Biomedical subjects

H Sugimoto

Publications and source records attributed to H Sugimoto.

At least 73 records · Page 4Linked to original sources

PubMed2000

Santonin-related compound 2 inhibits the expression of ICAM-1 in response to IL-1 stimulation by blocking the signaling pathway upstream of I kappa B degradation.

Santonin-related compounds (SRCs) were synthesized from the starting material L-alpha-santonin and tested for the biological activity on the expression of intercellular adhesion molecule-1 (ICAM-1) in response to IL-1 stimulation on human adenocarcinoma cells. One of the bromoketone derivatives termed SRC2 [11S-2 alpha-bromo-3-oxoeudesmanno-13,6 alpha-lactone] strongly inhibited the ICAM-1 expression at an IC(50) value of 5.9 microM, whereas L-alpha-santonin itself was totally inactive up to 100 microM. The blockage of ICAM-1 expression by SRC2 was not due to the direct inhibition of de novo RNA and protein synthesis. The nuclear translocation of NF-kappaB subunit p65 was markedly prevented by SRC2. Moreover, I kappa B alpha degradation upon IL-1 stimulation was strongly inhibited by SRC2. These observations suggest that SRC2 blocks the IL-1 signaling pathway upstream of I kappa B degradation.

Biological Transport↗

PubMed2000

Association of disease with isolation and virulence of Rhodococcus equi from farm soil and foals with pneumonia.

OBJECTIVE: To determine whether isolation and virulence of Rhodococcus equi from soil and infected foals are associated with clinical disease. DESIGN: Cross-sectional and case-control study. SAMPLE POPULATION: R equi isolates from 50 foals with pneumonia and soil samples from 33 farms with and 33 farms without a history of R equi infection (affected and control, respectively). PROCEDURE: R equi was selectively isolated from soil samples. Soil and clinical isolates were evaluated for virulence-associated protein antigen plasmids (VapA-P) and resistance to the beta-lactam antibiotics penicillin G and cephalothin. Microbiologic cultures and VapA-P assays were performed at 2 independent laboratories. RESULTS: VapA-P was detected in 49 of 50 (98%) clinical isolates; there was complete agreement between laboratories. Rhodococcus equi was isolated from soil on 28 of 33 (84.8%) affected farms and 24 of 33 (72.7%) control farms, but there was poor agreement between laboratories. Virulence-associated protein antigen plasmids were detected on 14 of 66 (21.2%) farms by either laboratory, but results agreed for only 1 of the 14 VapA-P-positive farms. We did not detect significant associations between disease status and isolation of R equi from soil, detection of VapA-P in soil isolates, or resistance of soil isolates to beta-lactam antibiotics. No association between beta-lactam antibiotic resistance and presence of VapA-P was detected. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of soil microbiologic culture and VapA-P assay results, it is not possible to determine whether foals on a given farm are at increased risk of developing disease caused by R equi.

Actinomycetales Infections↗

PubMed2000

Binding of the second generation non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding.

S-1153 (AG1549) is perhaps the most promising non-nucleoside inhibitor of HIV-1 reverse transcriptase currently under development as a potential anti-AIDS drug, because it has a favorable profile of resilience to many drug resistance mutations. We have determined the crystal structure of S-1153 in a complex with HIV-1 reverse transcriptase. The complex possesses some novel features, including an extensive network of hydrogen bonds involving the main chain of residues 101, 103, and 236 of the p66 reverse transcriptase subunit. Such interactions are unlikely to be disrupted by side chain mutations. The reverse transcriptase/S-1153 complex suggests different ways in which resilience to mutations in the non-nucleoside inhibitors of reverse transcriptase binding site can be achieved.

Anti-HIV Agents↗

PubMed2000

NXP-1, a human protein related to Rad21/Scc1/Mcd1, is a component of the nuclear matrix.

Nuclear matrix is a complex intranuclear network supposed to be involved in the various nuclear functions. In order to identify the nuclear matrix proteins, we isolated a cDNA clone from a human placenta cDNA library. This clone was partially represented a known cDNA clone HA1237. HA1237 encoded a 631-amino-acid peptide, which we designated NXP-1. NXP-1 was related to yeast Rad21/Scc1/Mcd1, Xenopus XRAD21, and mouse PW29, and identical with HR21spA isolated from a human testis cDNA library. We developed a polyclonal antibody to the purified NXP-1 bacterially expressed as a fusion protein with GST. Western blot analysis with anti-NXP-1 polyclonal antibody showed nuclear matrix localization of NXP-1 in HeLa cells. Indirect immunofluorescence staining also showed nuclear and nuclear matrix localization of the NXP-1. Results of in vitro binding assays employing nuclear matrix preparations indicated that the N-terminal region (16-128 amino acid) of NXP-1 has an important role in nuclear matrix distribution.

