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Biomedical subjects

A Hirano

Publications and source records attributed to A Hirano.

At least 127 records · Page 7Linked to original sources

Immunocytochemical study of pituitary oncocytic adenomas.

Using immunocytochemistry we have analyzed 8 pituitary oncocytomas, 14 null cell adenomas, and 2 oncocytomas of the parotid gland (Warthin's tumor). The proportions of adenoma cells that are positive for mitochondrial protein (MP), cytochrome oxidase (COX), and manganese-superoxide dismutase (Mn-SOD) were significantly higher in pituitary oncocytomas than in null cell adenomas (MP P < 0.001, COX P < 0.001, Mn-SOD P < 0.05). In pituitary oncocytomas, MP-positive cells were distributed unevenly but in clusters or in islets admixed with some MP-negative cells, and corresponded to COX-positive cells. In contrast, almost all of the oxyphilic epithelial cells of Warthin's tumor were positive for MP, COX, and Mn-SOD. On the other hand, both pituitary tumors displayed similar findings with regard to the proportion of adenoma cells immunoreactive for copper/zinc-SOD and adenohypophysial hormones, the Ki-67 (MIB-1) proliferating cell index, and the mean number of argyrophilic nucleolar organizer regions. It was confirmed that immunocytochemical identification of MP and COX is useful for distinguishing pituitary oncocytomas from null cell adenomas. Although it remains to be determined whether oncocytomas originate from oncocytic changes of tumor cells or from neoplastic transformation of oncocytic cells, it appears that tumorigenesis of pituitary oncocytomas differs from that of Warthin's tumor.

Adenolymphoma↗

Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor.

A new method for evaluating chemical selectivity of agonists towards receptor ion channel proteins is proposed by using glutamate receptor (GluR) ion channel proteins and their agonists N-methyl-D-aspartic acid (NMDA), L-glutamate, and (2S, 3R, 4S) isomer of 2-(carboxycyclopropyl)glycine (L-CCG-IV). Integrated multi-channel currents, corresponding to the sum of total amount of ions passed through the multiple open channels, were used as a measure of agonists' selectivity to recognize ion channel proteins and induce channel currents. GluRs isolated from rat synaptic plasma membranes were incorporated into planar bilayer lipid membranes (BLMs) formed by the folding method. The empirical factors that affect the selectivity were demonstrated: (i) the number of GluRs incorporated into BLMs varied from one membrane to another; (ii) each BLM contained different subtypes of GluRs (NMDA and/or non-NMDA subtypes); and (iii) the magnitude of multi-channel responses induced by L-glutamate at negative applied potentials was larger than at positive potentials, while those by NMDA and L-CCG-IV were linearly related to applied potentials. The chemical selectivity among NMDA, L-glutamate and L-CCG-IV for NMDA subtype of GluRs was determined with each single BLM in which only NMDA subtype of GluRs was designed to be active by inhibiting the non-NMDA subtypes using a specific antagonist DNQX. The order of selectivity among the relevant agonists for the NMDA receptor subtype was found to be L-CCG-IV > L-glutamate > NMDA, which is consistent with the order of binding affinity of these agonists towards the same NMDA subtypes. The potential use of this approach for evaluating chemical selectivity towards non-NMDA receptor subtypes of GluRs and other receptor ion channel proteins is discussed.

Animals↗

Cloning, expression and biological function of the bovine CD40 homologue: role in B-lymphocyte growth and differentiation in cattle.

Members of the tumour necrosis factor receptor superfamily play a key role in B-lymphocyte survival, proliferation, differentiation and programmed cell death. A member of this superfamily, the CD40 molecule plays an important role in the differentiation of B lymphocytes into effector cells and in early activation through cognate interaction with T lymphocytes. In this report, we describe a cDNA and its protein product identified in cattle with approximately 70% sequence conservation at the nucleic acid level with the human CD40 gene. Transcripts for the boCD40 molecule were identified in resting and activated B lymphocytes, some but not all CD4+ and CD8+ T lymphocyte clones, and peripheral blood-derived T lymphocytes. Coculture of resting B cells with simian virus 40 (SV40)-transformed NIH3T3 (MOP8) cells stably transfected with the ligand for CD40 (bovine CD40 ligand, boCD40L), resulted in proliferation which was enhanced by addition of rbo interleukin-4 (IL-4). Cross-linkage of CD40 on bovine B lymphocytes upon coculture with CD40L-transfected cells resulted in the increased production of secretory IgM and, to a lesser extent, of IgG. Addition of rboIL-4 to these cultures increased levels of IgM and IgG secretion approximately twofold over those induced by CD40L alone. Our results indicate that many of the functions described for human and mouse CD40 are also conserved in the bovine but that differences in subset distribution of expression of the CD40 molecule in lymphoid cell types in cattle may impact on regulation of the early activation steps in the acquired immune response.

