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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 235 records · Page 13Linked to original sources
PubMed1990

Training effects on blood zinc levels in humans.

Effects of physical training on fasting erythrocyte and plasma zinc distributions were studied on seven previously sedentary male students. The training consisted of running over 5 km, 6 times/week for 10 weeks. Maximum aerobic capacity (VO2max) and 12 min walk-run performance increased significantly (p less than 0.01) after training. The erythrocyte concentrations of total zinc and of zinc derived from carbonic anhydrase I (CA-I) rose significantly (p less than 0.05) after training, whereas no such effects were noted in CA-II-derived zinc, Cu2Zn2 superoxide dismutase-derived zinc, and other zinc. On the other hand, no effect of training was found in total or alpha 2-macroglobulin-bound zinc in plasma, although albumin-bound zinc concentration declined significantly (p less than 0.05). Following the training period, however, the response to a VO2max test of the van Beaumont quotient (J Appl Physiol 1973;34:102-6) for total plasma zinc had decreased significantly (p less than 0.05), suggesting a relative reduction of the circulating exchangeable zinc. In addition, there were significant (p less than 0.05) decreases in plasma iron and ferritin concentrations after training, indicating latent iron deficiency anemia. These results may suggest that the changes in CA-I-derived zinc and/or albumin-bound zinc portend zinc deficiency during running training and that sports anemia precedes hypozincemia in athletes.

Adolescent↗
PubMed1989

Strain dependency of B and T lymphoma development in immunoglobulin heavy chain enhancer (E mu)-myc transgenic mice.

The transgenic mice were produced by injecting eggs of B6 and C3H/HeJ mice with the human E mu-myc gene. Preferential development of B lymphomas was observed in the B6 transgenic mice, whereas the C3H/HeJ transgenic mice developed mostly T lymphomas. The phenotypic activation of B lineage cells but not of T lineage cells was detected in the prelymphomatous transgenic mice of both strains. The transgene was similarly expressed in B and T cells of the transgenic mice of both strains. These results suggest that a high incidence of T lymphomas in the C3H/HeJ transgenic mice may not be due to the preferential activation of or the preferential E mu-myc expression in T lymphocytes. When the bone marrow or fetal liver cells from the prelymphomatous transgenic mice of both strains were transferred into irradiated normal C3H/HeJ mice, most of the recipients developed T lymphomas. Moreover, even when irradiated B6 mice received the hematopoietic stem cells from the prelymphomatous B6 transgenic mice, the incidence of T lymphoma increased up to 50%. These findings suggest that B6 and C3H/HeJ mice might provide the environment that supports the development or growth of B and T lymphomas, respectively, and that such an environment could be modified by irradiation of the mice.

Animals↗
PubMed1989

Expression vector system based on the chicken beta-actin promoter directs efficient production of interleukin-5.

We examined the promoter activity of the 1.3-kb chicken beta-actin gene sequence located between the 5' flanking region and the proximal region of the second exon. This promoter region showed higher promoter activity than the simian virus 40 (SV40) early promoter or the Rous sarcoma virus (RSV) long terminal repeat (LTR) as assayed by transient lacZ gene expression in mouse L cells. Furthermore, replacement of the 3' splice sequence in this promoter by that derived from the rabbit beta-globin gene resulted in a approximately 2.5-fold enhancement in the synthesis of beta-galactosidase (beta Gal). Introduction of the SV40 origin of DNA replication (ori) into the vector carrying this hybrid promoter, which we designate the AG promoter, markedly enhanced the production of beta Gal in an SV40 T antigen-producing cell, BMT10. We have constructed a useful vector containing the strong AG promoter, several unique restriction sites, a SV40 polyadenylation signal and the SV40 ori for transient expression of cDNA in BMT10 or COS cells. We demonstrate the use of this vector for efficient production of interleukin-5 in BMT10 cells.

Actins↗
PubMed1989

Tissue- and developmental stage-specific expression of the rat ornithine carbamoyltransferase gene in transgenic mice.

Rat ornithine carbamoyltransferase (OCT; EC 2.1.3.3) is encoded by a large gene of 75 kilobases. Expression of this gene is restricted to the liver and small intestine, and there is an increase in expression late in gestation. The recombinant gene carrying 1.3 kilobases of the 5' flanking region of the gene fused to the rat OCT cDNA was microinjected into fertilized eggs, and 17 transgenic mice were produced. Expression in the liver of the transgene was detected in three mice. In these mice, the transgene expression was observed exclusively in the liver and small intestine. Expression of the transgene in the intestine was comparable to that of the endogenous mouse OCT gene, whereas expression in the liver was much lower than that of the endogenous gene. The developmental pattern of expression of the transgene was similar to that of the endogenous gene. Therefore, the 5' flanking sequence of the rat OCT gene seems to be sufficient for the developmental and tissue-specific expression of the gene. An explanation for low expression in the liver remains the subject of ongoing study.

Animals↗
PubMed1989

Effects of acute lead acetate exposure on adult guinea pigs: electrophysiological study of the inner ear.

