Search PubMed⌕ Search

Biomedical subjects

T Ohira

Publications and source records attributed to T Ohira.

At least 109 records · Page 6Linked to original sources
PubMed1994

Gene therapy for Lewis lung carcinoma with tumor necrosis factor and interleukin 2 cDNAs co-transfected subline.

Gene therapy with cytokine cDNA will provide a new tool for cancer treatment. We have already reported that immunization with interleukin-2 (IL2) cDNA transfected Lewis lung carcinoma (LLC) cells induced anti-tumor immunity, which, however, was not strong enough to eradicate an established tumor. In an attempt to develop more effective gene therapy methods, we have used tumor cells co-transfected with IL-2 and tumor necrosis factor (TNF) cDNAs. These cDNAs were introduced into pBMG-Neo and pcDV-X819 vectors, respectively, and then co-transfected into LLC cells. The co-transfectants were selected by incubating them in a medium containing G418 followed by the limiting dilution method twice to obtain IL2 and TNF cDNA co-transfected LLC (LLC-TNF-IL2) cells. When 5 x 10(5)/ml LLC-TNF-IL2 cells were incubated for 48 h, they secreted 7.56 U/ml TNF and 527.0 U/ml IL2 into the culture supernatant. When C57BL/6 mice were transplanted with 1 x 10(6) LLC-TNF-IL2 cells, all the tumors were rejected. The growth of transplanted LLC, but not B16F10 melanoma cells, was retarded in mice inoculated with LLC-TNF-IL2 on their contralateral sides, which suggests specific immunity was induced. The immunization effect by the co-transfectant was superior to that of the IL2- and TNF-transfectants alone.

Animals↗
PubMed1994

[Neurophysiological study of hemifacial spasm--F wave of the facial muscles].

We studied the F wave of the facial muscles on both the normal side and the spastic side in 14 patients with hemifacial spasm. The purpose of this study was to determine if the mechanism of hemifacials spasm originates in ephaptic transmission in the facial nerve at the site of vascular compression or in a hyperexcited facial motor nucleus. Larger amplitude, longer duration and shorter latency F waves in the peripheral nerves than in normals indicate anterior horn cell hyperexcitability. We found abnormal potentials exhibiting synkinesis (lateral spread), a typical electrophysiological finding in hemifacial spasm, in the facial nerve evoked electromyograms of the 14 patients, none of whom had experienced facial palsy or facial nerve block. Electrical stimulation was delivered transcutaneously to the most distal portion of the marginal mandibular branch of the facial nerve. Using surface electrodes the F waves were obtained over the mentalis muscle as the second response after the M wave. While the F waves were normal on the patients' normal side, on the spastic side, their duration was longer (mean duration about 1.9 times that of the normal side), their onset latency was slightly shorter, and their F/M amplitude latency was greater than on the normal side. After microvascular decompression, the facial spasm and abnormal F-wave findings resolved. Onset latency was not increased, and on the spastic side some patients displayed facial spasm clinically and electrophysiologically for one year after MVD. In other words, there was hardly any focal demyelination of the facial nerve, so it is possible that ephaptic transmission and ectopic excitation are the mechanism of HFS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Abnormal evoked EMG and blink reflex responses in patients with hemifacial spasm (HFS)].

Abnormal evoked EMG and blink reflex responses have been observed on the affected side in patients with HFS. These characteristic responses were used as methods of preoperative differential diagnosis, and the disappearance of these abnormal responses during intraoperative monitoring was assessed as confirmation of nerve decompression. The subjects were 30 patients with a diagnosis of HFS. Three responses were evaluated: 1) the orbicularis oris muscle (OR) response to stimulation of the orbicularis oculi muscle branch (OB), OB-->OR; 2) the orbicularis oculi muscle (OC) response to stimulation of the marginal mandibular branch (MB), MB-->OC; and 3) the (OR) response to stimulation of the supraorbital nerve (SO), SO-->OR. The facial nerve in the root exit zone was compressed by a vessel in all 21 patients diagnosed as typical HFS who had abnormal responses, and OB-->OR was always detected. The MB-->OC and SO-->OR detection rates were low (50% and 25%, respectively) when the interval since the onset of HFS was less than 3 years, but increased to 78% and 67%, respectively, when it was 3 to 5 years, and all three abnormal responses were always detected when the interval was more than 5 years. In 17 of the patients these responses began to change and eventually disappeared before decompression of the facial nerve, and in 2 patients they persisted even after decompression. Abnormal responses disappeared at the time of decompression in only 2 patients, and their HFS was completely cured postoperatively. These findings confirmed that disappearance of abnormal responses is not a very useful guide for facial nerve decompression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Cis-diamminedichloroplatinum(II) inhibits p34cdc2 protein kinase in human lung-cancer cells.

