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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 1,315 records · Page 73Linked to original sources

Intraoperative radiation therapy for gastric cancer.

From among 115 patients who were treated by intraoperative radiation therapy (IORT), 94 patients were classified according to the histologic findings. The control 127 patients who were treated by operation alone during the same period were also histologically classified, and survivals were compared between the two groups. No difference in the survivals of patients with stage I was observed for the two groups. On the other hand, the survivals of patients with stages II through IV who were treated by IORT increased by nearly 10% to 20% at 5 years. A comparative study was also performed on the survivals between patients treated by IORT and those treated by operation alone according to the presence or absence of the serosal invasion and the grade of the lymph node metastasis. The number of patients treated by IORT in whom the serosal invasion and the lymph node metastasis were histologically examined was 57. The 171 control patients who underwent operation alone were examined histologically in the same fashion, and survivals for the two groups were compared. IORT did not afford any benefit if the lymph node metastasis was limited within n1 group or serosal invasion was not found. On the other hand, the 5-year survival rates for patients who were treated by IORT increased by nearly 10% when the serosal invasion was observed and by nearly 18% when n2 and n3 lymph node metastases were found.

Combined Modality Therapy↗

Transcatheter hepatic segmental arterial embolization using lipiodol mixed with an anticancer drug and Gelfoam particles for hepatocellular carcinoma.

Transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anticancer drug followed by the injection of Gelfoam particles, introduced into the tumor-bearing hepatic segment as the target area (segmental Lipiodol-TAE), was carried out in 54 patients with hepatocellular carcinoma (HCC), 7 of whom were later resected. In 5 of the resected 7 cases, complete necrosis was histologically verified. No death due to HCC was encountered in 47 nonoperated cases, and better therapeutic results were obtained with segmental Lipiodol-TAE. It was concluded that this technique does not adversely affect normal tissues, and it does reinforce the effect of TAE.

Carcinoma, Hepatocellular↗

Effects of imidazole antimycotics on the liver microsomal cytochrome P450 isoforms in rats: comparison of in vitro and ex vivo studies.

We have studied the effects of three imidazole derivatives, clotrimazole (CLO), ketoconazole (KET) and miconazole (MIC) on the liver microsomal diazepam (DZ) metabolism. In in vitro experiments using rats and human liver microsomes, significant inhibition of CYP3A in terms of DZ-3-hydroxylase activity was observed. The inhibition of DZ metabolism was seen 1 h after CLO dosing. On the other hand, the induction of certain cytochrome P450 (CYP) isozymes was observed in in vivo studies 24 h after dosing. That is, CYP1A, CYP2B and CYP3A2, but not CYP2E, were observed 24 h after CLO or KET or MIC treatment. Under these conditions, CLO was the most potent inducer of CYP3A and MIC was a more potent inducer of CYP1A and CYP2B. KET induced CYP1A and CYP2B whereas the inducibility of KET was less than those of CLO and MIC. All of the imidazole derivatives tested here showed significant inhibition of CYP isozymes which overcame the induction of the CYP isozymes by those drugs in the data of Western blot analysis.

Animals↗

Tetralogy of Fallot with levoatrial cardinal vein.

A levoatrial cardinal vein is a rare congenital anomaly of the systemic veins. It is frequently associated with left-side obstructive anomalies. We report a case of tetralogy of Fallot with a levoatrial cardinal vein. The innominate vein was absent and two left upper pulmonary veins connected to this vein. There were no left-side obstructive anomalies.

Angiography↗

Transcatheter arterial embolization for malignant osseous and soft tissue sarcomas. II. Clinical results.

PURPOSE: To evaluate the clinical effects of transcatheter arterial embolization (TAE) on malignant bone and soft tissue tumors. METHODS: TAE was performed in 10 patients with primary bone and soft tissue sarcomas and in 31 patients with metastatic bone tumors. The embolized arteries were the internal iliac artery in 30 cases, the intercostal artery in six cases, the lumbar artery in five cases, the suprascapular artery in three cases, and the iliolumbar artery, the internal pudendal artery, and the lateral sacral artery in one case each. The embolized material was gelatin sponge particles. The chemotherapeutic drugs were usually 20-40 mg of doxorubicin for primary and metastatic tumors and 50-100 mg of cisplatin only for primary tumors. In addition, 50-60 Gy of 10-MV radiotherapy with or without radiofrequency (RF)-capacitive hyperthermia in four sessions was administered before TAE for primary tumors only. RESULTS: Even though the pain score increased immediately after TAE, 30 of 38 (79%) patients with pain (8 of 9 with primary tumors, and 22 of 29 with metastases) achieved pain control after TAE. A necrotic low-density area shown by computed tomography (CT) after TAE was found in 31 of 41 (76%) tumors [8 of 10 (80%) with primary tumors, and 23 of 31 (74%) with metastatic tumors]. The tumor size decreased in 14 of 25 (56%) primary and metastatic tumors after 3 months. Osteosclerotic changes appeared in two cases of metastatic tumors after 6 months. In five tumors resected after TAE, large areas of necrosis within the tumor were confirmed histologically. Transient local pain and numbness appeared after TAE, but were relieved by drug treatment within 1 week. No severe complications except a case of gluteal muscle necrosis were encountered after TAE. The 1-year survival rate of the patients with primary tumors was 38.1%, and the median survival was 18 months. The longest survival was 84 months. The 1-year survival rate of the patients with metastatic bone tumors was 38.9%; the median survival was 12 months. The longest survival was 24 months. CONCLUSION: TAE could be an effective treatment for pain control and local control of malignant bone and soft-tissue tumors.

