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Biomedical subjects

H Harada

Publications and source records attributed to H Harada.

At least 271 records · Page 15Linked to original sources

Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

Actins↗

Fate of the human liver after hemihepatic portal vein embolization: cell kinetic and morphometric study.

The favorable therapeutic effect of preoperative portal vein embolization (PVE) was analyzed by assessing various volumetric, cell kinetic and morphometric parameters and examining histologically the embolized and nonembolized lobes of 15 patients who underwent extended right lobectomy 2 to 3 weeks after PVE. Each lobar volume was calculated from computed tomography (CT) images, hepatocyte proliferation was evaluated by assessing proliferative cell nuclear antigen (PCNA) expression and mitosis, hepatocyte apoptosis was evaluated by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the hepatocyte numerical density as well as the sinusoidal volumetric ratio (Vvs) and the mean hepatocyte volume (Cv) were calculated using morphometric methods. PVE induced hepatocyte apoptosis and atrophy of the embolized lobe (from 798 +/- 213 to 708 +/- 222 cm3; P < .05). The increased sinusoidal volume in this lobe (17.7% +/- 4.5% and 21.7% +/- 5.7%, periportal and pericentral area, respectively) may have been attributable to hepatocyte deletion. Cells in the nonembolized lobe entered a highly active phase of proliferation within 2 weeks after PVE. Further evidence of cellular proliferation was provided by the increased nonembolized lobar volume (from 379 +/- 132 to 545 +/- 130 cm3; P < .01) and numerical density of hepatocyte nuclei (Nv) (5.38 +/- 1.26 vs. 3.11 +/- 0.85 x 10(5)/mm3; P < .01, nonembolized vs. embolized lobe, respectively). In conclusion, these results indicate that the favorable effect of PVE is attributable to a net gain of functional hepatocyte mass and/or early induction of hepatocyte proliferation following hepatectomy.

Adult↗

Increased prevalence of penicillin-resistant viridans group streptococci in Japanese children with upper respiratory infection treated by beta-lactam agents and in those with oncohematologic diseases.

BACKGROUND: Viridans group streptococci, especially penicillin-resistant strains, have been emerging as pathogens of bacteremia in neutropenic patients with hematologic malignancies. OBJECTIVES: To survey the penicillin susceptibilities of viridans group streptococci in Japanese children with and without oncohematologic diseases and to evaluate the effect of the short term administration of beta-lactam agents on the antibiotic susceptibility. METHODS: We tested 113 isolates of viridans group streptococci by the microdilution method for the minimal inhibitory concentrations (MICs) to 10 antibiotics. We isolated 40 isolates from the throats of children with an upper respiratory infection (URI) before beta-lactam antibiotic treatment, 32 isolates after the treatment, 33 isolates in hospitalized children with oncohematologic diseases and 8 isolates from blood. RESULTS: Twenty-five isolates (62.5%) from the children with URI before treatment were penicillin-intermediate or -high level resistant (MIC > or = 0.25 microg/ml). The prevalence of those isolates after antibiotic treatment (87.5%) was significantly increased compared with that before treatment (P = 0.03). The prevalences of the penicillin-high level resistant isolates (MIC > or = 4 microg/ml) in the children with oncohematologic diseases (39.4%) and in the isolates from blood (62.5%) were significantly higher than that in the children with URI before treatment (12.5%) (P < 0.01). Decreased susceptibilities to other beta-lactam agents were observed in the penicillin-high level resistant strains. CONCLUSIONS: The high prevalence of penicillin-intermediate or -high level resistant viridans group streptococci in healthy Japanese children was documented. The administration of beta-lactam agents decreased the prevalence of penicillin-susceptible isolates in the children with URI. High prevalences of penicillin-high level resistant isolates were observed in the oncohematologic patients and in the isolates from blood.

Anti-Bacterial Agents↗

Does recurrent acute pancreatitis lead to chronic pancreatitis? Sequential morphological and biochemical studies.

