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Biomedical subjects

T Shirai

Publications and source records attributed to T Shirai.

At least 343 records · Page 19Linked to original sources
PubMed1996

Age-related decrease in the inductability of heat shock protein 72 in normal human skin.

In order to know the effect of chronological ageing on the induction of heat shock protein (HSP) in normal human skin, the 72-kDa HSP (HSP72) was examined in organ-cultured samples of normal human skin which were obtained from 30 individuals (age range 17-86 years). The skin explants were first incubated at 37 degrees C for 24 h, and then heat-treated at 45 degrees C for 1 h. After heat treatment, the skin explants were incubated at 37 degrees C for 1 or 3 h. Immunohistological analysis, using a monoclonal antibody specific for the HSP72, revealed that although the time course of the heat-induced HSP72 expression was similar in the young and aged groups, a lower level of induction of HSP72 was observed in the aged group. This result indicates that there is an age-related dysfunction of the heat shock response in normal human skin.

Adolescent↗
PubMed1996

Trichilemmal carcinoma developing in a burn scar: a report of two cases.

Two cases of trichilemmal carcinoma (TLC) developing in burn scars are reported. In Case 1, a 73-year-old man developed a TLC on his left lower leg five years after a burn. In Case 2, a 43-year-old man developed a cauliflower-like mass on his head 42 years after a burn. Histologically, tumor cells showed a lobular proliferation in continuity with the epidermis. Tumor nests were mostly composed of large atypical cells with clear cytoplasms containing PAS-positive, diastase sensitive materials. Some of the nests showed trichilemmal-type keratinization. These cases were treated only with surgical excision, and there has been no evidence since of local recurrence or metastasis.

Adult↗
PubMed1996

[The pathogenesis of idiopathic portal hypertension].

Idiopathic portal hypertension (IPH), so called Banti's disease, is characterized by anemia, splenomegaly and portal hypertension. While sharing certain clinical features, IPH is distinct from liver cirrhosis not only in histopathology and natural history but also in vascular anatomy and portal hemodynamics. Our studies have shown that the majority of patients with IPH have high serum levels of immunoglobulins, including autoantibodies, associated with abnormally high frequencies of activated T cells and the biased usage of particular T cell receptor (TCR) V beta gene segments. These results suggested that IPH was an immunological disorder mediated by a continuous stimulation with either a certain antigen or more likely a superantigen.

Adult↗
PubMed1996

[A 63-year-old woman with muscle weakness, myotonia, and parkinsonism].

We report a 63-year-old woman who presented myotonia and parkinsonism. The patient was well until 15 years of the age when she noted that the ring finger of her left hand at times flexed when she did not intend to do so. She noted weakness in her left upper extremity at the age of 40, and difficulty in relaxing her hand grip at 45. She had an onset of tremor in her right foot at age 50, which was followed by difficulty in gait and hand writing. She was admitted to Juntendo University Urayasu Hospital when she was 63-year-old. Her mother, two sisters, and a son were affected with similar muscle weakness and myotonia. Although some of them developed stooped posture in the late stage of the disease, none of them had overt parkinsonism. General physical examination was unremarkable. Neurologic examination revealed an alert and oriented woman with some recent memory loss. She had bilateral ptosis, facial weakness, and a masked face. Myerson's sign was present. Her speech was small and monotonous. The sternocleidomastoid muscles were markedly atrophic and weak. The remaining of the cranial nerves were intact. She walked in small steps with freezing with support. She showed bradykinesia, retropulsion, and resting tremor in her right leg. Slight distal dominant weakness was noted in both upper and lower extremities more on the left. No cerebellar signs were noted. Muscle stretch reflexes were within normal limits in the upper extremities and diminished in the lower limbs. Sensation was intact. Routine laboratory findings were unremarkable. Cranial CT scan and MRI revealed slight cortical atrophy and leukoaraiosis. She responded to levodopa and she became able to walk by herself. She was transferred to another hospital one month after her admission. She had several bouts of airway obstruction with one episode of respiratory arrest. She expired six month after the transfer. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that this patient suffered from myotonic dystrophy and Parkinson's disease which set in later years. Postmortem examination on the iliopsoas muscle revealed uneven muscle fiber diameters, central nuclei, and type 1 fiber predominance; the pathologic finding was consistent with myotonic dystrophy. The substantia nigra showed marked cell loss and Lewy bodies in the remaining neurons. The finding was consistent with Parkinson's disease. In myelin stain, diffuse myelin pallor was noted in the cerebral white matter which was the pathologic substrate of leukoaraiosis in this patient. Combination of these two disorders have never been reported in the literature to our knowledge. It appears to be that the coincidence is just a by-chance phenomenon, but it seems interesting to note that accelerated aging process appears to be present in both myotonic dystrophy and Parkinson's disease.

