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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 721 records · Page 40Linked to original sources

Association of blood pressure variability with induction of atherosclerosis in cholesterol-fed rats.

The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high-cholesterol diet developed marked hypercholesterolemia and hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats.

Animals↗

Production of chimeric pigs and the analysis of chimerism using mitochondrial deoxyribonucleic acid as a cell marker.

Two injection methods were examined for making chimeras between Chinese pigs (Meishan) and European pigs (Landrace or Landrace x Large White). Furthermore, mitochondrial DNA (mtDNA) polymorphism was detected as a cell marker for the analysis of chimerism. In the first experiment, blastomeres were transplanted into embryos at the 4-16-cell stage. Of 41 transplanted embryos transferred into 3 females, 12 were single-colored, but no overt chimeras were obtained. Judging from coat color and mtDNA in white blood cells, 2 piglets in 2 litters were derived from injected blastomeres, and 10 piglets in 3 litters were derived from recipient blastomeres. In the second experiment, inner cell mass cells of Day 6 Landrace embryos were injected into blastocoels of Day 6 Meishan embryos. Of 35 injected embryos transferred into 3 females, 2 overt chimeras of each sex were obtained in a single litter. In the overt male chimera, mtDNA clearly showed chimerism in spleen, pancreas, brain, kidney, lung, liver, heart, testis, and small intestine. The overt female chimera showed chimerism not only in blood but also in germ line according to a progeny test. No chimerism was detected in any of the 21 single-colored piglets in the second experiment.

Animals↗

Decreased collagenase expression in cultured systemic sclerosis fibroblasts.

One cause of the excessive deposition of collagen in systemic sclerosis is thought to be abnormal functioning of fibroblasts. The purpose of this study is to determine whether there is decreased expression of collagenase in systemic sclerosis fibroblasts. In this study, we analyzed collagen and collagenase expression in dermal fibroblasts derived from eight patients with systemic sclerosis and compared the findings with those from nine sex- and age-matched healthy subjects. Increased collagen synthesis accompanying enhanced mRNA levels was observed in two of eight strains, whereas all eight strains showed remarkable decreases in collagenase activity and production. There were no differences in the levels of collagenase mRNA between the systemic sclerosis strains and the normal strains. Results suggest that decreased collagenase expression is a characteristic of systemic sclerosis fibroblasts, and both increased collagen expression and decreased collagenase expression in systemic sclerosis fibroblasts may result in the excessive accumulation of collagen in patients with systemic sclerosis. It is also suggested that decreased collagenase expression is altered at translational and/or post-translational levels.

Adult↗

Polymorphic sequence in the D-loop region of equine mitochondrial DNA.

The D-loop regions in equine mitochondrial DNA were cloned from three thoroughbred horses by polymerase chain reaction (PCR). The total number of bases in the D-loop region were 1114 bp, 1115 bp and 1146 bp. The equine D-loop region is A/T rich like many other mammalian D-loops. The large central conserved sequence block and small conserved sequence blocks 1, 2 and 3, that are common to other mammals, were observed. Between conserved sequence blocks 1 and 2 there were tandem repeats of an 8 bp equine-specific sequence TGTGCACC, and the number of tandem repeats differed among individual horses. The base composition in the unit of these repeats is G/C rich as are the short repeats in the D-loops of rabbit and pig. Comparing DNA sequences between horse and other mammals, the difference in the D-loop region length is mostly due to the difference in the number of DNA sequences at both extremities. The similarities of the DNA sequences are in the middle part of the D-loop. In comparison of the sequences among three thoroughbred horses, it was determined that the region between tRNA(Pro) and the large central conserved sequence block was the richest in variation. PCR primers in the D-loop region were designed and the expected maternal inheritance was confirmed by PCR-RFLP (restriction fragment length polymorphism).

Animals↗

Gene screening in Japanese families with complete deficiency of thyroxine-binding globulin demonstrates that a nucleotide deletion at codon 352 may be a race specific mutation.