The pathogenesis of chronic pancreatitis (CP) has been debated as to whether it is a de novo process or the consequence of acute pancreatitis (AP). We investigated whether recurrent AP in rats leads to CP, by sequential morphological and biochemical studies. Thirty male Wistar rats were fed a choline-deficient diet with intraperitoneal ethionine injections twice daily at a dose of 60 mg/100 g body weight twice weekly, and six rats were killed at 4, 6, and 8 weeks; the remaining 12 rats, followed without further treatment, were killed at 12 and 16 weeks. The pancreata from study and control groups were examined by histology, immunohistochemistry, and bio- and immunoassays. Histologically, moderate to severe intra- and perilobular fibrosis and other CP-like lesions appeared maximally at 8 weeks. Immunohistochemically, the earliest extracellular matrix change was strong fibronectin staining at 4 weeks, with a progressive increase to 8 weeks. Collagens I and III came to show strong, and collagen IV moderate, interstitial staining at 6-8 weeks. These morphological changes, however, returned to nearly normal at 16 weeks. Prolyl hydroxylase was significantly elevated at 4 and 6 weeks and normalized after 8 weeks, with no significant change in collagenase. In conclusion, our results suggest that even severe CP-like lesions induced by recurrent AP are reversible in the absence of persistently elevated prolyl hydroxylase and/or suppressed collagenase. The mechanism regulating these changes remains to be studied further.

Acute Disease↗

Idiopathic and spontaneously regressing thrombus in right renal vein and inferior vena cava.

We present the case of a 57-year-old woman with a thrombus in the right renal vein and the inferior vena cava that disappeared spontaneously during 6 months of observation. She had no thrombus-related disease such as kidney cancer, dehydration, multiple myeloma, nephrotic syndrome, or abnormal coagulability. While various examinations were being performed over a 2 month period the thrombus regressed spontaneously. After 6 months of follow-up the thrombus could not be seen on abdominal computerized tomography scan. Twenty months after disappearance of the thrombus the patient is doing well and has no recurrence of thrombus.

Abdomen↗

Kidney-alone transplantation in diabetic patients with end-stage renal disease.

From January 1989 to December 1995, 5 diabetic patients with end-stage renal disease (1 woman, 4 men) underwent kidney-alone transplantation. The mean age of the recipients at the time of transplantation was 37.4 years (range, 32 to 43). Craft function and glucose tolerance was evaluated for 5 to 72 months after surgery. Postoperative complications were seen in 2 patients; nonspecific subcutaneous infections and an asymptomatic partial allograft infarction. All renal allografts were functioning 1 year after transplantation, with a mean serum creatinine level of 1.10 mg/dL (range, 0.8 to 1.8 mg/dL), and a mean urinary protein level of 17.8 mg/dL (range, 5 to 27 mg/dL). The postoperative daily dose of insulin was higher than the preoperative dose, while the level of glycated hemoglobin (HbA1C) increased after surgery and peaked 6 months after transplantation; 1 year after transplantation it had reverted to the preoperative level. As long as the diabetic complications of the renal allograft recipients are not severe, the short-term survival and the renal function of diabetic patients with end-stage renal disease improves after kidney-alone transplantation, which is still the standard method of treatment in Japan.

Adult↗

Immunohistochemical demonstration of bcl-2 protein in ameloblastoma.

The bcl-2 gene is known through its product, bcl-2 protein, which prevents apoptosis, and also by its expression in development, especially in sites characterized by epithelial-mesenchymal interactions. In the developing tooth germ, bcl-2-protein is expressed in the epithelial component. In this study, we examined the expression of bcl-2 protein immunohistochemically in 25 ameloblastomas using a monoclonal antibody against anti-human bcl-2 oncoprotein. In all 25 cases, bcl-2 protein was found mainly in the outer layer of tumor cells, whereas the inner cells (stellate reticulum-like cells and squamoid cells) were negative. The bcl-2 protein is therefore thought to play a role in maintaining the stem-cell population in the peripheral layers of the tumor nests from which proliferating cells can be recruited.

Adolescent↗

Regulation of osteoclastogenesis by antisense oligodeoxynucleotides specific to zinc finger nuclear transcription factors Egr-1 and WT1 in rat bone marrow culture system.

