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Biomedical subjects

K Nakashima

Publications and source records attributed to K Nakashima.

At least 217 records · Page 12Linked to original sources
PubMed1999

A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains.

LIM-homeodomain (LHX) transcription factors play critical roles in cell fate determination during development, in particular, in CNS. The transcriptional activity of several LHX proteins is postulated to be regulated by interaction with an LIM-domain binding protein, Ldb1. We have now identified a novel LHX molecule, termed Lhx6.1, that is closely related to a recently reported Lhx6 molecule. The Lhx6.1 transcript is found in several restricted regions in the developing CNS, mostly within the embryonic forebrain. We further show that Lhx6.1 interacts with Ldb1 through tandem LIM-domains, implying transcriptional regulation of Lhx6.1 by Ldb1.

Amino Acid Sequence↗
PubMed1999

Induction of apoptotic cell death in human hepatocellular carcinoma SK-HEP-1 cells by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone).

The antitumor effects of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on the human hepatocellular carcinoma SK-HEP-1 cell line have been investigated. The growth of these cultured hepatocellular carcinoma cells was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels were dose-dependently depressed, and morphological changes due to programmed cell death (apoptosis) were observed in these MGBCP-treated hepatocellular carcinoma cells. These results suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in this human hepatocellular carcinoma cell line.

Antineoplastic Agents↗
PubMed1999

Alteration in brain presenilin-1 mRNA expression in sporadic Alzheimer's disease.

Expression of presenilin-1 (PS-1) mRNA in an alternative splicing at the 3' end of exon 3 was examined in brain tissue, lymphocytes and cultured skin fibroblasts using the RT- polymerase chain reaction (RT-PCR) method. We quantified the relative ratios of the densities of the long form of PS-1 mRNA, which contains a sequence encoding four amino acids (VRSQ, denoted as VRSQ+) to the short form, which lacks the VRSQ sequence (VRSQ-). The brain tissue of subjects with sporadic Alzheimer's disease (AD) had reduced levels of the VRSQ+ form of the PS-1 mRNA compared to a control group. No significant differences appeared in peripheral tissues, such as lymphocytes or cultured skin fibroblasts in AD with control subjects. Changes in the alternative splicing of exon 3 may be specific to the brain and may play an important role in the pathogenesis of sporadic AD.

Aged↗
PubMed1999

Transduction for sweet taste of saccharin may involve both inositol 1,4,5-trisphosphate and cAMP pathways in the fungiform taste buds in C57BL mice.

The transduction pathways for sweet and bitter tastes were investigated with assays of inositol 1,4,5-trisphosphate (IP3) and cyclic adenosine monophosphate (cAMP) levels in mouse fungiform taste buds. Recordings of taste responses were also made in the chorda tympani nerve. Stimulation of the tongue with saccharin elicited a significant increase in IP3 levels in the fungiform papilla only at 20 mM but in cAMP levels at 3 and 20 mM, without affecting those of the nonsensory epithelial tissue. Formation of both IP3 and cAMP induced by 20 mM saccharin was suppressed by pretreatment of the tongue with pronase, a proteolytic enzyme which specifically inhibits sweet responses. Quinine and denatonium elicited both significant increases in IP3 levels at a concentration of 20 mM and slight decreases in cAMP levels at concentrations of 1-20 mM in the fungiform papilla. Recording of the chorda tympani nerve showed good responses by saccharin, quinine, and denatonium at concentrations of 1 mM and higher. These results suggest that the fungiform taste cells in C57BL mice have pronase-sensitive receptors for saccharin, coupled to both the IP3 and the cAMP pathways; the former participates only at high concentration, while the latter acts from low to high concentrations. The results also do not rule out the possibility that a phosphodiesterase-mediated cAMP decrease may be involved in bitter transduction for quinine and denatonium.

Animals↗
PubMed1999

Pharmacological treatments for GH-induced insulin resistance.

Troglitazone (T) and d-chiroinositol (DCI) have been reported to improve insulin resistance associated with obesity and NIDDM. We tested whether these compounds counteract the insulin antagonistic effects of recombinant human GH. Male Wistar rats were allocated to 4 different treatment groups, rhGH (n=8), rhGH+T (n=7), rhGH+DCI (n=8) and control (saline, n=8). rhGH (2 IU/100 g/day) was injected sc twice daily for 2 days. T and DCI were given (20 mg/day) po for 5 days preceding and 2 days along with rhGH. Euglycemic hyperinsulinemic clamp studies were done to assess the hepatic glucose output (HGO) and glucose disappearance rate (GDR). Fasting plasma glucose, insulin, serum FFA and basal HGO were similar in all 4 treatment groups. During the hyperinsulinemic clamp which raised plasma insulin levels to 7.2 +/- 0.4 ng/ml, HGO was suppressed in the control and rhGH+T treated rats but not in the rats treated with rhGH and rhGH+DCI. GDR decreased in the rats which received rhGH (18.1 +/- 5.8 vs 30.3 +/- 5.2 mg/kg/min) compared to the control rats. The rats given either T (24.7 +/- 2.7) or DCI (31.4 +/- 2.7) along with rhGH showed comparable GDR to the control rats. These results indicated that rhGH induced hepatic and peripheral insulin resistance. Troglitazone counteracted the insulin-antagonistic action of rhGH both in the liver and the peripheral tissues. DCI was effective in offsetting peripheral insulin resistance but without any effect on hepatic insulin resistance associated with rhGH treatment.