Diagnosis, Differential↗
PubMed1996

[Three-dimensional images of hepatic tumors and hepatic vessels obtained by helical computed tomography].

Helical computed tomography was performed with intravenous contrast material administration in ten patients with hepatic tumors (metastatic tumor, n = 6; hepatocellular carcinoma, n = 4). Maximum intensity projection (MIP) images of intrahepatic portal venous branches and hepatic veins, and shaded surface display (SSD) images of the hepatic tumors were reconstructed for each patient. The MIP image and SSD image were fitted to overlap on a single display to obtain three-dimensional (3-D) images showing both the hepatic vessels and hepatic tumors. Subsegmental localization of the tumors determined from the 3-D images proved to be correct in all of the six patients who received hepatic resection after examination. 3-D images seem to be useful for preoperative assessment of hepatic tumors.

Carcinoma, Hepatocellular↗
PubMed1996

[A 43-year-old woman with 18 years history of parkinsonism].

We report a 43-year-old woman who died after 18 years history of parkinsonism. She was well until 25 years of the age (1976) when she noted a difficulty in stepping her feet. In the next year, she started to drag her feet. She was treated with levodopa with good response, however, she developed dyskinesia when she was 33 years of the age. She was evaluated in another hospital in 1984. She showed normal intelligence, normal ocular movement, masked face, small voice, small step gait, stooped posture, freezing of the gait, retropulsion, and cogwheel rigidity in limbs. No tremor or ataxia was noted. She received left ventrolateral thalamotomy at that time. Rigidity on the right side markedly reduced, however, she continued to show bradykinesia and motor fluctuations. On August 1 of 1994, she developed fever of 40 degrees C and dyspnea. On the next day, she expired from acute respiratory distress. She was able to walk unsupported until just before her last admission. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that this patient had Lewy body-positive young onset Parkinson's disease. Opinions were divided into two groups, i.e., young onset Lewy-body positive Parkinson's disease and Lewy-body negative young onset parkinsonism. Post-mortem examination revealed moderate loss of pigmented neurons in the substantia nigra more in the ventro-lateral part. Lewy bodies were found in the remaining neurons. Lewy bodies were more frequently seen in the locus coeruleus, although neuronal loss was less prominent in the locus coeruleus. The dorsal vagal motor nucleus showed moderate loss of neurons. Otherwise, the central nervous system was unremarkable. To our knowledge, this patient had the second youngest age of the onset so far reported in the literature for Lewy-body positive typical Parkinson's disease.

Adult↗
PubMed1996

[Mitral reconstruction in patients with infective endocarditis].

Between June 1992 and October 1993, 5 patients with infective endocarditis in native mitral valve underwent open heart surgery. The patients ranged in age from 51 to 64 years and were all males. According to NYHA functional classification, 4 patients were class II and one was class III. Surgery was indicated because of hemodynamic deterioration (2 pts), echocardiographic mobile vegetation with or without previous emboli (2 pts) and both condition (1 pt). Before surgery the patients were afebrile and had negative serum CRP and negative blood cultures for at least one week after adequate medical treatment. The leaflet lesions found in the 5 patients were vegetation (2 pts), perforation (1 pt), calcification (1 pt) and thickening (2 pts). The chordal lesions found were rupture (5 pts) and thickening (1 pt). The infective lesions did not extend to the annulus. The mitral leaflets, including all apparently infectious lesions, were resected in a V-shaped fashion and then valve reconstruction was performed. The resected parts were sutured together with anchoring chordae. The annuloplasty with Teflon-tapes was also added. Postoperatively, all 5 patients showed a dramatic improvement in hemodynamics and endocarditis did not recur during 22 to 38 months of follow-up. The patients who received the repair did not require Warfarin. This study shows that mitral valve repair is an acceptable operation in patients with infective endocarditis, giving the patients better quality of life than mitral valve replacement when (1) infectious lesion are limited to mitral leaflet and chordae, (2) there is no severe calcification of the mitral valve, (3) the infection is healed by the adequate antibiotic therapy.

Endocarditis, Bacterial↗
PubMed1996

Neuroimaging for differentiating vascular from Alzheimer's dementias.