Amino Acid Sequence↗

PubMed2000

Induction of IgA against Haemophilus parainfluenzae antigens in tonsillar mononuclear cells from patients with IgA nephropathy.

Much evidence suggests that IgA production in vivo and in vitro is enhanced in patients with IgA nephropathy (IgAN). We have demonstrated glomerular deposition of the outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of HP-specific IgA in the serum of patients with IgAN. In this study, we investigated the production of IgA and several cytokines by tonsillar mononuclear cells (TMC) from IgAN patients induced by stimulation with OMHP. The spontaneous production of total IgA and TGF-beta by TMC from IgAN patients was higher than that by TMC from patients with chronic tonsillitis (CT) (P < 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TMC from IgAN patients (P < 0.01), but not by TMC from CT patients. OMHP stimulation also enhanced the production of TGF-beta and IL-10 by TMC from IgAN patients (P < 0.001). These results suggest that the infection of HP in the tonsil may be involved in the etiology of IgAN.

Adolescent↗

PubMed2000

Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) act quite specifically on human immunodeficiency virus type 1 (HIV-1). In general, they are not effective on human immunodeficiency virus type 2 (HIV-2) or simian immunodeficiency virus (SIV). Only SIV strains from African green monkeys are sensitive to several NNRTIs. Here we isolated NNRTI- and 3TC-resistant SIVagm variants. Viruses resistant to delavirdine contained V112I and M231I substitutions, while those resistant to 3TC contained a M 185I substitution. These amino acids are highly conserved in HIV-1, HIV-2, SIVmac and SIVagm, and the M184I (M185I in SIVagm) substitution was observed in 3TC-resistant HIV-1 and SIVmac. The roles of the observed mutations in NNRTI-resistance of SIVagm and HIV-1 were further confirmed by site-directed mutagenesis. The present results have provided a new insight into the common mechanism of sensitivity of HIV- 1 and SIVagm to NNRTIs.

Amino Acid Sequence↗

PubMed2000

Age-related changes in the D-aspartic acid content of the teeth of the senescence-accelerated mouse.

It is known that D-aspartic acid increases with age in dentine. Here, age-related changes in the D to L-aspartic acid (D/L) ratios of the lower teeth of two different sublines of the senescence-accelerated mouse (SAM), SAMP2/Iw (SAM, prone 2/Iwate) and SAMR1/Iw (SAM, resistant 1/Iwate) were measured by gas chromatography. The D/L ratio of the molars increased with advancing age, whereas that of the incisors did not. In mice younger than 6 months of age the D/L ratio of the molars from SAMP2/Iw tended to be higher than that from SAMR1/Iw, whereas the converse applied to older mice. Racemization in the molars occurred significantly faster in SAMR1/Iw than SAMP2/Iw (p = 0.01-0.001). Analysis according to the kind of tooth showed that the D/L ratio increased gradually in the order incisors < third molars < second molars < first molars, indicating that the ratio was higher the earlier the molars formed. As racemization depends upon the environmental temperature, the rectal temperatures of the mice were also examined. The rectal temperature of SAMP2/Iw was highest when they were 2 months old, but declined rapidly thereafter, whereas the rectal temperature of SAMRI/Iw was highest when they were 6 months old, after which it declined gradually. These results indicate that the D-aspartic acid contents of the molars of SAMR1/Iw and SAMP2/Iw increase with age in a different fashion and suggest that the fashion was determined by the body temperature, but not by the senescence-accelerated age.

Aging↗

PubMed2000

Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold.

