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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 793 records · Page 44Linked to original sources
PubMed1989

Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes.

A genomic sequence and cloned complementary DNA has been identified for a novel receptor-like gene of the PDGF receptor/CSF1 receptor subfamily (platelet-derived growth factor receptor/colony-stimulating factor type 1 receptor). The gene recognized a 6.4-kilobase transcript that was coexpressed in normal human tissues with the 5.3-kilobase PDGF receptor messenger RNA. Introduction of complementary DNA of the novel gene into COS-1 cells led to expression of proteins that were specifically detected with antiserum directed against a predicted peptide. When the new gene was transfected into COS-1 cells, a characteristic pattern of binding of the PDGF isoforms was observed, which was different from the pattern observed with the known PDGF receptor. Tyrosine phosphorylation of the receptor in response to the PDGF isoforms was also different from the known receptor. The new PDGF receptor gene was localized to chromosome 4q11-4q12. The existence of genes encoding two PDGF receptors that interact in a distinct manner with three different PDGF isoforms likely confers considerable regulatory flexibility in the functional responses to PDGF.

Amino Acid Sequence↗
PubMed1989

Quantification of bone mineral content using dual-photon absorptiometry in a normal Japanese population.

The bone mineral content of lumbar spine and/or total body were quantified in 217 healthy Japanese (86 males and 131 females) using a Dichromatic Bone Densitometer (Norland Corp., Model 2600). The bone mineral density of the third lumbar vertebra (L3 BMD) decreased significantly after age 20 in males (r = -0.417, p less than 0.0002), with acceleration of the decrease after age 50 (r = -0.621, p less than 0.00002). A significant correlation was found between L3 BMD and age after age 40 (r = -0.747, p less than 0.0001) in females. L3 BMD correlated with both the body height (r = 0.335, p less than 0.0001) and the body weight (r = 0.340, p less than 0.0001). Total bone mineral content from the second to fourth lumbar vertebrae correlated significantly with total body bone mineral (r = 0.880, p less than 0.00001) in these normal subjects. Lumbar spine bone mineral as measured by dual-photon absorptiometry is lower in Japan than the bone mass in the United States, although not lower than in other parts of the world.

Adolescent↗
PubMed1989

Possibility of choriocapillary occlusion under experimental subretinal hemorrhage by photocoagulation with lasers of different wavelengths.

To clarify the possibility of occluding choroidal neovascularization in subretinal hemorrhage with various laser wavelengths, lesions of experimental subretinal hemorrhage were photocoagulated with argon, dye, and krypton lasers and were examined by light and electron microscopy. Our experimental results revealed that laser photocoagulation with wavelengths longer than 590 nm was effective in occluding the choriocapillaries under a thin subretinal hemorrhage. Complete occlusion of choriocapillaries was accomplished by red dye laser (630 nm) or krypton red laser. The choroidal lesion coagulated by 590 nm dye laser showed more extensive reaction than the other lesions at a posttreatment interval of 7 days. The red dye laser (630 nm) or krypton red laser is recommended for the treatment of neovascular maculopathy under thin subretinal hemorrhage because of less reaction and complete occlusion of the choroidal neovascularization.

Animals↗
PubMed1989

Phase II trial of carboplatin in patients with advanced germ-cell testicular tumors and transitional cell carcinomas of the urinary tract.

Carboplatin, an analog of cisplatin, was evaluated in a phase II study involving 25 patients with advanced testicular tumor and 45 with transitional cell carcinoma (TCC) of the urinary tract; 21 and 38 cases, respectively, were evaluable for response. Prior treatment with cisplatin-based chemotherapy had occurred in 7 of the testicular cancer patients and in 11 with TCC. The response rate (complete + partial response) in testicular tumors was 47.6%. The best response rate was observed in seminomas (70.0%), whereas the response rate in nonseminomas was 27.3%. The seminoma patients had mainly stage IIIA or less than IIIA disease, with metastatic lesions restricted to the lymph nodes. Three responses were seen in patients previously treated with cisplatin. In TCC, the response rate was 18.4%. Good-risk patients were treated with a dose of 400 mg/m2 every 4 weeks, whereas poor-risk patients received a lower dose of 300 mg/m2. The response rates for good-risk patients were 50.0% in testicular lesions and 26.1% in TCC. For poor-risk patients, the response rates were 40.0% and 6.7%, respectively. Carboplatin was well tolerated, with no significant renal impairment or ototoxicity detected. Nausea and vomiting were experienced by 51.7% of patients, but the severity was low; half of these patients demonstrated WHO grade I toxicity. However, myelosuppression was severe. In conclusion, carboplatin demonstrated activity in both testicular tumors and TCC and is worthy of further study, especially in combination with other active drugs.