Recent advances in the clinical and neuroimaging features of vascular dementia (VAD) versus Alzheimer type dementia (DAT) are described. The lacunar type of VAD, which is often accompanied by silent strokes and a progressive course, is easily confused with DAT. Measurements of cerebral blood flow (CBF) and metabolism (CMR) displayed as brain maps, identify VAD from DAT because of the multifocal and often subcortical nature of the infarcts in VAD, which are strikingly different from the diffuse cortical reductions of CBF and CMR in DAT. Thus, neuroimaging is important for establishing the diagnosis in these two most common forms of dementia in the elderly. A dramatic method for separating VAD from DAT is by utilizing the noninvasive acetazolamide test and xenon contrast CT scanning for measuring the cerebral vasomotor capacitance. In DAT the vasodilator reserve is increased due to the law of initial values. In VAD it is absent or severely blunted so that the differences between the two underlying causes of the dementias become readily apparent.

Aged↗
PubMed1995

Reconstitution ratio is critical for alloreactive T cell deletion and skin graft survival in mixed bone marrow chimeras.

Although allogeneic bone marrow (BM) transplantation is an effective way to induce donor-specific tolerance, its clinical application is hampered because of the risk associated with vigorous myeloablative pretransplant conditioning. One approach to overcome this problem is to establish a lower chimeric state by mild myeloablation. It is not clear, however, whether there is a threshold in the extent of chimerism that is required for tolerance induction. In this study, we establish a mixed BM chimera system to examine the correlation between the reconstitution ratio of BM chimerism, donor-reactive T cell deletion, and skin graft acceptance using I-E alpha transgenic C57BL/6 mice as the BM and skin graft donors and Ly5 congenic C57BL/6 mice as the recipients. In this system, the class II MHC molecule I-E was the transplantation Ag, and the extent of I-E-reactive T cell deletion was determined by flow cytometry using a mAb specific for the V beta 11 TCR. The degree of BM chimerism was measured by examining the expression of donor-derived Ly5.2 and host-derived Ly5.1 on peripheral blood cells. Transplantation of I-E+ transgenic donor BM cells resulted in deletion of V beta 11+CD4+ T cells in recipient's PBL, and the extent of deletion was proportional to the degree of chimerism. When mice of different degrees of chimerism were tested for skin graft survival, we found that recipient mice with > 30% chimerism could accept skin grafts from I-E+ donor mice, whereas those with < 10% chimerism showed prolonged but not permanent graft survival. These findings revealed the sequence of events for induction of tolerance. First, the degree of BM chimerism determines the number of I-E+ cells in the thymus, which then elicits negative selection of I-E-reactive T cells in a form of clonal deletion. The extent of T cell deletion ultimately determines the mode of tolerance. These data provide experimental evidence for the potential use of partial chimerism by bone marrow transplantation for the induction of donor-specific tolerance in clinical settings.

Animals↗
PubMed1995

Chemoprevention by dehydroepiandrosterone and indomethacin in a rat multiorgan carcinogenesis model.

The chemopreventive efficacy of dehydroepiandrosterone (DHEA) and indomethacin (IM) alone or in combination was investigated in a rat multiorgan carcinogenesis model. These two chemicals were selected as chemopreventive agents with different functions. Animals were sequentially given five carcinogens with different organ target sites in the first 4-week initiation period. One week after its completion, the rats received 0.3% DHEA in the diet, 20 ppm IM in the drinking water, or 0.3% DHEA + 20 ppm IM until experimental week 28. DHEA enhanced hepatocarcinogenesis, but concurrent treatment with IM suppressed tumor development as compared to the DHEA group. DHEA inhibited tumor development in the thyroid, with a similar tendency observed for the small intestine. In addition, treatment with this hormone decreased occurrences of preneoplasias in the urinary bladder and seminal vesicles. Treatment with IM clearly suppressed development of preneoplasias or neoplasias in the lung and small and large intestines. In the urinary bladder, treatment with IM tended to decrease preneoplastic lesion development. Analysis of multiplicity of total tumors of any category revealed comparable values for DHEA and control groups, while the IM group showed a significant reduction. IM in combination with DHEA caused suppression as compared to DHEA alone. In a separate 8-week experiment, DHEA or IM were administered for 4 weeks after prior carcinogen application, and biochemical responses in the target organs were investigated. DHEA increased glucose-6-phosphate dehydrogenase levels in the liver but caused a decrease in the small intestine. In addition, DHEA decreased serum T4 but not T3. IM decreased prostaglandin E2 content in the small intestine. In conclusion, although DHEA or IM exert significant chemopreventive effects in multiorgans with the exception of the DHEA-treated liver case, treatment in combination did not result in amplification of their beneficial influence. Our results suggest the possible application of IM for chemoprevention in high-risk individuals, but the question of effects of DHEA in the liver must be answered before this hormone can be considered for use in humans.