Adolescent↗

Auditory brain-stem responses in the rat brain isolated from the body trunk and maintained via cross-circulation.

The auditory brain-stem response (ABR) recorded from the vertex of the rat was analyzed before and after the brain was functionally isolated from the body trunk and maintained via cross-circulation. The ABR profile did not change for as long as 30 min after isolating the brain. The finding indicates that this experimental procedure is useful for studying the brain devoid of input from the trunk.

Analysis of Variance↗

Genetic control of immune response and disease susceptibility by the HLA-DQ gene.

The particular alleles of the HLA-DQ locus may control the low immune response to natural antigens by a dominant genetic trait through the immune suppression mediated by CD8+ suppressor T cells. The suppressor T cells may be activated by DQ-restricted and antigen-specific CD4+ suppressor/inducer T cells, because (1) a statistically significant association and linkage between low immune responsiveness to the natural antigens and the HLA-DQ gene were observed; (2) antigen-specific CD4+ T cells restricted by the DQ molecules encoded for by the HLA-DQ allele associated with low responsiveness were evidenced in many low responders; and (3) anti-HLA-DQ mAb restored the immune response to natural antigens, in some low responders. This HLA-DQ-controlled polymorphism of immune response to the natural antigens may account for the association between HLA-DQ alleles and organ-specific autoimmune diseases.

Autoantigens↗

Haloperidol effects on Na current in acutely isolated rat retinal ganglion cells.

Suppressive effects of haloperidol, one of the neuroleptic compounds that acts on the transient Na current (INa,t) were studied in freshly isolated 5-10-day-old rat retinal ganglion cells using a whole-cell patch clamp technique. High doses of haloperidol reversibly and dose dependently (2-200 mumol ) reduced the peak amplitude of INa,t. The half-inhibition dose was 27.1 mumol. The inactivation curve of INa,t was shifted toward a hyperpolarizing direction by about 42% when the amplitude was suppressed with 20 mumol haloperidol. This indicates that haloperidol suppression of INa,t is probably affected through changes in the inactivation of Na channels.

Animals↗

Effect of hyperbaric oxygen on ophthalmic artery blood velocity in patients with diabetic neuropathy.

To assess the relationship between blood flow and the complications of diabetes mellitus, we investigated the changes in the velocity of blood flow in the ophthalmic artery before and after hyperbaric oxygen therapy (HBO), one of the treatments for diabetic neuropathy. Color Doppler imaging was used before and after HBO. Seven diabetic neuropathy patients, 3 diabetics without neuropathy, and 7 normal, control subjects were enrolled. The patients were subjected to breathing 100% oxygen at 2.0 atmosphere absolute (ATA) for 1 hour. Hyperbaric oxygen therapy resulted in an average decrease in blood velocity by 15.0 +/- 9.0% (mean +/- SD) in normal subjects and 10.7 +/- 8.6% in diabetics without neuropathy. Blood velocity returned to the baseline level 4 hours after discontinuation of HBO. In contrast, blood velocity increased by 20.6 +/- 9.5% in diabetic patients with neuropathy irregardless of the severity of the diabetic retinopathy. The resistance index of the ophthalmic artery was not changed during HBO in the group with diabetic neuropathy, indicating that other mechanisms may be implicated, leading to the compensatory changes of blood flow. These results suggest that the increase in the blood velocity in the ophthalmic artery after HBO in diabetic neuropathy patients could be attributed to an imbalance in autonomic nervous function.

Autonomic Nervous System↗

Immuno-suppressive peptides for a human T cell clone autoreactive to a unique acetylcholine receptor alpha subunit peptide presented by the disease-susceptible HLA-DQ6 in infant-onset myasthenia gravis.

