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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 37 records · Page 2Linked to original sources

Hyperthermia combined with radiation therapy for primarily unresectable and recurrent colorectal cancer.

The value of adjuvant hyperthermia to radiotherapy in the treatment of locally advanced colorectal cancers was investigated. Between 1981 and 1989, 71 primarily unresectable or recurrent colorectal tumors were treated with radiotherapy at the Department of Radiology, Kyoto University Hospital. Of the 71 tumors, 35 were treated with radiotherapy plus hyperthermia (group I), while 36 tumors (group II) were unsuitable for hyperthermia mainly because of difficulties with the insertion of temperature probes or the thickness of the patient's subcutaneous fat (greater than 2 cm). The mean total radiation dose was 58 Gy and 57 Gy for groups I and II, respectively. Thirty deep-seated pelvic tumors were treated with an 8 MHz radiofrequency capacitive heating device, and five subsurface tumors were treated with a 430 MHz microwave hyperthermia system. Hyperthermia was given following radiotherapy for 30-60 min for a total of 2-14 sessions (mean 5.7). In 32 of the 35 tumors heated, direct measurement of tumor temperature was performed. For the five tumors treated with the microwave heating device, the means of the mean maximum, average, and minimum measured intratumoral temperatures were 45.4 degrees C, 43.3 degrees C, and 40.6 degrees C, respectively. The corresponding values were 42.2 degrees C, 41.3 degrees C, and 40.3 degrees C for the 27 tumors treated with the capacitive heating device. Effective heating of deep-seated pelvic tumors was more difficult than heating of abdominal wall or perineal tumors. The local control rate at 6 months after the treatment, which was defined as absence of local progression of the tumors, was 59% (17/29) and 37% (11/30) for groups I and II, respectively. The objective tumor response rate (complete regression plus partial response) evaluated by computed tomography was 54% (19/35) in group I, whereas it was 36% (10/28) in group II. A better response rate of 67% was obtained in the 15 tumors with a mean average tumor temperature of greater than 42 degrees C. Although limitation of our current heating devices exist, the combination of hyperthermia with radiotherapy is a promising treatment modality in the treatment of locally advanced colorectal cancer.

Adenocarcinoma

Regional hyperthermia combined with radiotherapy in the treatment of lung cancers.

Twenty locally advanced lung cancers were treated by hyperthermia in combination with radiotherapy between November 1980 and January 1990. All tumors selected had invaded or were in contact with the chest wall, so that transcutaneous insertion of thermal probes into the tumor was possible. Using an 8 or 13.56 MHZ RF capacitive heating device, hyperthermia was given once or twice a week after irradiation for 30-60 min per session (1-12 sessions in total). Radiotherapy was delivered at dose of 13.6-70 Gy. The thermal parameters analyzed were a) maximum, average, and minimum intratumor temperatures (Tmax, Tav, and Tmin), which were recorded at the termination of each treatment, and b) the percentages of the intratumor points that exceeded 41 C (%T greater than or equal to 41 C). The mean +/- SD for Tmax, Tav, Tmin, and %T greater than or equal to 41 C was 42.9 +/- 1.7 C, 41.6 +/- 1.2 C, 39.7 +/- 1.1 C, and 56.2 +/- 25.8, respectively. Larger tumors showed higher thermal parameters than the smaller tumors. Of the 12 tumors treated by definitive therapy, 2 (17%) achieved CR, 7 (58%) PR, and 3 (25%) NR. Four of 10 tumors that did not achieve CR showed large intratumor low density areas on post-treatment CT, reflecting massive coagulation necrosis. Higher thermal parameters were closely related to the appearance of low-density areas but not to changes in tumor size. Four tumors treated preoperatively were successfully resected 2 weeks after thermoradiotherapy, whereas four palliatively-treated tumors showed no regression. The side effects associated with hyperthermia were pain in 12 patients (60%) and dyspnea in 3 (15%), all of which resolved after termination of treatment. A skin abscess and a pneumothorax attributed to thermal probe insertion were observed in one patient each. These results indicate that regional RF capacitive hyperthermia is clinically feasible for local treatment of selected lung cancers.

Adenocarcinoma

The superior cervical ganglion: origin of sympathetic fibers in the facial and hypoglossal nerves in the cat.

