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Biomedical subjects

A Shimizu

Publications and source records attributed to A Shimizu.

At least 19 recordsLinked to original sources
PubMed1992

Biased distribution of recombination sites within S regions upon immunoglobulin class switch recombination induced by transforming growth factor beta and lipopolysaccharide.

We have characterized extrachromosomal circular DNAs from adult mouse spleen cells that were induced to switch to immunoglobulin A (IgA) with bacterial lipopolysaccharide (LPS) and transforming growth factor beta (TGF-beta), and identified breakpoints of S mu/S gamma 3, S mu/S gamma 2, S mu/S alpha, S gamma 3/S alpha, and S gamma 2/S alpha recombinants. The S mu recombination donor sites clustered in the 3' half of the S mu region, while the S alpha recombination acceptor sites clustered in the 5' half of the S alpha region. In addition, donor and acceptor sites of S gamma regions also clustered in the 3' and 5' parts, respectively. These site preferences are in sharp contrast to the dispersed distribution of S mu/S gamma 1 breakpoints within both S mu and S gamma 1 regions upon IgG1 switch induced by LPS and interleukin 4. Our results support the hypotheses that TGF-beta increases the frequency of switch recombination events to IgA and that the switch recombination to IgA often proceeds by successive recombination of S mu/S gamma and S gamma/S alpha.

Animals↗
PubMed1992

Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in transgenic mice.

Studies on transgenic mice expressing immunoglobulins against self-antigens have shown that self-tolerance is maintained by active elimination (clonal deletion), functional inactivation (clonal anergy) of self-reactive B cells, or a combination of both. We have established and characterized a transgenic mouse line expressing an anti-erythrocyte autoantibody. In contrast to other autoantibody transgenic lines, about 50% of the animals of this transgenic line suffer from autoimmune disease, indicating a loss of self-tolerance. Here we show that peritoneal Ly-1 B cells (also known as B-1 cells) are responsible for this autoimmune disease in our transgenic mice. A few self-reactive Ly-1 B cells that have somehow escaped the deletion mechanism expand in the peritoneum because of the absence of self-antigen. These Ly-1 B cells are eliminated in vivo by apoptosis once exposed to self-antigen. On the basis of these results we propose a novel autoantibody production mechanism whereby self-reactive B cells sequestered in compartments free of self-antigens may survive, proliferate and be activated for generation of pathogenic autoantibodies in autoimmune diseases.

Anemia, Hemolytic, Autoimmune↗
PubMed1992

Photoaffinity labeling of the primary fibrin polymerization site: isolation and characterization of a labeled cyanogen bromide fragment corresponding to gamma-chain residues 337-379.

Human fibrinogen and the plasmin-generated fibrinogen fragment D were photoaffinity labeled specifically with the peptide [14C]Gly-Pro-Arg-N(4-azido-2-nitrophenyl)Lys amide. In the case of fibrinogen, greater than 85% of the incorporated radioactivity was found in the gamma chain. Similarly, when fragment D (Mr, 90,000) was labeled with the same derivatized peptide, virtually all the radioactivity was found in the gamma-chain portion. The labeled fragment D was treated with CNBr and an initial purification was achieved by two gel-filtration steps. The labeled material was purified further by HPLC and was also compared with CNBr digests of unlabeled material. Amino acid analysis and gas-phase sequencing showed the labeled fragment to be gamma-chain residues 337-379.

Amino Acid Sequence↗
PubMed1992

Mapping of the nu gene using congenic nude strains and in situ hybridization.

The chromosomal location of the nu gene, which is responsible for hairlessness and athymus, was determined using six DNA markers (interleukin 3 [Il-3], Myhs, Acrb, Evi-2, Mpo, and Hox-2) on mouse chromosome 11. We constructed the high-resolution physical mapping of the six DNA markers on chromosome 11 by in situ hybridization using fluorescence-labeled cosmid probes. The results indicate the order of centromere-(41cM)-Il-3-(3cM)-Myhs- (4cM)-Acrb-(6cM)-Evi-2-(3cM)-Mpo-(5cM)- Hox-2. We have used congenic nude strains and examined which of the six DNA markers were derived from the original nude mouse. We found the Evi-2 locus is linked to the nu gene in all the informative, independent congenic nude strains. From these data, we could estimate the location of the nu gene, not only genetically but also physically within a region that spans approximately 17 megabases (9 cM) between the Acrb and Mpo genes.

