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Biomedical subjects

S Hirai

Publications and source records attributed to S Hirai.

At least 91 records · Page 5Linked to original sources

Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression.

Expression of the proteasome subunits LMP2 and LMP7, the MHC-encoded transporter subunits TAP1 and TAP2, and HLA Class I antigens was examined by immunoperoxidase staining in 10 nevi and 98 melanoma lesions (60 primary and 38 metastatic), because these molecules play an important role in the presentation of melanoma-associated peptide antigens to cytotoxic T cells. LMP2 was less frequently expressed than LMP7 in primary and metastatic melanoma lesions. TAP1, TAP2, and HLA Class I antigen expression was more frequently (P < 0.05) down-regulated in metastatic than in primary melanoma lesions and in nevi. A synchronous TAP1, TAP2, and HLA Class I antigen down-regulation was observed in 58% of primary and 52% of metastatic lesions. TAP and HLA Class I antigen down-regulation in primary lesions was significantly associated with lesion thickness, stage of disease, reduced time to disease progression, and reduced survival. These results suggest that TAP down-regulation plays a role in the clinical course of malignant melanoma, probably by providing melanoma cells with a mechanism to escape from cytotoxic T lymphocyte recognition during disease progression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Unusual cranial nerve palsy caused by cavernous sinus aneurysms. Clinical and anatomical considerations reviewed.

BACKGROUND: Two cases of intracavernous internal carotid artery aneurysm with unusual clinical findings are reported. The pathomechanism and clinical significance are discussed. CASE DESCRIPTION: The first patient was a 49-year-old woman who presented with 6th nerve palsy and Horner's syndrome caused by a posteriorly located intracavernous aneurysm. The symptoms improved gradually in proportion to the size of the aneurysm. The second patient was a 69-year-old woman with isolated oculomotor superior division palsy caused by an anteriorly located large aneurysm. CONCLUSION: In the first case, a local aneurysmal compression at both the 6th nerve and the sympathetic fibers sent from the plexus on the intracavernous internal carotid artery is the most probable explanation. In the second case, the aneurysm might have selectively compressed the superior division of the oculomotor nerve at the anterior cavernous sinus. Clinical recognition of these syndromes results in a better diagnostic orientation. The authors discuss the pertinent anatomy and pathophysiology of the lesions because these findings are rarely seen clinically or in the literature.

Abducens Nerve↗

Oxidative damage to mitochondrial DNA and its relationship to diabetic complications.

Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OHdG) in DNA, which is linked to increased mitochondrial DNA (mtDNA) deletions. We investigated mtDNA deletions and 8-OHdG in the muscle DNA of non-insulin-dependent diabetes mellitus (NIDDM) patients. mtDNA deletion of 4977 bp (delta mtDNA4977) and the content of 8-OHdG in the muscle DNA of the NIDDM patients were much higher than those of the control subjects. There was a significant correlation between delta mtDNA4977 and the 8-OHdG content (P < 0.0001). Both delta mtDNA4977 and the 8-OHdG content were also correlated with the duration of diabetes. Delta mtDNA4977 and the 8-OHdG content in muscle DNA increased in proportion to the severity of diabetic nephropathy and retinopathy. This is the first report that an increase in delta mtDNA4977 and 8-OHdG is proportional to the severity of diabetic complications. Oxidative mtDNA damage is speculated to contribute to the pathogenesis of diabetic complications though a defect in mitochondrial oxidative phosphorylation or other mechanisms. 8-OHdG and delta mtDNA4977 are useful markers to evaluate oxidative mtDNA damage in the diabetic patients.

8-Hydroxy-2'-Deoxyguanosine↗

Fukuyama-type congenital muscular dystrophy: close relation between changes in the muscle basal lamina and plasma membrane.