Animals↗
PubMed1995

Frequent mutations of Ki-ras codon 12 in N-bis (2-hydroxypropyl)-nitrosamine-initiated thyroid, kidney and lung tumors in Wistar rats.

N-Bis (2-hydroxypropyl) nitrosamine (DHPN) is a very potent mutagen and wide spectrum carcinogen in rodents. In the present study, we investigated mutational activation of the Ki-ras gene in eight thyroid, five kidney (four mesenchymal and one transitional cell lesion) and two lung tumors induced with DHPN. Mutations were identified using single-strand conformation polymorphism, restriction fragment length polymorphism and DNA sequencing analysis. All of the 15 neoplasms could be shown to have mutations in codon 12 (GGT-->GAT). These results suggest that Ki-ras mutations are frequent events during the development of DHPN-induced carcinomas in these organs. In a separate experiment, moreover, we analyzed the presence of Ki-ras mutations in various tissues 8 weeks after DHPN treatment. One of five thyroid tissues treated with DHPN was found to have the same characteristic mutation, suggesting that it may represent an early event during carcinogen-induced tumor formation in the thyroid.

Animals↗
PubMed1995

Increasing development of pepsinogen-altered pyloric glands and adenocarcinoma in glandular stomach of analbuminemic rats.

The susceptibility of pepsinogen-altered pyloric glands (PAPG) and neoplastic glandular stomach lesions induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and catechol or sodium cholate in Nagase analbuminemic rats (NAR) was compared to Sprague-Dawley rats (SD). Male NAR and SD rats were given a single dose of 80 mg/kg body weight of MNNG by gastric intubation and, 2 weeks later, fed basal diet containing 0.8% catechol or 0.3% sodium cholate for 18 weeks. The animals were killed at the end of week 20 or after maintenance on basal diet at week 60. The number of pepsinogen-altered pyloric glands at week 20 was significantly (P < 0.001) higher in NAR fed either catechol or sodium cholate compared with SD rats. At week 60, adenomatous hyperplasias and adenocarcinomas were observed in 7 (88%; P < 0.01) and 3 (38%; P < 0.01) of 8 NAR fed catechol and in 4 (22%) and 0 of 18 SD rats, respectively. The results show that the frequency of PAPG in NAR and SD rats is related to the susceptibility to glandular stomach carcinoma. PAPG is a useful endpoint lesion for evaluation of gastric carcinogenicity in a 20-week carcinogenicity test, and NAR are sensitive for glandular stomach carcinogenesis.

Adenocarcinoma↗
PubMed1995

Isolation of cDNA clone encoding human homologue of senescence marker protein-30 (SMP30) and its location on the X chromosome.

We have isolated and characterized a cDNA clone encoding human homologue of senescence marker protein-30 (SMP30), a calcium binding protein also called regucalcin (RC). This clone (pHSMP6) has 1356 base pairs (bp) and contains an open reading frame of 897 bp, which encodes 299 amino acids. The estimated molecular weight of the deduced polypeptide is 33,250 and pI is 5.836. The homology of amino acid sequences between human homologue and rat SMP30 is 88.6%. Using pHSMP6 as a probe, the chromosomal location of the human homologue of SMP30 gene was determined. The results of regional mapping using a panel of 11 rodent-human somatic hybrids indicated that the gene is located in the p11.3-q11.2 segment of the X chromosome. This gene thus could be a candidate for one of the X-linked diseases mapped to this regions.

Amino Acid Sequence↗
PubMed1995

Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model.