Animals↗
PubMed1992

A transgenic model of autoimmune hemolytic anemia.

We made double transgenic mice bearing immunoglobulin heavy and light chain genes encoding an autoantibody against the mouse erythrocyte by the cross of C57BL/6 mice carrying the transgene for each chain of the immunoglobulin. Although no obvious disorders were found in the single-chain transgenic mice, severely anemic symptoms were found in some of the double transgenic mice, in which most B cells express, at least on their surface, the autoantibody reactive to self-antigens on the erythrocyte. Individual double-transgenic mice showed a wide variation of phenotypes between severe anemia and no symptoms. Both deletion and anergy of autoreactive B cells were seen in each individual mouse, but their relative contribution to self-tolerance was variable and not directly related to the severity of anemia or the amount of the autoantibody produced. This transgenic system provides a good autoimmune disease model for exploring its onset mechanism, and means of its treatment and prevention.

Anemia, Hemolytic↗
PubMed1992

Role of the vertebral venous system in metastatic spread of cancer cells to the bone.

Bromodeoxyuridine (BrdU) labeled human prostatic cancer cells, PC-3, and murine osteosarcoma cells, POS-1 were injected into the tail veins of male mice under concomitant temporal occlusion of inferior vena cava. Five minutes after release of the venous occlusion, animals were sacrificed and various tissues, organs and the vertebral bones were examined immunohistochemically using an application of BrdU-anti-BrdU methods. Obvious BrdU labeled tumor cells, isolated or clumped, were demonstrated within the venous channels along the vertebral column, the epidural venous channels around spinal nervous tissues, in the bone marrow of lumbo-sacral vertebrae and intra- and peri-prostatic venous channels. The results suggest that a blockade of short duration of venous flow at the inferior vena cava can result in the bypassing of tumor cells through the vena cava to the vertebral venous system, which has a close connection with the peri-prostatic venous plexus. Thus, the vertebral venous system may play an important role in the metastasis of prostatic carcinoma to bone. In addition this experimental procedure is a very valuable model for studying mechanisms and prevention of bone metastases from prostatic carcinoma.

Adenocarcinoma↗
PubMed1992

Ultrastructure and movement of the ependymal and tracheal cilia in congenitally hydrocephalic WIC-Hyd rats.

The aim of the present investigation is to determine whether or not hydrocephalus occurring in hydrocephalic Wistar-Imamichi strain rats (WIC-Hyd) is caused by functional and structural disorders of ependymal cilia. Ultrastructures and movement of cilia in the ependyma of the lateral, III and IV ventricles and aqueduct of Sylvius and in the trachea walls of the animals were examined by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), and light microscopy using a phase-contrast microscope equipped with a high-speed video recording system. SEM revealed that a marked decrease in the length and number of cilia in the ependymal and tracheal walls occurred in affected male WIC-Hyd. This finding was noted even before the development of ventricular dilatation and was not related to the degree of ventricular enlargement after development of hydrocephalus. A moderate decrease in length and number of cilia was also seen among the normal ciliary tufts in affected female rats which developed a mild degree of hydrocephalus. TEM cilia findings included abnormal axonemal structures such as a lack of dynein arms and displacement of microtubules. The incidence of these ultrastructural abnormalities was found to be greater in affected male rats than in affected female rats. All cilia in affected male rats before and after development of hydrocephalus were immotile. A variety of movement disorders such as immobile, rotatory, and vibratory cilia were observed beside normally beating cilia (motile cilia) in affected female rats which never developed hydrocephalus as severe as that seen in affected male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

A molecular genetic linkage map of mouse chromosome 10, including the Myb, S100b, Pah, Sl, and Ifg genes.

