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Biomedical subjects

T Serikawa

Publications and source records attributed to T Serikawa.

At least 127 records · Page 7Linked to original sources
PubMed1992

Chromosomal assignments of 17 structural genes and 11 related DNA fragments in rats (Rattus norvegicus) by Southern blot analysis of rat x mouse somatic cell hybrid clones.

DNA from 18 rat x mouse somatic cell hybrid clones, which segregated individual rat chromosomes, was analyzed by Southern blot for chromosomal gene assignments. Through the use of 17 DNA probes cloned from 7 rat genes, A2M, ATP1A1, ATP1A2, ATP1A3, B2M, GSTP, and SMST; 5 mouse genes, Ncam, Ngfg, Pim-1, Tcp-1, and Trp53; and 5 human genes, MBP, MYB, NEFM, SCN2A, and TCRGC1, 17 structural genes including 15 newly assigned genes and 11 related DNA fragments were assigned to particular rat chromosomes. Syntenic conservation of the genes among rats, mice, and humans is discussed.

Animals↗
PubMed1992

Rat gene mapping using PCR-analyzed microsatellites.

One hundred and seventy-four rat loci which contain short tandem repeat sequences were extracted from the GenBank or EMBL data bases and used to define primers for amplification by the polymerase chain reaction (PCR) of the microsatellite regions, creating PCR-formatted sequence-tagged microsatellite sites (STMSs). One hundred and thirty-four STMSs for 118 loci, including 6 randomly cloned STMSs, were characterized: (i) PCR-analyzed loci were assigned to specific chromosomes using a panel of rat x mouse somatic cell hybrid clones. (ii) Length variation of the STMSs among 8 inbred rat strains could be visualized at 85 of 107 loci examined (79.4%). (iii) A genetic map, integrating biochemical, coat color, mutant and restriction fragment length polymorphism loci, was constructed based on the segregation of 125 polymorphic markers in seven rat backcrosses and in two F2 crosses. Twenty four linkage groups were identified, all of which were assigned to a defined chromosome. As a reflection of the bias for coding sequences in the public data bases, the STMSs described herein are often associated with genes. Hence, the genetic map we report coincides with a gene map. The corresponding map locations of the homologous mouse and human genes are also listed for comparative mapping purposes.

Animals↗
PubMed1992

Alterations of benzodiazepine receptor binding in tremor rats with absence-like seizures.

Tremor rats begin to exhibit clinical or electrical absence-like seizures after 6 weeks of age, and by 14 weeks of age, all have seizures. Central-type benzodiazepine receptor binding was investigated in tremor rats and control rats, aged 4 weeks and 16 weeks. Significantly lower benzodiazepine receptor density and no differences in affinity were found in the hippocampus of the tremor rats in comparison with that of control rats at both ages. This abnormality is considered to be due to a tremor gene and may be the cause of absence-like seizures in tremor rats. A significantly lower receptor density was found in the cerebellum at 4 weeks of age in the tremor rats than in the control rats. These changes may be related to tremorous movements in the tremor rats. Receptor density was significantly lower in the brainstems of tremor rats and control rats at 16 weeks of age than at 4 weeks of age, and the decrease was more marked in control rats. These facts may reflect a reduced decrease in the response to the dysfunction of gamma-aminobutyric acidergic neurons, or the function of the gamma-aminobutyric acid/benzodiazepine receptor system may be secondarily increased to suppress seizures in 16-week-old tremor rats.

Animals↗
PubMed1991

Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats.

The spontaneously hypertensive rat and the stroke-prone spontaneously hypertensive rat are useful models for human hypertension. In these strains hypertension is a polygenic trait, in which both autosomal and sex-linked genes can influence blood pressure. Linkage studies in crosses between the stroke-prone spontaneously hypertensive rat and the normotensive control strain Wistar-Kyoto have led to the localization of two genes, BP/SP-1 and BP/SP-2, that contribute significantly to blood pressure variation in the F2 population. BP/SP-1 and BP/SP-2 were assigned to rat chromosomes 10 and X, respectively. Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin I-converting enzyme gene (ACE). This encodes a key enzyme of the renin-angiotensin system, and is therefore a candidate gene in primary hypertension. A rat microsatellite marker of ACE was mapped to rat chromosome 10 within the region containing BP/SP-1.