Location of superior cervical ganglion (SCG) neurons, sending axons into the facial and hypoglossal nerves, was investigated in the cat by means of retrograde axonal transport of horseradish peroxidase (HRP). After wheat germ agglutinin conjugated HRP (WGA-HRP) was injected into these nerves, many retrogradely labeled neurons were found widely in the ipsilateral SCG, particularly around the caudal half of the SCG. These neurons were round or oval in shape and 70-80% of these were medium in size. In fluorescent experiments, fast blue (FB) was used in combination with diamidino yellow (DY). After injections of FB into the facial nerve and DY into the hypoglossal nerve, a few FB-DY double-labeled neurons occurred in the SCG ipsilaterally.

Adrenergic Fibers

A case of congenital ossicular malformation with mild auricular deformity: embryological and surgical considerations.

A case of bilateral congenital conductive deafness with mild auricular deformity is presented, and the anomalous structure deformity of the ossicles was multi-focal in this case, and a previous report indicates that ossicular malformation in the ear with congenital conductive deafness is multi-focal when the external ear is only slightly deformed. Bilateral ossicular reconstruction with replacement of the stapes yielded satisfactory results.

Acoustic Impedance Tests

Neonatal cerebral infarction: symptoms, CT findings and prognosis.

In a retrospective multi-center study, we investigated eighteen infants with unilateral cerebral infarctions confirmed by computed tomography (CT) scans. The initial symptoms were observed in all the patients between 0 and 3 days of age. Convulsions or apneic attacks were the initial symptoms in all but one. Only 4 patients had complicated obstetric histories and none showed polycythemia or electrolyte abnormalities. All of the initial CT scans revealed unilaterally localized hypodense areas. In 10, the initial CT scans were performed within 24 hours after the clinical onset. In 16, the lesions were within the territory of the middle cerebral artery, 9 of which also involved the cortico-spinal tract (CST). In the remaining 2 patients, the lesions were located within the territory of the posterior cerebral artery. None of the 9 patients without CST involvement developed hemiplegia, whereas 5 (56%) of the 9 with CST involvement had hemiplegia, which is a fairly low incidence compared with that in adult cases. This difference was thought to be related to neonatal brain plasticity.

Cerebral Infarction

Production of monoclonal antibodies specific to major allergens of Cryptomeria japonica pollen.

Monoclonal antibodies (MAbs) directed against Cryptomeria japonica pollen antigen (CPAg) were prepared. CPAg was precipitated with these MAbs and both MAbs CPA7 (IgG2a) and CPA9 (IgG1) recognized two major glycoproteins (m = 41 kDa and 46 kDa) of CPAg. MAb CPA7 or CPA9 was coupled to CNBr activated sepharose and affinity purification of the major allergen of CPAg from the crude extract was performed. The affinity purified CPAg bound IgE antibody present in patients with Cedar pollinosis.

Allergens

Possible involvement of cathepsin L in processing of rat liver hexokinase to eliminate mitochondria-binding ability.

A previously found proteinase possibly involved in the modification of hexokinase to eliminate the mitochondria-binding ability without appreciable change in the catalytic activity (called hexokinase-processing enzyme hereafter), was purified by sequential chromatographies from rat liver and its properties were examined. The hexokinase-processing enzyme had carbohydrate moieties as evidenced by adsorption on immobilized concanavalin A, and had a molecular weight of about 23,000 as estimated by SDS-PAGE and gel filtration chromatography. Benzyloxycarbonyl-phenylalanyl-L-arginine-4-methylcoumaryl-7-amide (Z-Phe-Arg-MCA)-hydrolyzing activity was co-purified with this processing activity throughout the purification, while the hydrolyzing activity for benzyloxycarbonyl-L-arginyl-L-arginine-4-methylcoumaryl-7-amide (Z-Arg-Arg-MCA) was not. The processing activity, as well as Z-Phe-Arg-MCA hydrolyzing activity, was highly sensitive to cysteine proteinase inhibition, for example, by leupeptin and N-[N-3-(trans-carboxirane-2-carbonyl)-L-leucyl]agmatine (E-64). Furthermore, the enzyme preparation reacted with an antibody against cathepsin L purified from rat kidney. These results indicated that cathepsin L may be involved in the above-mentioned processing of hexokinase.

Animals

Activation of human monocytes by interleukin-2 and various cytokines.

