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Biomedical subjects

M Tanimura

Publications and source records attributed to M Tanimura.

At least 37 records · Page 2Linked to original sources

Short-term hemodynamic effects of mibefradil in dogs with chronic heart failure: comparison with diltiazem.

Despite the marked vasodilator and antiischemic actions of existing calcium channel blockers, their use in the treatment of patients with chronic heart failure (HF) remains highly controversial. We compared the short-term hemodynamic effects of i.v. mibefradil, a predominant T-type calcium channel blocker with only partial L-type calcium channel antagonism, and diltiazem, a selective L-type calcium channel antagonist in dogs with chronic HF. Each of three drugs namely, mibefradil, diltiazem and normal saline (as placebo control), were studied in random order (6 days between each drug intervention), in each of 8 dogs with chronic HF produced by multiple intracoronary microembolizations. Intravenous mibefradil and diltiazem were administered as a 100 micrograms/kg bolus followed by a continuous infusion of 6 and 4 micrograms/kg/min, respectively, for 15 min. Equal volumes of normal saline were administered in an identical fashion. In all instances, hemodynamics were obtained at base line and at 5, 10, 15, 30 and 60 min after bolus drug administration. Left ventriculograms were obtained at baseline, and at 15 and 60 min after bolus drug administration. Saline infusion had no effects on hemodynamic or angiographic indexes of left ventricular (LV) function. At 15 min, mibefradil caused significant increases of LV stroke volume and LV ejection fraction compared to baseline (40 +/- 5 vs. 31 +/- 3 ml, P < .05 and 41 +/- 1 vs. 28 +/- 1%, P < .05, respectively). In contrast, at 15 min, diltiazem produced no significant changes of LV stroke volume or ejection fraction compared to baseline despite reducing mean aortic pressure to the same extent as mibefradil. Short-term i.v. mibefradil improves LV function in dogs with chronic HF. The beneficial effects of mibefradil compared to diltiazem may be a consequence of T-type calcium channel selectivity resulting in a vasodilatory response that is free of negative inotropy.

Animals↗

Association between hepatoblastoma and very low birth weight: a trend or a chance?

Hepatoblastoma, a malignant hepatic tumor in children, is thought to be an embryonal tumor resulting from developmental disturbances during organogenesis. Although factors that might be involved in the tumorigenesis have been suggested, an association between hepatoblastoma and the patient's birth weight has not been reported. We have accessed the data in the Japan Children's Cancer Registry and have analyzed patients' diagnoses and birth weights. During the 9 years from 1985 to 1993, 38 (0.38%) patients with tumors who weighted less than 1500 gm at birth were identified among 9923 registered patients. Hepatoblastoma was diagnosed in 9 patients of very low birth weight, representing 3.9% of the 231 patients with hepatoblastoma registered. A significant linear trend toward an increase in the percentage of patients with a birth weight of less than 1500 gm was observed specifically in hepatoblastoma (p = 0.0047). The percentage rose from 0.7% (1/138) in the 5-year period of 1985 to 1989 to 8.6% (8/93) in the next 4-year period (1990 to 1993). This increase was attributed to the significant increase in the percentage of patients who weighed less than 1000 gm at birth (p = 0.0028). A separate peak in the number of patients in the birth weight range of less than 1000 gm suggests that the cause of hepatoblastoma related to very low birth weight may be different from that of other patients. Full analysis of the patients' data is an urgent matter.

Birth Weight↗

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure.

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfunction.

Animals↗

Short-term hemodynamic effects of endothelin receptor blockade in dogs with chronic heart failure.

BACKGROUND: Plasma endothelin levels are increased in heart failure and may contribute to the increased peripheral vasoconstriction that characterizes this disease state. In the present study, we examined the effects of intravenous bosentan, a nonpeptide, competitive endothelin-1 receptor antagonist, on hemodynamics in dogs with chronic heart failure. METHODS AND RESULTS: Chronic heart failure was produced in 11 dogs by multiple sequential intracoronary microembolization. At the time of study, left ventricular (LV) ejection fraction was 25 +/- 2%. Hemodynamic and echocardiographic measurements were made at baseline and at 15, 30, and 60 minutes after a bolus injection of bosentan (10 mg/kg). Bosentan had no significant effect on heart rate or mean aortic blood pressure. At 60 minutes, bosentan reduced LV end-diastolic pressure (17 +/- 2 versus 11 +/- 2 mm Hg; P < .05) and systemic vascular resistance (3891 +/- 379 versus 3071 +/- 346 dyne .s. cm-5; P < .05) compared with baseline and increased cardiac output (2.63 +/- 0.29 versus 3.33 +/- 0.46 L/min; P < .05), peak rate of change of LV pressure during isovolumic contraction and relaxation (1751 +/- 92 versus 2197 +/- 170 mm Hg/s; P < .05), and LV fractional shortening determined by echocardiography (30 +/- 2% versus 36 +/- 2%; P < .05). CONCLUSIONS: Short-term intravenous bosentan reduced systemic vascular resistance and improved overall LV performance in dogs with chronic heart failure. These results suggest that endothelin-1 receptor antagonists may be useful therapeutic agents in the treatment of heart failure.