The effects on humans of lead acetate exposure may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported in lead workers; however, there exist only a few reports concerning the dose effects of lead acetate both on the cochlea and the eighth cranial nerve. The effects of lead acetate on the cochlea and the eighth nerve were investigated systematically using cochlear microphonics (CM), whole-nerve action potential (AP), and endocochlear potential (EP) in guinea pigs (male albino Hartley). Guinea pigs were injected with 2 ml of a 1% solution of lead acetate (20 mg) once a week for 1-5 weeks. The threshold of whole-nerve AP (N1) was elevated by injection of lead acetate, even 40 mg, and whole-nerve AP (N1) output voltage decreased after injection of 100 mg of lead acetate. On the other hand, no change was observed in CM after lead acetate injection (100 mg) or in EP after lead acetate exposure (40 mg). The blood concentrations of lead acetate were as follows (mean): control, 4.5 micrograms/dl; Expt 1, 80 micrograms/dl; Expt 2, 126 micrograms/dl; Expt 3, 142 micrograms/dl. We conclude that dysfunction of the eighth nerve is induced by high-dose lead exposure, but that lead exposure does not induce electrophysiological dysfunction of the organ of Corti and the stria vascularis.

Animals↗
PubMed1989

Expression and replication of hepatitis B virus genome in transgenic mice.

We produced transgenic mice by microinjecting a partial tandem duplication of the complete hepatitis B virus (HBV) genome into fertilized eggs of C57BL/6 mice. One of eight transgenic mice was a high producer for HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. The HBV genomes were transmitted to the next generation and these F1 mice also produced HBsAg and HBeAg. mRNAs of 3.5, 2.1, and 0.8 kilobases were detected in the livers and the kidneys of these mice. In addition, a 0.8-kilobase RNA was detected in the testis. Single-stranded and partially double-stranded HBV DNAs were shown to be produced in the cytoplasm of the liver and kidneys. These HBV DNAs were associated with the core particles, indistinguishable from nucleocapsid produced in an infected human liver. Viral genome DNA was detected in the serum. These results demonstrate that the HBV genome integrated into the mouse chromosome acted as a template for viral gene expression, allowing viral replication. Thus, these transgenic mice should be useful for detailed studies of the replication and expression of HBV and for pathological studies of hepatitis, including the development of hepatocellular carcinoma.

Animals↗
PubMed1989

IgG1 plasmacytosis in interleukin 6 transgenic mice.

Interleukin 6 (IL-6) has been suggested to be involved in the pathogenesis of polyclonal and monoclonal plasma cell abnormalities. To address this possibility, transgenic mice carrying the human IL-6 genomic gene fused with a human immunoglobulin heavy chain enhancer were generated. High concentrations of human IL-6 and polyclonal increase in IgG1 (120- to 400-fold) in sera of all transgenic mice were observed. A massive plasmacytosis in thymus, lymph node, and spleen and an infiltration of plasma cells in lung, liver, and kidney were observed. However, the plasma cells were not transplantable to syngeneic mice and were found not to contain chromosomal aberrations including c-myc gene rearrangements. The evidence indicates that deregulated gene expression of IL-6 can trigger polyclonal plasmacytosis but cannot induce plasmacytoma. It is suggested that additional genetic changes may be required for the generation of plasma cell neoplasia. Other interesting findings in these transgenic mice were the development of mesangio-proliferative glomerulonephritis and an increase in megakaryocytes in bone marrow.

Animals↗
PubMed1989

Demethylation by 5-azacytidine results in the expression of hepatitis B virus surface antigen in transgenic mice.

In 14p3HB transgenic mice, which carry three tandem copies of hepatitis B virus (HBV) DNA, the HBV DNA was significantly methylated and no viral proteins were produced. To analyze the causal relationship between hypermethylation and gene inactivity, 5-azacytidine was injected into the mice to demethylate HBV DNA. When postnatal 14p3HB mice were treated with the drug, hepatitis virus surface antigen was produced in these mice by 3 weeks of age, and the integrated HBV DNA of the liver was less heavily methylated. Our results suggest that injection of 5-azacytidine can be used to efficiently activate a silent transgene such as HBV DNA in transgenic mice.

Animals↗
PubMed1989

Clinical and photobiological characteristics of xeroderma pigmentosum complementation group F: a review of cases from Japan.

A 61-year-old female patient with xeroderma pigmentosum (XP), registered as XP46KO, was assigned to complementation group F by the cell fusion-complementation method. The XP46KO fibroblasts in culture exhibited a defective DNA repair capacity of 10-15% unscheduled DNA synthesis and a 3-fold sensitivity to the lethal effect of 254 nm ultraviolet light compared with normal cells. The patient had mild clinical symptoms consisting of numerous pigmented freckles and a small number of seborrheic keratosis-like papules. She had no skin cancers in the sun-exposed areas of the skin and so far no neurological abnormalities. A review of 11 Japanese group F patients revealed very mild skin symptoms with no ocular or neuro-psychiatric abnormalities. Single skin cancers occurred in only 3 of the 11 patients with an average age of 52 years for their first skin malignancy.

