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Biomedical subjects

S Niwa

Publications and source records attributed to S Niwa.

At least 91 records · Page 5Linked to original sources
PubMed1996

Role of enteric bacteria in the pathogenesis of rheumatoid arthritis: evidence for antibodies to enterobacterial common antigens in rheumatoid sera and synovial fluids.

OBJECTIVE: To study antibodies to Escherichia coli O:14, which expresses large amounts of enterobacterial common antigen (ECA), and their corresponding antigen molecules in serum and synovial fluid samples from patients with rheumatoid arthritis (RA). METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure antibodies to heat killed E coli O:14 in serum and synovial fluid samples from patients with RA and control subjects including healthy donors and patients with osteoarthritis. ELISA was also used to perform absorption analyses of antibodies to E coli O:14 with several enteric bacteria and their lipopolysaccharide (LPS). In addition, antigenic molecules reacting with E coli O:14 antibodies from patients with RA were examined using immunoblot analysis and N-terminal amino acid analysis. RESULTS: Compared with control subjects, patients with RA showed significantly increased titres of antibodies against heat killed E coli O:14 in 33 of 83 serum samples (39.8%) and 38 of 58 joint fluid samples (65.5%). Absorption analyses with enteric bacteria and their LPS resulted in the reduction of antibody titres to heat killed E coli O:14 in serum and synovial fluid samples from the RA patients. In addition, immunoblot analysis of the samples from RA patients revealed not only a ladder-like banding pattern equivalent to ECA associated with LPS, but also two clear bands of bacterial outer membrane proteins of 35 kDa (Omp A) and 38 kDa (Omp C), having amino acid sequence homology with those of other Enterobacteriaceae. CONCLUSION: These results suggest that some patients with RA are sensitised to antigens common to Enterobacteriaceae, and this may prove relevant to the future development of immunotherapy for RA. Furthermore, this sensitisation to antigens found commonly in Enterobacteriaceae may have a key role in the pathogenesis of human RA similar to that described previously in our animal model.

Adult↗
PubMed1996

[Study on anaerobic threshold in normal pregnant women].

We evaluated the anaerobic threshold (AT) in 104 normal pregnant women mainly in their second trimester. Each exercise testing was performed by using incremental bicycle ergometry at a pedal frequency of 60rpm while monitoring maternal heart rate, maternal blood pressure, minute ventilation (VE),oxygen uptake (VO2) and carbon dioxide output (VCO2) every 30 seconds. The AT was determined by estimating the point of departure from linearity of the plot of VE as a function of VO2. We could determine the AT in 100 cases (96.2%), and their AT values and the heart rates at AT point were 14.7 +/- 1.7ml/min/kg (mean +/- S.D.) and 128 +/- 12bpm, respectively. AT decreased significantly (p < 0.01) with the length of gestation, because of increased maternal body weight. The heart rate at the AT also declined significantly (p < 0.05) with gestational age, but it had no relation with maternal body weight. These results show that the maternal heart rate becomes hard to increase with gestational age, so that the maximal heart rate, as an index of exercise intensity during exercise should decrease with advancing gestational age.

Adult↗
PubMed1996

Obesity and risk of renal cell cancer.

In a population-based case-control study including 449 directly interviewed cases and 707 controls, we assessed the risk of renal cell cancer associated with height, weight, body mass index (BMI), and frequency of weight changes. Odds ratios and 95% confidence intervals were estimated by using logistic regression models. Among women, risk increased with increasing usual BMI (P for trend < 0.001). A nearly 4-fold risk was found among the 10% of women with the highest usual BMI (odds ratio = 3.8; confidence interval = 1.7-8.4). Among men, no clear trend was observed with usual weight or BMI, although the highest risk (30-50%) generally was seen among those in the upper deciles of weight or BMI. There was no clear indication that excess BMI early or late in life disproportionately affected risks. Risk also was not related to patterns of weight fluctuations or use of diet pills. Our study supports previous observations linking renal cell cancer risk to increased BMI among women and suggests a weaker association in men. Given the increasing prevalence of obesity and the rising incidence of renal cell cancer in the United States, additional studies are needed to disentangle the effects of BMI from various correlates and to identify the mechanisms by which obesity affects risk.