Restriction endonuclease fragment length variations (RFLV) on mouse chromosome 10 were detected in four genes, namely, the Myb protooncogene (Myb) and the genes for S100 beta protein (S100b), phenylalanine hydroxylase (Pah), and interferon-gamma (Ifg). RFLV were found in restriction patterns generated with BamHI for Myb, in those generated with BglII for S100b, in those generated with EcoRV for Pah, and in those generated with TaqI for Ifg. A multipoint backcross was carried out by the mating (129/Sv-Sl/+ x MOL-MIT)F1 x 129/SvJ(-)+/+. The Sl mutation has phenotypic effects which include deficiencies in pigment cells, germ cells, and blood cells. The following order of genes was derived from the results of the multipoint backcross, with distances between genes in parentheses: centromere--Myb--(34.9 cM)--S100b--(8.5 cM)--Pah--(8.5 cM)--Sl--(12.3 cM)--Ifg--telomere. Most laboratory strains and two strains of Mus musculus domesticus of wild origin carry the Myba, S100a, Paha, and Ifga alleles. In contrast, a strain of M. m. musculus, two strains of M. m. yamashinai, and two strains of M. m. molossinus carry the Mybb, S100b, Pahb, and Ifgb alleles. Other strains of wild origin carry various combinations of these alleles.

Alleles↗
PubMed1992

Development of hepatocellular carcinoma associated with increases in DNA synthesis in the surrounding cirrhosis.

The relationship between DNA synthesis activity in hepatocytes from cirrhotic tissue and development of hepatocellular carcinoma was studied in 33 posthepatitic patients with Child's grade A cirrhosis. DNA synthesis activity was measured by a bromodeoxyuridine (a thymidine analogue) labeling index, using the bromodeoxyuridine-antibromodeoxyuridine in vitro method, and the patients were followed up prospectively with frequent liver ultrasonography for 2 years. During the 2-year follow-up, 11 of the 33 cirrhotic patients developed hepatocellular carcinoma; they included 8 of the 15 patients (53%) in the high labeling index (greater than 1.5%) group compared with only 3 of the 18 patients (17%) in the low labeling index (less than 1.5) group (P less than 0.05). Five of the latter 18 subsequently had increased synthesis activity. Of these 20 patients who showed high synthesis activities either initially or subsequently, 10 (50%) developed hepatocellular carcinoma, in contrast to 1 of 13 (8%) with persistently low activities (P less than 0.05). Thus, hepatocellular carcinoma seems to develop or may become detectable when DNA synthesis in the background cirrhosis is increasing or remains high.

Adult↗
PubMed1992

Electrophysiological abnormalities of the atrial muscle in patients with sinus node dysfunction without tachyarrhythmias.

The duration and the number of fragmented deflections of the right atrial electrograms were assessed and quantitatively measured in 74 patients who underwent endocardial catheter mapping during sinus rhythm. The bipolar electrograms were recorded at 12 sites in the right atrium. An abnormal atrial electrogram was defined as a duration of 100 ms or longer, and/or 8 or more fragmented deflections, according to our previous criteria. The patients were divided into two groups. The control group consisted of 41 age-matched patients with normal sinus node function and without paroxysmal atrial fibrillation. The study group comprised 33 patients with sinus node dysfunction but without tachyarrhythmias. Abnormal atrial electrograms were observed in 8 (19.5%) control patients, and in 16 (48.5%) sinus node dysfunction patients; p < 0.02. The total number of abnormal electrograms was 14 (2.89%) of 483 atrial electrograms in controls, and 36 (9.38%) of 384 in the study group; p < 0.0002. The mean duration (75.6 +/- 17) and the mean number of fragmented deflections (4.1 +/- 2) of the total atrial electrograms in the sinus node dysfunction group was significantly greater than that in controls (70.9 +/- 11 and 3.6 +/- 1, respectively); p < 0.01. The mean number of abnormal electrograms per patient in the study group (1.06 +/- 1.8) was significantly higher than that in the control group (0.3 +/- 0.8); p < 0.05. These data suggest that: (1) there is a significantly greater electrophysiological abnormality of the atrial muscle in patients with sinus node dysfunction but without paroxysmal atrial fibrillation than in age-matched controls, and (2) not only the sinus node but also the atrial muscle is electrophysiologically altered in patients with sinus node dysfunction but without tachyarrhythmias.

