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Biomedical subjects

M Okazaki

Publications and source records attributed to M Okazaki.

At least 289 records · Page 16Linked to original sources
PubMed1994

Effect of KCA-098, a new benzofuroquinoline derivative, on bone mineral metabolism.

The effect of 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one designated as KCA-098) on the bone mineral metabolism of chick embryonic bone was examined. KCA-098 dose-dependently inhibited bone resorption of cultured chick embryonic femora and calvariae. It increased the length, dry weight, and calcium and phosphorus contents of 9-d-old chick embryonic femurs cultivated for 6 d, indicating that it stimulated bone formation. These results show that KCA-098 has the unique effects of inhibiting bone resorption and stimulating bone formation of chick embryo. In addition, in an in vivo experiment, oral administration of KCA-098 (3.0 mg/kg/d) for 16 weeks led to an increase in calcium and phosphorus content as well as an increase in the amount of force required to break the femur from ovariectomized rats, suggesting that it may be useful for the treatment of bone diseases.

Animals↗
PubMed1994

Induction of osteopenia in confined rats.

We have developed a simple model of osteopenia in rats which is induced by confinement without requiring surgical operation. Each rat was maintained for 8 weeks in a compartment of a commercially-available wire netting cage subdivided into 10 areas (compartment size, 9 x 16 x 14 cm) to restrict exercise. The femora isolated from the confined rats showed significant decreases in mineral (calcium and phosphorus) content, compared with the level in normal rats, 2 weeks after the start of their confinement. Confined rats showed significantly lower values for the physical properties of bones such as breaking energy and breaking force and also density composed with normal rats 4 weeks after the start of confinement. KCA-098 (1 mg/kg), a new benzofuroquinoline derivative that inhibits bone resorption and at the same time stimulates bone mineralization in organ culture, protected against these decreases when given orally for 8 weeks. All these results show that confinement of rats offers a simple and useful animal model of osteopenia.

Animals↗
PubMed1994

Aconitine-induced increase and decrease of acetylcholine release in the mouse phrenic nerve-hemidiaphragm muscle preparation.

The effect of aconitine on acetylcholine (ACh) release from motor nerve terminals in the mouse phrenic nerve-diaphragm muscle preparation was studied by a radioisotope method. Both electrical stimulation-evoked release and spontaneous release of 3H-ACh from the preparation preloaded with 3H-choline were measured. The change in the muscle tension was simultaneously recorded in the same preparation. Aconitine (0.1 microM) increased electrically evoked 3H-ACh release, while at higher concentrations (0.3-3 microM) it decreased the evoked release and muscle tension. High concentrations of aconitine (3-30 microM) caused a concentration-dependent increase in spontaneous 3H-ACh release. All these effects were suppressed by tetrodotoxin. The aconitine-induced spontaneous release consisted of two different components: a Ca(2+)-dependent phasic release that was inactivated within a few minutes and a Ca(2+)-independent, long lasting release at a low level. The depression of the Ca(2+)-dependent quantal release seems attributable to the decline of Ca2+ influx into the nerve rather than inactivation of sodium channels. We conclude that aconitine increases and then decreases electrical stimulation-evoked ACh release from the motor nerve through prolonged activation of sodium channels. Further activation of the channels enhances spontaneous release and the subsequent complete inactivation of the quantal release may be due to block of Ca2+ influx.

Acetylcholine↗
PubMed1994

A transient increase of phenylalanine ammonia-lyase transcript in kinetin-treated tobacco callus.

In tobacco cell culture (Nicotiana tabacum L. "Bright Yellow" T-13), phenylalanine ammonia-lyase (PAL) activity was induced in response to an exogenously added kinetin. RNA blot hybridization analysis showed that a single species of PAL transcript 2.9-kb in size was detected using the PAL cDNA cloned from kinetin-treated cells. The cellular content of this transcript increased transiently (2.5-fold) 4 h after the addition of kinetin followed by an increase in PAL enzyme activity at 16 h.

Adenine↗
PubMed1994

Correlation between plasma fibrinogen and serum lipids in rats with hyperlipidemia induced by cholesterol free-high fructose or high cholesterol diet.