Animals↗
PubMed1991

Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis.

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.

Animals↗
PubMed1991

Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats.

The effects of thyrotropin-releasing hormone (TRH) were investigated on absence-like seizures, which are characterized by the sudden appearance of 5-7 Hz spike-wave-like complexes in the cortical and hippocampal EEG, and on tonic convulsions of spontaneously epileptic rats (SER; zi/zi, tm/tm), a double mutant obtained by mating zitter homozygote (zi/zi) with tremor heterozygote rats (tm/+). TRH (5 and 10 mg/kg i.v.) inhibited the appearance of both absence-like seizures and tonic convulsions of SER without inducing obvious changes in the background EEG. The inhibitory effects were seen 5-20 min after injection of 10 mg/kg TRH and were antagonized by pretreatment with haloperidol (0.5 and 1.0/kg i.p.), although haloperidol alone did not affect the seizures. These results suggest that TRH has an antiepileptic effect in the genetically defined animal model, SER, and that the effect is mediated by the central dopaminergic system.

Animals↗
PubMed1991

PCR-analyzed microsatellites: data concerning laboratory and wild-derived mouse inbred strains.

We have investigated 67 primers designed by Dr. J. Todd and co-workers to amplify microsatellites sequences in the mouse. We report on additional polymorphisms concerning seven laboratory inbred strains, complementary to those already published. We include the survey of three independently derived strains of Mus spretus: SPE/Pas, SEG/Pas and SPR/Smh. SPE/Pas and SEG/Pas are very close (3% polymorphism), whereas the third one, (SPR/Smh), is very different from the other two strains (33% polymorphism). Seventy-four to 84% of the microsatellites analyzed in this study are polymorphic between C57BL/6Pas and Mus spretus strains. By comparison, 36-46% are polymorphic between laboratory inbred strains involved in established sets of recombinant inbred strains. A strain derived from Mus musculus musculus (PWK/Pas) was found to be very different from both C57BL/6Pas (70% polymorphism) and SPE/Pas (82% polymorphism). These results emphasize the interest of using Mus musculus musculus inbred strains to establish interspecific crosses, particularly when considering their breeding performances.

Animals↗
PubMed1991

Semidominant expression of absence-like seizure in tremor rats.

Tremor rats (tremor homozygous rats) exhibit spontaneous absence-like seizure, which is characterized by a sudden immobility with staring and the appearance of 5- to 7-Hz spike and wave complexes in cortical and hippocampal electroencephalogram (EEG). In this study, we examined the development of the seizure and the mode of inheritance. All tremor homozygous and heterozygous rats exhibited the seizure by 14 and 26 weeks of age, respectively. The frequency and total duration in tremor heterozygous rats were significantly lower in comparison with those in tremor homozygous rats. None of the seven tremor wild-type homozygous rats exhibited the seizure. In an EEG study of backcross progeny of (BN/fMaiKyo x tremor heterozygous rats)F1 (tm/+) x tremor heterozygous rats at 5 months of age, the ratio of rats with and without the seizure was 23:7 (chi 2 = 0.09 for 3:1 ratio). These results suggest that the absence-like seizure is semidominantly expressed, in contrast to other recessive mutant traits in tremor rats.

Animals↗
PubMed1991

Benzodiazepine receptor binding in the spontaneously epileptic rat and its parent strains.