cis-Diamminedichloroplatinum(II) (CDDP) induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as p34cdc2 protein kinase. p34cdc2 protein kinase activity was maximum in G2 phase and decreased after G2/M transition in synchronized PC-9 human lung cancer cells. Evidence for a phosphorylated p34cdc2 protein kinase complexed with cyclin B was obtained from cells in G2 phase and the p34cdc2 protein kinase appeared to be dephosphorylated at M phase. After exposure to CDDP in G1 phase, PC-9 cells were arrested in G2 phase. The activation of p34cdc2 protein kinase was inhibited by CDDP. Cyclin A and wee-I kinase were not affected by the exposure to CDDP. Cyclin B was degraded in M phase in PC-9 cells. Exposure to CDDP did not affect the degradation of cyclin B. Our data suggest that the effect of CDDP on cell-cycle phase might be regulated by the dephosphorylation of p34cdc2 protein kinase. To determine whether the p34cdc2 protein kinase is a primary target for CDDP, we examined the direct effect of CDDP on tyrosine dephosphorylation of p34cdc2 protein kinase in cellular extracts. Cell lysates from synchronized PC-9 in G2 phase were immunoprecipitated with p13-Sepharose beads. In vitro dephosphorylation of phosphotyrosine of p34cdc2 protein kinase was observed after exposure to okadaic acid in a concentration-dependent manner. The dephosphorylation of p34cdc2 protein kinase by okadaic acid was inhibited by CDDP. We hypothesize that inhibition of p34cdc2 dephorphorylation by CDDP is important for its growth-inhibiting properties.

CDC2 Protein Kinase↗
PubMed1993

Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2.

To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl2. SBC-3/Bcl2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3, with relative resistance values of 3.4, 7.6 and 5.7, respectively. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and taxol between SBC-3 and SBC-3/Bcl2. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC, in a concentration-dependent manner. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl2. Treatment with CDDP resulted in the same degree of DNA fragmentation in SBC-3 and SBC-3/Bcl2. These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis.

Animals↗
PubMed1993

Combination effect of vaccination with IL2 and IL4 cDNA transfected cells on the induction of a therapeutic immune response against Lewis lung carcinoma cells.

In order to develop a more effective method of immunotherapy we have transfected mouse interleukin-2 (IL2) or mouse interleukin-4 (IL4) cDNA into a spontaneous non-immunogenic murine lung cancer. Lewis lung carcinoma (LLC). IL2 cDNA transfection more strongly decreases tumorigenicity of LLC than IL4 cDNA transfection. Recombinant-human-IL2 treatment of mice that were transplanted with untransfected LLC could not prolong their survival. In contrast, vaccination with IL2-cDNA-transfected LLC (LLC-IL2) and LLC-IL2 mixed with IL4-cDNA-transfected LLC (LLC-IL4) could significantly suppress tumor growth of LLC in a tumor-specific manner. The vaccination with LLC-IL2 mixed with the same number of LLC-IL4 cells was more suppressive to the growth of LLC than that with LLC-IL2 cells alone, while LLC-IL4 vaccination alone was ineffective. Nude, severe-combined-immune-deficient (SCID) and beige mice were unable to reject LLC-IL2 cells. However, immunodeficient mice responded to LLC-IL2, but not to LLC, since their survival times after transplantation with LLC-IL2 cells were significantly longer than the survival time of normal or immunodeficient mice transplanted with untransfected LLC cells. We conclude that vaccination with IL2-producing tumors and, with more pronounced effect, in combination with IL4-producing tumors, is able to induce an immune response to this normally non-immunogenic tumor. Tumor rejection appears to be achieved by the combined activity of CTL and NK cells. This strategy has potential for new immunotherapeutic interventions in cancer patients.

Animals↗
PubMed1993

Crystallographic characterization of a PHO4-DNA complex.

Crystals have been obtained of the DNA-binding domain of the yeast transcription factor PHO4 in complexes with several synthetic fragments of DNA with appropriate cognate sequences. Crystals suitable for X-ray diffraction studies were produced in the case of a complex of the protein with a 17 base-pair fragment of DNA from a solution in polyethylene glycol and calcium chloride. The crystals have the space group of P4(1)2(1)2 or P4(3)2(1)2 with unit cell dimensions a = b = 56.7 A, c = 447.8 A. The diffraction data at 3 A resolution were collected using synchrotron radiation with a Weissenberg camera for macromolecular crystallography.

Base Sequence↗
PubMed1993

Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice.

HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 10(6) ml-1) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ng ml-1 within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-IL6 cells were transplanted into C57BL/6 mice subcutaneously, the mean +/- s.d. of survival times of these mice were 33.3 +/- 9.7, 34.3 +/- 7.1 and 17.0 +/- 3.1 days, respectively. The survival time of LLC-IL6 cells transplanted mice was significantly shorter than that of LLC (P < 0.01) or LLC-Neo (P < 0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-IL6 transplanted mice than in LLC transplanted mice. Mouse IL-1 alpha and mouse TNF-alpha were not detected in the plasma of LLC-IL6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-1 alpha and TNF-alpha in the plasma. This state may be responsible for the shortened survival of LLC-IL6 tumour-bearing mice.

Animals↗
PubMed1993

[Transcranial magnetic stimulation of the facial nerve--identification of the actual excitation site in the cat].

The site where transcranial magnetic stimulation excites the facial nerve was studied in 6 cats. Transcranial magnetic stimulation of the facial nerve was recorded from the left mentalis muscle. A figure-of-eight shaped magnetic coil was used, and coil induction direction had more influence on the facial nerve evoked compound muscle action potentials (CMAPs) than the coil position. No change could be detected in the CMAPs before and after craniotomy, after cerebellar lobectomy and after exposure of the facial nerve in the facial canal. The facial nerve was stimulated electrically at the porus, meatal portion, geniculum and horizontal portion. The latencies of the CMAPs for each portion were measured and compared with the magnetic response, which was coincidental with that of the meatal portion. The facial nerve was then transected distally from the porus, and CMAPs following magnetic stimulation were recorded at each step. The CMAPs disappeared when the nerve was transected at the fundus. The results of both approaches in this study led to the conclusion that transcranial magnetic stimulation excites the facial nerve at the meatal portion.

Action Potentials↗
PubMed1992

[Induction of tumor immunity by cytokine cDNA transfected Lewis lung carcinoma].

It is difficult to induce anti-tumor immunity in tumors with low antigenicity. In order to develop a more effective method of immunotherapy, we transfected interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6) genes into Lewis lung carcinoma (LLC) cells. Then, 1 x 10(6) LLC-IL-2, LLC-IL-4 or LLC-IL-6 cells were transplanted into C57BL/6 mice subcutaneously. All mice transplanted with LLC-IL2 and half those with LLC-IL-4 rejected the tumor cells. Survival time of LLC-IL-6 transplanted mice was significantly shorter than that of LLC transplanted mice, with no difference in tumor growth. These data suggest that transplantation of IL-2 or IL-4 gene transfected cells could effectively induce immunity against LLC. IL-6 transfection did not induce immunity, but induced cachexia.

Animals↗
PubMed1991

Brain stem auditory-evoked potentials in meningomyelocele. Natural history of Chiari II malformations.

Brain stem auditory-evoked potentials (BAEPs) were recorded in 30 patients with meningomyelocele and shunted hydrocephalus ranging in age from birth to 33 years. Twenty-two of them had Chiari II malformation, one of which was symptomatic. In 22 cases, including 15 with Chiari II malformation, BAEPs were recorded repeatedly after periods ranging from 18 months to 7 years. The results were as follows: (1) III-V interpeak latency (IPL) decreased progressively from prolonged to the normal range with growth until 25 years of age; (2) I-III IPL tended to prolong gradually from the normal range; (3) these findings may indicate that the natural history of Chiari II malformation is delayed maturation of the brain stem and intensification in the elongation and stretching of the hindbrain and lower cranial nerves.

Adolescent↗
PubMed1991

Actinomycosis of the larynx.

Actinomycosis is a disease characterized by a chronic suppurative and granulomatous process which tends to form multiple pyogenic draining sinus tracts. The most common site in which it occurs is the cervico-facial region, especially in the submandibular area. The exudates from the fistulous tracts usually contain yellow granules known as "sulfur granules," which can be considered as a hallmark of actinomycosis. We report a rare case of laryngeal actinomycosis which occurred in a 68-year-old male who had been irradiated 8 years before due to laryngeal carcinoma. During the admission, the patient was also diagnosed as being a myelodisplastic syndrome carrier. The patient was treated successfully with penicillin 10 million IU administered daily over 40 days. The etiologic agents, predisposing factors, diagnostic procedures, and available treatments are discussed, and the pertinent literature is reviewed herein.

Actinomycosis↗
PubMed1991

Histochemical localization of calcium with potassium pyroantimonate in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease.