Effects of dietary supplementation with the antioxidants ellagic acid, quercetin and vanillin were examined using a medium term multi-organ carcinogenesis model in rats. Groups of 10-15 male F344 rats were given i.p. injections of diethylnitrosamine (DEN, 100 mg/kg body wt.) and N-methylnitrosourea (MNU, 20 mg/kg body wt), s.c. injections of 1,2-dimethylhydrazine (DMH, 40 mg/kg body wt.), together with 0.05% N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) and 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), both in the drinking water, for a total multiple initiation period of 4 weeks (DMBDD) treatment). Ellagic acid, quercetin or vanillin, each at a dose of 1% each in the diet were administered from 1 day before and throughout the carcinogen exposure period, or after completion of the initiation regimen. All surviving animals were sacrificed at the end of week 36, and major organs were examined histopathologically. In the small intestine, significant reductions in the incidence and number of tumors (adenomas and carcinomas) were observed in the groups administered ellagic acid during (8%, 0.08 +/- 0.29) or after (8%, 0.08 +/- 0.29) DMBDD treatment, and those receiving quercetin after DMBDD treatment (0%) compared to the control value (57%, 1.07 +/- 1.21). Although the incidences were not statistically significant, slightly decreased numbers of small intestinal tumors were found in the groups receiving vanillin during (0.33 +/- 0.72), or after (0.40 +/- 0.83) DMBDD treatment. The incidence of large intestinal carcinomas in the group treated with vanillin during DMBDD treatment was significantly higher (73%) than the control value (21%). These results indicated that while ellagic acid and quercetin exerted potent chemopreventive action in both the initiation and promotion stages in the present experimental system, their beneficial effects were restricted to the small intestine. Since small intestinal carcinomas are very infrequent in humans, the advantages of these phenolic compounds for human application as chemopreventors should not be overestimated.

1,2-Dimethylhydrazine↗
PubMed1995

Chronic transection of post-ganglionic parasympathetic and nasociliary nerves does not affect local cerebral blood flow in the rat.

The role of post-ganglionic parasympathetic nerve fibers from the sphenopalatine ganglion and nasociliary nerve fibers from the trigeminal ganglion in the regulation of basal cerebral blood flow (CBF) was examined using rats, which had been divided into three groups; a sham group, a denervation group and a denervation+NG-monomethyl-L-arginine (L-NMMA) group. In the denervation and denervation+L-NMMA groups, unilateral chronic transection of the above nerve fibers had been performed at the ethmoidal foramen (EF) for 2 weeks. In the sham group, the above nerve fibers were only exposed at EF and not severed 2 weeks before the CBF measurement. Local CBF was measured by the [14C]iodoantipyrine autoradiographic method after intravenous administration of saline in the sham and denervation groups or L-NMMA (30 mg/kg) in the denervation+L-NMMA group. No significant difference in CBF was noted on each side in any of the regions between the sham and denervation groups. L-NMMA induced a significant reduction in local CBF on either side in each brain region. Neither the animals which were administered saline nor those with L-NMMA showed any side-to-side differences in local CBF in any of the brain regions examined. These findings suggest that the perivascular nerve fibers running through the EF, which are known to contain substantial nitric oxide synthase (NOS), may not play a pivotal role in the regulation of basal CBF. The reduction in CBF induced by the acute administration of L-NMMA was not affected by the chronic denervation of the above NOS-containing perivascular nerves.

Animals↗
PubMed1995

Glycosphingolipid composition of rat placenta: changes associated with stage of pregnancy.

The composition of glycolipids and their changes in the placenta were investigated in the normal pregnant rat. Total lipid fractions extracted from the placenta between days 12 and 20 of pregnancy (day 0 = oestrus) were subjected to glycolipid analysis using DEAE-Sephadex chromatography, silica-gel HPLC, silica-gel TLC, TLC/immunostaining, matrix-assisted secondary-ion mass spectrometry in the negative-ion mode and 1H NMR. Glycolipids identified in the rat placenta were: gangliosides GM3 (NeuAcLacCer and NeuGcLacCer) and GD3 (NeuAcNeuAcLacCer, NeuAcNeuGcLacCer and NeuGcNeuAcLacCer), and neutral glycolipids ceramide monosaccharide (CMH) (GlcCer), ceramide disaccharide (CDH) (LacCer), ceramide trisaccharide (CTH) (Gb3Cer) and ceramide tetrasaccharide (CQH) (Gb4Cer). The content of neutral glycolipids was higher than that of gangliosides throughout pregnancy. Of the neutral glycolipids, CMH and CTH predominated and the level of CDH was low at mid-pregnancy. During late pregnancy, CMH and CTH decreased and CDH increased markedly. CQH remained at a low level throughout pregnancy. Of the gangliosides, GM3 was predominant on days 12-16 and then decreased, whereas GD3, which was low on day 12, increased slightly on day 16 and maintained the same level thereafter. Immunohistochemical studies indicated that these changes in the expression of major gangliosides from GM3 to GD3 occurred in labyrinthine trophoblasts. Thus expression of these glycolipids appears to change markedly during pregnancy.

Animals↗