Adult↗
PubMed1996

[The mechanism of controlling regional cerebral blood flow in patients with localization-related epilepsy].

INTRODUCTION: Hypoperfusion around the seizure foci has been reported in interictal CBF studies of partial epilepsy. Hypoperfusion may reflect some interictal pathophysiology characteristic of epilepsy, but the mechanism remains to be elucidated. In order to elucidate the controlling system of rCBF in patients with CPS (complex partial seizure), we measured by positron emission tomography rCBF and CO2 vasoreactivity performing a hyperventilatory task, and made comparisons between the affected and contralateral sides of the temporal lobes in CPS patients and the temporal lobe of normal volunteers. We also measured PaCO2, pH, PaO2 and respiratory rate at rest to elucidate the CBF maintaining system. SUBJECTS: 15 volunteers and 12 medically controlled patients with CPS were examined. The affected side of the brain of the patients was determined by dominance of EEG paroxysm. METHOD: For measuring rCBF, the Shimadzu HEADTOME-IV system (8mm FWHM) and H2(15)O (740-1480 [MBq]/scan) bolus injection method were employed. First a rest scan, then a hyperventilatory task scan was performed, at 20 min. intervals between each scan. During the rest scans, the subjects were required to close their eyes, which were covered through the transmission scan and all the other scans. They were monitered with EEG to insure that they were not asleep. Room lights were dimmed, room sounds were kept to a minimum and noises were damped with earplugs. During the hyperventilatory tasks, the subjects were asked to inspire deeply at a rate of 15/min. for 4.5 min. from 3 min. before the scan up to the end of the 1.5 min. scan, and monitored with a respiratory band around the abdomen. Arterial blood gas pressures (PaCO2, pH and PaO2) were also measured with a blood gas analyzer (Radio Meter ABL 330) at the beginning and at the end of the scans. [HCO3-] was calculated on the formula of Henderson-Hasselbalch. Vascular response to PaCO2 change: VrCO2 was defined as follows: VrCO2 = 100 x (CBFh-CBFr)/CBFr/(PaCO2h-PaCO2r) the subscripts h: hyperventilatory r: resting conditions. RESULTS: Blood gasses, rCBF and corrected-rCBF at rest: In the patients, PaCO2 (mmHg) = 46.11 +/- 2.32, pH = 7.374 +/- 0.020, [HCO3-] (mEq/ml) = 25.98 +/- 1.15, CBF (ml/100g/min) = 45.51 +/- 9.33, corrected-CBF (ml/100g/min) = 40.06 +/- 7.27. In the volunteers, PaCO2 = 40. 67 +/- 2.37, pH = 7.400 +/- 0.021, [HCO3-] = 24.36 +/- 1.66, CBF = 48.76 +/- 8.54, corrected-CBF = 48.02 +/- 9.04. PaCO2 and [HCO3-] in the patients were significantly higher than those in the volunteers. pH and corrected-CBF were significantly lower than those in the volunteers. CBF showed no difference. VrCO2 in the temporal lobe: In the affected side of the patients, VrCO2 = 1.976 +/- 0.54. In the contralateral side of the patients, VrCO2 = 2.145 +/- 0.667. In the temporal lobe of the volunteers, VrCO2 = 2.557 +/- 0.898. In both sides of the temporal lobe of the patients, VrCO2 was significantly lower than those in the volunteers. COMMENTS: The effect of anticonvulsant drugs and the suppressive mechanism around the foci are supposed to reduce CBF of CPS patients. We suppose another mechanism, which is vasoconstriction. A significant difference was noted in CO2-vasoreactivity in the temporal lobe between patients and volunteers. Also no difference was noted in rCBF in the temporal lobe between the volunteers and the patients, when the arteries were maximally constricted with the HIV-task. These two results suggest that vasoconstrictive mechanism may be among the factors for the hypoperfusion seen in the temporal lobe of the patients. In patients, PaCO2, [H+], [HCO3-] were significantly higher compared with the volunteers, which suggests the mechanism of respiratory acidosis. Owing to this hypercapnia, global CBF in the patients is maintained in compensation for the hyperfusion and vasoconstriction seen around the foci. CO2 acts as an anticonvulsant and also reduces glucose metabolites which accumulate around the foci.