The ultrastructural localization of calcium in the articular cartilage, meniscus, and synovium of patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease was examined by using potassium pyroantimonate. Focal areas with deposition of CPPD crystals in each tissue showed electron-dense precipitates of the antimony-calcium complex: (1) in the cytoplasm of hypertrophic chondrocytes around CPPD crystals, especially on the margins of intracellular lipid droplets or within electron-dense amorphous material or both; and (2) on the margins of lipid droplets and within electron-dense amorphous material in the degenerated matrix surrounding the hypertrophic chondrocytes. The slender rodlike structures consisting of electron-dense precipitates of the antimony-calcium complex, suggestive of the precursor to rodlike CPPD crystals, were also observed in the degenerated matrix. These findings suggest that the hypertrophic chondrocytes may contribute to the formation of CPPD crystals by intracellular accumulation of calcium and subsequent release of high concentration of calcium into their surrounding matrix.

Aged↗
PubMed1989

Vector analysis of three-dimensional evoked potentials: eccentric dipoles.

The quantitative description of three-dimensional cerebral evoked potentials is extended to include eccentric dipolar sources. Eccentricity-related distortions in dipole orientation and magnitude are assessed. The use of nonstandard montages, the prediction of topographic surface maps, dynamic analysis, and theoretical mechanisms of planar segment formation are discussed.

Brain↗
PubMed1989

[Comparisons of bioavailability of various calcium salts. Utilization incisor dentin in parathyroidectomized rats].

In the present study, we compared the bioavailability of various calcium salts in the diet such as calcium lactate, calcium carbonate and calcium phosphate by examining the effects of these calcium salts on serum calcium concentration and on the mineralization of incisor dentin in parathyroidectomized (PTXed) rats. Each rat was given daily 12 g of a low calcium (0.1% Ca) diet beginning from 3 days before the operation and continuing for 11 days after. Then the diet was changed to those containing various calcium salts (1.5% Ca). The serum calcium and phosphorous concentrations were examined every three days, just before feeding time and 6 hours after. The degree and site of the mineralization of incisor dentin were examined histologically by a time marking method using lead acetate. In the PTXed rats maintained on a low calcium diet, the serum calcium concentration decreased to about 4.5 mg/dl and the mineralization of incisor dentin was inhibited. On the 11th day, just before feeding on diets containing various calcium salts, the serum calcium concentrations were very similar for each group, but at 6 hours after feeding, concentration was 7.6 mg/dl in the calcium lactate group, 6.2 mg/dl in the calcium carbonate group and 4.8 mg/dl in the calcium phosphate group. On the 17th day following administration of the high calcium diets, the serum calcium concentrations were 9.8 mg/dl in the calcium lactate group, 8.4 mg/dl in the calcium carbonate group and 4.4 mg/dl in the calcium phosphate group. Mineralization of the incisor dentin was best in the calcium lactate group, moderate in the calcium carbonate group and poor in the calcium phosphate group. We also examined the effects of dietary phosphorus contents on serum calcium concentrations and on the mineralization of incisor dentin using PTXed rats. On the 17th day following the administration of diets (1.5% Ca, with calcium lactate) containing various amounts of phosphorus, the serum calcium concentrations in the calcium lactate group were 8.8 mg/dl (0.4% P), 6.9 mg/dl (0.8% P) and 4.2 mg/dl (1.6% P) respectively. Mineralization of incisor dentin was also inhibited in rats fed a high phosphorus diet. These results suggest that in PTXed rats, absorption of calcium from the intestines and mineralization of the incisor dentin is best by the administration of calcium lactate, moderate by calcium carbonate and poor by calcium phosphate, and that phosphorus in the diet inhibits calcium absorption from the intestines.

Animals↗
PubMed1989

A histological study of calcium pyrophosphate dihydrate crystal-deposition disease.

Synovial, meniscal, articular cartilage, and other connective tissue from fifty-seven patients who had calcium pyrophosphate dihydrate crystal-deposition disease was examined by light microscopy, electron microscopy, and electron-probe microanalysis. Safranin O-positive hypertrophic chondrocytes that contained proteoglycans were observed in the tissues of each patient. Microcrystals that were suggestive of early precipitation of crystals were found in the degenerating matrix surrounding hypertrophic chondrocytes. The matrix contained electron-dense amorphous material, including proteoglycans and debris of cellular components. The microcrystals were often seen in contact with degenerating collagen fibers. There was never any histological evidence of formation of crystal in the areas that had no hypertrophic chondrocytes. Chondrocytes of this kind, surrounded by characteristic degenerating matrix, were never observed in the articular tissue from sixty-one patients who had only osteoarthritis. On the basis of our results, we speculate that electron-dense amorphous material containing proteoglycans and debris of cellular components, and the degenerating collagen fibers that were seen around the hypertrophic chondrocytes, may play important roles in the formation of calcium pyrophosphate dihydrate crystals.

Adult↗