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Biomedical subjects

T Horiguchi

Publications and source records attributed to T Horiguchi.

At least 91 records · Page 5Linked to original sources

Immobilized DPP and other proteins modify OCP formation.

Osteonectin, gamma-carboxyglutamic acid-containing (Gla) protein, and dentin phosphoprotein were covalently attached to sepharose beads and inoculated in solutions at two different degrees of supersaturation with respect to both octacalcium phosphate (OCP) and hydroxyapatite. In both solutions, the inhibitory activity towards de novo formation of calcium phosphate that these proteins display when freely dissolved in solution was completely eliminated when they were immobilized on the sepharose at concentrations of up to 5 micrograms/mg wet beads. In the solution that was more highly supersaturated with respect to OCP, the immobilized dentin phosphoprotein, moreover, was found to induce de novo formation of OCP in proportion to the concentration of the protein immobilized. For example, at 10 micrograms/ml of the immobilized dentin phosphoprotein, the induction period was reduced more than 50%. However, in the solution considerably less supersaturated with respect to OCP, none of the immobilized proteins were capable of inducing OCP or apatite deposition. These findings suggest that the immobilized dentin phosphoprotein could work as a nucleating substrate for the OCP phase in solutions where calcium and phosphate concentrations are sufficiently higher than equilibrium saturation levels for the OCP phase.

Animals↗

The effect of protease inhibitor on reperfusion injury after unilateral pulmonary ischemia.

Reperfusion injury is a large problem in the early stage after lung transplantation. Its prevention by protease inhibitor was evaluated experimentally. Warm ischemic models were made with the left lungs of adult mongrel dogs. The time for the warm ischemic procedure was set at 2 hr, and the lungs were reperfused for 2 hr. The experimental group was divided into a control group, a UTI (urinary trypsin inhibitor) group and a GM (gabexate mecilate) group. To the UTI group, 10,000 units/kg of UTI was administrated during reperfusion, and to the GM group, 20 mg/kg of gabexate mecilate was administrated similarly. In the control group, the pulmonary vascular resistance and the lung tissue wet and dry weight ratios (W/D ratios) increased significantly, and thickened interstitium and infiltration of neutrophils were observed histologically after reperfusion. In the GM group, W/D ratios increased significantly, and histological appearances were similar to the control group. In the UTI group, the pulmonary vascular resistance increased slightly, but the W/D ratio did not increase significantly, and no changes were seen histologically after reperfusion. In the survival experiment, only two of the five dogs survived for more than seven days in the control and GM groups, while all five dogs survived for more than seven days in the UTI group. These results indicate that UTI significantly attenuates reperfusion injury, perhaps by inhibiting neutrophil proteases.

Animals↗

Mortality and morbidity in two-year disease-free survivors of small cell lung cancer after treatment with combination chemotherapy with or without irradiation.

We evaluated the long-term outcome of 148 patients with small cell lung cancer (SCLC) who had been entered into clinical trials of chemotherapy with or without thoracic and prophylactic cranial irradiation (PCI) between 1981 and 1987. Eighteen patients (12%) survived for 2 or more years. With a minimum follow-up of 4.5 years, 10 of the 18 patients who remained disease-free at 2 years are currently alive and free of SCLC. Seven of these 10 patients currently function as they did before diagnosis. However, three suffer from central nervous system changes of varying degrees in severity which appeared 2-3 years after PCI. Eight of the 18 patients who were disease-free at 2 years have died. Two died of isolated relapse in the brain at 3.6 and 4.2 years after initiation of chemotherapy. Five died of other malignancies while continuing their complete response to SCLC; two of non-small cell lung cancer, two of acute myelogenous leukemia, and one of hepatocellular carcinoma. Another patient died of an unrelated disease without any evidence of SCLC. A small but substantial proportion of patients who underwent intensive treatment will achieve long-term survival; however, these patients remain at higher risk for second cancers and late toxicities. Therefore, attention must be directed to defining the safest way to employ such treatment in the management of SCLC.

Adult↗

[Immunohistochemical study in acquired cystic disease of the kidney--expression of vimentin, epidermal growth factor, epidermal growth factor receptor and c-erb B2 gene product].