We studied the coagulative and fibrinolytic activity in intrinsic or extrinsic hyperlipidemia using 4-week-old male Wistar rats. Intrinsic hyperlipidemia was induced by a cholesterol-free high-fructose diet (HFD) and extrinsic hyperlipidemia, by a high-cholesterol diet (HCD) for 14 days. In intrinsic hyperlipidemic rats fed on the HFD, serum lipids were significantly increased as compared with the levels in control rats fed on a standard diet. An apparent increase in plasma fibrinogen level and coagulant factor XIII activity was also observed in HFD rats. In extrinsic hyperlipidemic rats fed on the HCD, significant increases in plasma fibrinogen level compared with that of control rats were found with the increases in serum lipids. Activities of antithrombin III and alpha 2-plasmin inhibitor in HFD-fed rats significantly increased compared with those of control and HFD rats. There was a significant positive correlation between plasma fibrinogen and serum total cholesterol, free cholesterol, or phospholipid in diet-induced hyperlipidemia (p < 0.01). Because of the increase in coagulant XIII activity in HFD-fed rats and the increase in alpha 2-plasmin inhibitor activity in HCD-fed rats, both diet-induced hyperlipidemic rats were shown to have enhanced coagulative activity compared with the control rats. These results suggest that the HFD as well as the HCD causes a pre-hypercoagulative state due to the increase in plasma fibrinogen level and activities in other coagulative and fibrinolytic factors.

Animals↗
PubMed1994

[Treatment modalities and hypothalamo-pituitary-adrenal (HPA) axis suppression in Japanese patients with asthma].

We examined HPA axis function using a short tetracosactrin test in 94 asthmatics treated with three different modalities. The first group, (B + S), consisted of 41 patients taking BDP (910 +/- 320 micrograms, daily) plus a short term burst of oral steroids (20-40 mg daily, 3-7 days/course, 1-18 courses/year). The second group, (B + R), consisted of 19 patients taking BDP (1076 +/- 410 micrograms, daily) plus continuous oral steroids (2.5-20 mg/day for 1.8-24 years). The third group, (B alone), consisted of 34 patients taking BDP only (615 +/- 258 micrograms, daily). All patients had been inhaling BDP for more than 1 year. The rise in cortisol in response to tetracosactrin in B + S, B + R, and B alone was 12 +/- 4.3 micrograms/dl, 7.0 +/- 5.0 micrograms/dl and 14 +/- 4.5 micrograms/dl, respectively, and achieved cortisol was 21 +/- 4.5 micrograms/dl, 12 +/- 7.2 micrograms/dl and 23 +/- 4.2 micrograms/dl;, respectively. Both values were significantly lower in the B + R group than in either B + S or B alone. However, there was no difference between B + S and B alone, although the BDP dose was significantly larger in the B + S group. Significant HPA axis suppression (rise in cortisol < 7 micrograms/dl and achieved cortisol < 18 micrograms/dl) was seen in 7 patients. Although HPA axis suppression was more frequently seen in B + R (10/19), no significant difference was seen between B + S and B alone (4/41 and 1/34, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

[A case of mediastinal parathyroid adenoma diagnosed by transtracheal needle aspiration].

Chest radiography of a 73-year-old man with upper abdominal pain showed hypercalcemia and an upper mediastinal mass. Functional mediastinal parathyroid adenoma was diagnosed, because of abnormally high levels of PTH in his serum and in fluid collected by transtracheal needle aspiration from the mediastinal mass. We resected the adenoma operatively. It a cystic tumor located behind the superior vena cava and the trachea. The inferior end of the tumor was as low as the aortic arch, and superiorly the tumor was attached to the inferior pole of the thyroid gland by a vascular pedicle. Histologically adenoma cells were predominant. This tumor was a mediastinal parathyroid adenoma by location, but because it was attached to the thyroid gland superiorly, it may have originated from the superior parathyroid gland and then descended because of its weight into the posterior superior mediastinum. Thus, it cannot be considered an ectopic parathyroid adenoma in origin. Mediastinal parathyroid adenoma is a rare disease, and these tumors are usually so small that correct localization of the adenoma is often difficult even by CT scan or scintigram. This is the first reported case of a mediastinal parathyroid adenoma that appeared as a mediastinal mass on a plain chest radiography and in which the level of PTH in the fluid collected from the mass by transtracheal needle aspiration was high.