OBJECTIVE: Thyroxine-binding globulin (TBG) is a serum protein that transports 75% of circulating thyroxine. Eleven naturally occurring mutations in the human TBG gene have been identified, ten of which alter the properties of the molecule. Three of these mutations produce complete deficiency of TBG (TBG-CD) and four are associated with a second mutation in codon 283 (TBG-poly) which is polymorphic in some ethnic groups but, when present alone, does not alter the properties of the TBG molecule. In this communication we investigate whether two unrelated Japanese families with TBG-CD harboured the TBG-CDJ mutation in codon 352 associated with TBG-CD in families residing in more distant locations of the Japanese Islands. In addition we examined the possible association with TBG-poly and its incidence in the Japanese population. DESIGN: Mutant alleles were identified by amplification of genomic DNAs by the polymerase chain reaction, using allele-specific oligonucleotide primers. PATIENTS: Eight family members and 25 normal subjects. MEASUREMENTS: Serum free thyroxine and TBG concentration were measured by a conventional radioimmunoassay and a more sensitive enzyme immunoassay. Genomic DNAs were extracted from white blood cells and specific mutations at codons 352 and 283 were identified by allele-specific amplification. RESULTS: Three males and three females, whose serum TBG levels were decreased, had mutations at codon 352 as hemizygous and heterozygous, respectively. This mutation was not present in the DNA of any of the related or unrelated subjects with normal TBG concentration. The presence of TBG-poly was demonstrated in only one heterozygous family member and in six out of 30 alleles (20%) in normal unrelated subjects. The frequency of this TBG polymorphism in the Japanese is similar to that of 16% reported in French Canadians. CONCLUSIONS: We conclude that TBG-CDJ might be a prevalent cause of complete deficiency of thyroxine-binding globulin in the Japanese and that TBG-poly probably appeared before the divergence of human races.

Alleles↗

Effect of terdecamycin on experimentally induced Mycoplasma hyopneumoniae-infection in pigs.

The effect of terdecamycin, a new antibiotic, was evaluated on experimentally induced Mycoplasma hyopneumoniae infection in pigs. Tylosin and josamycin were used as the positive control drugs. Five to 7-week-old pigs were inoculated intranasally with homogenate of pig lung lesions containing M. hyopneumoniae. In experiments 1 and 2, drugs were given in feed for 42 days, from 7 days before inoculation to 35 days after inoculation, and necropsy was carried out 35 days after inoculation. In experiment 3, drugs were given in feed for 10 days, from 3 days before inoculation to 7 days after inoculation and necropsy was carried out 28 days after inoculation. Drug efficacy was evaluated on the basis of clinical signs, lung lesions, (including percentage of gross lung lesion area), isolation of M. hyopneumoniae and growth performance data. The total number of days on which coughing was observed and the mean percentage of lung lesion area in pigs given feed containing terdecamycin at 50 ppm or above were lower than those in unmedicated control pigs. Average daily weight gain in terdecamycin-treated pigs was higher than that in unmedicated control pigs. Treatment with terdecamycin showed equal or better efficacy as compared with treatment with tylosin or josamycin.

Animals↗

Acetylsalicylate (ASA)-induced mitochondrial dysfunction and its potentiation by Ca2+.

Although it has been suggested that acetylsalicylate (ASA)-induced mitochondrial dysfunction plays an important role in the pathogenesis of Reye's syndrome, administration of ASA alone does not cause this syndrome in therapeutic doses. We noted, however, that Ca2+ plays important roles in the regulation of cellular functions. ASA at concentrations of 250 microM or less, which had little effect on succinate-linked respiration, impaired Ca2+ accumulation in liver mitochondria by causing an increase in Ca2+ release. ASA plus Ca2+, which in concentrations of 150 microM or less alone had little effect on mitochondrial respiration, inhibited state 3 respiration and dinitrophenol-induced uncoupling of respiration. In addition, ASA plus Ca2+ increased state 4 respiration and ATPase activity. These results indicate that ASA plus Ca2+ impaired mitochondrial ATP synthesis, and suggest that ASA and ASA-induced Ca2+ increases in cytosol form a vicious circle of effects. Furthermore, oral administration of ASA (150 mg/kg for 5 days running) to rats did not affect mitochondrial structure or liver function, but resulted in aberrations of mitochondrial respiration. These results suggest that even therapeutic doses of ASA may induce alteration in mitochondrial function.

Adenosine Triphosphatases↗

Cloning of the macrolide antibiotic biosynthesis gene acyA, which encodes 3-O-acyltransferase, from Streptomyces thermotolerans and its use for direct fermentative production of a hybrid macrolide antibiotic.

A gene encoding the macrolide modification enzyme 3-O-acyltransferase (acyA) was cloned by chromosome walking onto the carbomycin biosynthetic region in Streptomyces thermotolerans TH475, with the 3' region of the gene encoding the macrolide modification enzyme 4"-O-acyltransferase (acyB1) as a probe. A shortened fragment (1.8 kb) containing acyA was subcloned with pIJ350. A high-level tylosin producer, Streptomyces fradiae MBBF, transformed with the plasmid could produce a hybrid macrolide, 3-O-acetyltylosin, most efficiently.