DNA↗
PubMed1989

Clinical and statistical evaluation of the occurrence of acute myocardial infarction in the cold inland area of Hokkaido.

We made a clinical and statistical evaluation of the occurrence of acute myocardial infarction with respect to the relation between its occurrence and the meterology of the cold inland area of Hokkaido (the Kamikawa Basin) over a period of 10 years (1976-1985). A total of 581 cases were studied. Monthly fluctuation of incidence was not found to be statistically significant. A cold period in the Kamikawa Basin was defined in this study as the period when ordinary mean atmospheric temperatures were below 0 degree C (from 7 Nov. to 16 Apr.). Canonical discriminant analysis was applied to 10 meterological factors between the days with occurrences and those without occurrences (245 days vs 245 days) in the cold periods of the investigated 10 years, and between the days with outdoor occurrences and those without occurrences (37 days vs 37 days). In order to compare the regional difference, this analysis was done on the same 10 factors for the cold periods over 3 years in Yamagata (46 days vs 46 days). The F values of 0.0003, 0.0155 and 0.0098 respectively in the above 3 analyses were small (much less than F 1(9) (0.25) = 1.51). A circadian rhythm of 2 cycles/day was recognized concerning the time of occurrence by power spectral analysis of the data of 562 patients for whom the time of the onset of myocardial infarction was known. Subdividing the patients into 2 groups according to physical activity just before the occurrence, the group who experienced an occurrence at rest showed a rhythm of 1 cycle/day, and the group who experienced an occurrence on effort showed a rhythm of 2 cycles/day. Therefore, the 10 meterological factors could not discriminate the probabilities between the days with occurrences and the days without occurrences of myocardial infarction in the cold periods. On the other hand, it was suggested that biological intrinsic rhythm participates in triggering the occurrence of myocardial infarction.

Adult↗
PubMed1989

[Transgenic mice and their use in cancer study].

The ability to introduce the cloned gene into the mouse germ line has made possible to analyze the cis-acting DNA sequence which is involved in the tissue-specific and developmental regulation of the gene. In addition, this system can also be applied to analyze the patho-physiological roles of the introduced gene product within the mouse whole body. Therefore, this system is one of the best approaches to analyze the mechanism of oncogenesis. The chromosomal translocation is one of the mechanisms leading to the activation of oncogene. In the case of lymphoid cell tumors, the reciprocal translocation between chromosome No. 8 and No. 14 is frequently observed. With this translocation, c-myc gene can be activated by the enhancer of immunoglobulin heavy chain (E mu). We and others have demonstrated that the E mu-myc gene could induce lymphomas in transgenic mice. Following these observation we have currently many examples that activated oncogene can induce variety tumors, giving basic knowledge about the relationship between activated oncogene and cell-type specificity of tumor. On the other hand, molecular mechanism of oncogenesis which is caused by viruses such as hepatitis B virus (HBV) or human T cell leukemia virus (HTLV) is totally unknown. One main reason is the absence of animal model for these diseases. To overcome this problem, we have attempted and succeeded to produce a transgenic mouse model which consistently produces HBV. Using these mice, it will be possible to elucidate the molecular mechanism of development of hepatitis and hepatocellular carcinoma.

Animals↗
PubMed1989

Transgenic mouse model of familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited disorder, characterized by the extracellular deposition of amyloid fibrils composed of variant transthyretin (TTR), and by prominent peripheral nerve involvement. We demonstrate that the main cause of this disease is the presence of a point mutation in the TTR gene. However, neither the time of onset nor the clinical course is predictable. To elucidate the molecular pathogenesis of this disease, we constructed transgenic mice carrying and expressing the human mutant TTR gene. In these mice, amyloid is deposited in the alimentary tract as early as age six months, and becomes more remarkable with aging. These transgenic mice should be useful in elucidating factors which modulate the time of onset and the clinical course of FAP, and in establishing therapy for this intractable disorder.

Amyloidosis↗
PubMed1989

[Second surgical intervention for contralateral recurrence or second primary lung cancer].

Resection of contralateral lung cancer (6 cases of pulmonary metastasis from the first lung cancer and one case of second primary lung cancer) were evaluated retrospectively in terms of postoperative complication, pulmonary function and survival rate. Out of 691 cases with resected non small cell lung cancer, 7 cases (1.0%) had contralateral lung cancer which were resected as the second operation. Six cases were squamous cell carcinoma and one case was adenocarcinoma. The interval between the first and the second operation was 12 months to 10 years (average 46 months). The post-operative stage of first lung cancer were stage I in 5 cases and stage IIIB in 2 cases, but no case had lymphadenopathy at the first operation. Operative procedures for contralateral lung were as follows; one case of lobectomy----lobectomy, one case of lobectomy----segmentectomy, two cases of lobectomy----partial resection, two cases of pneumonectomy----partial resection. For a metachronous lung cancer, right upper sleeve lobectomy was done as the first operation followed by left lower sleeve lobectomy as the second cancer five years later. Contralateral lung resection impaired pulmonary function, but all cases well tolerated the second operation. The five-years survival rate after second operation was 40.0%.

Aged↗