Despite the recent advance in genetic study of Fukuyama-type congenital muscular dystrophy (FCMD), the mechanism of muscle degeneration in the disease remains unclear. To clarify it, muscle biopsies from six cases of FCMD were subjected to immunohistochemical and ultrastructural studies. On the muscle cell surface, decreased expression of laminin alpha2 subunit was seen along with aberrant expression of laminin alpha5 and neural cell adhesion molecule. Electron microscopy revealed breach of muscle basal lamina. The electron density of plasma membrane was significantly lower at the places without identifiable basal lamina. Thus in FCMD changes of laminin and other proteins on the cell surface involve a process common to developing muscles, and loss of normal structure of the basal lamina is closely associated with changes of the plasma membrane. This suggests that the primary cause of FCMD is related to formation and maintenance of the basal lamina.

Adult↗

HIV and HCV infection among drug users in Japan.

AIMS: To assess seroprevalence of human immunodeficiency virus (HIV), hepatitis C virus, injecting drug use, unsafe sexual behaviours, self-mutilation and tattoos in patients attending a drug and alcohol treatment centre in Japan. DESIGN: Cross-sectional survey. SETTING: The work was carried out at the National Sanitarium of Shimousa, Chiba, Japan, a 32-bed inpatient centre specializing in drug and alcohol treatment. MEASUREMENTS: Laboratory analyses for HIV antibody, hepatitis C antibody, hepatitis B antigen and antibody; questionnaires for history of sexual activities, needle and syringe use; physical examination with assessment of self-amputated finger joints, tattoos, scars from lacerations and cigarette burns. FINDINGS: No patients tested positive for anti-HIV. The seroprevalence of anti-HCV positives was 53.8% of methamphetamine-dependent patients, 18.4% of solvent-dependent patients and 5.6% of alcohol-dependent patients. Past needle sharing was reported by 82.1% of methamphetamine-dependent patients, 18.4% of solvent-dependent patients and 5.6% of alcohol-dependent patients. A history of syringe sharing was reported by 87.2% of methamphetamine-dependent patients. More than two-thirds of all patients reported contact with commercial sex workers. Casual sexual contacts were more common among solvent and methamphetamine-dependent patients than those dependent on alcohol. Tattoos and cigarette burns were more common among methamphetamine and solvent-dependent patients than among alcohol-dependent patients. Among the methamphetamine-dependent patients, 20.5% reported self-amputated finger joints compared with none in the other patient groups. CONCLUSIONS: HCV prevalence is a significant problem among methamphetamine users in Japan, probably because of a high rate of needle and/or syringe sharing. Although HIV infection is currently negligible, the very high rate of needle and syringe sharing could give rise to a significant increase in the HIV rate among drug users in the future.

Adult↗

Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection-comparison with omeprazole and lansoprazole.

BACKGROUND: A recent trend in curative therapy for Helicobacter pylori infection is the so-called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials. Various regimens employing this triple therapy have been reported. However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy. AIM: To validate its usefulness by comparing rabeprazole with omeprazole and lansoprazole, in combination with amoxycillin and clarithromycin. PATIENTS AND METHODS: 221 H. pylori-positive patients with peptic ulcer disease were randomized to receive one of three different proton pump inhibitor/amoxycillin-clarithromycin (PPI/AC) regimens for 7 days. (i) OAC regimen (n = 75): omeprazole 20 mg b.d., amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (ii) LAC regimen (n = 74): lansoprazole 30 mg b.d. , AMOX 500 mg t.d.s. and CAM 200 mg b.d.; and (iii) RAC regimen (n = 72): rabeprazole 20 mg b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d. Cure of the infection was determined by the 13C urea breath test 1 month after completion of the treatment. RESULTS: Intention-to-treat based cure rates for OAC, LAC and RAC regimens were 85% (95% CI, 75-92), 84% (95%, CI 73-91) and 88% (95% CI, 78-94), respectively, and per protocol based cure rates of these regimens were 88% (95% CI, 78-94), 91% (95%, CI 82-99) and 93% (95% CI, 84-98), respectively. Adverse effects in the entire study population, which included diarrhoea, glossitis or skin rash, were reported by 15% of the patients, and complete compliance was achieved in 95% of these patients. CONCLUSION: 1-week proton pump inhibitor/AC regimens for H. pylori infection were effective in the Japanese population. Rabeprazole can be considered as equivalent to omeprazole and lansoprazole in the PPI/AC triple therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Regional cerebral blood flow abnormalities in chronic solvent abusers.

