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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 523 records · Page 29Linked to original sources
PubMed1995

Tubulointerstitial injury induced in rats by a monoclonal antibody that inhibits function of a membrane inhibitor of complement.

The kidney widely expresses membrane-associated complement regulatory proteins (membrane inhibitors of complement). The aim of this work was to evaluate the roles of these molecules in rat kidneys in vivo. To suppress functions of rat membrane inhibitors of complement, two mAbs, 512 and 6D1, were used. 5I2 and 6D1 inhibit functions of membrane inhibitors of complement at C3 level (rat Crry/p65) and C8/9 level (rat CD59), respectively. F(ab')2 fragment of 5I2 or 6D1 was perfused in the left kidneys, and perfusate was discarded from the renal vein. After perfusion, the left kidneys were connected to systemic circulation. In rats perfused with 5I2, mouse IgG was found in glomeruli, peritubular capillaries, vascular bundles, and tubules 15 min after recirculation. Binding of C3 and C5b-9 was evident in these areas. 1 d after perfusion with 5I2, cast formation, dilatation of tubular lumen, and tubular cell degeneration were observed. At day 4 through day 7, significant mononuclear cell infiltration and proximal tubule damage were observed. These changes were completely prevented by complement depletion. Rats perfused with 6D1 showed the binding of mouse IgG in the similar areas as 5I2, but C3 or C5b-9 deposition was not observed. Rats perfused with 6D1 or vehicle only did not show any pathology in the left kidneys. These results suggest that rat Crry/p65 plays protective roles against spontaneously occurring indiscriminate attack to tubulointerstitial tissues by autologous complement and that rat Crry/p65 is one of the important factors to maintain normal integrity of the kidney in rats.

Animals↗
PubMed1995

Ultrastructural and histomorphometric evaluations of gallium nitrate on bone in nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy.

Gallium is a group IIIa transition metal that lowers serum calcium by an unknown mechanism and has been utilized in the treatment of cancer-associated hypercalcemia. The purpose of this study was to histomorphometrically investigate the ultrastructural effects of gallium nitrate on osteoclasts and osteoblasts in trabecular bone of normal nude mice and nude mice with humoral hypercalcemia of malignancy. Two groups of normal nude mice (n = 7 and n = 8, respectively) and two groups of hypercalcemic nude mice (n = 9) bearing a serially transplantable canine adenocarcinoma (CAC-8) were treated with vehicle or gallium nitrate. Osteoclasts were hypertrophied in vehicle-treated tumor-bearing nude mice as compared with vehicle-treated nontumor-bearing nude mice. Osteoclasts from tumor-bearing nude mice treated with gallium nitrate were significantly decreased in size and had fewer intracytoplasmic vesicles as compared with osteoclasts from vehicle-treated tumor-bearing nude mice. Degenerate osteoclasts, characterized by pyknotic nuclei and increased cytoplasmic vacuolation, were observed in both groups of gallium-treated nude mice. Osteoblasts from vehicle-treated tumor-bearing nude mice were hypertrophied and had extensive lamellar arrays of rough endoplasmic reticulum as compared with osteoblasts from vehicle-treated nontumor-bearing nude mice. Osteoblasts in gallium-treated nude mice (tumor-bearing and nontumor-bearing) were small and flattened with poorly developed cytoplasmic organelles. This investigation demonstrated that osteoclasts and osteoblasts in nude mice treated with gallium nitrate had ultrastructural evidence of decreased metabolic and functional activity. The results suggest that gallium nitrate lowers serum calcium by inhibiting osteoclastic bone resorption.

Adenocarcinoma↗
PubMed1995

Immunohistochemical demonstration of parathyroid hormone-related protein in thyroid gland of sheep.

Thyroid and parathyroid glands from normal adult sheep and sheep with vitamin D3-induced hypercalcemia were evaluated immunohistochemically for the presence of parathyroid hormone-related protein (PTHrP) and calcitonin (CT). Thyroid follicular cells, C-cells, and parathyroid chief cells stained moderately to strongly positive for PTHrP in both groups of sheep. C-cells were identified as cells positive for cytoplasmic staining of CT. Staining of C-cells for calcitonin in hypercalcemic sheep was diminished in intensity. The data demonstrated that PTHrP is present in the sheep thyroid and parathyroid glands. PTHrP may function as a local paracrine factor in these organs, but its staining intensity was not affected by the induction of hypercalcemia.

