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Biomedical subjects

M Yamakido

Publications and source records attributed to M Yamakido.

At least 19 recordsLinked to original sources
PubMed2001

Helicobacter pylori infection and the development of gastric cancer.

BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.

Adult↗
PubMed2001

Efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma.

OBJECTIVE: The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI. METHODOLOGY: Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials. RESULTS: At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated. CONCLUSION: Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.

Anti-Inflammatory Agents↗
PubMed2001

Mechanism of increased serum soluble interleukin-2 receptor levels in patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: The aim of this study was to investigate the mechanism underlying the increase of serum soluble interleukin-2 receptor (IL-2R) levels in patients on continuous ambulatory peritoneal dialysis. MATERIAL AND METHODS: In 13 dialysis patients and 17 healthy controls, serum soluble IL-2R levels were determined by enzyme-linked immunosorbent assay, and CD25-positive (cell surface IL-2R-positive) cells were detected by flow cytometry. Soluble IL-2R levels were also measured in the supernatant of cultured peripheral blood mononuclear cells. RESULTS: The serum soluble IL-2R level was significantly higher in the patients than in the healthy controls (p < 0.0001). In contrast, both the percentage and the absolute count of CD25-positive cells showed no significant differences, and neither did the soluble IL-2R level in culture supernatant. Serum soluble IL-2R levels showed a positive correlation with the serum beta2-microglobulin level (p < 0.01), the age of the patients (p < 0.05), and duration of dialysis (p < 0.05), as well as a negative correlation with the urine volume (p < 0.05). CONCLUSIONS: The increase of serum soluble IL-2R in patients on peritoneal dialysis may be caused by accumulation due to its low transperitoneal clearance and low urinary excretion.

Adult↗
PubMed2001

Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese.

Polymorphisms at three loci in the thiopurine methyltransferase (TPMT) gene are known to be responsible for azathioprine and 6-mercaptopurine (6MP) toxicity. Among them, only TPMT*3C variant allele with A719G mutation was found in 15/522 (2.9%; 17/1044 alleles; 1.6%) Japanese individuals including two homozygotes. The allele frequency was different from that in Caucasians, and investigation of TPMT polymorphisms with consideration of ethnic differences before administration of azathioprine or 6MP may provide clinically useful information.

Alleles↗
PubMed2001

Multiple logistic regression analysis of risk factors for the development of steroid-dependent asthma in the elderly: a comparison with younger asthmatics.

BACKGROUND: The percentage of the aged among all patients with bronchial asthma is increasing. OBJECTIVE: To investigate the risk factors for the development of steroid-dependent asthma in the elderly. METHODS: A multiple logistic regression analysis involving various clinical factors between steroid-dependent and -independent asthma was carried out for 59 asthmatics aged over 60 years, including 16 patients with steroid-dependent asthma. The calculated risk for each factor was compared with that obtained from 122 younger asthmatics aged 20-59 years. RESULTS: Among the factors examined (sex, age, period from onset of asthma, type of asthma and family history of asthma, plus history of smoking, atopic dermatitis, allergic rhinitis, chronic sinusitis and nasal polyps), the significant risk factors for the development of steroid dependency in the elderly asthmatics were only family history of bronchial asthma (relative risk 3.6) and smoking history (relative risk 6.9). CONCLUSIONS: Some risk factors for steroid-dependent asthma in younger individuals were not significant in the elderly. Since the smoking history was most closely associated with the development of steroid dependency in the elderly, even though most of them had quit smoking, it is important for patients with asthma to avoid smoking.

Adult↗
PubMed2001

Association of apolipoprotein E phenotype with hypertension in Japanese-Americans: data from the Hawaii-Los Angeles-Hiroshima Study.

