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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 685 records · Page 38Linked to original sources
PubMed1993

Effects of K+ channel openers on ischemic dysfunction and metabolic disturbance in isolated perfused rat heart.

The effects of two structurally different K+ channel openers, KRN2391 and cromakalim, on cardiac mechanisms during ischemia and reperfusion were studied in isolated perfused rat hearts. Isolated buffer-perfused rat hearts pretreated with KRN2391, cromakalim and vehicle were subjected to 25 min of ischemia followed by 30 min of reperfusion. Before ischemia, KRN2391 (1-10 microM) and cromakalim (1-10 microM) increased coronary flow, but did not modify cardiac function or biochemical parameters (adenine nucleotides, energy charge potential: ECP, lactate). During ischemia, KRN2391 (3, 10 microM) and cromakalim (10 microM) significantly accelerated the reduction in cardiac function and attenuated the decreased levels of ATP and ECP, but did not change the lactate content. After 30 min of reperfusion, pretreatment with KRN2391 and cromakalim resulted in a significant improvement in cardiac function, ischemic contracture and biochemical parameters. Thus, both KRN2391 and cromakalim have beneficial effects on biochemical parameters during ischemia and reperfusion, effects which may be related to cardiodepression during ischemia.

Animals↗
PubMed1993

In vitro selection of optimal DNA substrates for T4 RNA ligase.

We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 RNA ligase. We find that the ensemble of selected sequences ligated about 10 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly, the majority of the selected sequences approximated a well-defined consensus sequence.

Bacteriophage T4↗
PubMed1993

Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia.

One of the most frequent cytogenetic abnormalities in human leukemia and myelodysplasia is an interstitial deletion within chromosome 5q. A tumor suppressor gene has been hypothesized to lie in 5q31, the smallest commonly deleted region. IRF-1, a gene whose product manifests anti-oncogenic activity, was mapped to 5q31.1. IRF-1 lies between IL-5 and CDC25C and is centromeric to IL-3 and GM-CSF. Among these genes, only IRF-1 was consistently deleted at one or both alleles in 13 cases of leukemia or myelodysplasia with aberrations of 5q31. Inactivating rearrangements of one IRF-1 allele, accompanied by deletion of the second allele, were also identified in one case of acute leukemia. Thus, IRF-1 may be a critically deleted gene in human leukemia and myelodysplasia.

Base Sequence↗
PubMed1993

Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2.

Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The IRF-1 gene is itself interferon-inducible and hence may be one of the target genes critical for interferon action. When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the IRF-1 gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors.

3T3 Cells↗
PubMed1993

Callosal atrophy parallels decreased cortical oxygen metabolism and neuropsychological impairment in Alzheimer's disease.

OBJECTIVE: To evaluate the relationship of corpus callosum atrophy to cerebral cortical oxygen metabolism and cognitive function in patients with Alzheimer's disease. DESIGN: Prospective clinicoradiologic correlation with magnetic resonance imaging and positron emission tomography. SETTING: A university hospital. PATIENTS, PARTICIPANTS: Ten right-handed male patients with Alzheimer's disease, aged 46 to 70 years (mean +/- SD 57 +/- 6 years), and 14 age- and sex-matched right-handed control subjects. MAIN OUTCOME MEASURES: The midsagittal corpus callosum areas (on T1-weighted magnetic resonance images), cerebral metabolic rate of oxygen (measured with positron emission tomography using the oxygen-15 steady-state technique), and the IQs of the Wechsler Adult Intelligence Scale. RESULTS: Compared with control subjects, the patients had significantly decreased callosal areas with a posterior predominance of the degree of atrophy. The area of anterior and posterior halves of the corpus callosum had a significant correlation with the value of oxygen metabolism in the frontal and parietotemporo-occipital association cortices, respectively. The total area of the corpus callosum was significantly related to the total and verbal IQs of the Wechsler Adult Intelligence Scale. CONCLUSION: Atrophy of corpus callosum reflects the severity and pattern of cortical damage associated with hypometabolism and cognitive impairment in Alzheimer's disease.