Adult↗
PubMed1992

Scanning eye movements in schizophrenic patients. Relationship to clinical symptoms and regional cerebral blood flow using 123I-IMP SPECT.

Eye movements during the Benton Visual Retention Test were examined using an eye-mark recorder in 32 schizophrenic patients and 32 normal controls. The patients had significantly fewer eye fixations, longer mean duration of fixation and shorter length of mean scan path than the controls. In the patients, these eye movement parameters were significantly correlated with the negative symptom score but not with the positive symptom score on the Positive and Negative Syndrome Scale. These parameters had a significant correlation with the composite score on the Scale for the Assessment of Negative Symptoms (SANS). In particular, they were highly correlated with avolition-apathy and affective flattening or blunting scores on SANS subscales. Thus, examination of scanning eye movements seemed to be a good objective index of negative symptoms. Secondly, regional cerebral blood flow (rCBF) was examined using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and single photon emission computer tomography in 17 of 32 patients. With regard to the relationship between the eye movement parameters and rCBF, the mean duration of fixation was negatively correlated with 123I-IMP uptake in the left superior frontal area and left basal ganglia. The mean length of the scan path was correlated with uptake in the left superior frontal area. These findings suggest that the characteristic eye movements of schizophrenic patients are likely to be related with dysfunction of the frontal-basal ganglia neural circuit.

Adult↗
PubMed1992

Esophageal ulcer complicated by Reiter's syndrome. A case report.

A 40-year-old woman with Reiter's syndrome had low-grade fever, a psoriasislike eruption on feet and hands, and multiple esophageal ulcers. She had keratoderma blennorrhagica, aseptic vaginitis, and ileosacral arthritis, but no ocular lesions. The patient was HLA-B27 negative. Radiographic and endoscopic examinations of the upper gastrointestinal (GI) tract showed multiple round or irregularly shaped small ulcers in the middle and distal portion of the esophagus. One month later, all esophageal ulcers disappeared spontaneously. A case like this of Reiter's syndrome with esophageal involvement has not been reported before.

Adult↗
PubMed1992

Histopathological development of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

The development of carcinoma was examined in male Wistar rats (n = 120) exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (83 micrograms/ml) for 16 weeks. After MNNG administration, rats were investigated by endoscopic observation, visualization of microvascular structure, and estimation of lectin binding sites. Changes of bile reflux to the stomach was observed endoscopically at 24 weeks as well as the development of gastric mucosal erosions. Protruding and expansive ulcerating carcinomas developed at 36 weeks and had a microvascular pattern similar to that of human adenocarcinoma. Estimation of lectin binding site and pattern was useful to evaluate the malignant potential of cell proliferation. We postulate that endoscopic observation is valuable in investigating the development of gastric carcinoma, and microvascular structure and lectin binding pattern may be useful to demonstrate the mechanism of growth of gastric carcinoma.

Animals↗
PubMed1992

Electrophysiological abnormalities of the atrial muscle in patients with manifest Wolff-Parkinson-White syndrome associated with paroxysmal atrial fibrillation.

