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Biomedical subjects

K Ishida

Publications and source records attributed to K Ishida.

At least 397 records · Page 22Linked to original sources

[Experimental study of biochemical modulation of 5-fluorouracil with l-leucovorin against human esophageal cancer].

Potentiation of cytotoxic effects of 5-fluorouracil (5-FU) were investigated by simultaneous or sequential combination of l-leucovorin (LV) against human esophageal cancer cell line (TE-1, TE-2) and 23 human clinical cancer samples in vitro. LV enhanced the cytotoxic effects of 5-FU on human esophageal cancer cell line as a dose dependent manner, and increased the cytotoxic effect of 5-FU about 1.5-fold with 10 microM and about 2-fold with 100 microM. The incubation time did not affect the effects. The potentiation with LV was also demonstrated against human clinical cancer samples, and the cytotoxic effects of 5-FU increased 7.6% in esophageal cancer, 20.9% in gastric cancer and 25.5% in colorectal cancer. As a result, the potentiating effects of LV against 5-FU seemed to be limited on human esophageal cancer.

Colonic Neoplasms↗

[A case of pulmonary alveolar proteinosis with invasion of macrophages in alveolar interstitial region].

A 24-year-old woman was admitted to our hospital on November 2, 1989 for investigation and treatment of abnormal shadows detected in her routine chest radiograph on July 19, 1989. The chest X-ray film on admission showed diffuse infiltrative shadows in the peripheral regions of the bilateral middle and lower lung fields. In addition centrilobular shadows in the subpleural regions with increases irregular densities were found on chest CT. We therefore suspected pulmonary alveolar proteinosis. Bronchoalveolar lavage from the right middle bronchus and transbronchial lung biopsy of the right upper and lower lobes were performed. Electron microscopic examination of a specimen of bronchoalveolar lavage fluid revealed many multilamellar bodies, characteristic of pulmonary alveolar proteinosis. In addition, proteinaceous material containing multilamellar bodies was observed within the alveolar lumina. We diagnosed this case as pulmonary alveolar proteinosis. Electron microscopy also revealed many macrophages in the alveolar walls, some of which contained a few or numerous multilamellar bodies within the secondary lysosomes. We treated this patient with oral and inhaled Ambroxol, with improvement of her clinical condition.

Adult↗

Phase II evaluation of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japanese Esophageal Oncology Group Trial.

Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects.

Adult↗

[Heat conservation during abdominal surgery].

Intraoperative hypothermia is a major problem in anesthetic management. We compared the heat conserving effect of a forced air warming system (Bair Hugger, Augustine Medical Inc.) with that of a warming blanket. Sixteen patients undergoing abdominal surgery were studied. Patients were anesthetized with nitrous oxide and oxygen combined with epidural anesthesia. Patients received tympanic, rectal, bladder and core temperature monitorings. Patients were divided randomly to Bair Hugger group (BH, n = 8) or warming blanket group (WB, n = 8). Temperature were measured every one hour over three hours. The BH group showed significantly higher temperatures than WB group. Bair Hugger system is an efficient way to maintain intraoperative body temperature.

Abdomen↗

[The effect of ageing on airway responsiveness].

In order to evaluate the significance of airway responsiveness in the elderly: 1. Airway responsiveness in the healthy elderly was evaluated and compared with that of the healthy young adults. Methacholine dose response curve was constructed by measuring total respiratory resistance using the modified partial airway occlusion method which provides a simple, convenient, and non-invasive assessment of the resistance of the total respiratory system. Although the responders were fewer and the average threshold values were higher in the elderly, there was no significant differences in the methacholine dose response curve. 2. In vivo and in vitro methacholine dose response relationship was measured in the old guinea pigs (20 to 25 months old) and was compared with that of the young adult guinea pigs. Although no significant differences in the threshold values was observed, the in vivo airway response to the methacholine dose of 1 mg/ml was significantly lower in the old guinea pigs than in the young. The old guinea pig showed small but significant right side shift in the in vitro methacholine dose response relationship. 3. The intra-tracheal instillation of hydrochloric acid to the guinea pig was used as an animal model of aspiration pneumonia. The airway responsiveness was evaluated before and after the instillation. The acid instillation caused the acute and transient bronchoconstriction and the airway responsiveness was markedly increased one hour after the instillation. We conclude that the airway responsiveness may be unchanged or somewhat decreased in the elderly and that the increased airway responsiveness may play a role in the phathologic state such as an aspiration pneumonia.