Aged↗
PubMed1993

Comparative study of modification and degradation of neurofilament proteins in rats subchronically treated with allyl chloride, acrylamide, or 2,5-hexanedione.

Allyl chloride (ALL), acrylamide (ACR), and 2,5-hexanedione (2,5-HD) are all industrial neurotoxicants and known to produce accumulation of neurofilament (NF) proteins in both the central and peripheral nervous systems. To clarify whether any common mechanisms underlie these neurofilamentous axonopathies, the ability of ALL, ACR, and 2,5-HD to cross-link the NFs and the effects on NF degradation by Ca(2+)-activated neural protease were investigated in spinal cords from rats subchronically treated with these chemicals. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis revealed the appearance of high-molecular-weight species of NF triplets immunoreactive to each anti-68K, anti-160K, and anti-200K NF antibody in the 2,5-HD-treated rats, whereas it was not found in those treated with ALL or ACR. A time course study on the degradation of NF proteins conducted by the co-incubation with Ca2+ showed degradation resistance in all three NF subunits from animals treated with 2,5-HD, while no significant alterations in the rate of NF degradation were observed in the ALL- or ACR-treated group. The present results suggest that neurofilament-filled axonopathy induced by ALL or ACR and axonopathy induced by 2,5-HD may not share a common mechanism, though the initial step for the pathogenesis of this chemically induced neurotoxicity is not fully understood at present.

Acrylamide↗
PubMed1993

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) decrease in diastolic left ventricular function assessed by echocardiography.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are known to be associated with cardiomyopathy. Systolic and diastolic left ventricular functions were assessed by M-mode and Doppler echocardiography in four patients with MELAS and in 14 normal controls. The interventricular septal thickness and left ventricular posterior wall thickness were greater (11.0 +/- 1.6 mm vs. 5.8 +/- 0.7 mm and 11.0 +/- 2.2 mm vs. 5.9 +/- 0.8 mm) in patients with MELAS than in a control group. Parameters of systolic left ventricular functions (ejection fraction, shortening fraction, systolic time intervals, and mean Vcf) and left ventricular dimensions were not significantly different between the two groups. To assess the diastolic function, blood flow velocity across the mitral valve was measured by Doppler echocardiography and various indexes were obtained. In patients with MELAS, the impairment of diastolic left ventricular filling was demonstrated by decrease in the following indexes: peak flow velocity in the early passive filling period (E) (0.76 +/- 0.10 m/s vs. 0.94 +/- 0.09 m/s), integrated velocity for total E (10.2 +/- 1.3 vs. 13.0 +/- 0.9), the ratio of E and late atrial filling integrated velocities (1.72 +/- 0.06 vs. 2.49 +/- 0.29).

Adolescent↗
PubMed1993

Effects of sialoadenectomy and epidermal growth factor administration on 9,10-dimethyl-1,2-benzanthracene-induced tumor formation in hamster cheek pouch.

The effects of removal of the submandibular gland (sialoadenectomy) and administration of human urinary epidermal growth factor on the 9,10-dimethyl-1,2-benzanthracene-induced tumor formation were investigated with the use of a hamster cheek pouch model. Syrian hamsters were treated with 0.5% 9,10-dimethyl-1,2-benzanthracene for 6 weeks. Thereafter hamsters in group 1 underwent a sham operation and those in groups 2 and 3 underwent a sialoadenectomy. Subsequently, hamsters in groups 1 and 2 were given 0.9% sodium chloride and group 3 received the human urinary epidermal growth factor at a dose of 0.25 mg/kg body weight subcutaneously three times a week for 8 weeks. Sixteen weeks after the start of the experiment, the mean number of tumors that were less than 3-mm in diameter in groups 1 and 3 was significantly greater than that in group 2 (p < 0.05). The overall incidence and mean number of all carcinomas irrespective of size showed no differences among the experimental groups. These results indicate that epidermal growth factor synthesized in the submandibular gland may enhance the induction of cheek pouch tumor.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Genetic and chemical polymorphisms of saponins in soybean seed.