Acyltransferases↗

Hepatocellular carcinoma: treatment with a combination of transcatheter arterial chemoembolization and transportal ethanol injection.

PURPOSE: To evaluate the efficacy and complications of transportal ethanol injection (TPEI) combined with transcatheter arterial chemoembolization to achieve complete tumor necrosis and prevent intrahepatic metastases in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In 13 patients with HCC, chemoembolization was performed with injection of a mixture of iodized oil and doxorubicin hydrochloride followed by administration of gelatin sponge; 1-4 weeks later, TPEI was performed with percutaneous transhepatic portography. Ethanol (15-65 mL) was injected in the portal veins around the tumor until occlusion. RESULTS: TPEI was successfully performed in all patients. Two patients subsequently underwent surgery; their tumors were resected completely. Two died of hepatic failure. Seven of the nine other patients showed no recurrence or intrahepatic metastasis during follow-up (7-42 months). Histologic examination, performed in nine patients, showed complete necrosis of tumor and scattered or severe necrosis of surrounding tissues. CONCLUSION: This treatment has a strong anticancerous effect and is expected to be used in treatment of properly selected patients with HCC.

Aged↗

Axial myoclonus mediated by the propriospinal tract: a case report.

We describe a patient with axial myoclonus. Myoclonus first occurred in the upper abdominal muscle and spread up to the neck muscle and down to the lower abdominal muscle. Physiological studies of the jerks revealed that the myoclonus arose in the thoracic spinal cord and spread slowly up and down the spinal cord at about 3 m/s. We conclude that the myoclonus is mediated by the propriospinal tract.

Adult↗

Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats.

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardiac responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha 2-adrenergic receptor in the nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension.

Adrenergic alpha-1 Receptor Antagonists↗

Molecular mechanism of adipogenic activation of the angiotensinogen gene.

Angiotensinogen gene expression is controlled in a tissue- and development-specific manner. Interestingly, the angiotensinogen gene is abundantly expressed in adipose tissues other than the liver, where it is mainly produced. We investigated the molecular mechanism of angiotensinogen gene expression in a 3T3-L1 preadipocyte-adipocyte system. Although angiotensinogen mRNA was barely detectable in preadipocytes, its levels increased significantly during differentiation. As a whole, the pattern of the change in transcriptional activity of the angiotensinogen promoter was similar to that of the angiotensinogen mRNA levels during adipogenic differentiation, indicating that the activation of the angiotensinogen promoter might be involved in the adipogenic differentiation-coupled gene expression. The proximal promoter region, from -96 to +22 of the transcriptional start site, was sufficient to confer adipogenic activation, and the proximal element from -96 to -52 of the transcriptional start site was necessary for this promoter stimulation. DNA-protein binding experiments showed that this proximal element specifically bound to a nuclear factor induced by adipogenic differentiation. These results suggest that the proximal promoter element from -96 to -52 plays a role in adipogenic activation of the angiotensinogen promoter.

3T3 Cells↗

Effects of ionic and nonionic contrast media on cardiohemodynamics and quality of radiographic image during canine angiography.

Cardiovascular responses and radiographic image quality during cerebral angiography, aortofemoral angiography and left ventriculography with nonionic ioxilan, iohexol or iopamidol were compared with those of ionic sodium meglumine diatrizoate in pentobarbital anesthetized dogs. Injection of all contrast media caused cardiovascular changes to a greater or lesser degree, e.g., hypotension, bradycardia, tachycardia, a decrease in left ventricular pressure (LVP) and its first derivative (dP/dt), and prolongation of the P-Q and Q-T intervals. Ionic diatrizoate had a greater effect on cardiovascular parameters than nonionic contrast media during angiography in all areas. Moreover, diatrizoate produced cardiac arrhythmias and prominent changes in blood rheology concerned with blood viscosity and deformability of the erythrocyte. The cause of various effects of contrast media seemed to lie mainly in osmolality, viscosity and partially ionic additives. The radiographic image quality of all of the contrast media used was similar, but nonionic ioxilan and iohexol with lower iodine content and low osmolality gave better radio opacity than ionic diatrizoate in cerebral angiography. These results suggested that nonionic contrast media should be recommended as a diagnostic tool for both animals and human patients in poor health.

Angiography↗

Four patients with polyendocrinopathy with associated pituitary hormone deficiency.