Amino Acid Sequence↗

Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly.

To determine at the tissue level whether the proteasome (Ps), a unique nonlysosomal protease, is involved in the metabolism of ubiquitinated proteins, we examined for the first time the immunocytochemical localizations of both Ps and ubiquitin (Ub) in sections of various abnormal structures that are known to be ubiquitinated in various neurodegenerative diseases and in the elderly. Concomitant increases of Ps and Ub were observed at the sites of most dystrophic neurites in Alzheimer disease (AD) and parkinsonism-dementia complex on Guam (PDC) and in Lewy bodies in Parkinson's disease and diffuse Lewy body disease, but not in neurofibrillary tangles in AD or PDC, in filamentous inclusions within anterior horn cells in sporadic motor neuron disease, or in eosinophilic granules in the olivary nucleus of the elderly. These results at the tissue level indicated that Ps is involved in the metabolism of some, but not all, ubiquitinated proteins and structures in various neurodegenerative disorders. This suggests that the involvement of Ps in the metabolism of ubiquitinated structures differs in different cases and at different stages of disease. These results and our previous immunocytochemical studies of lysosomal cathepsin proteases suggest that both nonlysosomal and lysosomal systems are involved in the metabolism of various ubiquitinated proteins and that their involvements differ in different structures and at different stages of degeneration of the structures.

Aged↗

Recurrence of primary superficial bladder cancer treated with prophylactic intravesical Tokyo 172 bacillus Calmette-Guérin: a long-term follow-up.

BACKGROUND: Long-term results after transurethral resection (TUR) and prophylactic intravesical Tokyo 172 bacillus Calmette-Guérin (BCG) therapy for primary superficial bladder cancer were analyzed by multivariate analysis, and factors affecting the recurrence of bladder tumors after this therapy were examined. METHODS: One-hundred and forty-one consecutive patients with primary superficial bladder cancer who consulted the Department of Urology at Wakayama Medical College and affiliated hospitals between May 1985 and May 1990 were studied. Tokyo strain BCG was given intravesically (80 mg in 40 ml saline) weekly for 6 weeks. RESULTS: The 5-year cumulative recurrence-free rate by the Kaplan-Meier method was 0.702 in 141 patients with primary superficial bladder cancer. The 5-year recurrence-free function using the proportional hazard model was 0.743. Using the Cox proportional hazard model, variables that significantly contributed to recurrence after intravesical BCG included female sex, tumor size less than 1 cm in diameter, and T1 tumor stage. Patient age, tumor type, multiplicity, tumor grade, and concomitant carcinoma in situ did not contribute to recurrence. CONCLUSION: Long-term results showed that prophylactic intravesical Tokyo strain BCG after TUR for primary superficial bladder cancer is also effective in preventing the recurrence of bladder cancer, and the biologic behavior of superficial bladder cancer other than stage T1 tumor may be altered after intravesical BCG.

Adjuvants, Immunologic↗

PCNA and p53 in urinary bladder cancer: correlation with histological findings and prognosis.

BACKGROUND: This study aimed to immunohistochemically examine the expression of proliferating cell nuclear antigens (PCNA) and p53 protein in transitional cell carcinomas (TCC) of the urinary bladder, and to investigate possible correlations of this expression with the tumor grade or stage, tumor recurrence, and prognosis of the disease. MATERIALS AND METHODS: The immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and DO7 as the primary antibodies. Positive stainings were represented by scores (Labeling Index; LI, %) calculated as the percent of positive cells among all neoplastic cells counted. The findings were compared to the patients' histopathological features. Patients who underwent transurethral resection were divided into groups with "low" and "high" scores for PCNA and p53, respectively, and the tumor recurrence rate was compared among the groups. Patients who underwent total cystectomy were similarly divided into "low" and "high" score groups, and survival rates of the groups were compared. RESULTS: PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling index of 26.6%. Overexpression of p53 was observed in 65 of 128 patients (50.8%), with a mean labeling index of 35.3%. There were significant correlations of the PCNA and p53 indices with both histological grade and stage of the tumor. In the TUR group, there were no statistically significant differences in recurrence rate between the groups with high or low scores for either PCNA or p53. In the total cystectomy group, there was a significant correlation between survival rate and positive staining for PCNA, but not for p53. The relationship between 2 parameters, PCNA and p53 scores, was not significant (linear correlation coefficient, r = 0.67). CONCLUSIONS: PCNA and p53 status in transitional cell carcinomas of the urinary bladder is related to the histopathological findings. We also suggest that immunohistochemical staining for PCNA provides significant clinical information which may be useful in the initial selection of therapy. However, overexpression of p53 does not appear to represent an independent prognostic marker in bladder tumors.