Infant-onset myasthenia gravis, an autoimmune disease specific to Asians predominantly affects neuromuscular junctions in ocular muscles. An AChR alpha peptide (p71-91) specific autoreactive CD4+ alpha beta T cell clone was established by stimulating PBMC from a patient heterozygous for two disease-susceptible HLA-DR9-DQ9 and DR13-DQ6 haplotypes with a mixture of overlapping peptides covering AChR alpha. The T cell clone recognized the AChR alpha peptide in the context of the HLA-DQ6 molecule and produced a large amount of IFN-gamma and a trace amount of IL-4. A part (p75-83) of the core epitope of the autoantigenic peptide (p75-87) is encoded for by an exon P3A of the AChR alpha gene which can be alternatively spliced. The T cell clone responded to the recombinant AChR alpha protein with a P3A exon product, but not without a P3A exon product. We investigated responses of the T cell clone to 114 analogue peptides carrying single residue substitutions of the core AChR alpha peptide. The majority of analogues substituted at residues Phe-77, Leu-80 and Asn-82 stimulated proliferation of the T cell clone. Conversely, the majority of analogue peptides substituted at either Gln-81 or Glu-83 did not stimulate proliferative responses, and all exhibited strong or intermediate inhibitory effects on proliferative responses of the T cell clone to the wild type peptide, possibly by TCR antagonism. Thus, an HLA class II allele specific to Asians may directly control susceptibility to the Asian-specific type of myasthenia gravis. Analogues of the auto-antigenic AChR alpha peptide may prove effective for new immunosuppressive therapy.

Antibodies, Blocking↗

A murine monoclonal antibody (928) recognizing a new epitope formed with a combination of HLA-DPA1*0201 and DPB1*0301 gene products.

A murine monoclonal antibody (mAb), 928, that recognizes a cell surface antigen (928 Ag) on a human Epstein-Barr virus-transformed fetal liver-derived lymphoid progenitor cell line (FL4.4) was generated. The 928 mAb reacted with only FL4.4; it did not react with any other 57 cell lines tested. Two color flowcytometry analysis of peripheral blood mononuclear cells (PBMC) revealed that the 928 mAb reacted with B cell and monocyte fractions from only two individuals out of 63 unrelated donors. Biochemical analyses showed that the 928 Ag composes of two molecules (33 and 34 Kd) and forms a SDS-resistant, noncovalently linked dimer conformation, the feature being similar to that of peptide-bound MHC class II molecules. Treatment of FL4.4 cells with the 928 mAb significantly facilitated homotypic cell aggregation. In addition, treatment of PBMC of the 928 Ag+ donor with recombinant IL-4 augmented the expression of the 928 Ag on CD64+ monocytes. Typing of HLA-DRB1, DPA1 and DPB1 alleles of the 928 Ag expressing and nonexpressing cells revealed that the 928 Ag is expressed only on PBMC of HLA-DPA1*0201 and DPB1*0301 positive donors. Finally, anti-DP antibody precleared 928 Ag from the cell lysate. These results demonstrate that the 928 mAb recognizes a polymorphic determinant of HLA-DPA1*0201-DPB1*0301 gene products. The possibility that amino acids in the groove of the peptide-binding site of HLA-DP molecules are critical for the 928 epitope is discussed.

Animals↗

Segmental transcatheter hepatic artery chemoembolization with iodized oil for hepatocellular carcinoma: antitumor effect and influence on normal tissue.

PURPOSE: Segmental transcatheter arterial embolization (TAE) with use of iodized oil mixed with an anticancer drug, followed by injection of gelatin sponge particles, was undertaken to evaluate its antitumor effect and its influence on normal tissue in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Histologic findings in 12 patients who underwent hepatectomy after segmental TAE were compared with findings on plain radiographs and computed tomographic (CT) scans. Visualization of the portal veins contiguous to the tumor on radiographs and the pattern of iodized oil accumulation in the tumor and vicinity on CT scans after TAE were assessed. RESULTS: Complete necrosis of the tumor was achieved in 10 cases (83%), while complete necrosis of daughter nodules and capsular invasion was observed histologically in eight of these 10 patients (80%). The degree of tumor necrosis correlated with the pattern of iodized oil accumulation in and near the tumor. Partial necrosis of normal tissue near the tumor correlated with accumulation of iodized oil. CONCLUSION: Segmental TAE may be an excellent therapeutic method for treatment of HCC that is localized in one or a few segmental or subsegmental regions.

Aged↗

GABA and GAD immunoreactivity of photoreceptor terminals in primate retina.

Within the vertebrate retina, two types of photoreceptor cells--the rods and cones--transduce visual signals and convey this information through synapses with bipolar and horizontal cells. Although the neurotransmitter at these first-order synapses has not been identified, electrophysiological studies suggest that it might be excitatory. In the present study, however, we have found photoreceptor terminals in the rhesus monkey retina which are immunoreactive with antibodies to either gamma-aminobutyric acid (GABA) or L-glutamic acid decarboxylase (GAD, an enzyme involved in the synthesis of GABA). In the perifoveal region of the retina, approximately 25% of presynaptic profiles having ultrastructural characteristics of either rod or cone terminals are immunoreactive with one or the other antibody. This evidence for a putatively inhibitory neurotransmitter in photoreceptor terminals challenges present understanding of retinal synaptic function.

Animals↗