Prescription of aerobic exercise for Type 2 diabetes mellitus (Type 2 DM) in clinical practice is frequently based on exercise intensity at maximum heart rate (60<HR(max)<79%), heart rate reserve (50<HR(reserve)<74%), and rating of perceived exertion (12<RPE<13). We examined these parameters in Japanese males with Type 2 DM at ventilatory threshold (VT) to investigate the exercise capacity of Type 2 DM patients and re-evaluate the exercise prescription. Fifty-six Japanese Type 2 DM males without autonomic neuropathy [age, 53.5+/-7.7 years; body mass index (BMI), 23.7+/-3.6 kg/m(2)] were enrolled and compared with 56 age- and BMI-matched healthy Japanese males. VT was determined breath by breath during exercise test using a ramp protocol and rates of oxygen consumption (VO(2)), work rate (WR), HR, DeltaHR, %HR(max), %HR(reserve), and RPE were measured at VT. Type 2 DM patients had significantly lower VO(2) (3.6+/-0.4 metabolic equivalents (METs)) and WR (62+/-14 W) than controls (VO(2), 3.9+/-0.6 METs; WR, 74+/-13 W). %HR(reserve), (32.6+/-7.7%) was also significantly lower compared with controls (37.6+/-8.3%), while %HR(max), was not different. RPE was also similar in diabetics (12.4+/-1.5) and controls (12.9+/-1.2), however, it was significantly lower in diabetic patients aged 60-69 years (11.8+/-2.0) and those with distal symmetric sensory neuropathy (12.2+/-1.0). Our results indicate reduced exercise capacity in Japanese Type 2 DM males and the exercise intensity of 60%HR(max), 30%HR(reserve), and RPE 12 is recommended in elderly diabetics and those with diabetic sensory neuropathy.

Blood Pressure↗

PubMed2000

Synthesis and biological evaluation of 1-(4-[18F]fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine for in vivo studies of acetylcholinesterase.

We synthesized and evaluated 1-(4-fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (4-FDP), which is an analog of donepezil. The 4-[(18)F]FDP was prepared by reductive alkylation of debenzylated donepezil with 4-[(18)F]fluorobenzaldehyde in high radiochemical yield (decay-corrected, 40-52%) and with high effective specific activity (30-38 GBq/micromol). Tissue distribution studies in mice demonstrated nonspecific distribution of the 4-[(18)F]FDP in brain regions, suggesting that this radioligand may not be a suitable agent for in vivo studies of acetylcholinesterase (AChE), despite its potent in vitro biological activity.

Acetylcholinesterase↗

PubMed2000

In vivo antioxidative activity of propolis evaluated by the interaction with vitamins C and E and the level of lipid hydroperoxides in rats.

In vivo antioxidative activity of propolis was evaluated on the basis of ameliorative effects on the oxidative stress induced by vitamin E deficiency in rats. The control group was fed vitamin E-deficient diet, and the propolis group was fed vitamin E-deficient diet supplemented with 1% of propolis for 4 and 8 weeks. Comparisons were made in tissue concentrations of vitamin C, vitamin E, and lipid hydroperoxides between these groups. No significant difference was observed in tissue vitamin E concentration between these groups after both 4 and 8 weeks. After 4 weeks, the plasma vitamin C concentration of the propolis group was significantly higher than that of the control group. After 8 weeks, the tissue concentrations of vitamin C in the kidney, stomach, small intestine, and large intestine of the propolis group were significantly higher than those of the control group. These results suggest that some components of propolis are absorbed to circulate in the blood and behave as a hydrophilic antioxidant that saves vitamin C. The concentration of lipid hydroperoxides in the large intestine of the propolis group was significantly lower than that of the control group after 8 weeks. These results suggest that propolis exerts its antioxidative effect where it is assumed to accumulate, such as on the kidney, where it is excreted, and on the gastrointestinal tract, where propolis influences these tissues even from the outside of the cell.

Animals↗

PubMed2000

IDPN-induced monoamine and hydroxyl radical changes in the rat brain.

beta-beta'-iminodipropionitrile (IDPN)-induced monoamine and hydroxyl radical changes in the rat brains were studied. IDPN caused decreases in 5-HT and 5-HIAA levels in all brain regions, strongly indicating that IDPN's neurotoxicity primarily affects 5-HT containing neurons. Dopamine and its metabolites' levels decreased in the some regions, most likely due to depression of dopamine metabolic turnover. Our results more clearly demonstrate IDPN-induced monoamine alterations in the rat brain more than previous reports. To clarify one of the pathogenesis of IDPN-induced neurological disorders, we measured hydroxyl radical levels. 2,3-DHBA increased at 1st day, and decreased in some regions at 7th days after discontinuing IDPN. We conclude, hydroxyl radical formation causes neuronal damage, and monoamine changes contribute to IDPN-induced neurological disorder.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

The impact of a catastrophic earthquake on morbidity rates for various illnesses.