Animals↗

Contribution of HLA class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans.

The HLA multigene family consists of HLA class I (HLA-A, B and C) and class II (HLA-DR, DQ and DP) genes, and plays a central role in the regulation of immune response. To investigate how each HLA gene and each HLA allele contribute to the human immune response, we immunized 339 healthy Japanese medical students with recombinant hepatitis B surface antigen (rHBsAg) and determined the HLA types of all vaccinated subjects at the DNA level. The anti-HBs antibody titers showed a log-normal distribution, implying that the immune response to HBsAg in humans is a multifactorial and continuous trait. A stepwise multiple regression analysis demonstrated the alleles at the HLA-class I (HLA-A and B) and class II (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1) loci significantly contributed to antibody production to HBsAg. The predicting equation of anti-HBs antibody levels for individuals with any HLA phenotype was proposed based on a multiple regression analysis. The multiple correlation coefficient of antibody production to HBsAg with the HLA-DRB1 locus was highest (0.34) among all of the HLA loci, whereas those with whole HLA class I or class II loci were 0.36 or 0.44 respectively. The incorporated correlation coefficient of the presence of all HLA gene families with antibody production became 0.50, suggesting that HLA class I and class II loci within the HLA multigene family are dynamically involved in regulation of the immune response to HBsAg.

Alleles↗

Tuberculoma arising in the inguinal portion of the spermatic cord: a case report.

A 50-year-old man was treated with excisional surgery for an asymptomatic inguinal spermatic cord mass. The lesion was proved to be tuberculous, and there was no apparent coexisting active disease elsewhere in the body. In addition to an intraoperative frozen-section examination, clinical findings of a strongly positive tuberculin skin test and normal erythrocyte sedimentation rate are considered to be helpful in establishing the diagnosis of a tuberculoma arising in either the scrotal or inguinal position.

Blood Sedimentation↗

Proximal subtotal gastrectomy for the treatment of carcinoma of the upper third of the stomach: its indications based on lymph node metastasis and perigastric lymphatic flow.

To clarify the indications for a proximal subtotal gastrectomy in the treatment of carcinoma in the upper third of the stomach based on lymph node metastases, 1055 patients in whom either a D2 or greater lymph node removal was performed were reviewed. In the patients in which the lesion was confined to the upper stomach and did not invade beyond the muscularis propria of the stomach wall, no metastases to either the lymph nodes above and below the pylorus or the lymph nodes along the greater curvature were observed. A lymphatic flow study revealed a minimal flow to these nodes from the upper stomach in patients without lymph node metastasis, but in cases with lymph node metastases the lymphatic flow changed. The indications for a proximal subtotal gastrectomy for a carcinoma of upper third of the stomach therefore must fulfill the following two conditions: (1) The deepest layer of cancerous invasion does not extend beyond the muscularis propria of the stomach wall, and (2) No macroscopic evidence of lymph node metastasis can be detected during surgery.

Case-Control Studies↗

Analysis of child abuse cases admitted in pediatric service in Japan. I. Two types of abusive process in low birth-weight infants.

A very high rate (43.0%) of low birth-weight (LBW) was shown in 331 abused/neglected cases reported from pediatric clinics of major hospitals in Japan. Of 87 LBW cases, 82.8% had medical problems and/or unsatisfactory reunion after non-home care and were abused at a particular age when each of the problems may have caused difficulties in caring. Two types of processes to abuse these intractable LBW were estimated: (i) abusers with psychiatric, mental problems or poor knowledge abused their children during the first 2 years, presumably because of an inability in child rearing; and (ii) abusers with neurosis or abnormal personality abused at ages over 2 years, complained of difficulties with rearing their children, and were suspected to be unable to cope with the difficulties. In both types, a combination of child and parental problems increased at risk. Obstetricians and neonatologists, who first encounter both high-risk mothers while pregnant and LBW, should give due care to the prevention of child abuse.

Child Abuse↗

Analysis of child abuse cases admitted in pediatric service in Japan. II. Backgrounds of child abuse in non-low birth-weight infants.