We evaluated the association between the phenotypes or alleles of apolipoprotein E and hypertension in Japanese-Americans living in Hawaii or Los Angeles. The study consisted of 932 nondiabetic participants aged 40-79 years. Of these participants, 315 were hypertensive, while the remainder were normotensive. The prevalence of hypertension was higher in subjects with the e2 allele than in those without. Using a multivariable prediction model that included age, serum glucose, insulin, lipids, and body mass index, we found the epsilon2 allele to be associated with hypertension in men (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.05-2.24) and for both sexes combined (OR, 1.35; 95% CI, 1.05-1.73). In a follow-up study, 37 of the 352 (11%) normotensive subjects had developed hypertension 4 years after the baseline examination. The frequencies of the apolipoprotein E phenotype E3/2 and the epsilon2 allele were higher in the subjects who became hypertensive than in those who remained normotensive. The E3/2 phenotype was associated with incidence of hypertension after adjustment for age, sex, baseline body mass index, and systolic blood pressure (OR, 1.75; 95% CI, 1.01-2.90). When serum lipids, glucose, and insulin were included in this analysis, the E3/2 phenotype tended to be associated with the incidence of hypertension. In conclusion, the epsilon2 allele of apolipoprotein E was associated with hypertension in Japanese-Americans. This association may be mediated via high levels of serum triglycerides that in turn are mediated in part by the epsilon2 allele. Nonlipid mechanisms may also be responsible for the effect of the epsilon2 allele on hypertension.

Aged↗
PubMed2001

Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study.

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.

Blood Glucose↗
PubMed2001

Two cases of severe bronchopneumonia due to influenza A (H3N2) virus: detection of influenza virus gene using reverse transcription polymerase chain reaction.

We report two cases of severe bronchopneumonia due to influenza A (H3N2) virus. The severity of the disease necessitated initiation of empiric therapy based on the present illness and clinical data on admission. Both patients were improved by artificial ventilation with positive end-expiratory pressures and administration of broad spectrum antibiotics and corticosteroids before confirming the diagnosis of viral bronchopneumonia using viral culture and serological tests. Within 24 hours, influenza A (H3N2) virus was identified by amplification of the pathogen genes by reverse transcription polymerase chain reaction (RT-PCR) using the stored bronchoalveolar lavage (BAL) fluids of both cases. This suggests that a combination of detection methods of pathogens using RT-PCR and BAL fluid will facilitate determination of rational treatment aimed at influenza A virus.

Aged↗
PubMed2001

[A case of lung adenocarcinoma showing diffuse air-space consolidation with idiopathic interstitial pneumonia].

Routine chest radiography demonstrated abnormal opacities in the right lower lung field of a 54-year-old man with idiopathic interstitial pneumonia. A high-resolution chest CT scan showed diffuse air-space consolidation in the right lower lung with replacement of a honeycomb area. The diagnosis was adenocarcinoma, and a right lower lobectomy was performed. Histopathologic examination showed moderately differentiated adenocarcinoma and the pathological stage was T3 N0 M0 (Stage IIB). About 1 year later, the cancer recurred with diffuse air-space consolidation in the whole of the right lung and the left middle and lower lung, which resulted in the patient's death. It was difficult to discriminate between an acute change for the worse of idiopathic interstitial pneumonia and a recurrence of lung cancer on the basis of the CT findings in this patient. It is important to elucidate the CT features of lung cancer associated with idiopathic interstitial pneumonia.

Adenocarcinoma↗
PubMed2001

[A case of idiopathic interstitial pneumonia that responded well to intermittent intravenous administration of high doses of cyclophosphamide and a steroid].

A 78-year-old man was hospitalized on February 29, 2000 because of dyspnea. A chest radiograph showed diffuse bilateral interstitial shadows associated with pulmonary volume loss. We could not obtain histological evidence of idiopathic interstitial pneumonia (IIP) because of his advanced age and severe respiratory dysfunction. IIP was diagnosed on the basis of radiographic findings and clinical symptoms. The patient was intubated and mechanical ventilation was performed. After one course of pulsed cyclophosphamide (CPM) and methylprednisolone therapy, the hypoxemia improved and it became possible to wean the patient from the ventilator. After five courses of pulsed CPM therapy, the dose of oral corticosteroid was tapered. CPM was administered safely without any severe side effects. Pulsed CPM therapy appears to be a viable alternative method of treatment for IIP.

