Search PubMed⌕ Search

Biomedical subjects

T Serikawa

Publications and source records attributed to T Serikawa.

At least 55 records · Page 3Linked to original sources
PubMed1998

Production of WTC.ZI-zi rat congenic strain and its pathological and genetic analyses.

A new rat congenic strain, WTC.ZI-zi, was produced after eleven generations of backcrossing between ZI strain as a donor strain and WTC strain as an inbred partner. WTC.ZI-zi/zi homozygous rats generally exhibit more conspicuous body tremor and much earlier occurrence of flaccid paresis than the original ZI strain. The average life span of the congenic strain is approximately nine months, which is also much shorter than that of the original ZI strain. Pathological analysis of the central nervous system of the congenic strain revealed more aggravated vacuolation and hypomyelination than in the original ZI strain. Establishment of the genetic profile with microsatellite markers showed that the congenic strain was genetically almost identical to the WTC strain except for a small chromosome segment bearing the zitter gene. Analysis of markers in this region implied that the length of the donor segment was approximately 13.4 centimorgans which corresponded to 0.65% of the total genome. Thus, these results suggested that expressional alterations of zitter gene were due to replacement of the genetic background from the original ZI strain to the WTC strain. Furthermore, the WTC.ZI-zi congenic strain could provide a refined tool for the analysis of zitter mutation, because the congenic strain has a strict control strain, WTC, and the length of the donor chromosome is genetically defined.

Animals↗
PubMed1998

Extension of conserved regions in the rat and mouse genomes by chromosomal assignments of 29 rat genes.

We recently constructed a comparative genetic map of the rat, mouse and human genomes based on information obtained from several databases. In this study, we performed chromosomal assignments of 29 rat genes with somatic cell hybrid clones, in order to clarify and extend the conserved regions in the rat and mouse genomes. As a result, the conserved regions were extended by 89 cM. Together with our previous report, the length of the conserved regions in the rat and mouse spans 847 cM on the mouse linkage map, indicating that 53% of the mouse genome is covered by homologous regions in the rat. In addition, four conserved regions were newly revealed. The method described in this study appears to be simple and efficient for constructing a whole genome comparative map of the rat and mouse.

Animals↗
PubMed1998

[Combination effect of granisetron plus corticosteroid for prevention of cisplatin-induced emesis: a cross-over study comparing methylprednisolone and dexamethasone].

Granisetron (G) is an effective antiemetic drug that is used to prevent cisplatin-induced emesis, although it is less effective for delayed emesis. To enhance the antiemetic effects of granisetron, corticosteroid analogues such as methylprednisolone (M) and dexamethasone (D) were employed in a study of patients treated with cisplatin (CDDP). We investigated the clinical response and urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), the main metabolite of serotonin, in 31 patients with ovarian cancer or uterine endometrial cancer who received CAP therapy (CDDP 75 mg/m2) in a 3-day cross-over trial comparing G + M and G + D treated patients. Both regimens were and delayed emesis than G + D. We conclude that G + D is a more efficacious combination than G + D in protecting patients from CDDP-induced acute and delayed emesis.

Adult↗
PubMed1998

Prevalence of herpes B virus antibody in nonhuman primates reared at the National University of Japan.

A serological investigation by means of an enzyme immuno assay test for herpes B virus (cercopithecine herpesvirus 1) was performed on 961 sera of healthy nonhuman primates reared in laboratory animal facilities which belong to the Association of Laboratory Animal Facilities of the National University of Japan. An antibody prevalence of 40% (384/ 961) was demonstrated. The antibody titer was shown to be higher among macaques (60% of cynomolgus monkeys, 53% of rhesus monkeys, and 34% of Japanese monkeys) than among non-macaque species (21%). These data indicate that nonhuman primates reared in animal facilities may present an occupational health problem and a potential zoonotic biohazard as demonstrated in limited cases in the United States.

Animals↗
PubMed1997

A non-MHC locus essential for autoimmune type I diabetes in the Komeda Diabetes-Prone rat.

The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type I) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic beta cells, and no significant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to severe insulitis within 220 d of age. The cumulative frequency of IDDM was 70% at 120 d of age, and reached 82% within 220 d of age. Here, we performed the first genome-wide scan for non-MHC IDDM susceptibility genes in this strain. The analysis of three crosses has led to the revelation of a major IDDM susceptibility gene, termed Iddm/kdp1, on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM. Comparative mapping suggests that the homologues of Iddm/ kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previously reported IDDM susceptibility genes.