This study aimed to reveal regional abnormalities of cerebral blood flow (CBF) and their relation to amotivational syndrome which causes poor social prognosis in solvent abusers Sixteen chronic solvent abusers (12 males and four females) along with five normal subjects underwent single photon emission computed tomography with N-isopropyl-p[123I]iodoamphetamine. The patients received a clinical evaluation with the Scale for the Assessment of Negative Symptoms. Using a semiquantitative method (normalized by the parietal cortex count), patients showed a statistically significant decrease in regional cerebral blood flow (rCBF) in the bilateral prefrontal cortices (P<0.01). In addition, the severity of hypoperfusion in the bilateral prefrontal cortices was related to the degree of severity of the avolition-apathy scale on SANS (left; P<0.05, right; P<0.01) even after excluding the effect of antipsychotics. These results suggest that rCBF abnormalities, especially in the prefrontal cortex, develop in chronic solvent abusers, and that this frontal hypoperfusion may be a biological basis of amotivational syndrome.

Adolescent↗

Ultrastructure and serotonin immunocytochemistry of the parietal-pineal complex in the Japanese grass lizard, Takydromus tachydromoides.

The fine structure and immunocytochemical localization of serotonin in the cells of the receptor line were studied in the parietal eye and pineal organ proper of the Japanese grass lizard, Takydromus tachydromoides. Typical photoreceptor cells (PC) were the predominant cell type in the receptor line of the parietal eye, the outer segments of which had regular stacks of numerous disks similar to those of cones. The pineal organ contained relatively few PCs, which showed less well-developed outer segments than those of the parietal eye. In contrast, secretory rudimentary photoreceptor cells (SRPC) accounted for the majority of receptor cells in the pineal organ. These cells were structurally characterized by whorl-like lamellar outer segments and numerous dense-cored vesicles (80-280 nm in diameter). A small number of SRPC were also found in the parietal retina, which were similar to those in the pineal organ. In the parietal-pineal complex, numerous mitochondria located in the PC were larger and rounder than those in the SRPC. In the PC, basal processes prossessed only synaptic ribbons, whereas in the SRPC some of these processes contained synaptic ribbons and others contained dense-cored vesicles, rarely having both. Serotonin-immunoreactive cells were found not only in the pineal organ but also in the parietal eye, which closely resembled the cells of the receptor line in their size and shape. Furthermore, on immunoelectron microscopy for serotonin using the protein A-gold technique, gold particles indicating serotonin-immunoreactive sites were restricted in the core of dense-cored vesicles in the SRPC of the pineal organ. Regional differences in the distributions of the PC, SRPC and serotonin-immunoreactivity were found in the parietal-pineal complex.

Animals↗

Seasonal variations in serotonin immunoreactivity and ultrastructure in the pineal organ of the Japanese grass lizard, with special reference to environmental temperature.

The seasonal variations in serotonin immunoreactivity and ultrastructure of the secretory rudimentary photoreceptor cells (SRPC) were studied in the pineal organ of the Japanese grass lizard, Takydromus tachydromoides in relation to the environmental temperature. Our results clearly demonstrated that serotonin immunoreactivity in the lizard pineal organ displayed seasonal variations under an artificial photoperiod of LD 12:12 and natural temperature in the laboratory. Immunoreactivity became intense with increase in temperature from spring to summer, showing the strongest reaction in the summer, and subsequently became weak with the drop in temperature to winter. Also, the SRPC of the lizard showed distinct seasonal variations in number and size of the dense-cored vesicles correlated to the serotonin immunoreactivity. In contrast, the changes in size of the lysosomes and nucleoli of the SRPC were inversely proportional to that of the dense-cored vesicles. Furthermore, the lysosomes ingested some dense-cored vesicles after the autumn, and they coalesced to form huge autophagosomes or residual bodies during the winter. The present study provided serotonin-immunohistochemical and ultrastructural evidence for seasonal variations in the secretory activity of the lizard pineal organ in accordance with changes in the environmental temperature. However, there may be few functional relationships between the pineal gland and the reproductive organs in the male Japanese lizard in relation to environmental temperature.