Adult↗

Immunoelectron microscopic demonstration of estrogen receptors in osteogenic cells of Japanese quail.

The localization of estrogen receptors (ERs) in osteogenic cells was immunoelectron microscopically examined in the femurs of female and estrogen-treated male Japanese quail. An electron dense reaction product showing ER localization was observed in the nuclei of osteoblasts and immature osteocytes in the medullary bone of the female quail. However, reaction product was not seen in the osteoclasts. On the endosteal bone surface of male quail, nuclear reaction product was detected in bone lining cells. After 24 h of estrogen treatment, reaction product was observed in the nuclei of preosteoblasts on the endosteal bone surface. After 48 h, the medullary bone partly appeared along the endosteal surface. Nuclear reaction product was seen in osteoblasts on the medullary bone surface.

Animals↗

The usefulness of cyclophosphamide pretreatment for subrenal capsule assay against human esophageal cancer.

In order to suppress the host immune reaction in subrenal capsule assay (SRCA) using normal immunocompetent mice, the effects of cyclophosphamide (CPM) pretreatment were compared to those obtained after cyclosporine A (CSA) treatment. CPM and CSA suppressed the host reaction until day 6 and day 12, respectively, however, the histological evaluation of the tumors on day 6 revealed no differences between the two groups. The cytotoxicity of CPM in mouse serum against P388 cells was measured to evaluate the residual activity of CPM against the implanted tumor. No cytotoxicity was observed in the serum 36 hours after the CPM injection. In the histological analysis of clinical samples, inflammatory infiltration was observed in only 4 of 25 samples and tumor cell preservation recognized in 27 of 28 samples. A persistence of tumor cells was recognized in the samples rich in tumor cells. Adequate growth of the tumor in the control groups was obtained from 30 of 33 tumors (91 per cent), and the response rates of this assay were comparable to those of prior clinical experiences on each of these drugs. These results indicated the feasibility of SRCA with CPM pretreatment as a predictive test of chemotherapeutic agents for esophageal cancer.

Animals↗

Estrogen target cells during the early stage of medullary bone osteogenesis: immunohistochemical detection of estrogen receptors in osteogenic cells of estrogen-treated male Japanese quail.

The localization of estrogen receptors (ER) in osteogenic cells during the early stage of medullary bone osteogenesis was studied immunohistochemically in the femurs of estrogen-treated male Japanese quail. Alkaline phosphatase (ALP) activity was used as a marker for osteogenic cells. ER immunostaining was observed in the nuclei of weak ALP-positive bone lining cells on the endosteal bone surface of nontreated birds. After 24 hours of estrogen treatment, nuclear immunostaining was detected in ALP-positive preosteoblasts on the endosteal bone surface. After 48 hours, the medullary bone appeared to some degree along the endosteal surface. ER immunostaining was observed in the nuclei of ALP-positive osteoblasts on the medullary bone surface. This study demonstrates that ER are present in osteogenic cells, and suggests that estrogen directly acts on medullary bone osteogenesis.

Alkaline Phosphatase↗

Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations.

To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment.

Aged↗

Intravenous bolus of prednisolone decreases 15-hydroxyeicosatetraenoic acid formation in the rat model of acid aspiration.

BACKGROUND AND METHODS: To test the hypothesis that the effect of steroids on hydrochloric acid aspiration may be involved in the metabolism of eicosanoids, we investigated the effects of an iv bolus of prednisolone on the metabolism of 15-hydroxyeicosatetraenoic acid and 11-dehydrothromboxane B2 (11-dehydro-TxB2) in the rat model of acid aspiration. Wistar rats were randomly selected for three groups and treated with either a) an iv bolus of saline after intratracheal injection of saline (control group), b) an iv bolus of saline after intratracheal injection of acid (acid-saline group), or c) an iv bolus of prednisolone after intratracheal injection of acid (acid-prednisolone group). The concentrations of 15-hydroxyeicosatetraenoic acid and 11-dehydro-TxB2 in bronchoalveolar lavage fluid were measured by radioimmunoassay. RESULTS: The concentration of 15-hydroxyeicosatetraenoic acid in bronchoalveolar lavage fluid of either acid-saline group (804 +/- 129 pg/mL) or acid-prednisolone group (748 +/- 112 pg/mL) was significantly greater than that of the control group (143 +/- 27 pg/mL, p less than .01) 1 hr after the administration. The iv bolus of prednisolone caused a significant decrease in 15-hydroxyeicosatetraenoic acid (acid-saline group 1027 +/- 43 pg/mL; acid-prednisolone group 514 +/- 62 pg/mL; p less than .01) and cell counts of bronchoalveolar lavage fluid 48 hrs after intratracheal injection of acid, while there was no significant change in 11-dehydro-TxB2. CONCLUSION: These findings suggest that corticosteroid administration may contribute to the inhibition of the inflammatory process of lungs after acid aspiration by decreasing the release of 15-hydroxyeicosatetraenoic acid in the distal lung unit.