Animals↗
PubMed1997

Analysis of expression of lymphocyte homing-related adhesion molecules in ALY mice deficient in lymph nodes and Peyer's patches.

The aly, alymphoplasia, is an autosomal recessive mutation in mice of an unknown etiology, which induces total aplasia of lymph nodes and Peyer's patches. We hypothesized that the lack of lymphoid tissue may be due to abnormalities of lymphocyte traffic into these tissues. Therefore, we analyzed the expression of various adhesion molecules associated with lymphocyte homing. Among the adhesion molecules examined, all were normally expressed except the mucosal addressin MAdCAM-1. In aly/aly mice MAdCAM-1 was absent in the spleen at mRNA and protein levels, but was normally expressed in the intestinal venules. The FISH analysis and linkage analysis using microsatellite markers demonstrated that the MAdCAM-1 gene is located on chromosome 10, indicating that MAdCAM-1 is not encoded by the aly gene, which is located on chromosome 11. Our results indicate that the aberrant expression of MAdCAM-1 is not the direct cause of aly mutation but rather a secondary defect.

Animals↗
PubMed1997

Effects of breeding environments on generation and activation of autoreactive B-1 cells in anti-red blood cell autoantibody transgenic mice.

In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut. About one-half of the auto Ab Tg mice suffer from autoimmune hemolytic anemia (AIHA) in the conventional condition. Oral administration of lipopolysaccharides activates B-1 cells and induces autoimmune symptoms in the Tg mice, suggesting that the autoimmune disease in anti-RBC autoAb Tg mice is triggered by infections. To examine the association of bacterial infections with the generation of B-1 cells and the occurrence of the autoimmune disease, we analyzed anti-RBC autoAb Tg mice bred in germ-free and specific pathogen-free conditions. In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions. In both conditions, no mice suffered from AIHA. However, when these Tg mice were transferred to the conventional condition or injected with lipopolysaccharide, peritoneal B-1 cells expanded and some of these mice suffered from AIHA. These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

Animals↗
PubMed1997

Alternative splicing of the erythropoietin receptor gene correlates with erythroid differentiation in rat hematopoietic and leukemic cells.

An alternative splicing of the rat erythropoietin receptor (EpoR) gene was identified in normal and erythroleukemia cells. A 105 bp insert was found at a region corresponding to the extracellular domain of EpoR. The alternative transcript was translated to a soluble EpoR (EpoR-S) expressed in spleen, bone marrow, and cultured erythroleukemia cells in addition to the full-length EpoR (EpoR-F). One of the rat erythroleukemia sublines, K4DT, which partially lost erythroid phenotypes and manifested monocyte/macrophage characteristics also lacked EpoR-S expression. Thus, expression of EpoR-S may play an important role in differentiation of rat erythroid cells.

Alternative Splicing↗
PubMed1997

Detection of apoptosis in the brain of the zitter rat with genetic spongiform encephalopathy.

Zitter rat develops genetic spongiform encephalopathy accompanied with whole-body tremors and flaccid paresis. To elucidate the mechanism of a neuronal cell death in the brain, we determined involvement of apoptosis in this rat. By Northern blot analysis, the elevation of mRNA levels were observed in c-jun, c-fos, c-myc and p53 genes which were induced by apoptotic signals: conversely, expression of bcl-2 was shown to be decreased in the zitter rat brain in contrast to the WTC control rat. Furthermore, TUNEL staining of fragmented DNA indicated apoptotic morphology in this brain. These results strongly suggested that the spongiform encephalopathy of the zitter rat was due to apoptosis in the brain cells.

Animals↗
PubMed1997

Antiepileptic effects of 20-hydroxyecdysone on convulsive seizures in spontaneously epileptic rats.

We examined the effect of 20-hydroxyecdysone (20-HE), a neurosteroid found in insects that is involved in their developmental process, on both tonic convulsion and absence-like seizure in spontaneously epileptic rat (SER). When 20-HE was given orally to SER at 25-200 mg/kg, significant decreases of the tonic convulsion were observed with 100 and 200 mg/kg. Pretreatment of the animal with bicuculline (1 mg/kg, i.p.) antagonized the inhibitory effects of 20-HE. However, absence-like seizures were not affected by 20-HE. These findings indicate that 20-HE produces antiepileptic effects on tonic convulsion by acting on the modulatory site of GABA(A) receptors.