Adult↗

Identification of a cytoplasmic Tyr-X-X-Leu motif essential for down regulation of the human cell receptor CD46 in persistent measles virus infection.

To investigate the sequence requirements for measles virus (MV)-induced receptor down regulation, we transfected the human CD46 gene into simian cells persistently infected by the Biken strain of MV. Surface expression of CD46 is drastically reduced in these cells. Deletion analysis has shown that the juxtamembrane region of the CD46 cytoplasmic domain is essential for down regulation. Deleting a Tyr-Arg-Tyr-Leu sequence in this region or changing these residues to Ala prevents CD46 down regulation from the infected cell surface. Alanine-scanning mutagenesis has identified two amino acid residues, Tyr and Leu, forming a Tyr-X-X-Leu motif critical for CD46 down regulation. Mutations that prevent CD46 down regulation enhance syncytium formation. These results indicate that CD46 down regulation limits the cytopathic effects in a persistent MV infection and that CD46 down regulation requires a cytoplasmic Tyr-X-X-Leu sequence which resembles known motifs for membrane protein trafficking and receptor signalling.

Alanine↗

Effects of CD40 stimulation in the prevention of human EBV-lymphomagenesis.

CD40 is a molecule present on B lineage cells, both normal and neoplastic. Signalling through CD40 has been demonstrated to promote B cell growth and differentiation in vitro. In contrast to its effects on normal B cells, we have found that CD40 stimulation can inhibit the growth of various aggressive histology human B cell lymphomas both in vitro and in vivo. Moreover, using a human/mouse chimera model in which human EBV-induced B cell lymphomas can spontaneously arise, we have found that CD40 stimulation an prevent the occurrence of this human lymphoma in mice. However, normal human B cell engraftment and function was not adversely affected in these mice by CD40 stimulation. This indicates that CD40 stimulation is selective in its effects on aggressive histology B cell lymphomas. Thus, CD40 stimulation either by antibody or a recombinant soluble ligand, may be of potential clinical use, not only in the treatment of EBV-induced B cell lymphomas, but also in their prevention.

Animals↗

Hirano bodies and Alzheimer's disease.

Hirano bodies are refractile eosinophilic rod-like structures, initially observed in Guamanian (Chamorro) patients with amyotrophic lateral sclerosis and parkinsonism-dementia complex. Subsequent investigations revealed that Hirano bodies have a distinct topographic distribution in the hippocampus, and that their number increases in the pyramidal layer of Sommer's sector but not in the stratum lacunosum with advancing age. Since patients with Alzheimer's disease (AD) have significantly more Hirano bodies than normal subjects in the same age range, the inclusions appear seem to be of relevance in this disease. Immunohistochemical and electron microscopic studies have demonstrated that the main components of Hirano bodies are abnormal micro-filaments, and that not only molecules associated with cell cytoskeleton, but also some stress-related proteins and growth factors such as beta-amyloid precursor protein, hippocampal cholinergic neurostimulating peptide (HCNP), transforming growth factor beta 3 are present in Hirano bodies. The accumulation of HCNP in Hirano bodies suggests that patients bearing these inclusions may have a disturbance of the septohippocampal cholinergic system, considered to be of importance for le arning and memory formation, and hence be related to the memory impairment of AD.

Alzheimer Disease↗

[Two cases of delayed posttraumatic vasospasm followed by brain SPECT].