We previously reported that human macrophages cultured with IL-2 for a long period (lymphokine-activated macrophages, LAMs) showed high tumoricidal activity against human and murine leukemic cell lines through a different mechanism from lymphokine-activated killer (LAK) cells. In this report, we investigated the effects of various cytokines on the tumoricidal activity of IL-2-induced LAMs against HeLa cells. CSF-1 and IL-1 were found to enhance the tumoricidal activity of LAM in a dose-dependent manner, whereas IFN-gamma and TNF had inhibitory effects. CSF-1 in combination with a low dose of IL-2 synergistically induced LAMs with highly tumoricidal activity. We also found that monocytes from some donors that did not respond to IL-2 were differentiated to tumoricidal macrophages by treatment with a combination of CSF-1 and IL-2. Furthermore, IL-2-induced LAMs were found to produce cytotoxic factors in the culture medium when they were cocultured with tumor cells, and the cytotoxic activity in the culture supernatant of LAMs was also increased by the incubation of LAMs with CSF-1. The cytotoxicity of the supernatants from macrophages with different tumoricidal activity correlated with their cell-mediated cytotoxicity. It is suggested from these results that the cytotoxicity of LAMs is regulated by CSF-1, IL-1, IFN-gamma, and TNF, and that the production of cytotoxic molecules is involved in cell-mediated killing by LAMs.

Cytokines

Daily intakes of 232Th and 238U in Japanese males.

Diet samples were collected by a duplicate portion method from 31 locations in Japan and were analyzed by inductively coupled plasma mass spectrometry. Average daily intakes per adult male were estimated at 1.7 mBq for 232Th and 8.8 mBq for 238U.

Adult

A serine protease-inhibitory benzamidine derivative inhibits the growth of human colon carcinoma cells.

The inhibitory effect of a serine protease-inhibiting tetra-benzamidine derivative, TAPP-Br, on the cell growth of 8 human colon carcinoma cell lines was examined and the mechanism of the inhibition was analyzed. TAPP-Br inhibited the cell growth of all the colon carcinoma cell lines, and this effect was irreversible. The expression of mRNAs for nuclear oncogenes such as MYC, FOS and JUN was decreased by TAPP-Br after treatment for 3 h and the effect continued for 48 h. mRNA expression of epidermal growth factor receptor, transforming growth factor-beta and type IV collagenase was suppressed at 48 h after the initiation of TAPP-Br treatment, suggesting an indirect action of TAPP-Br. TAPP-Br decreased protein kinase C activity in the particulate fraction, whereas it increased the enzyme activity in the soluble fraction. These findings overall suggest that the serine protease inhibitor, TAPP-Br, might inhibit the cell growth of colon carcinoma cell lines through suppressing the expression of genes whose promoter contains a 12-O-tetradecanoylphorbol-13-acetate-responsive element or serum-responsive element.

Antineoplastic Agents

HLA-DP antigen and Takayasu arteritis.

Sixty-four patients with Takayasu arteritis and 317 healthy individuals in the Japanese population were examined for HLA-A, -B and -C alleles by serological typing and for HLA-DR, DQ and DP alleles by DNA typing using PCR/SSOP analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601 and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the combination or haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.

Alleles

L-leucyl-L-arginine, naltrindole and D-arginine block antinociception elicited by L-arginine in mice with carrageenin-induced hyperalgesia.

1. Intraplantar injection of carrageenin into the mouse hind paw produced hyperalgesia when measured by the paw pressure test (Randall & Selitto method). 2. Subcutaneous administration of L-arginine (100-1,000 mg kg-1), a possible precursor of kyotorphin which is an endogenous analgesic neuropeptide, inhibited carrageenin-induced hyperalgesia in a dose-dependent manner. This effect was blocked by subcutaneous administration of naloxone, naltrindole, a selective delta-opioid receptor antagonist (enkephalin antagonist), and D-arginine. 3. Intracerebroventricular administration of L-leucyl-L-arginine inhibited the antinociceptive effect of systemically administered L-arginine in hyperalgesic mice. 4. Intracerebroventricular administration of L-arginine (3 and 30 micrograms per mouse) and kyotorphin (300 ng-3 micrograms per mouse) produced antinociception in hyperalgesic mice. The antinociceptive effects of L-arginine but not kyotorphin were blocked by intracerebroventricular administration of D-arginine. 5. These results suggest that L-arginine-induced antinociception is mediated by activation of 'kyotorphinergic' nerves followed by activation of the 'opioidergic' (possible 'enkephalinergic') nerves in the central nervous system.

Analgesics

IgM M-protein in a patient with sensory-dominant neuropathy binds preferentially to polysialogangliosides.