Animals↗
PubMed1995

Noninvasive measurement of cerebral blood flow and glucose metabolic rate in the rat with high-resolution animal positron emission tomography (PET): a novel in vivo approach for assessing drug action in the brains of small animals.

The cerebral metabolic rate of glucose (CMRglc) and cerebral blood flow (CBF) in rats were estimated noninvasively with a high-resolution animal positron emission tomography (PET) system that we recently developed. Qualifications of CMRglc and CBF were attempted with radiotracers, 18F-2-fluoro-2-deoxyglucose and 15O-water, respectively. From the data obtained with PET, the CMRglc and CBF values under pretreatment conditions were respectively calculated as 51 +/- 14 mumol/min/100 g and 61 +/- 7 ml/min/100 g under pentobarbital-anesthesia. These values were in close agreement with published data obtained with the autoradiographic technique. Moreover, an increase of 69% (mean) in CBF was detected after i.v. acetazolamide administration. The results indicate that this high-resolution animal PET scanner holds great potential for the assessment of drug-related metabolic and circulatory effects in intact and experimental animals.

Acetazolamide↗
PubMed1995

Activation of homologous complement via the alternative complement pathway by quail cells transformed by Rous sarcoma virus.

After incubation of the cells with fresh quail serum, deposition of the third component of complement (C3) was demonstrated on the cell surface of various quail cell lines transformed by Rous sarcoma virus (RSV) as well as on that of primary quail embryo (QE) cells transformed by RSV. The C3 deposition occurred irrespective of virus production. On the other hand, the C-3 deposition was not observed on two quail cell lines transformed by a chemical carcinogen, QE cells infected with avian leukosis virus or normal QE cells. Moreover, QE cells infected with a temperature-sensitive mutant of RSV activated the complement at 37 degrees C but not at 41 degrees C. Since the progeny virus was generated even at 41 degrees C, viral molecules on the cell surface may not play an essential role for the activation. The activation of complement was blocked by EDTA but not by EGTA-Mg++. Therefore, the complement activation on the transformed cells appears to be mediated via the alternative complement pathway (ACP). Similar results were obtained with the complement consumption test; the residual cytolytic activity of fresh quail serum via ACP was markedly reduced by pre-incubation of the serum with transformed cells.

Animals↗
PubMed1995

Biodegradable microspheres in drug delivery.

General aspects of biodegradable microspheres prepared from natural and synthesized polymers used in drug delivery systems are reviewed first from various viewpoints: characteristics of biodegradable polymers (physicochemical properties, bioerosion mechanism, biocompatibility), preparation method for the microspheres, drug release from parenteral products and briefly nonparenteral products. The relationship between release pattern and pharmacological activity of therapeutic peptides and proteins and rational controlled release design are also discussed. In the latter half, successful sustained release depot formulations of peptides, leuprorelin acetate, and thyrotropin-releasing hormone (TRH), utilizing poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA) microspheres are reviewed with respect to preparation, drug release, biocompatibility, pharmacological effects, and results of clinical studies. Thereafter, studies on antitumor therapy by chemoembolization using PLGA microspheres containing an angiogenesis inhibitor (TNP-470) are described as an example of targeted drug delivery with biodegradable microspheres.

Animals↗
PubMed1995

The role of a complement regulatory protein in rat mesangial glomerulonephritis.

The host cells are protected from the indiscriminate attack of homologous complement by the membrane-associated complement regulatory proteins. A mouse monoclonal antibody (mAb) 512 (immunoglobulin G1 subclass) has recently been described that recognizes and inhibits the function of a rat complement regulatory protein, a rat homologue of mouse Crry/p65. The aim of this work is to assess the role of a complement regulatory protein (512Ag) recognized by mAb 512 in the complement-dependent glomerular injury induced by mAb OX7 against rat Thy-1.1. For the induction of mesangial injury, the left kidney of a rat was perfused with a combination of OX7 and 512 and the perfusate was discarded from the renal vein (Group I). After the renal artery and vein were restored, the left kidney was connected to the systemic circulation. Rats were euthanized 3 h, 2 days, and 14 days later. Rats perfused either with OX7 (Group II) or with 512 (Group III) or with vehicle only (Group IV) were used as controls. At 3 h, rats of Group I showed more prominent cellular infiltration and mesangial lysis and more C3 deposition in the glomeruli than rats of Group II. Rats of Groups III and IV showed no significant changes. At Day 2, there was still significant mesangial lysis and leukocyte infiltration in Group I rats, whereas rats in other groups showed an almost normal appearance. Glomerular injury in Group I rats returned to normal by Day 14.