Differentiation of osteoclasts is defined by the transcription factors expressed in response to bone microenvironments. In this work, we examined the effects of an expressional blockage of Egr-1 and/or WT1 on the differentiation of osteoclasts using specific antisense oligodeoxynucleotides (ODN). In a culture system forming preosteoclast-like cells (POC) from rat bone marrow cells depleted of marrow stromal cells, POC formation was markedly stimulated by the addition of Egr-1 antisense ODN compared to that in cultures in which sense ODN was added, whereas Egr-1 antisense ODN inhibited the formation of macrophage-like cells. The formation of multinucleated osteoclast-like cells was also stimulated by the addition of Egr-1 antisense ODN in whole bone marrow cultures. In contrast, WT1 antisense ODN did not affect POC formation induced by the treatment with Egr-1 antisense ODN; however, WT1 antisense ODN dramatically suppressed the formation of osteoclast-like multinucleated cells induced by the blockage of Egr-1 expression using Egr-1 antisense ODN. These data suggest that Egr-1 acts as the suppressor, not as the inducer, in osteoclastogenesis. The findings also suggested that WT1 could be involved in the multinucleation step of osteoclastogenesis, at least when Egr-1 expression was blocked.

Animals↗

Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood.

We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.

Adult↗

Selective antitumor activity in vitro from marine algae from Japan coasts.

In vitro selective antitumor activity was tested as a general screening parameter for biologically active substances from a wide range of species of seaweed, 1446 samples of 306 species of marine algae from Japan's coasts. The algae extracts were prepared successively first by phosphate buffered saline (PBS) and then by methanol, and then tested for in vitro selective antitumor activity against murine lymphoid leukemia L1210 cells and for low cytotoxic activity against NIH-3T3 normal cells. Strong cytotoxic activity against L1210 cells was found in 47 species of algae, also showing similar cytotoxicity to mouse NIH-3T3 normal cells. However, four species of green algae showed strong activity specifically against L1210 cells, with low cytotoxicity to normal cells. Such selective activity was conspicuous in two brown and two green algae extracts. In particular, methanol extracts from the green alga, Cladophoropsis vaucheriaeformis, exhibited high viability (86%) to normal cells, showing selective cytotoxicity to tumor cells. This alga extract was no cytocidalic, but cytostatic against L1210 cells. Furthermore, the results of a cytotoxic spectrum test with 9 cell lines including those of L1210 and NIH-3T3 demonstrated that this extract acted strongly only against leukemic cell lines L1210 and P388.

Animals↗

Adverse effects of colophony.

Regarding colophony, the use in industries, adverse effects, diagnosis, pathophysiology and control are reviewed. Colophony is an unhomogeneous mixture of resin acids as like abietic acid and neutral substances. Colophony is used everywhere, in industry, daily life and medical supplies. Soldering workers are exposed to the colophony fumes heated up to the temperature of soldering irons. The effects of exposure to colophony are classified into bronchial asthma and contact dermatitis. Colophony fumes cause bronchial asthma by its nonspecific irritation. Inhalation challenge test and repeated spirometry during working day may help the diagnosis of colophony induced asthma. Improvement of working environment for soldering and development of new flux instead of colophony will be necessary. A study on contact dermatitis revealed that colophony and its related compounds are one of major causes for contact dermatitis. Cases of dermatitis by depilatory agents used to remove hair from slaughtered swine, anti-slipping cream for ballet shoes or resin for cello strings have been reported. Patch test may contribute to the diagnosis of dermatitis caused by colophony.

Asthma↗

A rare case of the right-sided aortic arch that has the right subclavian artery as the last branch.

This report describes a rare case of the right-sided aortic arch with the right subclavian artery as the last branch, which was encountered in a Japanese male cadaver in the dissecting room at Kurume University School of Medicine in 1995. In this subject, the ascending aorta arose from the left ventricle and ascended obliquely, curving forward and to the right, and became the right-sided aortic arch. The aortic arch passed upwards, reaching a summit at the level of the third thoracic vertebral body, then curved dorsally. The left brachiocephalic, the right common carotid and the right subclavian arteries came off the aortic arch in that order. After the right subclavian artery, the aortic arch dilated and formed the aortic diverticulum behind the trachea and the esophagus. The right thoracic aorta, a continuation of the aortic arch, descended to the right of the vertebral column. This case is a type M anomaly according to the Adachi-Williams-Nakagawa's classification, and is the twelfth case with this type of vascular variation to be reported in Japan.