Adult↗
PubMed1995

International renal-cell cancer study. VIII. Role of diuretics, other anti-hypertensive medications and hypertension.

Risk of renal-cell cancer in relation to use of diuretics, other anti-hypertensive medications and hypertension was assessed in a multi-center, population-based, case-control study conducted in Australia, Denmark, Germany, Sweden and the United States, using a shared protocol and questionnaire. A total of 1,732 histologically confirmed cases and 2,309 controls, frequency-matched to cases by age and sex, were interviewed. The association between renal-cell cancer and the drugs was estimated by relative risks (RRs) and 95% confidence intervals (CIs). Risks were increased among users of diuretics and other anti-hypertensive medications. After adjustment for hypertension, risk for diuretics was reduced to unity, except among long-term (15+ years) users. Risk for use of non-diuretic anti-hypertensive drugs remained significantly elevated and increased further with duration of use. Overall risk was not enhanced when both classes of medications were used. Excess risk was not restricted to any specific type of diuretic or anti-hypertensive drug and no trend was observed with estimated lifetime consumption of any particular type of product. The RR for hypertension after adjustment for diuretics and other anti-hypertensive medications was 1.4 (95% CI = 1.2-1.7), although among non-users of any anti-hypertensive medications, there was little excess risk associated with a history of hypertension. Exclusion of drug use that first occurred within 5 years of cancer diagnosis or interview did not alter the associations. Our findings suggest small effects on renal-cell cancer risk associated with hypertension and use of diuretics and other anti-hypertensive medications. However, because of potential misclassifications of these highly correlated variables, it is difficult to distinguish the effect of treatment from its indication, hypertension.

Antihypertensive Agents↗
PubMed1995

Reproductive factors and the risk of renal cell cancer among women.

In etiologic studies of renal cell carcinoma the role of reproductive variables and the use of exogenous hormones have not been well examined. In a population-based case-control study including 165 female cases and 227 controls, we assessed the risk of renal cell cancer associated with reproductive factors and use of oral contraceptives and menopausal hormones. Odds ratios were computed using logistic regression analyses. Risk was positively associated with number of births and inversely associated with age at first birth, with the largest increases in risk (more than 2-fold) among women with 5 or more births after age 25. After adjustment for age, smoking status, body mass index and age at first birth, women with 5 or more births had a 2-fold risk (OR = 2.2, 95% CI = 1.2-4.0) relative to those with 1 or 2 births. Age at first birth, however, was no longer a risk factor when the number of births was adjusted for. The association with parity was considerably stronger among women with a history of hypertension or above-median body mass index than among those without these conditions. In addition, risk was reduced among long-term oral contraceptive users but elevated among women who had had a hysterectomy or used menopausal hormones. Our findings suggest that reproductive factors, particularly the number of births, may play an etiologic role in renal cell cancer among women and deserve further study.

Adult↗
PubMed1995

International renal-cell cancer study. II. Analgesics.