Adult↗
PubMed1989

Close linkage of MEN2A with RBP3 locus in Japanese kindreds.

The gene responsible for multiple endocrine neoplasia type 2A (MEN2A) has recently been assigned to the pericentromeric region of chromosome 10 in European Caucasian kindreds by linkage analysis using a DNA marker, interstitial retinol-binding protein 3 (RBP3). We have found tight linkage between the MEN2A and RBP3 loci in Japanese MEN2A kindreds. The maximum lod score is 5.19 at a recombination fraction of 0.00. This result suggests that mutation of a certain gene close to RBP3 is responsible for MEN2A irrespective of ethnic backgrounds.

Female↗
PubMed1989

Preclinical detection in Japanese families with myotonic dystrophy using polymorphic DNA markers.

Myotonic dystrophy (DM) is a genetic disease inherited by an autosomal dominant trait and characterized by multi-organ disorders. Although its biochemical basis has been unknown, the DM locus is closely linked to D19S19 and APOC2 on the long arm of chromosome 19 both in Japanese and Caucasian populations. Linkage studies of Japanese DM families using these polymorphic DNA markers detected two asymptomatic gene carriers in two unrelated families.

Adult↗
PubMed1989

The developmental expression pattern of a new murine homeo box gene: Hox-2.5.

To examine the possible role of homeo box genes in murine development we have studied the structure and expression pattern of Hox-2.5, a newly isolated homeo box gene that maps to the left end of the mouse Hox-2 locus on chromosome 11. The sequence of the Hox-2.5 homeo box has been determined. It is highly homologous to Hox-1.7 and Hox-3.2, demonstrating extended conservation among three homeo box complexes in the mouse. Northern and in situ hybridization analyses of Hox-2.5 demonstrate a novel, regionally restricted pattern of expression in developing mesoderm and neurectoderm. We detect localized Hox-2.5 transcripts as early as 8.5 days postcoitum. The expression pattern of Hox-2.5 was analyzed over the next 3 days of ontogeny, as well as in later embryonic, newborn, and adult stages. Three-dimensional reconstruction of Hox-2.5 transcript localization within the central nervous system of early embryos clearly illustrates the neural expression domain. Although the Hox-2.5 expression pattern is regionally restricted during all of these stages of development, the pattern changes along the anteroposterior and dorsoventral axes of the CNS as the embryo undergoes complex morphogenetic movements and cytodifferentiation.

Amino Acid Sequence↗
PubMed1989

Human tooth dosimetry for gamma-rays and dental x-rays using ESR.

The effect of secondary electron equilibrium on the ESR dosimetry of x- and gamma-ray irradiation has been studied by using acrylic plates to simulate the soft tissue of the human mouth. Dental x-rays create a different ESR signal pattern at the front surface of the tooth vs the back surface. The effect on radiation build-up of the acrylic plate on gamma-irradiation is dominant at the front but is not appreciable at the back side of the tooth.

Cobalt Radioisotopes↗
PubMed1989

Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.

A related DNA fragment distinct from the epidermal growth factor receptor and ERBB2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. Characterization of the cloned DNA fragment mapped the region of v-erbB homology to three exons with closest identity of 64% and 67% to a contiguous region within the tyrosine kinase domains of the epidermal growth factor receptor and ERBB2 proteins, respectively. cDNA cloning revealed a predicted 148-kDa transmembrane polypeptide with structural features identifying it as a member of the ERBB gene family, prompting us to designate the gene as ERBB3. It was mapped to human chromosome 12q13 and was shown to be expressed as a 6.2-kilobase transcript in a variety of normal tissues of epithelial origin. Markedly elevated ERBB3 mRNA levels were demonstrated in certain human mammary tumor cell lines. These findings suggest that increased ERBB3 expression, as in the case of epidermal growth factor receptor and ERBB2, may play a role in some human malignancies.

Amino Acid Sequence↗
PubMed1989

Lymphotoxin cDNA clones from a HTLV-I-carrying T cell line HUT-102.

The conditioned medium of a HTLV-I-carrying T cell line HUT-102 showed cytotoxic activity against a mouse fibroblast cell line L-M. We prepared the cDNA library from HUT-102 poly(A)+ RNA and screened it using oligonucleotide probes that correspond to the amino acid sequences conserved in tumor necrosis factor (TNF) and lymphotoxin (LT). As a result we obtained two kinds of cDNA clones encoding LT in which amino acid residue 26t of mature LT is different; one is Asn and another is Thr. The sequence of the genomic clones obtained using a polymerase chain reaction method showed that the HUT-102 genome also contains two types of LT genes. Recombinant LTs expressed in Escherichia coli exhibited the same level of cytolytic activity against L-M cells. These results indicate that the cytotoxin constitutively produced by HUT-102 cells include two kinds of LT.