A 77-year-old man presented sensory-dominant neuropathy associated with IgM M-protein reacting with various gangliosides. The M-protein bound to gangliosides with polysialosyl residue, such as GD1b, GD3, GT1b, GT3, GQ1b, and GQ1c. In addition, GD1a, GM3 and LM1, having a terminal monosialosyl epitope, were also recognized. Previously, Ilyas et al. described a similar case in which sensory symptoms were associated with IgM M-protein reacting with gangliosides containing a disialosyl group, such as GD3, GD1b, and GT1b, but not GM3 and GD1a. It is suggested that the reactivity of IgM M-protein with polysialogangliosides may be associated with the pathogenesis of sensory-dominant neuropathy.

Aged

The stable maintenance system pem of plasmid R100: degradation of PemI protein may allow PemK protein to inhibit cell growth.

We constructed plasmids carrying heat-inducible pemI and pemK genes, which were fused with the collagen-lacZ sequence in frame. The PemK-collagen-LacZ (PemK*) protein produced from the fusion gene upon heat induction inhibited the growth of cells and killed most of the cells in the absence of the PemI protein but did not do so in the presence of the PemI protein. This supports our previous assumption that the PemK protein inhibits cell division, leading to cell death, whereas the PemI protein suppresses the function of the PemK protein. We also constructed the plasmid carrying the heat-inducible pem operon which consists of the intact pemI gene and the pemK gene fused with collagen-lacZ. The simultaneously induced PemI and PemK* proteins did not inhibit the growth of cells. However, the temperature shift to 30 degrees C after induction of both proteins at 42 degrees C caused inhibition of cell growth and death of most cells. This suggests that the PemI protein is somehow inactivated upon the arrest of de novo synthesis of the PemI and PemK* proteins, allowing the PemK* protein to function. We observed that the PemI-collagen-LacZ (PemI*) protein was degraded faster than the PemK* protein, perhaps by the action of a protease(s). In fact, the lon mutation, which caused no apparent degradation of the PemI* protein, did not allow the PemK* protein to function, supporting the suggestion described above. Instability of the PemI protein would explain why the cells which have lost the pem+ plasmid are preferentially killed.

Bacterial Proteins

Animal model for ischemic facial nerve paralysis with selective vascular embolization.

An experimental model that reliably and easily produces acute ischemic facial nerve paralysis would be useful for the controlled study of treatment and to improve our understanding of the pathophysiology and treatment of facial nerve palsy. Most documented models that simulate clinical facial nerve palsy cause direct damage to the nerve. We describe an experimental model for ischemic facial nerve paralysis in the cat that employs arterial block of the internal and external maxillary and posterior auricular arteries using embolizing material (Avitene). All animals develop stable acute ischemic facial nerve palsy lasting for approximately 2 months. Electromyographic study of this model revealed that the site of the lesion resulting from selective embolization may be within the temporal bone. This model has the advantages of simplicity of technique, cost-effective use of cats, and reproducibility of facial nerve palsy.

Animals

Clinical analysis of a series of vertebral aneurysm cases.

We reviewed 38 cases of aneurysms of the vertebral artery treated over the last 10 years: 26 (68%) located at the junction of the vertebral and posterior inferior cerebellar arteries, 10 (26%) at the vertebral artery, and 2 (5%) at the vertebrobasilar union. There were three distinct forms of aneurysms: 20 saccular (53%), 10 fusiform (26%), and 8 dissecting (21%). Among these 38 aneurysms, 33 (87%) had ruptured: 18 of the saccular aneurysms (90%), all 10 of the fusiform aneurysms (100%), and 5 of the dissecting aneurysms (63%). Computed tomography of the 28 ruptured aneurysms revealed diffuse subarachnoid hemorrhage in the basal cistern combined with intraventricular hemorrhage in 24 cases (86%). Magnetic resonance imaging was useful for differentiating between fusiform and dissecting aneurysms. Abnormalities such as a double lumen of the vertebral artery were demonstrated in four of the dissecting aneurysms. The overall surgical results were good for 22 of the 27 surgically treated cases (81%). New bleeding was observed in 8 (24%) of the 33 ruptured aneurysms. The rate of new bleeding was high (60%) in the patients with dissecting aneurysms, and occurred mostly in the acute stage. The incidence of vasospasm was 27%, and only two patients suffered permanent neurological deficits. These findings indicate that the rate of new bleeding tends to be high in patients with saccular and dissecting aneurysms, and thus, they should be treated as early as possible. A preoperative balloon occlusion test should be conducted if proximal occlusion of the vertebral artery is necessary, since proximal occlusion is not always safe, despite angiographic evidence of sufficient contralateral arterial flow.

Aortic Dissection