It has been reported that some natural catastrophes increase morbidity rates for illness. In this study, we investigated the impact of the 1995 Hanshin-Awaji earthquake on morbidity rates for various illnesses by analysis for correlations between the extent of damage due to the earthquake and occurrences of various illnesses. We searched the medical records of 1948 patients hospitalized due to illness in 48 hospitals during the first 15 days after the earthquake. In each of 14 affected areas, the hospital admission rate and estimated morbidity ratio for each illness were calculated. Destruction ratios were determined based upon the number of dwellings completely destroyed in each area. For total illnesses and each major illness, linear regression analyses were performed comparing hospital admission rates, estimated morbidity ratios, and destruction ratios. Hospital admission rates and estimated morbidity ratios among the 1948 patients were significantly correlated to destruction ratios. With pneumonia, dehydration, acute heart failure, asthmatic attack, and peptic ulcer, hospital admission rates and estimated morbidity ratios were significantly related to destruction ratios, while no significant correlations between estimated morbidity ratios and destruction ratios existed for cerebral vascular disease or ischemic heart disease. Peptic ulcer and pneumonia showed especially high correlation values (age- and sex-adjusted R2>0.7). The present study revealed a strong link between the extent of damage due to the catastrophic earthquake and an increase in morbidity rates for acute illnesses, especially peptic ulcer and pneumonia.

Adolescent↗

PubMed2000

Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy.

The pathogenesis of IgA nephropathy (IgAN) is unclear. We have previously shown glomerular deposition of Haemophilus parainfluenzae (HPI) antigens and the presence of IgA antibody against HPI antigens in patients with IgAN. We examined the immune response to HPI antigens in tonsillar lymphocytes from patients with IgAN. Lymphocytes isolated from the palatine tonsils of 13 IgAN patients and 16 patients with chronic tonsillitis but without renal disease were used as controls. We examined lymphocyte proliferation and production of IgA antibody against HPI antigens by measuring thymidine uptake and IgA antibody in culture supernatants after lymphocyte incubation with HPI antigens. Patients with IgAN showed a significantly higher stimulation index to HPI antigens (thymidine incorporation in tonsillar lymphocytes with HPI/thymidine incorporation in unstimulated tonsillar lymphocytes) than controls (P < 0.002). Lymphocytes from patients with IgAN also showed a significantly higher level of IgA antibody and IgA1 antibody against HPI antigens in culture supernatants than lymphocytes from controls (P = 0.0002 and P = 0.004, respectively). Our results suggest that HPI antigens stimulate tonsillar T and B lymphocytes in patients with IgAN and that an immune response to HPI antigens may play a role in the pathogenesis of this disease in some cases.

Adolescent↗

PubMed2000

Helicobacter pylori infection occurs via close contact with infected individuals in early childhood.

BACKGROUND: The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet, to date, the exact mode of transmission remains uncertain. METHODS: The seroprevalence of H. pylori in a relatively isolated rural town in Japan (A-town) was examined to analyse the H. pylori infection route. The immunoglobulin G antibodies against H. pylori in 1684 subjects who had received public health examinations in A-town were determined with an enzyme-linked immunosorbent assay. The seroprevalence was compared in five areas according to the water source. The possibility and frequency of intrafamilial infection was analysed by comparing the seroprevalence among family members residing in the same home. RESULTS: The seroprevalence of H. pylori did not differ significantly between the five areas examined. Seropositivity was significantly more common in the children whose mothers were seropositive (45.0%, 27/60) than in the children whose mothers were seronegative (10.0%, 2/20; odds ratio (OR) = 7.36, P = 0.0036, 95% confidence interval (CI) = 1.57-34.59). Seropositivity was significantly more common in the children whose older siblings were seropositive (55.0%, 22/40) than in the children whose older siblings were seronegative (23.5%, 20/85; OR = 3.97, P = 0.00051, 95% CI = 1.79-8.84). There was no significant relationship in seroprevalence between children and fathers, grandchildren and grandfathers, grandchildren and grandmothers, or within couples. Seropositivity was significantly more common in the adolescents who had attended a nursery school (44.4%, 20/45) than in the adolescents who had not attended a nursery school (25.6%, 109/426) (OR = 2.33, P = 0.0070, 95% CI = 1.24-4.36). CONCLUSIONS: The acquisition of H. pylori infection occurs by close contact with infected individuals in early childhood, especially via contact with infected mothers and other infected children.

Adolescent↗

PubMed2000

Changes in contused lung volume and oxygenation in patients with pulmonary parenchymal injury after blunt chest trauma.