Amino Acid Sequence↗
PubMed1989

Effect of chloride on blood pressure and sympathetic nervous system activity in deoxycorticosterone acetate-treated rats.

The effect of selective chloride loading on blood pressure and sympathetic nervous system activity was studied in deoxycorticosterone acetate (DOCA)-treated rats. The rats fed a normal sodium-high chloride and fed a high sodium chloride diet had higher blood pressure and lower cardiac norepinephrine concentrations than those fed a normal sodium chloride diet. Furthermore, cardiac norepinephrine concentrations were significantly correlated with systolic blood pressure. These data suggest that selective chloride loading can raise blood pressure in DOCA-treated rats due to augmented sympathetic nervous system activity.

Animals↗
PubMed1989

Prevalence of small round structured virus infections in acute gastroenteritis outbreaks in Tokyo.

During the three-year period from 1984 to 1987, 506 acute gastroenteritis outbreaks involving 14,383 patients were reported to the Bureau of Public Health, Tokyo Metropolitan Government. Eighty (4,324 patients) of 150 outbreaks (4,860 patients) from which etiologic agents were not identified were subjected to virological investigation. Spherical particles of 28-32 nm in diameter with capsomere-like structures on the surface were detected in patients' stool specimens. Buoyant density of the particles appeared to be 1.36 to 1.40 g/ml in CsCl. Seroconversion to the particles was observed in patients by immune electron microscopy. From these observations, we concluded that the detected particles were members of small round structured virus (SRSV), and that they were implicated in the etiologically ill-defined outbreaks encountered. Prevalence of SRSV infections in these outbreaks was examined by electron microscopy. SRSV was positive in 83.8% of the outbreaks, and 96.4% of the cases. SRSV-positive outbreaks usually occurred during winter in contrast to bacterial outbreaks which often occurred in the summer season. Of 80 outbreaks examined, 53 were associated with the ingestion of oysters, and the remaining 27 mostly with food other than oysters. Oyster-associated outbreaks usually occurred on a small scale, while unassociated ones on diverse scales ranged from family clusters to large outbreaks.

Acute Disease↗
PubMed1989

Differential neutralizing effect of tiopronin on the toxicity of neocarzinostatin and SMANCS: a new rescue cancer chemotherapy.

The toxic effect and antitumor activity of neocarzinostatin (NCS) and SMANCS [copoly(styrenemaleic acid)-conjugated NCS] were greatly affected by N-(2-mercaptopropionyl)-glycine [tiopronin] both in vitro and in vivo, in cultured HeLa cells and RL male 1 tumor-bearing mice. The cytotoxicity of NCS and SMANCS against HeLa cells was remarkably reduced by the addition of tiopronin during drug treatment. Interestingly, the neutralizing effect of tiopronin on the toxicity of SMANCS was greater than that in the case of NCS. In the continuous presence of 10 mM tiopronin during a 1 h drug treatment, the 50% cell-killing doses of NCS and SMANCS were increased 72 and 208 times as compared to those without tiopronin, respectively, whereas tiopronin itself has no cytotoxicity to HeLa cells up to 100 mM. Furthermore, more effective reduction of the lethal toxicity of SMANCS was observed by the intraperitoneal (ip) administration of tiopronin after ip injection of a lethal dose of SMANCS as compared to the same protocol in the case of NCS in mice. Therapeutic studies on RL male 1 tumor-bearing mice revealed that delayed (time lag) ip administration of tiopronin after high-dose SMANCS administration ip was much superior to the combination of NCS with tiopronin, or SMANCS alone. In this time-lag combination chemotherapy of SMANCS with tiopronin, 60% of treated mice survived more than 60 days after tumor inoculation, while all the untreated control mice died within 20 days.

Animals↗
PubMed1989

Western blot (immunoblot) assay of small, round-structured virus associated with an acute gastroenteritis outbreak in Tokyo.