Four cases of polyglandular endocrine disorders associated with pituitary hormone secretion failure are reported. Three of them had both insulin dependent diabetes mellitus (IDDM) and Hashimoto's disease. Each of these patients (cases 1-3) showed isolated deficiency of ACTH, TSH or gonadotropin, respectively. Another patient (case 4) had both Hashimoto's disease and isolated ACTH deficiency. Anti-pituitary antibody to AtT-20 cells was detected in case 1. Serum gamma-globulins from patients 1 and 4 attenuated corticotropin releasing hormone-induced ACTH release in monolayer cultured rat anterior pituitary cells. Gamma-globulins from patients 1 and 2 decreased baseline TSH release but stimulated baseline prolactin release in pituitary cell cultures. It is possible that pituitary hormone deficiency in these patients may be caused by autoimmune disorders.

Adrenocorticotropic Hormone↗

Mapping of the human gene for inducible heme oxygenase to chromosome 22q12.

Heme oxygenase is an essential enzyme in heme catabolism that cleaves heme to form biliverdin, releasing carbon monoxide and iron. There are two isozymes of heme oxygenase: heme oxygenase 1 (HO-1) and heme oxygenase 2, each of which is encoded by a separate gene. It is noteworthy that HO-1 is inducible by various environmental factors, while heme oxygenase 2 is not. Here we have localized the human HO-1 gene to chromosome 22 by polymerase chain reaction (PCR) analysis of human-hamster somatic cell hybrids. The precise region of the HO-1 locus was then determined by fluorescence in situ hybridization, revealing that the human HO-1 gene is localized to 22q12.

Animals↗

Recording of single fiber electromyography in patients with peripheral facial palsy.

We determined muscle fiber density with single fiber electromyography (SFEMG) to discuss the condition of re-innervation after the recovery of facial movement in cases of peripheral facial palsy. Muscle fiber density was then compared with electroneurography (ENoG) which is thought to correlate with the severity of facial neuropathy in the early stage after the onset. The degree of neuropathy and subsequent recovery of innervation was also discussed. The subjects were 36 patients with peripheral facial palsy (30 patients with Bell's palsy and 6 with Hunt's syndrome), treated at our hospital, in whom ENoG could be recorded within 2 weeks after the onset. Muscle fiber density was determined after the recovery of facial movement. As a control, muscle fiber density was determined in 11 normal adults, and muscles on the healthy side in 23 patients with Bell's palsy. Muscle fiber density was 1.44 +/- 0.15 (mean +/- S.D.) in normal adults and 1.51 +/- 0.18 on the healthy side in patients, showing no significant difference. Data on the affected side were divided into 4 groups according to the minimum ENoG level within 2 weeks after onset and were compared with the normal group. In all cases with an ENoG level of 40% or more, muscle fiber densities were normal, and no significant differences were noted between the affected side and the healthy side. In cases with an ENoG level of less than 40%, muscle fiber density increased significantly with increasing severity of denervation. These findings suggest that collateral sprouting is absent in cases of peripheral facial palsy who show an ENoG level of 40% or more, or no wallerian degeneration.

Action Potentials↗

Clinical evaluation of sizofilan as assistant immunotherapy in treatment of head and neck cancer.

Sizofilan (SPG), a simple glucan produced in a culture medium by Schizophyllum commune Feries, was used as an assistant immunotherapy in 15 patients with head and neck cancer. The cumulative 5-year survival rate was 86.7% in the SPG-treated group and 73.4% in the control group. Immunological parameters showed that the SPG group quickly recovered the cellular immunity damaged by radiation, chemotherapy and surgical procedure. SPG was found to be effective as an assistant immunotherapeutic agent in the treatment of head and neck.

Adult↗

Expression of serine/threonine kinase receptors during ectopic bone formation induced by bone morphogenetic protein (BMP).

To understand the precise mechanism of bone formation induced by bone morphogenetic proteins (BMPs), it is important to elucidate the receptor system of BMPs. In this study, expression of mRNAs for serine/threonine kinase receptors, including BMP receptors, during ectopic bone formation induced by BMP, was investigated, and also the molecular cloning of rat BMP type IA receptor (BMPR-IA) was performed. Polymerase chain reaction (PCR)-based analysis revealed that mRNAs for BMP type IA and type IB receptors were expressed in the BMP-induced bone forming tissues throughout the stages tested and that mRNA for activin type IA receptor, which was shown to serve as a receptor for BMP as well, was also expressed. These results suggest that these three receptors play important roles for the ectopic bone formation induced by BMP. In addition, expression of mRNAs for TGF-beta type I and type II receptors and activin type IB and type II receptors was also detected in the BMP-implanted tissues, which suggested the possible involvement of TGF-betas and activins as ligands in the ectopic bone formation. The comparison of the rat BMPR-IA with the human and mouse counterparts showed high conservation among species. This finding suggests that BMPs may exert their effects through highly conserved pathway among species.

Amino Acid Sequence↗