Child abuse of 126 non-low birth-weight (non-LBW) cases reported from pediatric clinics of major hospitals in Japan in 1986 were examined. Compared to LBW infants abused children's medical problems were few (25.4%) but the presence of step-parents and a history of rearing outside the home were evident (41.3%). The abuse of a child with medical problems by real parents showed similar characteristics to abuse of LBW, occurring at 0-1 and 4 years and two types of abuser's problems were apparent; one problem was the lack of child rearing ability and the other was the inability to cope with the stress involved in child rearing. In abuse of a child by step-parents, most abusers expressed emotional problems with their abused children. Child abuse by a real parent following a period of non-home care occurred soon after the child returned home, and abusers complained that the abused child did not take to its real parents. Abuse of a child without medical problems by real parents occurred at or around birth and indicated a poor ability to rear a child due to parental problems or low tolerance to cope with child rearing. Abuse both of a child and siblings by real parents implied a deficiency of understanding and inability in child rearing due to parental problems that may have resulted in abuse of the children at 0-1 year. It seems that two processes are critical in non-LBW child abuse as well as LBW child abuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Abuse↗

Mass screening and age-specific incidence of neuroblastoma in Saitama Prefecture, Japan.

PURPOSE: To provide the population-based incidence rate of neuroblastoma and to determine the effect of mass screening on the annual age-specific incidence of the tumor in Saitama Prefecture, Japan, from 1981 to 1992. METHODS: Data on screened infants and patients detected by the screening were obtained from the records of the Prefectural Screening Center. Data on neuroblastomas in this area were obtained from the Children's Cancer Registry of the Saitama Prefectural Government (Prefectural Registry) and from the Japan Children's Cancer Registry (National Registry). Population data were obtained from the Prefectural Census. Mass screening for 6-month-old infants was performed by qualitative assessment of urinary vanillylmandelic acid (VMA) from June 1981 to September 1989 and by quantitative measurement of VMA/creatinine (Cre) and homovanillic acid (HVA)/Cre from October 1989 to December 1992. RESULTS: Between 1981 and 1992, 199 cases of neuroblastoma, which include 74 cases detected by mass screening, were identified in Saitama Prefecture. The incidence rate for children under 15 years of age increased from 6.4/10(6) to 20.1/10(6), that for children 0 to 4 years of age increased from 17.0/10(6) to 64.1/10(6), and that for infants under 1 year of age increased from 27.9/10(6) to 260.4/10(6) during these 12 years. No significant reduction in the incidence rate was observed for children over 1 year of age. CONCLUSION: The incidence rate for children under 15 years of age increased with mass screening. The rate for infants was sharply increased, with no corresponding decrease in the rate for children at older ages. These data suggest that there is a subset of neuroblastoma that can be detected by mass screening at 6 months of age but would not be diagnosed later clinically.

Adolescent↗

Early detection of pancreatic glucagonoma.

Glucagonoma is a rare islet cell tumor of pancreas. Only 122 proven cases have been reported in the English literature so far. Diagnosis of glucagonoma has usually been delayed. The average size of clinically detected glucagonomas was 5.8 cm, and 54.7% of them exhibited metastasis. We describe the case of a 0.7-cm asymptomatic pancreatic glucagonoma. A 45-yr-old female was demonstrated to have a demarcated, small, low echoic mass in the pancreatic head by routine ultrasonography. Table incremental dynamic computed tomography showed a small well-enhanced mass recognized only in an early phase. A 0.7 x 0.7 cm firm nodule on the pancreatic head was excised at operation. Immunohistochemical and ultrastructural studies revealed that this tumor was a glucagon-producing adenoma. This may be the smallest glucagonoma detected by image diagnostics that has been reported in the English literature. Possible early detection of glucagonoma was discussed in this report.

Female↗

The significance of proliferating cell nuclear antigen (PCNA) expression in cancer of the ampulla of vater in terms of prognosis.

Seventeen patients with cancer of the ampulla of Vater were studied retrospectively using immunohistochemical staining with a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The relationships between the PCNA-positive rate, being the number of PCNA-positive cancer cells to total cancer cells, the clinicopathological findings, and the clinical course were evaluated. The PCNA-positive rate in patients with lymph node metastasis (47%) was significantly higher than that in patients without metastasis (29%), while that in patients with advanced cancer invading the pancreatic parenchyma (47%), was significantly higher than that in patients with early cancer without invasion of the sphincter of Oddi (32%). All of five patients with early cancer are still alive, whereas five with semi-advanced cancer invading the sphincter of Oddi but not the pancreatic parenchyma, and two with a PCNA-positive rate of over 40% died of recurrent cancer. Of seven patients with advanced cancer, only one with a low PCNA-positive rate of 23% is alive, but the other six with a PCNA-positive rate of over 40% all died. The results suggest that the PCNA-positive rate provides a prognostic index for cancer of the ampulla of Vater.

Ampulla of Vater↗

Nucleotide sequence comparison of the mycobacterial dnaJ gene and PCR-restriction fragment length polymorphism analysis for identification of mycobacterial species.