Administration, Oral↗
PubMed1997

TM rats: a model for platelet storage pool deficiency.

TM rats have a light brown hooded coat pattern resembling that of Fawn hooded (FH) rats which are a model of platelet storage pool deficiency (SPD). We examined whether the TM strain has the same platelet SPD as the FH strain. TM rats had a prolonged bleeding time and a low blood serotonin level, although their blood coagulation time and platelet counts were normal. The light coat color of the TM strain was judged to be associated with the red-eyed dilution gene as in the FH strain, but not pink eye dilution as in the RCS rat strain. Platelet SPD seen in TM rats may be a pleiotropic effect of the red-eyed dilution gene proposed in FH rats. Despite these similarities, the genetic background of the TM strain was obviously different from that of the FH strain. The TM strain, developed independently of the FH strain, will therefore be used as a model of platelet SPD.

Animals↗
PubMed1997

[A novel epilepsy animal model (NER)].

A mutant showing convulsive seizures spontaneously in a CJ: Wistar colony was named the Noda epileptic rat (NER). The NER exhibits tonic-clonic convulsion without any external stimuli once every 30 h. However, we succeeded in inducing similar convulsive seizures by applying priming sound stimuli (95 dB, 8 kHz, 30 sec) from 3 weeks of age in all 24 NER examined. When the effects of clinically available antiepileptics were tested on the seizures of such primed NER, the most potent agents were carbamazepine, diazepam, valproate, phenobarbital and trimethadione, while phenytoin and zonisamide showed lower potency. Furthermore, ethosuximide was not effective in inhibiting the seizures. In hippocampal slices of NER with convulsive seizures, repetitive firing accompanied by long-lasting depolarization was observed when a single stimulation was delivered to the mossy fibers in the CA3 pyramidal cell. This depolarization shift was completely blocked with a Ca2+ antagonist (nicardipine 10 nM). The long-lasting hyperpolarization that followed the repetitive firing was also observed with mossy fiber stimulation in the hippocampal CA3 pyramidal cells of the NER. These findings suggest that Ca2+ channel abnormality of the hippocampal CA3 pyramidal cells may be involved in the convulsive seizures.

Animals↗
PubMed1996

Genetic linkage of the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase II gene to intracellular Ca2+ concentration in the spontaneously hypertensive rat.

A cosegregation analysis of sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (SERCA) II genotype, systolic blood pressure and platelet intracellular Ca2+ concentration was performed to dissect polygenic hypertensive traits in spontaneously hypertensive rats. Backcross analysis between spontaneously hypertensive rats and normotensive. Donryu rats demonstrated the existence of an inferred single major gene locus (ht). Thrombin-stimulated intraplatelet Ca2+ concentration was significantly higher in the SERCA II homozygotes than in the heterozygotes. The SERCA II genotype did not cosegregate with the blood pressure level. The SERCA II gene was assigned to rat chromosome 12. These results suggest that the SERCA II gene on rat chromosome 12 contributes to increased thrombin-stimulated intraplatelet Ca2+ concentration and that the SERCA II gene is not identical to ht.

Animals↗
PubMed1996

A rat genetic map constructed by representational difference analysis markers with suitability for large-scale typing.

Representational difference analysis (RDA) was applied to isolate chromosomal markers in the rat. Four series of RDA [restriction enzymes, BamHI and HindIII; subtraction of ACI/N (ACI) amplicon from BUF/Nac (BUF) amplicon and vice versa] yielded 131 polymorphic markers; 125 of these markers were mapped to all chromosomes except for chromosome X. This was done by using a mapping panel of 105 ACI x BUF F2 rats. To complement the relative paucity of chromosomal markers in the rat, genetically directed RDA, which allows isolation of polymorphic markers in the specific chromosomal region, was performed. By changing the F2 driver-DNA allele frequency around the region, four markers were isolated from the D1Ncc1 locus. Twenty-five of 27 RDA markers were informative regarding the dot blot analysis of amplicons, hybridizing only with tester amplicons. Dot blot analysis at a high density per unit of area made it possible to process a large number of samples. Quantitative trait loci can now be mapped in the rat genome by processing a large number of samples with RDA markers and then by isolating markers close to the loci of interest by genetically directed RDA.

Alleles↗