Aged↗

Characterization of acute leukemia with t(4;12).

Acute leukemia with t(4;12)(q11-13;p12-13) is rare but has unique characteristics. The incidence of t(4;12) in acute leukemias was about 0.6% in our laboratory. Twelve patients with acute leukemia with t(4;12) have been reported until now. They included eight acute myeloid (AML: M0 2, M1 3, M2 1, M4 1, and M7 1), three acute lymphoblastic (ALL: L1) and one acute unclassified leukemia (AUL). There were some differences between adults and children with t(4;12). The eight adult patients included seven with AML and one with AUL, two of whom had a history of exposure to mutagenic agents and/or genotoxic therapy. Three patients had the CD7+ HLA-DR+ CD13+ CD34+ c-kit+ phenotype, suggesting that the leukemic cells were of stem cell origin. Four children expressed the B lymphoid phenotype (HLA-DR+ CD10+ CD19+) although one had myeloperoxidase positivity. It was difficult for adult patients to achieve complete remission with the usual therapy regimen, whereas children with t(4;12) seemed to be easier to treat. Rearrangement of the TEL gene located on the short arm of chromosome 12 (12p13), was investigated in two adult patients. FISH analysis using the YAC probe that covers the TEL gene region, revealed split signals in these patients, suggesting a break inside or near the TEL gene. The t(4;12) abnormality is associated with unique characteristics of acute leukemia namely stem cell or secondary AML in adults, and B lymphoid leukemia in children.

Acute Disease↗

[Clinical evaluation of donor renal artery reconstruction in kidney transplantation].

UNLABELLED: This retrospective study describes the experience of arterial reconstruction of donor kidney in our institute since 1982. MATERIALS AND METHODS: Of total 56 living related kidney transplantations 15 required renal arterial reconstruction or ligation of donor kidneys. Renal arterial reconstruction was employed for 11 cases (end to side anastomosis [4 cases], conjoined anastomosis [3], hypogastric artery graft interposition [3], other [1], while simple ligation was employed for 4. Bench surgery with microsurgical techniques was employed for the repair. Elective surgery was done for preoperatively defined multiple renal arteries [10] and aneurysm [1], while imperative surgery for intraoperatively detected accessory arteries [2] and surgical injuries [2]. Postoperative patency of arteries and renal function (GFR) and evaluated by 99mTc-DTPA renoscintigraphy. RESULTS: The mean total ischemic time of reconstructed cases was 135 min., while that of ligated ones was 67 min. None of them required hemodialysis due to acute tubular necrosis. Postoperative graft arterial patency was impaired in 2 of 11 reconstructed cases (18%), while it was impaired in 3 of 4 ligated cases (75%). Two failure attempts of arterial reconstruction cases were all imperative ones. Postoperative GFR of the graft was well preserved in all cases. CONCLUSION: We conclude that (1) Ligation and imperative surgery tend to be associated with renal infarction, although it does not affect GFR. (2) Renal artery reconstruction was highly successful in preserving renal mass (or normal cortical image), albeit longer ischemic time than simple ligation. (3) Considering importance of preserved nephron mass in clinical renal transplantation every attempt should be made to repair the donor arterial anomalies when expected (elective) or found (imperative). (4) Thorough preoperative evaluation of donor renal arteries is mandatory.

Adult↗

Basic study on the rectangular numeric keys for touch screen.

The present study was conducted to examine the optimum inter-key spacing of numeric rectangular keys for touch screens. Six male students (22-25 years old) and three female students (21-24 years old) participated in the experiment. Each subject performed the data entry task using rectangular keys of touch devices. These keys were arranged in both horizontal and vertical layouts. The sizes of the rectangular keys in both layouts were 12 x 21 mm and 15 x 39 mm, and each of the inter-key spacing of each key was 0, 3, 6, 12 and 21 mm. The response time with inter-key spacing of 3 mm was significantly faster than with the inter-key spacing of 0, 12 and 21 mm (p < 0.05). Keys of vertical position produced faster response time than that of horizontal position. The subjective ratings showed that the inter-key spacing of 6 mm was significantly better than the inter-key spacing of 0, 3, 12 and 21 mm (p < 0.05).

Adult↗