Animals↗

The induction of bone by an osteogenic protein and the conduction of bone by porous hydroxyapatite: a laboratory study in the rabbit.

The influence of the addition of an osteoinductive protein, capable of inducing extraskeletal ossification, on bone ingrowth into coralline porous hydroxyapatite was evaluated in the rabbit using a calvarium onlay model. Twenty-three rabbits received hydroxyapatite implants (10 x 10 x 2 mm) prepared with and without osteoinductive protein. These were implanted on the frontal bone and secured by wire fixation after 0.25 mm of the cortical surface was abraded. The implants were harvested at 3 and 4 months and analyzed for percentage of bone ingrowth by histologic examination of decalcified H&E sections and by scanning electron microscope backscatter image analysis. The osteoinductive protein-treated implants demonstrated significantly greater amounts of bone ingrowth at both 3 (52.0 versus 10.3 percent; p less than 0.001) and 4 months (66.1 versus 39.2 percent; p less than 0.005) than the untreated implants. The type of bone found in all osteoinductive protein-treated implants was predominantly lamellar. Untreated implants contained mostly woven bone at 3 months, with increasing amounts of lamellar bone appearing at 4 months. These results suggest that the combination of a bone-inducing protein and a suitable osteoconductive matrix may provide an alternative to bone grafting.

Animals↗

Nedocromil sodium inhibits airway hyperresponsiveness and eosinophilic infiltration induced by repeated antigen challenge in guinea-pigs.

1. Repeated exposure to ovalbumin aerosol produced significant increases in epithelial eosinophils of airways of all sizes and produced increased pulmonary resistance (RL) to inhaled acetylcholine (ACh) in guinea-pigs. 2. Nedocromil sodium 10 mg ml-1, by nebulization prior to each ovalbumin (OA) challenge inhibited both the airway eosinophilia and hyperresponsiveness to ACh. 3. Nedocromil sodium pretreatment (10 mg ml-1 by nebulization) 10 min prior to OA completely inhibited the acute bronchoconstrictor response to OA. 4. Our findings suggest that nedocromil sodium inhibits airway hyperresponsiveness by inhibiting eosinophilic infiltration, or by simultaneously inhibiting mechanisms involved in both processes.

Acetylcholine↗

Smooth muscle mechanics: implications for airway hyperresponsiveness.

Human bronchial smooth muscle preparations from 10 freshly dissected pneumonectomy samples were evaluated for their mechanical characteristics and compared with results obtained for similar samples obtained from porcine trachea. Length-tension relationships of in vitro smooth muscle were evaluated for passive stretching as well as active isometric force generation and isotonic shortening using electrical field stimulation. At the length (Lmax) producing maximal force (Pmax) resting tension was very high (60.0 +/- 8.8% Pmax) compared with porcine trachealis (5.2 +/- 2.3% Pmax). Maximum shortening was 25.0 +/- 9.0% at a length of 75% Lmax with suboptimal shortening occurring at Lmax (12.0 +/- 3.4%) for the human bronchus, whereas optimal shortening of porcine trachealis (71.4 +/- 3.6%) occurred at Lmax. Morphometric evaluation revealed threefold less muscle per cross-sectional area of tissue for human (8.7 +/- 1.5%) versus porcine (24.8 +/- 1.9%) preparations. We conclude that the high passive tension and the decreased maximum shortening are produced by a relatively large load which must be overcome for the muscle to shorten, presumably provided by the greater connective tissue elastic component present in the airway. We suggest that a decrease in airway wall elastance would increase smooth muscle shortening, thereby leading to excessive responses to contractile agonists as seen in vivo in asthma.