Central type benzodiazepine (BDZ) receptor binding in spontaneously epileptic rats (SER) and their parent strains, tremor rats and zitter rats, and Kyoto/Wistar rats were investigated. Significantly lower BDZ receptor densities (Bmax) and no differences in affinity (KD) were found in the hippocampus of the two epileptic strains, SER and tremor rats, in comparison with Kyoto/Wistar rats and zitter rats. This abnormality is considered to be due to a tremor gene and to be related to absence-like seizures in SER and tremor rats. A significant decrease of KD and an increase of Bmax in the brain stem were found in SER in comparison with Kyoto/Wistar rats. These changes may be due to a zitter gene, since zitter rats show the same tendency, and they may be related to tonic seizures in SER. Bmax was significantly increased in the cerebellum and hippocampus of the zitter rats, while KD was not changed, in comparison with Kyoto/Wistar rats and tremor rats. These changes may reflect the relatively selective loss of tissue lacking BDZ receptors or an upregulation in response to the loss of GABAergic neurons in zitter rats.

Animals↗
PubMed1991

CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER.

The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER.

Aging↗
PubMed1991

Detection of Pneumocystis carinii sequences by polymerase chain reaction: animal models and clinical application to noninvasive specimens.

Pneumocystis carinii is a eukaryotic microbe which causes fatal pneumonia in patients with AIDS. Oligonucleotide primers were used to amplify the 5S rDNA sequence of P. carinii by the polymerase chain reaction (PCR) in various clinical and animal samples. Of 35 independent lung specimens tested, PCR detected the P. carinii sequence in all 23 cases which were known to be P. carinii infected, i.e., 15 from mice, 1 from rat, 3 from human autopsy, and 4 from biopsy of AIDS patients by needle aspiration. The results were consistent with clinical and microscopic diagnosis. The detection was highly sensitive and specific. Direct sequencing of these amplified DNAs revealed homogeneity of 5S rDNA sequences of independent isolates from mice, rats, and humans. Preliminary trials manifested efficacy of the PCR method to detect P. carinii sequences in induced sputum or blood from AIDS patients, the latter case suggesting that P. carinii might enter peripheral blood via phagocytosis or direct intrusion. Development of less-invasive or noninvasive PCR diagnostic techniques to detect P. carinii infection would greatly facilitate therapeutic and prophylactic management of P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Chromosomal assignments of 23 biochemical loci of the rat by using rat x mouse somatic cell hybrids.

A panel of 18 rat x mouse somatic cell hybrid clones segregating individual rat chromosomes in different combinations was used to assign 23 biochemical loci to rat chromosomes. The chromosomal locations for these 23 loci were determined as follows: GOT1 on rat chromosome 1; HAGH on 2; ACP2, ADA, GANC, ITPA, and SORD on 3; LDHB on 4; PEPB on 7; GLB1 and HEXA on 8; IDH1 on 9; UMPH2 on 10; GUSB on 12; FH and PEPC on 13; PEPS on 14; ESD and NP on 15; DIA4 on 19; and PP on 20. In addition, ACP1 and GLO1 were reassigned to rat chromosomes 6 and 20, respectively. The chromosomal assignments of these loci extends the known syntenic homologies among rats, mice, and humans.

Animals↗
PubMed1991

Ontogeny of absence-like and tonic seizures in the spontaneously epileptic rat.

The ontogeny of epileptic seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) was studied by examining behaviour and electroencephalogram (EEG) simultaneously. Weight gain and survival time were also studied. Compared with the control Kyo:Wistar rats, SER showed a much smaller increase in body weight. All male and female SER died before 20 and 18 weeks of age, respectively. Body tremor was observed at 2 weeks of age but disappeared after 11 weeks. Staggering gait appeared after 7 weeks of age, and intensified with age. Absence-like seizures characterized by paroxysmal appearance of 5-7 Hz spike-wave-like complexes were observed in the cortical or hippocampal EEG after 5 weeks of age, and tonic seizures with low voltage fast waves were observed after 6 weeks of age. All SER exhibited both absence-like and tonic seizures with high frequencies from 12 weeks of age. Differences with other spontaneous rat models of epilepsy and application methods for estimating seizure-inhibitory effects of anti-epileptic drugs are discussed.

Animals↗