Aged↗
PubMed2000

Glutathione S-transferase-pi gene expression and platinum drug exposure in human lung cancer.

We examined the association between the gene expression levels of glutathione S-transferase-pi (GST-pi) and platinum drug exposure in human lung cancer. First we monitored GST-pi gene expression levels in two lung cancer cell lines and in peripheral mononuclear cells of ten previously untreated lung cancer patients after platinum drug exposure. Next we examined GST-pi gene expression levels in 40 lung cancer autopsy specimens. The GST-pi gene expression levels were assessed by the quantitative reverse transcription-polymerase chain reaction or Northern blot analysis. The GST-pi gene expression was not induced by platinum drugs either in vitro and in vivo within 24 h of exposure. In contrast, GST-pi gene expression levels in lung cancer tissues of patients who had been exposed to platinum drugs at least 1 month before death were significantly higher than that in those of patients who had not been exposed. These results suggest that GST-pi gene expression is associated with chronic exposure to platinum drugs in lung cancer and/or the stress response to xenobiotics.

Antineoplastic Agents↗
PubMed2000

Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer.

To investigate the role of the multidrug resistance-associated protein (MRP1) homologue MRP5 in relation to platinum drug resistance, we examined the steady-state levels of the mRNAs for MRP5 in both lung cancer cell lines and peripheral mononuclear cells (PMN) after exposure to platinum drug and in normal lung and lung cancer tissue specimens. Firstly, we examined MRP5 gene expression levels in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients who had died from lung cancer. Next, we monitored MRP5 gene expression levels within 24 hr in both lung cancer cell lines incubated with cisplatin and in PMN from 10 previously untreated lung cancer patients after carboplatin administration alone. The MRP5 gene expression levels were assessed by quantitative reverse transcription polymerase chain reaction or RNase protection assay. The MRP5 expression levels in normal lung tissues and in tumors from patients exposed to platinum drugs during their lifetime were significantly higher than those in tissues from non-exposed patients. On the other hand, the MRP5 expression levels were not rapidly induced by platinum drugs either in lung cancer cell lines or in PMN within 24 hr. Our results suggest that increased expression levels of the MRP5 gene are associated with exposure to platinum drugs in lung cancer in vivo and/or the chronic stress response to xenobiotics.

ATP-Binding Cassette Transporters↗
PubMed2000

Association of sex hormone-binding globulin and insulin resistance among Japanese-American subjects.

An association between sex hormone-binding globulin (SHBG) and insulin resistance expressed by the homeostasis model (HOMA-R), and the significance of both variables as risk factors for the development of type 2 diabetes were investigated in 483 Japanese-American subjects. The serum SHBG level was significantly higher in women (68.7 nmol/l) than in men (45.1 nmol/l). This difference was also significant independently of age, body mass index (BMI), waist to hip ratio (WHR), and HOMA-R. When multiple regression analysis was performed after adjustment for age and BMI, SHBG was not correlated with HOMA-R in men. In women, SHBG was not significantly correlated with HOMA-R after adjustment for age, BMI, and WHR. In a 3-year prospective analysis, HOMA-R was significantly higher in converters to type 2 diabetes than non-converters in both men and women which was independent of age, BMI and WHR. However, after adjusting these variables, SHBG was not a significant risk factor either in men or women. These results indicate that SHBG might be related to insulin resistance secondarily via BMI and/or WHR in both men and women among Japanese-Americans. HOMA-R is a useful index for both men and women as a risk factor of type 2 diabetes when only fasting blood samples can be obtained.

Aged↗
PubMed2000

Allelotype and loss of heterozygosity around the L-myc gene locus in primary lung cancers.