Acquired cystic disease of the kidney (ACDK) reveals abnormal epithelial cell growth which suggests a cotinuum of cyst, adenoma and renal cell carcinoma (RCC). In the present study, we examined potential role of vimentin and growth factors for cyst growth and proliferation in 20 cases with ACDK by immunoperoxidase staining method. 1281 cysts with single-layered epithelia and 89 cysts with multi-layered epithelia (atypical cyst) were studied. Intermediated filament, vimentin was positive in staining in 41.6% of cysts with single-layered epithelia, in 73.1% of cyst with multi-layered epithelia and in 100% of adenomas and RCCs. Vimentin expression, therefore, may be considered as an indication of cellular differentiation among proliferating tubular or intracystic cells. In order to evaluate the growth and/or proliferative capabilities of cyst epithelia, epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and c-erb B2 gene product were determined in cyst epithelia, adenoma and adenocarcinoma. EGF showed positive staining in 49.1% of cyst with single-layered epithelia, in 68.4% of cyst with multi-layered epithelia, in 2 of 3 adenomas and in 5 of 8 RCCs. EGFR expression was observed in 61.7% of cyst with single-layered epithelia, in 94.7% of cyst with multi-layered epithelia, in 100% of adenomas and RCCs. Co-expression of EGF and EGFR was observed in 40.3% of cyst with single-layered epithelia and in 67.1% of cyst with multi-layered epithelia. C-erb B2 gene product was positive in 9.7% of cyst with single-layered epithelia, in 100% of cyst with multi-layered epithelia and in 3 of 7 RCCs. These findings indicate that the expression of vimentin and overexpression of these growth factors and receptors appear to be one of the mechanisms operating in potentiating the abnormal growth of cyst epithelia, including potential for oncogenesis of RCC.

Adolescent↗

[Severity of myasthenia gravis is related to the degree of neuromuscular blocking effect by isoflurane].

We studied neuromuscular blocking effects of isoflurane using a neuromuscular transmission monitor in three myasthenia gravis patients. Severity of myasthenia gravis was different among three patients. T1 decreased by 12% in a mild case (I type), by 18% in a moderate case (IIa type) and by 42% in severe case (III type) during isoflurane anesthesia. Also, TOF ratio decreased by 12% in a mild case, by 22% in a moderate case, and 48% in a severe case during isoflurane anesthesia. We conclude that in patients with more severe myasthenia gravis, neuromuscular blocking effect of isoflurane is more potentiated.

Female↗

[Assessment of antitumor activity rhizoxin for human lung cancer cell lines: a potent new drug for drug-resistant lung cancer].

Rhizoxin is a new macrocyclic lactone isolated from the fungus Rhizopus chinensis. In an attempt to predict the effectiveness of rhizoxin in the treatment of lung cancer, we compared the antitumor activity of rhizoxin with those of cisplatin and etoposide using four small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, and -7, and two non-small cell lung cancer (NSCLC) cell lines, ABC-1 and EBC-1. The concentrations producing 50% inhibition of the growth of these cell lines (IC50) for each drug were obtained by MTT assay. The IC50 of rhizoxin for these cell lines ranged 0.408 nM to 1.56 nM, which were significant lower than those of cisplatin (660 nM to 16,300 nM) and etoposide (275 nM to 31,300 nM). The ratio of IC50 for the most sensitive cell line, SBC-3, to that for the most resistant cell line was less than 4-fold in rhizoxin, in contrast to more than 20-fold in cisplatin and 100-fold in etoposide. Cross-resistance of rhizoxin to cisplatin and etoposide was investigated using a cisplatin-resistant SCLC subline, SBC-3/CDDP, and an etoposide-resistant SCLC subline, SBC-3/ETP. Of interest, the parent cell line, and the resistant sublines were equally sensitive to rhizoxin, indicating rhizoxin being non-cross-resistant to cisplatin and etoposide. In conclusion, rhizoxin may be beneficial in the salvage chemotherapy of drug-resistant SCLC and non-SCLC.

Antibiotics, Antineoplastic↗

Effects of non-collagenous proteins on the formation of apatite in calcium beta-glycerophosphate solutions.

The effects of the non-collagenous proteins; osteonectin, bone Gla protein and dentine phosphoprotein, on the formation of apatite were studied in calcium beta-glycerophosphate solutions containing catalytic amounts of alkaline phosphatase under physiological conditions. In the system used, calcium phosphate precipitates de novo at levels of supersaturation precisely determined through the enzymatic hydrolysis of beta-glycerophosphate. At 1.7 mM of calcium beta-glycerophosphate, calcium phosphate precipitated when inorganic phosphate accumulated to about 1.4 mM. In the presence of the proteins, however, a greater accumulation of inorganic phosphate was needed for calcium phosphate to precipitate, suggesting that a higher degree of supersaturation, though still a slight undersaturation with respect to dicalcium phosphate dihydrate, is required for calcium phosphate to precipitate in the presence of the proteins. At the same protein (micrograms/ml) concentration, dentine phosphoprotein was approximately four times as effective as bone Gla protein, which was about twice as effective as osteonectin in delaying precipitation. The proteins also retarded subsequent crystal growth, with apatite formed in the presence of the more inhibitory proteins having the smallest crystals, especially in width.