This is a report of two cases of delayed posttraumatic vasospasm. In case 1, a 68-year-old male was injured by falling. He did not show any neurological deficits on admission. CT scan revealed a diffuse subarachnoid hemorrhage (SAH) without brain contusion. Aneurysm was not disclosed by angiography. On the 7th day after admission, he presented disorientation. Reviewed angiography revealed diffuse delayed vasospasm. 123I-IMP brain SPECT showed an extensive low perfusion area in the bilateral parietal portion. In case 2, a 71-year-old female experienced immediate development of a deep comatose state after head injury. CT scan on admission disclosed a massive acute left subdural hematoma and the severe compression of the left cerebral hemisphere by the hematoma. But traumatic SAH was not diffuse and was restricted to the left basal cistern. After emergency operation, her consciousness level improved and the mass effect of the subdural hematoma was diminished. On the 7th day after the operation, her neurological condition worsened. CT scan showed some infarction lesions in the left cerebral hemisphere and mild left cerebral swelling. Angiography on the same day revealed vasospasm in M2-M3 portion of left middle cerebral artery. HM-PAO brain SPECT disclosed low perfusion in the left parietal region, but a state of high perfusion in the other region. In case 1, vasospasm might have been derived from diffuse clots of traumatic SAH caused by the same process as postruptured aneurysmal vasospasm. In case 2, the region of vasospasm was not associated with traumatic SAH. It corresponded to the site of the brain contusion. It was suggested that the cause of vasospasm might have been the direct mechanical injury to the arterial wall and chemical substances deriving from the contused brain tissues. We conclude that SPECT or transcranial Doppler monitoring should be used for the early detection of posttraumatic vasospasm.

Aged↗

Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis.

To clarify the pathological characteristics of astrocytic hyaline inclusions (Ast-HIs) in patients with familial amyotrophic lateral sclerosis (FALS) with neuronal Lewy-body-like hyaline inclusions (LBHIs), eight autopsies on members of four different families, including two long-term surviving patients with clinical courses of over 10 years, were analyzed. Ast-HIs were found only in the two long-term surviving patients who belonged to different families and to different races. Ast-HIs were ultrastructurally composed of 15- to 25-nm granule-coated fibrils that had immunoreactivities to superoxide dismutase 1 (SOD1) and ubiquitin. Approximately 50% of the Ast-HIs expressed alpha B-crystallin, metallothionein, glutamine synthetase, and tubulin (alpha and beta) at various intensities. Some Ast-HIs reacted with antibodies to tau protein, S-100 protein, and heat shock protein 27. The Ast-HIs were not stained for glial fibrillary acidic protein. Our results suggest a cooperative role of superoxide dismutase 1, ubiquitin, and cytoskeletal proteins in the formation of granule-coated fibrils (namely, Ast-HIs) and provide evidence that Ast-HIs are formed in certain long-surviving familial amyotrophic lateral sclerosis patients with neuronal Lewy-body-like hyaline inclusions.

Adult↗

[Diagnosis of unruptured cerebral aneurysms using magnetic resonance angiography and three dimensional computed tomographic angiography].

The purpose of this study is to confirm the use of magnetic resonance (MR) angiography and three-dimensional computed tomographic (3D CT) angiography, in the screening of unruptured cerebral aneurysms. Sixty-six unruptured cerebral aneurysms in forty-eight patients were examined by MR angiography, 3D CT angiography and digital subtraction angiography (DSA). All cases underwent surgery. Three out of sixty-six (4.5%) cerebral aneurysms detected by MR angiography and 3D CT angiography were false positive. The false aneurysms were located at the region of the internal carotid artery and the posterior communicating artery, and were under 2.0mm in size. The diagnosis of the infundibular dilatation at the junction of the internal carotid artery and the posterior communicating artery remained difficult. The true positive diagnosis of aneurysms using MR angiography or 3D CT angiography was 95.5%, in our hospital. All unruptured cerebral aneurysms over 2.0mm in size were detected correctly by using MR angiography and 3D CT angiography, as well as DSA. The inadequate diagnosis of aneurysms caused by MR angiography was due to the overlapping of vessels and the surrounding noise. Superselective maximum intensity projection (MIP) and interactive vascular imaging (IVI) were adopted for exact diagnosis. Furthermore, the three slab method of MR angiography was used for containing the limits between the vertebral artery and the distal anterior cerebral artery, and the triple method was able to decrease surrounding noise. Using MR angiography, we diagnosed and operated on about 100 cases of unruptured cerebral aneurysm in one year. Our conclusion is that we can diagnose any unruptured cerebral aneurysm, over 2.0mm in size, using MR angiography and 3D CT angiography.

Adult↗

Immunohistochemical studies on clustered pericapillary bodies in the spinal cord of post-poliomyelitis patients.