We investigated the electrophysiological properties of the atrial muscle in 33 patients with manifest Wolff-Parkinson-White syndrome. Group I consisted of 13 patients with paroxysmal atrial fibrillation and group II consisted of 20 patients without paroxysmal atrial fibrillation. The anterograde and retrograde effective refractory periods of the accessory pathway and the inducibility of atrioventricular reciprocating tachycardia were not significantly different between the two groups. Endocardial electrograms, obtained by right atrial catheter mapping, were recorded during sinus rhythm from 12 sites of the right atrium in 12 of the 13 group I patients and in all group II patients. An abnormal atrial electrogram was defined as 100 msec or longer in duration, and/or the occurrence of eight or more deflections. Ten (83%) of the 12 group I patients had abnormal atrial electrograms, while only two (10%) of the 20 group II patients had abnormal atrial electrograms, and the difference was significant (P less than 0.01). Thirty-six (26%) of the total 139 electrograms obtained from 12 group I patients and two (1%) of the total 199 electrograms obtained from 20 group II patients fulfilled the criteria for an abnormal atrial electrogram, and the difference was significant (P less than 0.01). The fragmented atrial activity zone, interatrial conduction delay zone, and repetitive atrial firing zone obtained by right atrial extrastimulation were significantly wider in group I than in group II, respectively. It was concluded that electrical abnormalities of the atrial muscle may play an important role in the occurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

Adult↗
PubMed1992

Different distribution of abnormal endocardial electrograms within the right atrium in patients with sick sinus syndrome.

BACKGROUND: Prolonged and fractionated right atrial endocardial electrograms are characteristic of paroxysmal atrial fibrillation (idiopathic or associated with sick sinus syndrome). The distribution of these abnormal atrial electrograms within the right atrium and the way it is related to the likelihood that patients with sick sinus syndrome will develop paroxysmal atrial fibrillation was studied. METHODS: Endocardial catheter mapping of the right atrium during sinus rhythm was performed in 41 control patients with normal sinus node function and without paroxysmal atrial fibrillation, in 33 patients with sick sinus syndrome but without tachycardia, and in 27 patients with sick sinus syndrome and paroxysmal atrial fibrillation (group 3). The bipolar electrograms were recorded at 12 sites in the right atrium and an abnormal atrial electrogram was defined as lasting > or = 100 ms and/or showing eight or more fragmented deflections. RESULTS: 1195 atrial endocardial electrograms were assessed and quantitatively measured. In patients with sick sinus syndrome and paroxysmal atrial fibrillation 54% of the abnormal atrial electrograms were recorded from the high right atrium, 28% from the mild right atrium, and 18% from the low right atrium. However, in patients with sick sinus syndrome without tachycardia 78% of the abnormal atrial electrograms were recorded from the high right atrium and 22% from the mid right atrium. No abnormal electrograms were recorded from the low right atrium. CONCLUSIONS: In patients with sick sinus syndrome without tachycardia abnormal atrial electrograms generally came from the high right atrium but in patients with sick sinus syndrome and paroxysmal atrial fibrillation abnormal atrial electrograms were more widely distributed in the right atrium. In patients with sick sinus syndrome the greater the extent of the compromised atrial muscle, the greater the likelihood that paroxysmal atrial fibrillation will develop.

Adult↗
PubMed1992

[Percutaneous absorption of drug from alpha-olefin oligomer gel bases].

The percutaneous absorption of drug from the alpha-olefin oligomer (alpha-OL) gel base prepared by using palmitate of dextrin (Rheopearl KL) as a gelling agent was investigated by using the abdominal skin of rats in vivo. The 20, 30, 40 and 50 alpha-OLs with average molecular weights of 288, 380, 440 and 535, respectively were used in this study. The flurbiprofen (FP) was selected as a model drug. The percutaneous absorption of FP from the alpha-OL gel base was observed to be influenced by the molecular weight of alpha-OL. The percutaneous absorption profiles of FP from 40 and 50 alpha-OLs gel bases were almost the same. On the other hand, the absorption of FP from 30 alpha-OL gel base was significantly higher than those of 40 and 50 alpha-OLs gel bases. Furthermore, the percutaneous absorption of FP from 20 alpha-OL gel base was observed to be the highest in the test gel bases. In order to establish the reason for the differences in the percutaneous absorption of FP from 20, 30, 40 and 50 alpha-OLs gel bases, the apparent partition ratios of FP between water and four different alpha-OLs were determined as a parameter of the affinity of FP for the vehicle. Consequently, it has become apparent that the partition ratio exerts an influence on the percutaneous absorption of FP from the alpha-OL gel bases.

Alkenes↗