The variation in saponin composition in soybean seeds is explained by different combinations of five genes controlling the utilization of soyasapogenol glycosides as substrates. The function of these genes is variety-specific and organ-specific. Phenotypes of over 1000 soybeans were classified into eight saponin types, and the frequency of phenotypes was different between the cultivated [Glycine max (L.) Merr.] and the wild soybean (G. soja Sieb. & Zucc.). The AaBc saponin type predominated in G. soja (58.4% of test collections), but was only found in 0.3% of G. max. Four unidentified arabinoside saponins were detected in the seeds of the AaBc type soybeans. The mode of inheritance of saponin types is explained by a combination of co-dominant, dominant and recessive acting genes. The combined chemical and genetic data show that the directed manipulation of soybean saponin composition is a possibility for the future.

Arabinose↗
PubMed1993

Florid duct lesion in primary biliary cirrhosis shows highly proliferative activities.

Primary biliary cirrhosis is characterized by non-suppurative inflammation and destruction of the interlobular bile ducts (IBDs) (florid duct lesions). The present study attempted to analyze the cell kinetics of florid duct lesions using the histometry, immunostaining of proliferating cell nuclear antigen and by counting argyrophilic nucleolar organizer regions. Florid duct lesions disclosed nuclear stratification, pseudopapillary infoldings and tortuosity. These findings suggest increased proliferative activity of epithelial cells in these affected ducts. Proportion of proliferating cell nuclear antigen positive interlobular bile ducts (88.8 +/- 7.9%) and counts of argyrophilic nucleolar organizer regions in biliary epithelial cells (3.89 +/- 0.73) were increased in florid duct lesions relative to non-inflamed interlobular bile ducts (45.0 +/- 25.4% and 2.65 +/- 0.67, respectively) in primary biliary cirrhosis and also relative to interlobular bile ducts (21.8 +/- 8.6% and 2.25 +/- 0.09, respectively) in normal livers, which supports the above-mentioned suggestion. The increased outer diameter of these affected bile ducts which was demonstrated histometrically, may be due to biliary epithelial proliferation with variable luminal dilatation. The present study showed that an increased proliferative activity of biliary epithelial cells is one of the characteristics of florid duct lesions and results in an increase in the size of the affected bile ducts. It remains unclear, however, why proliferation and extensive destruction of biliary epithelial cells coexist in primary biliary cirrhosis.

Aged↗
PubMed1993

Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer.

We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma.

Animals↗
PubMed1993

Effect of aminohydroxypropylidene diphosphonate on the bone metabolism of patients with parathyroid adenoma.

Aminohydroxypropylidene diphosphonate (APD), a potent inhibitor of bone resorption, is used to control hypercalcemia in various diseases. It is less effective, however, in the management of hypercalcemia induced by primary hyperparathyroidism. We investigated the effect of APD on the bone metabolism of five patients with parathyroid adenoma. Before parathyroidectomy, 30 mg of APD was administered intravenously. Serum calcium decreased in all cases one to two days after APD administration, although it did not decrease to the normal range. Serum phosphorus also decreased. Urine calcium and hydroxyproline excretion, markers of osteoclasts activity, decreased dramatically. Serum alkaline phosphatase (ALP) and osteocalcin, markers of osteoblast activity, decreased after APD administration. Serum intact parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D (1,25[OH]2D) increased. These results indicate that APD is partially effective in the management of preoperative serum calcium level in patients with parathyroid adenoma. As osteoclasts activity is inhibited by APD, osteoblasts activity is also suppressed. Elevation of PTH and 1,25(OH)2D after APD-induced decrease in serum calcium level may explain the partial and limited effect of APD on lowering serum calcium in patients with parathyroid adenoma.

Adenoma↗
PubMed1993

Analysis of cardiac assistance by latissimus dorsi cardiomyoplasty with a time varying elastance model.