Animals↗

Breast carcinoma diverging to aberrant melanocytic differentiation: a case report with histopathologic and loss of heterozygosity analyses.

A case of primary breast cancer showing differentiation to malignant melanoma is reported. To obtain insight into the clonal relationship between the two components of the tumor, polymerase chain reaction-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 1q, 3q, 4q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, and 18q with microdissected tissues of both components was performed in addition to histologic, histochemical, immunohistochemical, and ultrastructural techniques. The tumor consisted of a combination of carcinoma and melanoma with morphologic transition. Metastases in the lymph nodes and thoracic spinal bone marrow showed dual tissue structure. One of the metastatic lung tumors showed melanomatous tissue structure. The abundant pigment in the cells was positive for Fontana-Masson staining and bleached with potassium permanganate. The carcinoma component was positive for epithelial membrane antigen and CA19-9, but the melanoma component was negative. Conversely, the melanoma component was positive for HMB45 and vimentin, but the carcinoma component was negative. Electron microscopic analysis showed premelanosomes and melanosomes in the melanoma component. Microsatellite analysis showed the same genetic alterations with loss of heterozygosity on chromosome arms 1p, 3q, 4q, 6q, 9p, 10q, 11q, 13q, 16q, 17p, and 17q in in situ, invasive, and metastatic foci. We concluded that the carcinoma and melanoma components had arisen from the same clone and that this breast carcinoma might have diverged to aberrant malignant melanoma through multiple genetic alterations in the early period of ductal carcinoma in situ.

Aged↗

Hypercalcaemia in melanoma patients associated with increased levels of parathyroid hormone-related protein.

We analysed serum levels of calcium and parathyroid hormone-related protein (PTH-rP) in 59 patients with melanoma by immunoradiometric assay, since only a few studies have been conducted on hypercalcaemia and serum levels of PTH-rP in patients with melanoma. Hypercalcaemia was found in seven of the 59 patients with melanoma. The serum level of PTH-rP was increased in three of the 59 patients and two of the three showed hypercalcaemia. All the patients with hypercalcaemia and/or an increased level of PTH-rP had stage IV melanoma. These findings suggest that hypercalcaemia is much more common than previously reported in patients with advanced stage melanoma and that an increased serum level of PTH-rP is one of the causative factors in hypercalcaemia in melanoma. Analysis of the serum PTH-rP level will contribute to the monitoring of the clinical course of patients with advanced stage melanoma.

Adolescent↗

[Stenting for dissecting restenosis of the subclavian artery after balloon angioplasty: a case report].

A 51-year-old male presenting with dizziness and arm claudication was admitted to our hospital. The angiogram showed severe stenosis of the left subclavian artery accompanied by to and fro motion of left vertebral artery flow. He was treated at first by percutaneous transluminal angioplasty (PTA) resulting in satisfactory dilatation of the stenosis and transient amelioration of the symptoms. However, the symptoms recurred five months later and the angiogram revealed restenosis with subintimal dissection. We chose stent implantation as the second treatment, and, hemodynamically, it produced a good result. As some reports have suggested, because of the therapeutic limitation of surgery or PTA, stenting could be a good alternative for the treatment of such disease, since it is less invasive and safe even in patients with a wide range of systemic atherosclerosis.

Angioplasty, Balloon↗

[Location of primary somatosensory area in cerebral arteriovenous malformation involving sensorimotor area].