L-myc S-allele was reported to be associated with metastasis of lung cancer, indicating the existence of a putative tumor suppressor gene around the L-myc locus, in linkage disequilibrium. The relationship between the S-allele and inactivation of some tumor suppressor gene should be indicated by allelic loss. Therefore, we examined the association between the L-myc S-allele and loss of heterozygosity at 11 loci around the L-myc locus (1p34.3) in primary lesions or other biological characteristics in lung cancer. No associations between the S-allele and allelic loss around the L-myc locus or other characteristics were found. According to the deletion map, three shortest regions of overlap between D1S230 and D1S76 were identified. While loss of heterozygosity at SRO1, between D1S2797 and MYCL1, showed no relationship with the pathological stage, it was more frequently observed in squamous cell carcinoma than adenocarcinoma (P=0.019), and associated with high telomerase activity (P=0.046), an indicator of cellular immortality. In conclusion, we found three shortest regions of overlap (SROs) from D1S2797 to pter, and a tumor suppressor gene, which might be associated with suppression of lung cancer development but not with L-myc S-allele, may exist in SRO1.

Adult↗
PubMed2000

A double-blind, placebo-controlled steroid-sparing study with budesonide Turbuhaler in Japanese oral steroid-dependent asthma patients. Japanese Pulmicort Turbuhaler study group.

OBJECTIVE: The aim of this study was to evaluate the oral steroid-sparing capacity of budesonide Turbuhaler. METHODOLOGY: One hundred and thirteen oral steroid-dependent patients were treated for 6 months with placebo or budesonide 800 microg or 1600 microg daily. Every second week the oral steroid dose was reduced if asthma control permitted. RESULTS: The reductions in oral steroid doses were 9, 35 and 60% in the placebo and budesonide 800 microg and 1600 microg groups, respectively. Oral steroid treatment could be discontinued in 4% (placebo), 15% (800 microg) and 23% (1600 microg). Mean peak expiratory flow values increased by 21 and 24 L/min in the budesonide groups but decreased by 6 L/min in the placebo group. Asthma attack, activity and sleep scores remained unchanged showing maintained efficacy. Plasma cortisol levels increased and an adrenocorticotropic hormone test showed improved adrenocortical response in both budesonide groups, indicating improved safety. Adverse drug reactions were infrequent and mild in all study groups. CONCLUSION: Budesonide Turbuhaler, 800 microg and 1600 microg daily, resulted in a significant reduction in oral steroid usage in steroid-dependent patients. The effect was achieved with maintained asthma control together with improvements in lung and adrenal functions.

Administration, Inhalation↗
PubMed2000

A double-blind, placebo-controlled dose-response study with budesonide Turbuhaler in Japanese asthma patients. Japanese Pulmicort Turbuhaler study group.

OBJECTIVE: The aim of this study was to investigate the dose-response for inhaled budesonide via Turbuhaler in Japanese patients with mild to moderate asthma. METHODOLOGY: Inhaled budesonide 100 microg, 200 microg, 400 microg or placebo was administered twice daily via Turbuhaler for 6 weeks, to 267 adult Japanese patients (mean age 51 years) with mild-to-moderate, non-steroid-dependent bronchial asthma, in a double-blind, placebo-controlled, randomized, parallel group study. The patients had to be symptomatic for more than 3 days/week and have an average morning peak expiratory flow (PEF) 50-80% of predicted normal value. RESULTS: The response to budesonide was rapid, all treatments showing a significant improvement in morning PEF after 1 week (P<0.05). During week 6, mean improvements of 15, 45, 53 and 71 L/min were observed for the placebo, 200 microg, 400 microg and 800 microg budesonide groups, respectively. Compared with placebo all improvements in the budesonide groups were statistically significant and a significant dose-response was demonstrated (P<0.001). The difference between the 200 microg and 800 microg doses was significant. Also, for several secondary efficacy variables (e.g. evening PEF, symptom score, treatment score, daily activity score and sleep score) significant dose-responses were shown. Other variables included the investigators' assessments of improvement and usefulness. They also showed statistically significant dose-response relationships and confirmed the rapid onset of action. Budesonide was well tolerated at all tested doses, with a low incidence of adverse events, all of which were minor in severity. CONCLUSIONS: Budesonide Turbuhaler in the doses 100 microg to 400 microg twice daily was effective, well tolerated and showed a rapid onset of action in patients with mild-to-moderate asthma. Dose-response was demonstrated for several variables of clinical efficacy.

Administration, Inhalation↗