There has been concern about the role of analgesics in the development of renal-cell cancer, although a few studies have reported moderately elevated risks with regular or long-term use. In a large international case-control study of renal-cell cancer we examined, among other hypotheses, the effect of phenacetin-containing and of other types of analgesics: paracetamol (acetaminophen), salicylates (mainly aspirin) and pyrazolones (e.g., antipyrine or phenazone). Relative risks, adjusted for the effects of age, sex, body-mass index, tobacco smoking and study centre, were not significantly increased with intake of phenacetin, either when lifetime consumption was categorized at the level of > or = 0.1 kg or when subjects were subdivided further by amount. Nor were paracetamol, salicylates or pyrazolones linked with renal-cell cancer. No consistently increasing risks with consumption level was found. The lack of association was not altered by restricting analgesic use to that which occurred 5 or 10 years before the defined "cut-off" date or when analysis was restricted to exclusive users of a particular type of analgesic. Neither was the risk influenced by the rate of consumption or whether the consumption had occurred at a young age. Our study provides clear evidence that aspirin is unrelated to renal-cell cancer risk, and our findings do not support the hypothesis that analgesics containing phenacetin or paracetamol increase the risk, although the number of "regular" users and the amount of these types of analgesic consumed were too small to confidently rule out a minor carcinogenic effect of phenacetin and paracetamol.

Acetaminophen↗
PubMed1995

International renal-cell cancer study. III. Role of weight, height, physical activity, and use of amphetamines.

Although numerous studies have identified obesity or high relative weight as a risk factor for renal-cell cancer in women, the degree to which this effect is present in men remains unclear. A multicenter population-based case-control study concerning incident cases of histologically verified renal-cell cancer (n = 1,732) and age- and sex-matched controls (n = 2,309) was conducted in Australia, Denmark, Germany (2 centers), Sweden and the United States. Relative weight was estimated by the body mass index, and the association between this factor and other factors, such as height, physical activity and use of amphetamines, was measured by the relative risk estimated in logistic regression models. Body mass index was found to be a risk factor among women and, to a lesser extent, among men. A 3-fold increased risk (RR = 3.6, 95% CI = 2.3-5.7) was observed for women with a relative weight in the top 5% compared with those in the lowest quartile. Rate of weight change (estimated as weight change per annum in kilograms) appeared to be an independent risk factor among women but not among men. Physical activity and height were unrelated to risk of renal-cell cancer regardless of level of BMI, while use of amphetamines was associated with an increased risk among men, although no dose or duration effect was seen. Our findings verify the link between high relative weight and risk of renal-cell cancer, particularly among women. The mechanism that underlies this association is, however, still unclear, although the rate of weight change may play a role.

Adult↗
PubMed1995

Risk of renal cell cancer in relation to diuretics, antihypertensive drugs, and hypertension.

Although recent data have suggested an association between renal cell cancer and the use of diuretics, it remains unclear whether these medications or hypertension is the important risk factor. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with hypertension and use of diuretics and other antihypertensive medications. Risks increased with the use of diuretics or other drugs that lower blood pressure, especially among persons who reported no history of hypertension. After adjustment for hypertension, the use of diuretics alone was associated with a 40% excess risk (OR = 1.4; 95% CI = 0.8-2.2), while use of other antihypertensive drugs was linked to a 2-fold risk (OR = 2.0; 95% CI = 1.2-3.3). The excess risk was not restricted to any specific products, and no trend was observed with estimated lifetime consumption of any product. Furthermore, risk was not potentiated by the presence of both hypertension and the use of antihypertensive drugs. Among persons who did not use antihypertensive drugs, a history of hypertension was associated with a significant 40-50% excess risk of renal cell cancer. Excluding subjects with hypertension diagnosed within 5 years of cancer diagnosis or interview had only a small effect on risk. These findings suggest small effects on renal cell cancer risk associated with hypertensive disease and with the use of diuretics and other antihypertensive drugs, but it is difficult to disentangle the separate effects due to potential misclassification of highly correlated events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Use of analgesics and risk of renal cell cancer.

Although heavy or long-term use of analgesics has been related to risk of renal cell cancer in several studies, evidence for such an association remains inconclusive. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with lifetime consumption among those who reported during in-person interviews regular (at least 2 or more times per week for 1 month or longer) use of analgesics. Odds ratios (OR) were computed using logistic regression analyses. No excess risk was associated with regular use of aspirin, acetaminophen, phenacetin or combinations of these agents, nor did risks rise with increasing cumulative intake of these analgesics. A non-significant increased risk (OR = 2.1, 95% CI = 0.6-6.9) was observed among women who used only acetaminophen-containing analgesics, but little excess was seen in men. Earlier studies reported a link to phenacetin-containing analgesics, but no one reported exclusive use of phenacetin-containing drugs in our study. The findings suggest that use of analgesics is not likely to play a major role in renal cell cancer development and that for cases diagnosed in the late 1980s or later, after the earlier withdrawal of phenacetin-containing drugs from the market, a hazard from this analgesic no longer exists.