The purpose of this study was to investigate the cortical reorganization associated with congenital brain lesion such as intracerebral arteriovenous malformation (AVM). Dipole source localization of somatosensory evoked potential (SEP) was performed in five patients with AVM encompassing sensorimotor cortex. Dipole tracing method combined with the scalp-skull-brain head model (Homma et al., 1994) was used to locate dipole source of an early cortical component of SEP elicited by median nerve electrical stimulation. The location of dipole source of SEP, which could be considered as the hand area of primary somatosensory area, was shown in the realistic section of the head and could be easily superimposed on the magnetic resonance imaging. SEP was recorded three times in each patients and the results were reproducible. In 2 patients whose postcentral gyrus was not involved in AVM, the dipole source of SEP was localized in the intact postcentral gyrus. The locations of dipole sources of SEP in the both hemisphere were symmetrical. In 3 patients whose postcentral gyrus was encompassed by AVM, the dipole source of SEP was localized in the surrounding intact gyrus which was distant from the usual region of postcentral gyrus. Somatotopy was different from the normal pattern. The hand area was located more medially than usual observed in normal postcentral gyrus. Despite the paucity of the number of patients and data obtained by dipole source localization, our findings support the existence of reorganization in the cerebral cortex with congenital lesion such as AVM. These findings of aberrant mapping of cortical function may be explained by the plasticity of brain function. The developing brain can inherit function that would normally have been performed by the region of brain involved in the lesion. We demonstrated that dipole tracing of SEP was a noninvasive method used to localize areas of eloquent cortex in patients harboring AVM. This method is of value in treatment planning.

Adolescent↗

[A family of SCA1 with pigmentary macular dystrophy].

Pigmentary macular dystrophy (PMD) was detected in a 57-year-old Japanese man with SCA1, five years after the onset of ataxia. Family history revealed 7 other ataxic members in three generations. Among them, only his younger brother, who had already died, had developed central scotoma with normal peripheral fields, 15 years after the ataxia had appeared. None of the other family members, with or without ataxia, had visual disturbances. The numbers of CAG repeats in the patient's SCA1 gene were 27 and 47, the latter of which was within pathological range and belonged to mild to moderate CAG expansion in previously reported cases. The PMD seen in our patient could be one of the clinical features associated with SCA1, since patients with SCA1 often show various ocular changes. Although genetic analysis ruled out SCA7 in this patient, the phenotypic resemblance of this patient to SCA7 may reflect the necessity in the future, for genetic differentiation between SCA1 and SCA7 in patients with autosomal dominant cerebellar ataxia and PMD.

Adult↗

Evoked spinal cord potential monitoring reveals peroneal nerve ischemia during thoracoabdominal repair: a case report.

An 82-year-old man underwent thoracoabdominal aortic replacement under cardiopulmonary bypass with left femoral artery cannulation. Lumber descending evoked spinal cord potentials and segmental evoked spinal cord potentials were monitored simultaneously for detecting spinal cord damage. When the cardiopulmonary bypass was terminated, a peripheral nerve ischemia pattern was evident. Left peroneal nerve paralysis was present at emergence from anesthesia. This monitoring system revealed that peroneal nerve paralysis can occur due to leg ischemia caused by femoral artery cannulation. This is, to our knowledge, the first report that segmental evoked spinal cord potential monitoring reveals peroneal nerve ischemia during thoracoabdominal surgery.

Aged↗

Influence of anti-androgens on the anterior horn cells of rat spinal cord: morphometric and in-situ hybridization studies.

To examine the roles of the androgens for growth and maintenance of anterior horn cells (AHCs) of the spinal cord, one of the two anti-androgen agents, flutamide or cyproterone, was injected into young rats. Morphometric analysis of the spinal cords after the injections showed that the average area occupied by an AHC was significantly smaller in the rats treated with the anti-androgens than in the controls. By contrast, neurons in the posterior horns did not show significant difference in their size. Moreover, an in-situ hybridization of choline acetyltransferase (CAT) messenger RNA revealed a significant reduction in the signal density in AHCs in the treated rats. These results show that androgens play an important role in the growth and maintenance of AHCs, and influence a wide range of protein synthesis, including that of CAT.

Androgen Antagonists↗