This report concerns the study of clustered pericapillary bodies in the spinal cords of four post-poliomyelitis patients. All four had stable neurological deficits without new neurological symptoms after the initial poliomyelitis infection. Spinal cords from seven individuals who died of non-neurological disorders served as controls. Lumbar spinal segments were examined by using conventional staining procedures and immunohistochemical techniques. The histological features of the pericapillary structures were similar to those of the previously described pericapillary rosettes. The number of pericapillary bodies was strikingly greater in one post-poliomyelitis patient (a man who died at age 48) than in the other three. The great majority of the pericapillary structures were within the areas of the poliomyelitis lesions. A small number of the abnormal structures were detected in the lumbar spinal cord of three control individuals. The clustered pericapillary bodies were immunostained by antibodies to phosphorylated neurofilament, synaptophysin, and ubiquitin, but not by antibodies to glial fibrillary acidic protein, tau protein, and paired helical filaments. These results indicate that the structures may derive from presynaptic terminals and preterminal axons, and that their formation may be related, albeit not necessarily in a specific fashion, to the poliomyelitis disease process.

Adult↗

Comparative immunohistochemical study on synaptophysin expression in the anterior horn of post-poliomyelitis and sporadic amyotrophic lateral sclerosis.

This report concerns a comparative study of alterations of anterior horn presynaptic terminals in post-poliomyelitis and sporadic amyotrophic lateral sclerosis (S-ALS). Synaptophysin (SP) served as a marker for presynaptic terminals; immunohistochemical techniques were used throughout. Spinal cords from six individuals without neurological disease served as controls. Localized and well-delineated anterior horn neuropil areas with decreased SP immunoreactivity were observed in the five cases of post-poliomyelitis studied. These areas had few remaining neurons but had pronounced reactive gliosis which corresponded to those areas in which typical poliomyelitis lesions were present. Normal neuronal SP expression was preserved in the adjacent, non-affected areas. However, a small region with increased SP levels was observed in one case. By comparison, the decrease in anterior horn SP immunoreactivity was diffuse in the four S-ALS patients studied. The present data suggest that presynaptic terminals ending at the somata and processes of affected anterior horn neurons located in the area of the acute infection are degenerate in post-poliomyelitis. By contrast, in S-ALS the terminals ending at distal dendrite portions tend to be severely degenerate, while those terminating at the proximal portions of the neuron are relatively well preserved. Our results thus provide additional evidence that the pathogenesis of the post-poliomyelitis state differs from that of ALS.

Aged↗

Synaptophysin expression in the anterior horn of Werdnig-Hoffmann disease.

This report concerns the study of synaptophysin (SP) expression in the anterior horn in four cases of Werdnig-Hoffmann disease (WHD). All patients had distinct anterior horn cell degeneration, and died before the age of one year. Normal spinal cords from five age-matched children served as controls. Five cases of sporadic amyotrophic lateral sclerosis (S-ALS), three cases of lower motor neuron disease (L-MND), three cases of peripheral neuropathy with axonal reaction, and six adult cases with normal spinal cords were included for comparison. Immunohistochemical techniques were used throughout. The results show that normal spinal cords of children have similar SP immunoreactivity patterns as those of normal adults. We also found that despite relatively preserved or slightly increased SP immunoreactivity on the surface of the cell body and proximal processes of the remaining neurons, there was a diffuse decrease of immunoreaction product deposits in the anterior horn neuropil of the WHD cases. The ballooned neurons in the anterior horns of patients with WHD, S-ALS, L-MND, and axonal reaction had few SP immunoreactive dots or granules around the cell bodies and proximal processes. The perikarya of some ballooned neurons of the children with WHD was diffusely stained for SP. There was no SP immunoreactive structures within the empty cell beds of these patients. The observed decrease in SP expression around ballooned neurons in these disorders is indicative of a disconnection of presynaptic terminals of afferent fibers from the proximal portion of the swollen degenerated anterior horn cells.

Anterior Horn Cells↗

Hemifacial degloving approach to tumours in the infratemporal and pterygopalatine fossae: a preliminary report.

A new approach to tumours in the infratemporal or pterygopalatine fossa is presented. Through a midline skin incision, one side of the face from the forehead to the neck is completely degloved. Zygomatic and mandibular osteotomies improve access. All mimic muscles and the facial nerve are included in the elevated flap. This approach provides a widely exposed field from the temporal fossa to the neck without damage to major vessels or nerves other than the supra- and infraorbital nerves. Direct access to tumours in the infratemporal or pterygopalatine fossa is facilitated, thus making tumour resection easier, safer and more reliable. Details of this approach are described.

Craniotomy↗