Animals↗
PubMed1995

Evaluation of jawbone calcification in osteopetrotic (op/op) mice using computed tomography.

The study was conducted to evaluate the degree of calcification in the jawbones of 3 pairs of 4-week-old male op/op mice and littermates using computed tomography (CT) numbers. The mean CT numbers for op/op mice (n = 3) were 251.3 HU (range, 226 to 278) in the maxillary bone and 353.7 HU (range, 320 to 398) in the mandibular bone. The mean CT numbers for littermates were 336.7 HU (range, 324 to 350) and 596.6 HU (range, 580 to 604), respectively. The CT numbers of littermates were higher than in op/op mice for both maxillary and mandibular bones. These results indicated that the degree of bony calcification in littermates was higher than that in 4-week-old op/op mice in both the maxillary and mandibular bones. CT is able to demonstrate the degree of bony calcification in the jawbones of op/op mice using CT numbers, and it is suggested that CT is an extremely effective tool for examining the conditions of bone in vivo. This study also shows that op/op mice are useful for investigation of bone calcification or maturation.

Aging↗
PubMed1995

Malignant lymphomas in elderly patients. Four cases studied by immunohistochemistry and electron microscopy.

Four cases of malignant lymphomas in elderly patients are reported, along with the results of immunohistochemistry and electron microscopy. Light microscopy revealed that three cases consisted of diffuse neoplastic proliferation of medium-sized lymphocytes (diffuse) lymphoma, medium-sized cell type), while the remaining one showed follicular neoplastic proliferation of medium-sized lymphocytes (follicular lymphoma, medium-sized cell type). Immunohistochemical analysis revealed that most of the tumor cells in three cases had weak to moderate immunoreactivity for L26 and weak reactivity for IgM. Most of the tumor cells in one case showed weak reactivity for IgG. Some tumor cells in three cases had weak reactivity for vimentin, and some in two cases showed weak positivity for KP1 and PG-M1. Ultrastructural examination revealed that tumor cells in all four cases contained large nuclei with clear nucleoli and scant cytoplasm. Most of the intercellular junctions were smooth, but in one case, some areas exhibited desmosomes.

Aged↗
PubMed1995

Effect of nonpeptide vasopressin receptor antagonists on developing, and established DOCA-salt hypertension in rats.

Efficacy of orally available, selective vasopressin V1 and V2 receptor antagonists on the developing and established stage of DOCA-salt hypertension was investigated. Twenty-nine Wistar rats were heminephrectomized, and administered DOCA (50 mg/kg; intraperitoneally twice a week) and salt (5% NaCl diet) from week 0 to the end of study. Group 1 rats were served as control. Group 2 and 5 rats were given a V1 antagonist, and groups 3 and 6 rats were given a V2 antagonist, while groups 4 and 7 rats received both V1 and V2 antagonists. Each drug was started to groups 2, 3 and 4 at week 0, and to groups 5, 6 and 7 at week 4. Significant amelioration of the increase in blood pressure was observed in groups 3 and 4 at week 10, and a reduction in blood pressure occurred in groups 6 and 7 at week 10. Otherwise, a V1 antagonist alone slightly attenuated blood pressure rise in the group 2 without significance, and failed to lower blood pressure of the group 5 during the study. These results suggest that both V1 and V2 agonisms are involved in an increase in blood pressure at the developing stage of DOCA-salt hypertension, and that V2 agonism, but not V1 plays a major role in the maintenance of high blood pressure at the established stage.

Administration, Oral↗
PubMed1995

[Nephron sparing surgery of patients with renal cell carcinoma in a solitary kidney or bilateral renal cell carcinoma].