Alkaline Phosphatase↗

Sustained damage to energy metabolism of brain regions after microsphere embolism in rats.

BACKGROUND AND PURPOSE: Information on sustained damage to cerebral function and metabolism after cerebral ischemia is useful for prophylaxis and therapeutics of cerebral infarction. The purpose of the present study was to induce sustained damage to brain regions after cerebral ischemia in experimental animals. For this purpose, we examined animal behavior and cerebral energy metabolism following microsphere embolism in rats. METHODS: We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 110 rats and determined the time course of changes in the rats' behavior and the energy metabolism of the cortex, striatum, and hippocampus of both hemispheres. We injected the same volume of vehicle, without microspheres, into 28 sham-operated rats; there were 14 nonoperated control rats. RESULTS: Peak increase in lactate content and decrease in adenosine triphosphate and creatine phosphate of these brain regions of the right hemisphere were seen on the first day after microsphere embolism, whereas peak increases in glucose and glycogen contents of these regions were observed on the third day. Most of the metabolic alterations in all these regions continued for up to 28 days after operation, although they recovered toward control levels with time after the operation. The extent and trend of metabolite changes of the right hemisphere after microsphere embolism were similar in the three brain regions. In the left hemisphere, similar metabolic changes were observed, but to a lesser degree. The time course of changes in behavioral scores following microsphere embolism revealed marked stroke-like symptoms on the first day and relatively rapid disappearance of the symptoms with time after embolism. CONCLUSIONS: Microsphere embolism is capable of inducing widespread, sustained damage to energy metabolism of brain regions.

Adenosine Triphosphate↗

[Treatment of small cell lung cancer in the elderly: the progress and limitation of chemotherapy].

In order to assess the progress and limitation of chemotherapy in the treatment of small cell lung cancer in the elderly, we analyzed 218 patients who had entered into protocol studies between 1982 and 1990. Among those, there were 101 elderly patients (age of greater than or equal to 66 years) and 117 non-elderly patients (age of less than or equal to 65 years). Response to chemotherapy with or without chest irradiation was almost comparable for the elderly and the non-elderly; complete response rate was 52% for limited disease (LD) and 33% for extensive disease (ED) in the elderly, and it was 68% for LD and 23% for ED in the non-elderly. Survival figures of the two groups were quite similar: The median survival time was 12.6 months for the elderly and 14.5 months for the non-elderly, and the 3-year survival rate was 14% for both groups. An improvement of patient survival was observed along with the chronology of the protocols, i.e., with a escalation of dose intensity. Of interest, the improvement was rather evident in the elderly than in the non-elderly. Hematologic toxicity was considerable more frequent and severe in the elderly than in the non-elderly with non-significant statistics. The incidense of fever episodes while neutropenic was significantly more frequent in the elderly. Non-hematologic toxicity was almost comparable for the two groups, with a exception that the elderly showed a trend being predisposed to renal toxicity. In conclusion, such elderly patients as eligible for entry into a protocol study can benefit from intensive treatment as equally as non-elderly patients can.

Antineoplastic Combined Chemotherapy Protocols↗

[Serum neuron specific enolase (NSE) levels in patients with non small cell lung cancer].

Serum NSE levels were measured in 126 patients with previously untreated NSCLC. The NSE level was greater than 10 ng/ml in 29 patients (23.0%) and this was considered to be positive. Elevation of serum NSE levels correlated closely with clinical stage except stage I and II. The effect of chemotherapy was evaluated in 74 cases included 22 NSE-positive cases. The response rate was 50% in positive cases and 34.6% in negative cases. However, the median duration of response in positive cases (2.2 months) was significantly shorter than that in negative cases (6.6 months). The median survival time of 6.0 months in positive cases was brief compared with 9.6 months in negative cases. These results indicate that elevation of serum NSE level in patients with NSCLC may be a marker of poor prognosis.

Adenocarcinoma↗

[A case of locally advanced esophageal cancer effectively treated with concurrent chemotherapy and radiotherapy].