Although it is well known that pulmonary parenchymal injury impairs oxygenation, the relationship between hypoxemia and volume of the contused lung after blunt chest trauma remains unknown. We studied 23 blunt chest trauma patients who underwent thoracic computed tomography (CT) within 24 hours after admission and also underwent follow-up CT at 1-week intervals until abnormal lung findings disappeared. Contused lung volume was determined quantitatively by CT. CT findings of parenchymal injury were either a diffuse lesion that disappeared within 1 week (n = 9 patients, group 1), or a solitary lesion that remained a few weeks after resolution of the diffuse lesion (n = 14 patients, group 2). PaO2/FiO2 was positively correlated with the volume of contused lung during the first 24 hours in both groups, however, there was no significant correlation after 1 week after injury. Degree of impaired oxygenation is related to the volume of the diffuse lesion that is recognized soon after injury.

Adolescent↗

PubMed2000

Does blood type B protect against haemolytic uraemic syndrome? An analysis of the 1996 Sakai outbreak of Escherichia coli O157:H7 (VTEC O157) infection. The Osaka HUS Critical Care Study Group.

OBJECTIVES: Expression of the P1 blood type antigen is suggested to have a protective effect against post-enteropathic haemolytic uraemic syndrome (HUS). The B blood type may also protect against HUS, since terminal trisaccharide sequences similar to those of the B blood type determinants are reported to have an affinity to Vero cytotoxin that is 23% as strong as that of the P1 determinants. Thus, we studied whether ABO blood types were related to the occurrence or severity of HUS. METHODS: We obtained clinical and laboratory data of 49 HUS patients treated in 14 critical care facilities during the 1996 Escherichia coli O157:H7 outbreak in Sakai, Japan. We retrospectively studied whether ABO blood types were related to the occurrence or severity of HUS. RESULTS: The numbers of patients with blood types A, B, O or AB were 29, 8, 12, and 0, respectively. For each blood type, the number of patients with severe renal complications was 16, 6, 9, and 0, respectively. The distribution of blood types among the HUS patients deviated from a population-based distribution of blood types (P<0.05, Chi-squared test); i.e., the frequency of the A blood phenotype was significantly higher among our HUS patients. However, there was no significant difference in the frequency of patients with the A antigen (A and AB blood groups) among our HUS patients, whereas the frequency of B antigen expression was significantly lower (P<0.05, Chi-squared test). The risk of severe renal complications did not appear to be related to ABO blood types. CONCLUSIONS: Our data suggest that expression of the B antigen has a protective effect against the onset of HUS, but that it does not affect the severity of the disease.

ABO Blood-Group System↗

PubMed2000

Successful repair of tracheal defect using gelatin-resorcin-formaldehyde-glue-reinforced fascia patch.

We describe the case of a 63-year-old female who underwent repair of a membranous tracheal defect. The tracheal perforation occurred after subtotal esophageal resection, and was associated with empyema due to esophago-gastric anastomotic leakage. We employed a fascia patch reinforced with Gelatin Resorcin- Formaldehyde/Glutaraldehyde glue for the repair, as pedicle muscular flaps were not available due to thoracotomy and a pericardial patch was inadequate because of the empyema. Our method was uncomplicated and provided a satisfactory result.

Drug Combinations↗

PubMed2000

Production of interferon-gamma by tonsillar mononuclear cells in IgA nephropathy patients.

Much evidence, both in vivo and in vitro, suggests that patients with IgA nephropathy (IgAN) have enhanced IgA production. We hypothesized that Haemophilus parainfluenzae (HP) in the tonsil plays an important role in the IgA production of IgAN patients. In this study, we focused on interferon-gamma (IFN-gamma) and IgA production by tonsillar mononuclear cells (TMC) in patients with IgAN. Tonsillectomies were performed in patients with IgAN and chronic tonsillitis (CT). The induction of IFN-gamma and IgA in vitro by TMC from IgAN patients was compared with that from CT patients. In addition, we investigated whether stimulation with the outer membranes of HP (OMHP) enhanced IFN-gamma and IgA induction by TMC from patients with IgAN. Spontaneous IFN-gamma production and spontaneous total IgA production by TMC were higher in IgAN patients than in those patients with CT (p < 0.05). IFN-gamma induction by OMHP stimulation was also higher in IgAN patients than in CT patients. The stimulation of OMHP enhanced HP-specific IgA in IgAN but had no influence on the production of IFN-gamma in patients with either IgAN or CT compared with spontaneous IFN-gamma production. IFN-gamma production was positively correlated with total IgA values in both IgAN and CT patients, but not with HP-specific IgA. These results suggest that increased IFN-gamma production in patients with IgAN is not associated with HP infection but may play a role in the pathogenesis of IgAN.

Adenoids↗