduction efficiency was 32 and 42% in HSC-39 and MKN-28 cells, respectively. Adenoviral transduction efficiency did not correlate with the histological cell types. Flow cytometric analysis revealed relatively high expression of integrin alphavbeta5 in MKN-28 and OCUM-2M cells, followed by MKN-1, MKN-7, MKN-45, MKN-74, TMK-1 and KATO-III cells. HSC-39 cells minimally expressed integrin alphavbeta5. On the other hand, integrin alphavbeta3 was expressed only in MKN-1 cells. These results suggest that the adenovirus vector might be useful for gene transduction into human gastric carcinoma cells and the transduction efficiency partly correlates with the expression levels of integrin alphavbeta5 but not integrin alphavbeta3.

Adenoviridae↗
PubMed1998

[Study on blood glucose control of subjects with borderline type abnormality in 75 G oral glucose tolerance test values. The establishment of a high risk group on the basis of yearly observations].

SUBJECTS AND METHODS: 227 of subjects with a 2-hour plasma glucose concentration of 120-199 mg/dl were selected from 413 participants who had two or more 75 g OGTT in health examinations from 1987-1995. From these subjects we established 8 groups according to initial 2-hour plasma glucose concentration 120-199 mg/dl stratified by 10 mg/dl, and calculated the total percentages of participants whose 2-hour plasma glucose concentration reached 200 mg/dl or greater over a 1-8 years (2.7 +/- 1.7 years, mean +/- SD) observation period. In 36 subjects who were tested annually over a four year period (4 times), the mean values of their 4 values were analyzed for relationships to coefficients of variation of the 2-hour plasma glucose. RESULTS: By stratified groups (from lowest to highest) of those with an initial plasma glucose concentration of 120-159 mg/dl, 7.4%, 12.1%, 16.1%, and 15.0% attained values of 200 mg/dl and higher, respectively in 1-8 years. On the other hand, 29.6%, 29.6%, 39.1%, and 47.4% of those with an initial plasma glucose concentration of 160-199 mg/dl moved to a diabetic type after 1-8 years, respectively. The percentages of those who ended up with levels of 200 mg/dl and greater at 2-hours tended to increase in subjects whose initial 2-hour plasma glucose concentration was over 160 mg/dl in comparison with patients below that initial level. CONCLUSIONS: From these results, it appears that subjects with 160-199 mg/dl 2-hour glucose concentration, which is considered a borderline status, are at high risk for future abnormal levels (> 200 mg/dl at 2-hours) and should be managed as a high risk level group for prevention of diabetes.

Blood Glucose↗
PubMed1998

[Evaluation of therapy for dilated cardiomyopathy with heart failure by iodine-123 metaiodobenzylguanidine imaging: comparison with heart rate variability power spectral analysis].

The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine (123I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of 123I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of 123I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). 123I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data [left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)], plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data [mean low frequency (MLF) and high frequency power (MHF)] and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of 123I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the 123I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure.

3-Iodobenzylguanidine↗
PubMed1997

Effects of extracellular pH on receptor-mediated Ca2+ influx in A7r5 rat smooth muscle cells: involvement of two different types of channel.

1. The effects of extracellular pH (pHo) on receptor (vasopressin or endothelin-1)-mediated Ca2- entry and Ca(2+)-permeable channels were investigated in aortic smooth muscle cells (A7r5) from rat embryonic thoracic aorta. Intracellular Ca2+ ([Ca2+]i) was measured using fura-2 AM and whole-cell voltage clamp techniques were employed. 2. Vasopressin and endothelin-1 (100 nM) in the presence of nicardipine (10 microM) evoked a sustained rise in [Ca2+]i due to calcium entry. Extracellular acidosis decreased receptor (vasopressin or endothelin-1)-mediated Ca2+ entry, while extracellular alkalosis potentiated it. 3. Depletion of intracellular Ca2+ stores with thapsigargin (1 microM) also evoked Ca2+ entry activated by emptying of intracellular Ca2+ stores (capacitative Ca2+ entry). Extracellular acidosis decreased this capacitative Ca2+ entry, while extracellular alkalosis potentiated it. 4. Under voltage-clamp conditions with Ca+ internal solution, vasopressin and endothelin-1 activated non-selective cation currents (ICAT). Ba2+ or Ca2+ were also charge carriers of ICAT. Reducing the pHo inhibited ICAT, while increasing pHo potentiated it in a reversible manner. 5. Intracellular pH (pHi) changes did not cause the same marked effects as pHo changes, and a high concentration of Hepes (50 mM) in the patch pipette did not inhibit the effects of pHo on ICAT. 6. Similar results were obtained when ICAT was activated by GTP gamma S (1 mM) applied through the patch pipette, even in the absence of agonists, probably because of direct activation of GTP-binding proteins coupled to the receptors. 7. In cells treated with thapsigargin, addition of Ca2+ to the bath solution induced Ca(2+)-dependent K+ currents activated by capacitative Ca2+ entry. However, no measurable ionic currents activated by capacitative Ca2+ entry (ICRAC) were observed under conditions with Cs+ internal solution and EGTA (5 mM), although vasopressin still activated ICAT. 8. These results suggest that the contractile agonists vasopressin and endothelin-1 evoked Ca2+ entry through two different types of Ca(2+)-permeable channel (ICAT and ICRAC) and pHo affects these channels, which may modulate receptor-mediated Ca2+ influx in A7r5 cells. Thus, pH-induced changes of these channels may play a pathophysiological role in the control of receptor-mediated contractions.

Animals↗
PubMed1997

Congenital familial myopathy with type 2 fiber hypoplasia and type 1 fiber predominance.

A 12-month-old girl with delayed developmental milestones, due to muscle hypotonia and weakness from early infancy, exhibited type 2 fiber hypoplasia. A muscle biopsy specimen disclosed type 1 fiber predominance and type 2B fiber deficiency compatible with congenital myopathy. During the following 4 years, she continued to have mild muscle weakness, but no mental retardation. Her mother had similar symptoms from early infancy with minimal progression. Although type 2 fiber hypoplasia is a non-specific finding in various diseases, it may be a specific finding in a limited number of patients with hereditary congenital non-progressive myopathy.

Adult↗