PURPOSE: The objective of this study is to evaluate the efficacy of nephron sparing surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors. PATIENTS AND METHODS: From 1982 to 1994, a total of 12 patients with a solitary kidney or bilateral tumors underwent nephron sparing surgery. The survival and complications were examined. RESULTS: The patients were 11 males and 1 female. Three patients were in stage 1, 6 in stage 2, 2 in stage 3, and 1 in stage 4, and the mean tumor size was 3.4 cm (0.8-6.5). The complications were post-operative bleeding in one patient and slight transient renal dysfunction which didn't require hemodialysis in 3 patients. The local recurrence was observed in 1 patient (8.3%), metastasis in 3 (25%), no evidence of disease in 8 (66.7%), alive with cancer in 1 (8.3%), death due to cancer in 2 (16.7%), death due to other disease in 1 (8.3%), and the 5 year survival of all patients was 62.5%, that was almost the same as the result of 141 renal cell carcinoma patients treated with nephrectomy in our hospital. The disease free survival rate of the patients in stage 1 and 2 seems to be higher than in stage 3 and 4 with no significant difference (p = 0.0956). CONCLUSION: These results suggest that nephron sparing surgery for renal cell carcinoma in patients with a solitary kidney or bilateral tumors is a useful therapy.

Aged↗
PubMed1995

Apoptosis of HIV-infected cells following treatment with Sho-Saiko-to and its components.

Baicalein and baicalin are components of Sho-saiko-to (SST), a Chinese medical drug which is claimed to be therapeutically effective in treating HIV-infected patients. Although 20 micrograms/ml of baicalin was not cytotoxic to CEM cells, a cultured T cell line, it proved to be cytotoxic to HIV-infected CEM cells (CEM-HIV) with a higher HIV-releasing capacity and DNA fragmentation was detected within 24 hr of incubation. However, after incubation of CEM-HIV with a lower dose of baicalin (0.1, 0.3 and 2 micrograms/ml) for 24 and 48 hr, the viable cell number increased by about 25% and the p24 release into the medium was 25% lower than that of the control. After further incubation in the presence of the agent for 6 and 9 days, only cells with a lower HIV-releasing capacity survived. Baicalin might selectively induce apoptosis of CEM-HIV cells which have a high virus-releasing capacity, and stimulate proliferation of CEM-HIV which have a relatively lower capacity of HIV-production.

Apoptosis↗
PubMed1995

[Effect of a combination treatment using imipenem/cilastatin sodium with G-CSF on infections in neutropenic patients with hematological malignancies].

The clinical effectiveness of a combination treatment using imipenem/cilastatin sodium (IPM/CS) with G-CSF was studied in neutropenic patients (< 500/mm3) with hematological malignancies and secondary infections. Thirty seven patients were entered in the trial, and 30 patients were eligible. This combination was effective in 20 patients, thus the overall efficacy rate was 66.7 percent. The combination was effective in all 6 cases with septicemia, in 10 case out of 15 cases with fever after chemotherapy (efficacy rate; 66.7%), in 3 out of 8 cases with respiratory infections including 7 cases with pneumonia (efficacy rate; 37.5%), and a case with laryngopharyngitis. According to the order of the administration, the efficacy rates were 60.0% in 5 cases in whom G-CSF treatment was started before IPM/CS, 66.7% in 21 cases given both G-CSF and IPM/CS simultaneously, and 75.0% in 4 cases in whom IPM/CS was started before G-CSF. The difference was statistically not significant on the efficacy rates in the three groups. The efficacy in 18 cases treated with monotherapy on antibiotic was 72.2% and that in 12 cases treated with IPM/CS in combination with other antibiotics was 58.3%, and the difference in the efficacy rates in these two groups was not statistically significant. According to the neutrophil counts before and after the treatment, high response rate (60.0%) was obtained in cases of severe neutropenia (less than 100/mm3). Bacteriological examinations showed that all of bacteria detected as pathogens (10 strains of Gram-positive bacteria and 6 strains of Gram-negative bacteria) were eradicated, though 3 strains were replaced by other pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Aortitis syndrome with left coronary ostial occlusion and aortic regurgitation: a case report].