We recently reported a genus-specific PCR for the mycobacterial dnaJ gene. In the present study, we have determined the nucleotide sequences of the dnaJ gene from 19 mycobacterial species (Mycobacterium tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. microti, M. marinum, M. kansasii, M. gastri, M. simiae, M. scrofulaceum, M. szulgai, M. gordonae, M. avium, M. intracellulare, M. xenopi, M. fortuitum, M. chelonae, M. hemophilum, and M. paratuberculosis). On the basis of the amplified dnaJ gene nucleotide sequences, we constructed a phylogenetic tree of the mycobacterial species by using the neighbor-joining method and unweighted pairwise grouping method of arithmetic average. We found that the phylogenetic relationship inferred within the slowly growing species was in good agreement with the traditional classification, with three major branches corresponding to Runyon's groups I, II, and III. An exception was M. simiae, which was phylogenetically closer to the cluster including members of Runyon's group III than to that of Runyon's group I. On the other hand, the rapid growers, such as M. fortuitum and M. chelonae, did not form a coherent line corresponding to Runyon's group IV, indicating that our phylogenetic analysis based on the dnaJ gene reflects the phenotypic characteristics such as pigmentation but not the growth rate. Finally, we revealed the species-specific restriction sites within the amplified dnaJ gene to differentiate most of the mycobacterial DNA by a combination of PCR with restriction fragment length polymorphism analysis.

Amino Acid Sequence↗

Molecular evolution of the major capsid protein VP1 of enterovirus 70.

Nucleotide sequences of the genome RNA encoding capsid protein VP1 (918 nucleotides) of 18 enterovirus 70 (EV70) isolates collected from various parts of the world in 1971 to 1981 were determined, and nucleotide substitutions among them were studied. The genetic distances between isolates were calculated by the pairwise comparison of nucleotide difference. Regression analysis of the genetic distances against time of isolation of the strains showed that the synonymous substitution rate was very high at 21.53 x 10(-3) substitution per nucleotide per year, while the nonsynonymous rate was extremely low at 0.32 x 10(-3) substitution per nucleotide per year. The rate estimated by the average value of synonymous and nonsynonymous substitutions (W.-H. Li, C.-C. Wu, and C.-C. Luo, Mol. Biol. Evol. 2:150-174, 1985) was 5.00 x 10(-3) substitution per nucleotide per year. Taking the average value of synonymous and nonsynonymous substitutions as genetic distances between isolates, the phylogenetic tree was inferred by the unweighted pairwise grouping method of arithmetic average and by the neighbor-joining method. The tree indicated that the virus had evolved from one focal place, and the time of emergence was estimated to be August 1967 +/- 15 months, 2 years before first recognition of the pandemic of acute hemorrhagic conjunctivitis. By superimposing every nucleotide substitution on the branches of the phylogenetic tree, we analyzed nucleotide substitution patterns of EV70 genome RNA. In synonymous substitutions, the proportion of transitions, i.e., C<==>U and G<==>A, was found to be extremely frequent in comparison with that reported on other viruses or pseudogenes. In addition, parallel substitutions (independent substitutions at the same nucleotide position on different branches, i.e., different isolates, of the tree) were frequently found in both synonymous and nonsynonymous substitutions. These frequent parallel substitutions and the low nonsynonymous substitution rate despite the very high synonymous substitution rate described above imply a strong restriction on nonsynonymous substitution sites of VP1, probably due to the requirement for maintaining the rigid icosahedral conformation of the virus.

Base Sequence↗

Neurofibromatosis type 1 and childhood cancer.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) are prone to develop malignancy, particularly malignant schwannoma and glioma in adults. METHODS: To assess the risk for childhood malignancy in NF1, 26,084 patients with cancer younger than 15 years of age registered from 1969 to 1989 in the Japan Children's Cancer Registry were reviewed. The incidence of NF1 in each type of cancer was compared with that in the Japanese population. RESULTS: Fifty-six children with cancer had NF1 in the national registry. The incidence of NF1 (0.21%) was 6.45 times that of the expected estimated rate of 1 per 3000 in the Japanese population. These tumors tended to be type and site specific. The NF1 incidence was extremely high in optical nerve glioma (12.5%), other central nervous system gliomas (0.9%), and malignant schwannoma (31.4%). For nonneural tumors, NF1 incidence was increased in rhabdomyosarcoma (1.36%), particularly those in urogenital organs, and in myelogenous leukemia (0.27%). Epithelial carcinomas were not observed in the group of patients with NF1. CONCLUSION: The risk for glioma and malignant schwannoma increases in children and adults with NF1. Moreover, the risk for two childhood malignancies, myelogenous leukemia and rhabdomyosarcoma, increases in children with NF1. The NF1 gene seems to increase the risk not only for neural tumors but also for some non-neural tumors in an age-specific, organ-dependent pattern of carcinogenesis.

Adolescent↗