Acetaminophen↗
PubMed1994

Purification and properties of phosphatidylinositol-specific phospholipase C from Streptomyces antibioticus.

A novel type of phosphatidylinositol-specific phospholipase C (PI-PLC) was purified from culture supernatant of a strain of Actinomycetales, Streptomyces antibioticus. The purified enzyme showed a single band on native polyacrylamide gel electrophoresis (native PAGE) with a molecular weight of 32 kDa, but showed two polypeptides, named alpha- and beta-peptides, on sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) with molecular weights of 23 kDa and 15 kDa, respectively. From the results of both electrophoretic analysis and N-terminal amino acid sequencing, it was estimated that the enzyme was composed of alpha- and beta-peptides. The enzyme could hydrolyze phosphatidylinositol, but not any other glycerophospholipids. The enzyme had pH and temperature optima at around 7.0 and 30 degrees C, respectively, and was stable up to 50 degrees C when incubated at pH 8.0 for 30 min. The PI-PLC was strongly activated by SDS, sodium deoxycholate (SDC) and diethyl ether, but not by Triton X-100, and inhibited by cetylpyridinium chloride (CPC). The enzyme was activated a little by Ca2+ and was inhibited completely by a chelating agent such as ethylenediaminetetraacetic acid (EDTA) and glycoletherdiaminetetraacetic acid (EGTA). Their inhibitions were restored by the addition of Ca2+, suggesting that a certain amount of Ca2+ is essential for the enzymatic activity.

Amino Acid Sequence↗
PubMed1994

Protein intake and risk of renal cell cancer.

BACKGROUND: Renal cell cancer, although still relatively uncommon, has been increasing in incidence in the United States and other countries around the world. PURPOSE: Since previous studies have suggested an association with high intake of meat, we sought to further examine the role of diet in renal cell cancer risk. METHODS: Patients with histologically confirmed renal cell cancer that had been diagnosed between July 1, 1988, and December 31, 1990, were identified through the Minnesota Cancer Surveillance System, a statewide cancer registry. The patients eligible for inclusion in this study were white residents of Minnesota between 20 and 79 years of age. Control subjects were selected from the general population of Minnesota residents; subjects under age 65 were selected by use of a random-digit-dialing method and those 65 years or older were sampled from the Health Care Financing Administration files. Population-based control subjects were frequency-matched to cases by sex and 5-year age groups. A total of 690 patients and 707 control subjects were interviewed. Patients and control subjects were similar in distribution by sex, age, and educational level. Usual adult dietary intakes were assessed by questionnaire, and odds ratios were calculated by logistic regression analyses. RESULTS: Significantly increased risks of renal cell cancer were observed with increasing consumption of several food groups, including red meat (P for trend = .05), high-protein foods (P = .01), and staple (grains, breads, and potatoes) foods (P = .009). When examined by macronutrient status, risks increased monotonically with the amount of protein intake, from 1.2 (95% confidence interval [CI] = 0.7-1.9) to 1.4 (95% CI = 0.8-2.5) and 1.9 (95% CI = 1.0-3.6) (P for trend = .03) in the second, third, and fourth quartiles of intake, respectively, after adjustment for age, sex, caloric intake, body mass index, and cigarette smoking. No significant or consistent associations were detected with the intake of other dietary nutrients or beverages. CONCLUSION: Although an independent effect of dietary protein has not been previously associated with renal cell cancer, high protein consumption has been related to development of other chronic renal conditions that may predispose an individual to this cancer. IMPLICATION: These findings should prompt further study of dietary protein and its potential contribution to the origins of renal cell cancer.