A 22-year-old woman with left coronary ostial occlusion and aortic regurgitation due to aortitis syndrome was reported. The coronary artery bypass grafting, using saphenous vein and aortic valve replacement were performed. The distal anastomosis of saphenous vein was performed to left anterior descending artery (Seg. 6), just distal to the origin of circumflex artery. The postoperative course was uneventful. There was no peri-prosthetic valvular leakage and bypass graft was patent.

Adult↗
PubMed1995

Effects of parathyroidectomy on left ventricular mass in patients with hyperparathyroidism.

The effects of parathyroidectomy on left ventricular muscle volume and mechanical performance were evaluated echocardiographically in 24 patients with secondary hyperparathyroidism due to chronic renal failure and in 7 with primary hyperparathyroidism. Intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameters, shortening fraction, ejection fraction, and left ventricular mass index were measured by M mode recording by the parasternal short axis view prior to parathyroidectomy as baseline and repeated 12 months after parathyroidectomy. Serum basal carboxyterminal parathyroid hormone levels in patients with secondary hyperparathyroidism (34.4 +/- 13.7 ng/ml) were significantly higher than in those with primary hyperparathyroidism (3.4 +/- 5.1 ng/ml; p < 0.0001). At 12 months after parathyroidectomy, intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameter and left ventricular mass index were reduced from 11.8 +/- 3.1 mm, 10.9 +/- 1.7 mm, 53.8 +/- 6.3 mm, 200.8 +/- 57.1 g/m2 to 10.0 +/- 2.1 mm (p < 0.05), 9.8 +/- 1.9 mm (p < 0.05), 50.7 +/- 7.2 mm (p < 0.05), 149.6 +/- 38.7 g/m2 (p < 0.0001), in patients with secondary hyperparathyroidism. In patients with primary hyperparathyroidism, all echocardiographic parameters remained in the normal range and did not show any significant changes before or after parathyroidectomy. From this study, parathyroid hormone at extremely high concentrations as seen in secondary hyperparathyroidism appears to be a cardiotoxic substance. Therefore, all patients with secondary hyperthyroidism should be examined by echocardiography and parathyroidectomy should be considered if myocardial hypertrophy is present.

Adult↗
PubMed1995

Antagonistic peptides against human anaphylatoxin C5a.

Multivalent synthetic peptides derived from C5a were prepared in order to examine their effects on the C5a receptor (C5aR). Multiple antigen peptide (MAP) of the C5a C-terminal region (MAP61-74) bound to cells expressing C5aR with high affinity. On the other hand, N-terminal peptides (MAP3-16 and MAP12-26) and one with a sequence from the mid-portion of C5a (MAP37-53) did not bind to the cells. In addition, MAP61-74 inhibited Ca2+ mobilization and release of beta-hexosaminidase by C5a from dibutyryl cAMP-activated U937 cells. This Ca2+ mobilization was also inhibited by MAP12-26 and Mono61-74, the monomeric C-terminal peptide. Taken together, these data indicate that C5a binds to the C5aR via its C-terminal region. Furthermore, MAP61-74, a 14mer peptide that has additional amino acids at the N-terminal compared with the C-terminal octapaptide, can bind to C5aR and can be considered an antagonist of C5a which may prove useful as an agent for controlling the allergic response caused by complement activation.

Amino Acid Sequence↗
PubMed1995

[Clinical evaluation of patients with cardiopulmonary bypass by plasma granulocyte elastase].

To evaluate the role of granulocyte elastase (GEL) at cardiopulmonary bypass (CPB), the plasma GEL level was measured in 24 patients who underwent elective cardiac surgery and 47 patients who underwent elective gastroenterological surgery. The cardiac surgical patients were divided into two groups: 5 patients with CPB less than 120 minutes (HL group), and 19 patients with CPB more than 120 minutes (HH group). The patients with gastro-enterological surgery were also divided into two groups: 15 patients with postoperative complications (GC group), and 32 patients without postoperative complications (GU group). All the patients of GU, HL and HH groups were alive. Two patients of GC group died because of multiple organ failure (MOF). The serum levels of GEL in both the HH group and the GC group remained higher than in the GU group at 6 postoperative day (POD). The high serum level of IL-8 gave rise to high serum level of GEL in the HH group, even after cardiac surgery. We assumed that anti-cytokine therapy and aggressive administration of Ulinastatin are useful against postoperative complications and that careful management is need after long CPB.

Cardiac Surgical Procedures↗