OBJECTIVE: The clinical use of skeletal muscle cardiomyoplasty is limited because of its inadequate haemodynamic benefits. To facilitate experimental and clinical efforts to improve the efficacy of this technique, a mathematical model was proposed and its validity was tested in acute experiments. METHODS: The model was based on the assumption that the skeletal muscle wrapped around the heart behaves as a time varying elastance that is connected in series with another time varying elastance representing the native heart. From this model two predictions were made: (1) Skeletal muscle augments the contractility of the heart by increasing the slope (Ees) of the end systolic pressure-volume relation; (2) time varying elastance of the skeletal muscle chamber (Es(t)) can be estimated from that of the assisted heart. These predictions were examined in experiments. In nine anaesthetised, open chest dogs, preconditioned latissimus dorsi muscle was transposed to wrap the heart. Left ventricular pressure (catheter tipped micromanometer), and volume (conductance catheter) were measured while reducing the preload by vena caval occlusion to evaluate Ees with 1:2 (stimulation:heart beat ratio) stimulation of the skeletal muscle. RESULTS: With the stimulation of latissimus muscle, the end systolic pressure-volume relation was linear and Ees increased from 8.6(SEM 2.4) to 11.9(SEM 3.4) mm Hg.ml-1. Estimated Es(t) reflected the stimulation pattern and could account for the mechanism of the cardiac assistance. CONCLUSIONS: Skeletal muscle cardiomyoplasty improved the haemodynamic variable (Ees) as predicted by a mathematical model.

Animals↗
PubMed1993

Hemodynamic profile of KRN2391, a novel vasodilator, in anesthetized dogs.

In the present study, we compared the effects of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate), a novel vasodilator, with those of nicorandil and nifedipine on hemodynamic profiles. KRN2391 (1-30 micrograms), nicorandil (10-300 micrograms), and nifedipine (0.1-3 micrograms) increased coronary, mesenteric, renal and femoral blood flows in a dose-dependent manner when intraarterially administered. KRN2391 was approximately 18 times more potent than nicorandil and about five times less potent than nifedipine in increasing coronary blood flow. Intravenous (i.v.) administration of KRN2391, nicorandil, and nifedipine produced increases in coronary and mesenteric blood flows and decreases in these vascular resistances. Although nicorandil i.v. had no significant effect on renal blood flow (RBF), nifedipine i.v. decreased RBF whereas KRN2391 i.v. increased it. Femoral BF (FBF) decreased only at the highest i.v. dose of KRN2391 and decreased after an initial increase with nicorandil. Nifedipine i.v. had no significant effect on FBF. The effects of these three agents in increasing BF and in decreasing vascular resistance were most prominent in coronary vasculature. The duration of the effect of KRN2391 in increasing coronary BF (CBF) was longer than that of nicorandil but was similar to that of nifedipine. The hypotensive effect of KRN2391 was also weaker than its effect in increasing CBF in comparison with nicorandil and nifedipine. Thus, KRN2391 was demonstrated to possess a preferential activity on coronary vasculature.

Anesthesia↗
PubMed1993

Biologically active extracellular products of oral viridans streptococci and the aetiology of Kawasaki disease.

A bacteriological study of isolates from the oral cavity of patients with Kawasaki disease (KD), age-matched non-KD patients and healthy children, showed that over half the KD and control isolates had gram-positive, catalase-negative cocci. About 50% of these organisms were identified as viridans streptococci by means of an API Strep 20 kit. Further identification by fluorometric DNA-DNA hybridisation demonstrated that the predominant species were S. oralis and S. mitis, each of which accounted for 25% of the isolates of viridans streptococci; 40% of viridans strains were unidentifiable; and S. sanguis and S. parasanguis were minor components. Studies in vivo showed that insertion of culture supernates of most of the viridans streptococci increased capillary permeability and induced redness with swelling and occasional bleeding in rabbit skin. One-third of S. mitis strains and one-fifth of the unidentified strains caused aggregation of human blood platelets, whereas S. oralis and other strains had no such effect. The distribution of extracellular lipoteichoic acids and glucan produced in the presence of sucrose was also examined. There were no significant differences in the recovery rate of viridans streptococci forming these biologically active extracellular products between KD and control groups.

Adult↗