Adult↗
PubMed1994

New potent prolyl endopeptidase inhibitors: synthesis and structure-activity relationships of indan and tetralin derivatives and their analogues.

New compounds were synthesized by structural modification of 1-[1-(4-phenylbutanoyl)-L-prolyl]-pyrrolidine (SUAM-1221, 1) or 1-[1-(benzyloxycarbonyl)-L-proly]prolinal (Z-Pro-prolinal,2) and were tested for in vitro inhibitory activities against purified prolyl endopeptidase (PEP) from canine brain. In a series of compounds which lack a formyl or a cyano group, 3-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- thioprolyl]thiazolidine (13) exhibited an approximately 20-fold (IC50 = 2.3 nm) increase in potency compared with 1. Compounds having a formyl or a cyano group showed much more potent inhibitory activities than those which lack such a functional group. Among all compounds tested in vitro, 1-[1-(2-indanylacetyl)-L-prolyl]prolinal (27), 1-[1-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- prolyl]prolinal (29), 1-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)-acetyl]-L-thioprolyl]p rolinal (30), (S)-2-cyano-1-[2-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- prolyl]pyrrolidine (34), and (S)-2-cyano-1-[3-[(S)-2-(1,2,3,4-tetrahydronaphthyl)acetyl]-L- thioprolyl]pyrrolidine (35) showed an approximately 2-fold (IC50 congruent to 0.5 nM) increase in potency compared with 2. The structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1994

Cortical control of saccade in normal and schizophrenic subjects: a PET study using a task-evoked rCBF paradigm.

In this study, positron emission tomography (PET) was used to evaluate cortical control of saccades. Regional cerebral blood flow (rCBF) patterns demonstrated by 15O water PET during saccadic task performance were tested in 13 normal volunteers and 20 ICD-9 schizo phrenics (10 unmedicated and 10 medicated). The following 3 saccadic tasks, which were controlled for sensory input and oculomotor output, were applied: (1) reflexive saccade = visually guided saccade, (2) volitional saccade = visually guided saccade with distracting stimuli, and (3) memory guided saccade. Schizophrenics lacked the frontal eye field (FEF) activation during every saccadic task. The left dorsolateral prefrontal cortex (DLPFC) was activated during volitional saccade only in normal controls. The rCBF of posterior parietal cortex increased in parallel with that in the DLPFC. These findings suggest functional hypofrontality in schizophrenia and the left DLPFC-PPC's crucial role in saccade against distracting stimuli and its dysfunction in the disease.

Adolescent↗
PubMed1994

Risk factors for renal cell carcinoma in Denmark: role of medication and medical history.

BACKGROUND: Several recent studies of risk factors for renal cell carcinoma have indicated that use of diuretics may increase risk of this cancer. It has also been suggested that use of weak analgesics, which are known to increase risk of cancer of the renal pelvis and ureter, may also be associated with an increased risk of renal cell carcinoma--the most frequent type of kidney cancer. METHODS: A population-based case-control study was undertaken to investigate the role of diuretics, other anti-hypertensive drugs, analgesics, and medical history in the aetiology of renal cell carcinoma. The study base was the total Danish population, and 368 histologically verified cases and 396 sex- and age-matched controls who were interviewed from February 1989 to May 1992. RESULTS: Response rates were 76% among cases and 79% among controls. We found no general increase in risk among users of diuretics or analgesics, although women taking loop diuretics and heavy users of acetyl salicylic acid had slightly increased risks. The use of nondiuretic anti-hypertensive medications was associated with decreased risk in women. We found non-significantly increased risks for history of hypertension and other cardiovascular disorders. We also observed elevated risks for urological disorders in both sexes which may be a result of recall bias. CONCLUSION: This study provides only limited support for the suggested association between risk of renal cell carcinoma and use of diuretics and analgesics. The coexistence of renal cell carcinoma and cardiovascular diseases could be caused by risk factors that are common to these conditions.

Adult↗