Small, round-structured virus (SRSV) was detected in a stool specimen of a patient during an acute gastroenteritis outbreak in Tokyo and was tentatively named SRSV-9. SRSV-9 was purified by sucrose velocity gradient centrifugation after CsCl density gradient centrifugation. The buoyant density of SRSV-9 appeared to be 1.36 g/ml in CsCl. A Western blot (immunoblot) assay using the biotin-avidin system revealed that SRSV-9 was antigenically related to the Hawaii agent but distinct from the Norwalk agent and contained a single major structural protein with a molecular size of 63.0 +/- 0.6 kilodaltons. The prevalence of SRSV-9 infection in Tokyo was surveyed by the Western blot antibody assay by using a crude virus preparation as the antigen. Seroconversion was observed in 56.5% of the patients involved in the outbreaks from which SRSV was detected by electron microscopy.

Acute Disease↗
PubMed1989

Clinical availability of serum fructosamine measurement in diabetic patients with uremia. Use as a glycemic index in uremic diabetes.

Serum fructosamine levels were investigated in patients with uremia undergoing various modes of treatment. The serum fructosamine levels correlated positively with the blood glucose levels determined a week or two earlier. The fructosamine levels were significantly affected by the protein concentration, and those corrected for protein concentrations had a closer correlation to the blood glucose levels than did the uncorrected levels. The corrected fructosamine levels were not significantly different between healthy volunteers and nondiabetic patients with uremia on conservative treatment. In an in vitro system, fructosamine concentrations were hardly affected by urea, which is known to influence the level of hemoglobin A1. These results suggest that serum fructosamine measurement can provide us with reliable information on a short-term glycemic condition, even in azotemic patients. To be more precise, the serum level of fructosamine corrected for protein concentration can be an excellent glycemic index which is not susceptible to over- or dehydration and is of high clinical value, especially in the management of diabetic patients with chronic renal failure.

Adult↗
PubMed1989

Mechanism of development of asymmetric septal hypertrophy in patients with essential systemic hypertension.

In order to understand the mechanism of development of asymmetric septal hypertrophy (ASH) in hypertension, 290 patients with essential hypertension (HT) were examined echocardiographically. Out of them 84 cases of advanced left ventricular hypertrophy (LVH) [37 cases of symmetric hypertrophy (HT-SH group) and 47 cases of ASH (HT-ASH group)] were compared in their clinical and echocardiographic findings with hypertrophic cardiomyopathy (HCM). In the 290 HT cases, the highest systolic pressure in each patient's history was found to correlate with left ventricular (LV) posterior wall thickness (PWT), but not with the septal wall thickness (IVST). There were no differences in LV thickness (IVST + PWT) among patients in the HT-ASH, HT-SH and HCM groups. While the HCM group patients showed no significant differences in IVST and PWT from those in the HT-ASH group, they did have greater IVST and smaller PWT than HT-SH group patients. The rapid filling rate (RFR) was also not much different in the HCM and HT-ASH groups, but was significantly lower in the HCM group than in the HT-SH group. Furthermore, HT-ASH group patients has a milder degree of hypertension and a higher incidence of familial occurrence of HCM than did those in the HT-SH group. After treatment for HT, the HT-SH group showed a significant decrease in wall thickness during long-term observation, while the HT-ASH and HCM groups, failed to exhibit such changes. Moreover, the degree of myocardial disarrangement in the HT-ASH group did not differ significantly from that in the HCM group. These results suggested that LVH in HT is related not only to pressure load but also to genetic factors similar to that in HCM.

Adult↗
PubMed1989

[VM-26 and VP-16 salvage therapy for refractory germinal testicular cancers].

Thirteen evaluable patients with germinal testicular cancers failing to be cured with first-line therapy (refractory) were treated by salvage chemotherapy. Ten patients received salvage chemotherapy with VM-26 (50 mg/m2, twice a week X 6 weeks) and cisplatin (CDDP, 20 mg/m2 for 5 consecutive days every 3 weeks for 3-4 times) (P-VM), 3 patients were also treated by radiation therapy, and 3 patients received VP-16 (100 mg/m2) and CDDP (20 mg/m2) (P-VP), all given daily for 5 consecutive days every 3-4 weeks for 4-5 courses. Of 13 evaluable patients, 6 (46%) had complete response (CR) (three cases were also treated with radiation therapy), 4 (31%) achieved partial response (PR), and 3 (23%) had no response. Limited to 7 patients treated with only P-VM therapy, there were 3 (43%) CR and 4 (57%) PR. Nine patients (69%) remained alive and were continuously disease free 18 to 84 months (median 48 months). Hematologic toxicity was severe, but with no death related to sepsis. Salvage chemotherapy with VM-26 or VP-16 and cisplatin offers potentially curative treatment to patients with refractory testicular cancer. The addition of radiation therapy to salvage chemotherapy was also effective.

Adult↗