A case of a 69-year-old man with locally advanced esophageal cancer was reported. The patient received five courses of chemotherapy consisting of cisplatin (30 mg i.v. days 1-5), 5-fluorouracil (500 mg i.v. days 1-5) and bleomycin (5 mg i.m. days 1-5) every four weeks with a split course irradiation at a dose of 50 Gy, which was concurrently given at the second, third and fourth course of the chemotherapy. Treatment was effectively carried out without severe toxicities. The patient achieved a histologically-confirmed complete remission after completion of the treatment. The patient is disease-free and fully active 28 months after the beginning of chemotherapy. The treatment modality appears to be useful for advanced esophageal cancer.

Aged↗

[Pulmonary reaction after protamine reversal of heparin in goats and rabbits].

Protamine reversal of heparin is often associated with severe hemodynamic side-effects, including pulmonary hypertension in cardiovascular surgery. However, the precise mechanism of this transient pulmonary hypertension is not clear. Recently, it was reported that pulmonary intravascular macrophages (PIM) react avidly with and phagocytize various foreign particles (liposome, latex, red cells). Sheep, goat and pig have a large population of PIM, but rabbit, rat and human have few. To investigate whether the pulmonary reaction after protamine reversal is related to PIM, we compared the pulmonary reaction after protamine reversal between goats and rabbits. We also studied it in patients for cardiac surgery. Protamine sulphate (2 mg.kg-1) was injected in 2.5 min into femoral artery at five min after heparin sodium (200 IU.kg-1) injection in goats and rabbits. Mean pulmonary arterial and peak airway pressures increased significantly after protamine reversal in goat. On the other hand, in rabbit and human, mean pulmonary arterial and peak airway pressures showed no significant changes. Goat was far more sensitive to protamine reversal than rabbit and human. We conclude that PIM may be the main cause of the pulmonary reaction after protamine reversal.

Animals↗

Beneficial effects of naftidrofuryl oxalate on brain regional energy metabolism after microsphere-induced cerebral embolism.

The present study was undertaken to elucidate the possible therapeutic effects of naftidrofuryl on energy metabolism of brain regions impaired for extended periods by microsphere embolism. Nine hundred microspheres (48 microns in diameter) were injected into the right internal carotid artery of rats, and changes in their behavior and energy metabolism of the cortex, striatum and hippocampus of both hemispheres were determined with and without naftidrofuryl treatment. Microsphere embolism induced increases in lactate, glucose and glycogen contents and decreases in ATP and creatine phosphate of these brain regions of the right hemisphere for up to 28 days after the operation, suggesting long-lasting cerebral ischemia or sustained damage to energy metabolism. These changes were gradually reversed with time after the operation. Microsphere-injected rats were treated twice a day with 15 mg/kg naftidrofuryl, and their behavioral and metabolic protection were determined on the 3rd, 5th and 28th days after the operation. Treatment of embolized animals with naftidrofuryl improved these variables appreciably on the 3rd and 28th days, but little on the 5th day. The improvement on the 3rd day was more evident in all brain regions monitored than that on the 28th day. The results suggest that naftidrofuryl exerts beneficial effects on the energy metabolism of brains damaged by microsphere embolism, the mechanism of which may be due to protection against the development of embolism-induced derangement.

Adenosine Triphosphate↗

[Surgery versus detachable balloon embolization of pulmonary arteriovenous fistula: clinical experience].

We experienced 4 pulmonary arteriovenous fistula cases 2 of which were treated surgically and 2 were subjected to detachable balloon embolization therapy. Favorable results were obtained in the detachable balloon embolization therapy. In treating pulmonary arteriovenous fistula, if the lesion is in the position where the catheter can be reached easily and is composed of a single afferent-efferent vessel unit, it would be advisable to perform the embolization therapy first, and then to apply an operative procedure preserving lung tissue as much as possible.

Adult↗

[Prophylactic effect of ulinastatin on cisplatin-induced renal disorders in lung cancer patients].

In order to determine whether ulinastatin (US) can prevent renal dysfunction due to cisplatin (CDDP) or not, we comparatively studied serum BUN, serum creatinine (Cr), creatinine clearance (Ccr), urine gamma-glutamyl transpeptidase (gamma-GTP) excretion, urine N-acetyl-beta-D-glucosaminidase (NAG) excretion, fractional excretion of Na (FENa) and urine beta 2-microglobulin excretion between one group of 10 patients receiving single treatment with CDDP and another group of 10 patients receiving combination treatment with CDDP+US, in 20 subjects with primary lung cancer. In the US combination treatment group, urine gamma-GTP excretion, urine NAG excretion, and FENa elevation were significantly inhibited. Urine beta 2-microglobulin excretion was inhibited. In summary, US was considered to have a preventive effect against renal toxicity due to CDDP.

Aged↗