Animals↗
PubMed1999

Branched-chain amino acid therapy for spinocerebellar degeneration: a pilot clinical crossover trial.

OBJECT: The potential effects of branched-chain amino acids (BCAAs) on spinocerebellar degeneration (SCD) were explored in eleven patients. METHODS: The patients received 200 ml of BCAA-rich solution, 2 mg of thyrotropin-releasing hormone (TRH; protirelin), or a placebo daily for 7 days each in a random order. An SCD score was used to quantify the severity of symptoms. PATIENTS: Eleven patients with SCD (7 male, 4 female; mean age 60+/-11; mean disease duration 5.5 years) participated in this study. RESULTS: The mean SCD score of the eleven patients improved significantly by the BCAA treatment compared with the baseline. The conditions of five of the eleven patients (45%) were clearly improved by the BCAA treatment. All of the responders manifested predominantly cerebellar symptoms, but no prominent parkinsonian symptoms. Two patients with marked rigidity and akinesia did not respond to the treatment. CONCLUSION: We concluded that BCAAs do have a beneficial effect on functional improvement in patients with SCD, and that further large scale studies are needed.

Adult↗
PubMed1999

Analysis of the CAG repeat number in a patient with Huntington's disease.

This study was performed to confirm 1) the difference in the trinucleotide CAG repeat number among tissues, 2) somatic mosaicism in each tissue, 3) the correlation of the repeat number with pathological severity in Huntington's disease. The CAG repeat number was determined by analysis of the polymerase chain reaction (PCR) product in various tissues, including central nervous system (CNS) tissues and non-CNS tissues. We also determined the pathological severity grade in each brain section and compared this with the results of CAG repeat analyses. The patient was a Japanese male with Huntington's disease who died at 62 years of age. Genomic DNA was extracted from 10 parts of the central nervous system and 6 parts of other tissues from the patient. Each part of the formalin-fixed brain was subjected to gross and microscopic pathological assessment. The main peaks of CAG repeat in all tissues were 22 and 44. In analysis of somatic mosaicism, high degrees of mosaicism were obtained in the caudate nucleus, putamen and cerebral cortex, in which more severe degeneration was observed by pathological examination. These results, although this is a single case study, indicated that pathological severity did not correlate with the CAG repeat number, but it did relate to the degree of somatic mosaicism. Somatic mosaicism might reflect region-specific neuronal degeneration in Huntington's disease.

Brain↗
PubMed1999

Effect of renal denervation on the compensatory renal growth following nephrectomy in the cat.

The purpose of this study was to clarify the effect of denervation on the mass of the remaining kidney with or without unilateral nephrectomy using adult cats. The animals were divided into 4 groups: (1) control group, the weights of the right and left kidneys were measured intact in 5 cats; (2) nephrectomy group (Nx, n = 5 cats), the right kidney was removed and the left kidney was weighed 3-5 d after nephrectomy; (3) nephrectomy and denervation group (Nx+Dx, n = 7 cats), the left kidney was weighed on the 7th day after surgery in which the left kidney was denervated and the right kidney was removed; and (4) denervation group (Dx+Dx, n = 5 cats), both kidneys were weighed on the 7th day after denervation of the kidneys. In the control group, the left and right kidney weights per body weight (LKW and RKW) were the same (LKW, 0.74 +/- 0.06%; RKW, 0. 74 +/- 0.07%). In the Nx group, LKW increased to 0.90 +/- 0.03% 3-5 d after nephrectomy, although RKW of the removed kidney was 0.66 +/- 0.01%. In the Nx+Dx group, LKW increased to 0.97 +/- 0.15%, which was similar to that of the Nx group. In the Dx+Dx group, LKW (0.56 +/- 0.05%) and RKW (0.54 +/- 0.05%) were significantly less than those in the control group. We conclude that the renal nerves may contribute to maintaining the renal mass and that the neural effect on compensatory growth following nephrectomy may be covered by other growth factors.

Adaptation, Physiological↗
PubMed1999

HUB1 is an autoantigen frequently eliciting humoral immune response in patients with adult T cell leukemia.

The immunological screening of a cDNA phage expression library prepared from an adult T cell leukemia (ATL) cell line, ST1, was performed with IgG class antibodies in the serum of an ATL patient by the SEREX method to analyze the repertoire of antigen molecules in ATL. Ten different cDNAs, 7 previously reported and 3 newly identified, were isolated. One of the identified cDNAs was homologous to the recently reported gene, HTLV-I U5RE binding protein 1 (HUB1) encoding a protein binding to a possible repressor element of the long terminal repeat of the human T lymphotropic virus type I (HTLV-I). The obtained cDNA was expressed as a fusion protein with glutathione S-transferase. HUB1 protein was prepared by subsequent treatment of the fusion protein with thrombin. Reactivity of IgG serum samples from ATL patients, asymptomatic HTLV-I carriers and normal donors against the purified protein was examined by Western blot analysis. Twenty-one out of 30 samples (70.0%) from ATL patients, 10/24 samples (41.7%) from HTLV-I carriers and 9/24 samples (37.5%) from healthy donors showed positive reactivity, indicating the autoantigenicity of HUB1. The development of ATL may be related to higher production of antibodies against HUB1.