Animals↗

Efficacy of oral administration of ofloxacin in lower respiratory tract infections in aged patients with chronic lung disease.

The efficacy of ofloxacin for the treatment of lower respiratory tract infection was evaluated in aged patients with chronic lung disease. Results are the following: improvement of leukocytosis and arterial oxygen tension was observed; peripheral blood cell analysis showed a decrease in natural killer cell counts and in helper/suppressor T cell ratio; superoxide production by peripheral blood white cells was decreased after treatment; interleukin-2 production was rather increased. We concluded that improvement in the immunological parameters indicated the efficacy of ofloxacin for lower respiratory tract infection in aged patients with chronic lung disease.

Administration, Oral↗

Effect of phosphorylated organic compound on the adsorption of bovine serum albumin by hydroxyapatite.

The amount of adsorption of bovine serum albumin (BSA) by hydroxyapatite (HAP) increased with a concentration of CaCl2 due to the bridging effect of Ca2+ between adsorbate BSA and adsorbent HAP. On the other hand, it decreased remarkably with a concentration of K2HPO4. This was explained in terms of the effects of ionic strength and competitive adsorption between inorganic phosphate anion (Pi) and BSA, because BSA is in negatively charged over the examined pHs. A similar effect was observed in the presence of phosphorylated compounds such as phosphoserine, phytate, and phosphorylated polyvinylalcohol. The inhibiting effect of these compounds was stronger than that of their mother compounds (serine, inositol, and polyvinylalcohol). This result shows that phosphate groups bound to the mother compounds interfere with the adsorption of BSA by HAP in the same manner that Pi does. Although the adsorption of BSA was almost irreversible with respect to dilution with water, desorption was performed when these organic phosphorylated compounds were added after the accomplishment of the adsorption of BSA. However, the effective concentration of the phosphorylated compounds for the desorption of BSA was fairly higher than that for the competitive inhibition against the BSA adsorption.

Absorption↗

[Electron microscopic study on inner ear barotrauma: with emphasis on the cochlear damage].

In order to investigate inner ear barotrauma, guinea pigs were subjected to rapid decompression between 2 absolute pressure (ATA) and 1 ATA in a chamber. After pressure loading and observation for absence of Preyer's reflex, they were sacrificed immediately, 1 day, 1 week and 1 month later, respectively. Then, morphological changes of the organ of Corti and stria vascularis were studied under TEM and SEM. The immediate features noted were fracture of stereocilia with minimal intracellular changes. One day later, there was marked degeneration of outer hair cells and expansion of supporting cells. The damage to stereocilia clearly preceded morphological alterations within hair cell bodies and cannot be interpreted as arising secondary to hair cell degeneration. Most of outer hair cells eventually disappeared and were replaced by supporting cells. Inner hair cells degenerated slowly; 1 month later, some of them remained almost intact, despite disappearance of stereocilia. The continuity of reticular lamina was maintained not only immediately but also through the period of hair cell degeneration, thus preventing any leakage of endolymph into the organ of Corti. There was reversible dendritic swelling of inner hair cells immediately following the trauma. No changes of stria vascularis were observed over passage of time. The mechanism of hair cell damage due to inner ear barotrauma is presumed to be a deformity of the organ of Corti caused by pressure discrepancy between perilymph and endolymph resulting in an injury to stereocilia.

Animals↗

Corneal endothelial cell damage in penetrating keratoplasty.

Fifty-eight corneal grafts were examined by specular microscopy to determine the corneal endothelial cell damage following penetrating keratoplasty. The average postoperative follow-up period was 10.1 months. The cell density decreased continuously during the observation period, and the endothelial cell loss of the central area of the cornea in all the cases averaged 10.4% at two weeks after the surgery, 16.0% at one month, 33.0% at three months, 39.4% at six months, and 48.2% at one year. However, the cell loss in the keratoconus group averaged -1.9, 1.2, 9.9, 30.6 and 33.4% for the corresponding postoperative periods. The cell loss in the bullous keratopathy eyes showed higher values compared to those in the keratoconus and the corneal leukoma eyes. It was concluded that cell loss in penetrating keratoplasty during the first postoperative year depends on the host diseases.

Adolescent↗