Adult↗
PubMed1999

A strange calmodulin of yeast.

Calmodulin of Saccharomyces cerevisiae has different Ca2+ binding properties from other calmodulins. We previously reported that the maximum number of Ca2+ binding was 3 mol/mol and the fourth binding site was defective, which was different from 4 mol/mol for others. Their macroscopic dissociation constants suggested the cooperative three Ca2+ bindings rather than a pair of cooperative two Ca2+ bindings of ordinary calmodulin. Here we present evidence for yeast calmodulin showing the intramolecular close interaction between the N-terminal half domain and the C-terminal half domain, while the two domains of ordinary calmodulin are independent of each other. We will discuss the relationship of the shape and the shape change caused by the Ca2+ binding to the enzyme activation in yeast. The functional feature of calmodulin in yeast will also be considered, which might be different from the one of vertebrate calmodulin.

Animals↗
PubMed1999

[Population genetic study of Huntington's disease--prevalence and founder's effect in the San-in area, western Japan].

In order to confirm the prevalence rate of Huntington's disease (HD) in San-in area, the epidemiological study was performed in 1997. Ten patients were found, so that the prevalence rate of HD was 0.72 per 100,000 population. D4S136 and CCG polymorphism were investigated in HD patients in western Japan, Chugoku Districts, including the San-in area. The frequency of D4S136A3(242bp) type was higher in HD group of San-in area than Chugoku District (each 38.5% and 9.1%). Twelve of 13 HD chromosomes in the San-in area had the (CCG)7 polymorphism, while only 36.4% of HD chromosomes of Chugoku District had the (CCG)7 polymorphism. Although the HD patients in the San-in area may have a common ancestor except for only one patient, the HD patients in other areas of Japan may have the different HD ancestor from the San-in area.

Founder Effect↗
PubMed1999

[A resected case under thoracoscopic surgery of bilateral pulmonary metastases of renal cell carcinoma ten years after radical nephrectomy].

A 68-year-old male had received a left nephrectomy for renal cell carcinoma of the clear cell type in October, 1987. He had been given Interferon alpha (IFN alpha) for one year since then. He was referred to our hospital for bilateral abnormal shadows on the chest roentgenogram in December, 1997. He underwent a video-assisted thoracoscopic biopsy of bilateral lung in January, 1998, 11 years after his nephrectomy. The resected specimens contained a coin lesions measuring approximately 2 cm in diameter, and the lesions were microscopically diagnosed as a renal cell carcinoma of the clear cell type metastatic to the lung. The patient is doing well with no signs of re-recurrence five months after the resection of the metastatic lesion.

Aged↗
PubMed1999

A case of late onset cyclosporine-induced hemolytic uremic syndrome resulting in renal graft loss.

A case of late onset hemolytic uremic syndrome (HUS) associated with cyclosporine (CYA) is described in this report. A 50-yr-old man with end-stage renal failure due to immunoglobulin A (IgA) nephropathy received a renal transplant from his wife. Human leucocyte antigen was completely unmatched. Immunosuppressant was a combination of prednisolone, azathioprine, and CYA. He was discharged 1 month after transplantation, with no episode of acute rejection. Twenty-one months after transplantation, his platelet count and hematocrit began to decrease and lactate dehydrogenase began to increase. Graft biopsy showed thrombotic microangiopathy and recurrent IgA nephropathy. Graft function was rapidly deteriorated and methylprednisolone pulse therapy was not effective. Twenty-five months after transplantation, he returned to a regular hemodialysis. Hemolysis was immediately improved after a reduction of the dose of CYA to 50 mg/d. The trough level of CYA was less than 200 ng/mL in most periods of his clinical course. Blood pressure was high throughout the clinical course. Although acute vascular rejection or malignant hypertension could also cause a thrombotic microangiopathy, CYA was most likely a cause of HUS in the present case because of the following reasons: neither anti-acute rejection therapy nor an adequate control of his blood pressure was effective in improving clinical features of HUS; hemolysis and thrombocytopenia disappeared immediately after the reduction of the dose of CYA to 50 mg/d. It has been reported that HUS carried poor prognosis only when occurring shortly after transplantation in cadaver kidney recipients. The present transplant was from a living donor and HUS occurred 21 months after transplantation and was severe enough to result in graft loss. High blood pressure might be one of the predisposing factors of HUS associated with CYA in the present case. CYA should be stopped and other alternative immunosuppressants should be given in cases of acute graft deterioration with hemolysis and thrombocytopenia, irrespective of the interval from transplantation, CYA dose, or CYA trough level.

Cyclosporine↗