Adenoma↗
PubMed1994

[A case of sarcoidosis with systemic lymph node involvement presenting as multiple high-density masses on chest and abdominal CT].

We report a case of sarcoidosis with mediastinal and abdominal lymph node involvement presenting as multiple high-density masses on chest and abdominal CT. The patient was a 43-year-old housewife who came to our hospital because of a dry cough and exertional dyspnea. A chest radiograph showed bilateral diffuse reticulo-nodular shadows and widening of the mediastinum. On CT of the chest and the abdomen, lymph nodes were swollen throughout the mediastinum and the para-aortic area of the abdomen. They appeared as very-high-density masses on plain CT. Bronchoscopy revealed involvement of the bronchial walls. Punch biopsy of the bronchial wall, TBLB, and biopsy of the anterior mediastinal lymph node all revealed non-caseous epithelioid cell granulomas. These granulomas contained lamellated, irregularly shaped and darkly-stained structures (Schaumann bodies) that caused the high density of the involved lymph nodes on CT. This case shows at least a part of the mechanism of calcification of lymph node lesions in patients with sarcoidosis.

Adult↗
PubMed1994

[Phase II study of a continuous five-day intravenous infusion of cisplatin and etoposide with concurrent chest radiation therapy in limited stage small cell lung cancer].

The efficacy of continuous five-day intravenous infusion of cisplatin (CDDP) and etoposide with concurrent chest radiation therapy was evaluated in patients with limited stage small cell lung cancer. The first group of patients registered from February 1989 to September 1990 received three courses of chemotherapy (CDDP 20 mg/m2/day x 5 days, etoposide 40 mg/m2/day x 5 days) and concurrent chest radiation therapy on the third course with dose reduction of etoposide. The second group of patients registered after February 1991 received four courses of chemotherapy (CDDP 20 mg/m2/day x 5 days, etoposide 50 mg/m2/day x 5 days) and concurrent chest radiation therapy on the first and second courses with dose reduction of etoposide. The response rates were 91.7% and 93.3%, respectively. The median duration of survival was 32.0 months and 20.1 months, respectively. Major toxicity was leukocytopenia and 64% and 80% of patients encountered leukocytopenia of Grade 3 or 4. In conclusion, these regimens show remarkable efficacy with acceptable toxicity.

Aged↗
PubMed1994

[The significance of intra-arterial infusion therapy for neoadjuvant chemotherapy].

Arterial infusion therapy with anticancer drugs is now attracting attention as a valuable modality for locally advanced breast cancer. Since 1977, we have used this therapy in 122 patients with primary breast cancer. The present report mainly discusses the clinical and histological response as well as the prognosis. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR, 4'-epi-ADR and THP-ADR were jointly or individually made in each artery. Clinical response, defined as CR + PR, was noted in 48.4% of 5-FU group and 72.7% of ADR-MMC group. Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 45.2% of main tumors and 25.4% of metastatic lymph nodes in the 5-FU group, and 70.9% main tumors and 46.3% of metastatic lymph nodes in the ADR-MMC group. The non-infusion group contained 27.7% of stage IIIb, against 72.2% in the infusion group. The 5-year overall survival rates were non-infusion group 62%, 5-FU group 34.1% and ADR-MMC group 66.2%. A significant difference was seen between the 5-FU infusion group and the ADR-MMC group (p = 0.03). Administration of high dose medroxy progesterone acetate for two weeks and 4'-epi-ADR infusion chemotherapy resulted in an excellent histological response. This combination therapy is a promising neoadjuvant chemo-endocrine therapy for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Can patients with chronic asthma discontinue inhaled corticosteroid?].

As an initial investigation to determine whether or not inhaled corticosteroids can be discontinued, we evaluated the results of discontinuation in patients who had been well controlled with inhaled corticosteroids for more than one year prior to this study. The average dose of BDP which the patients had been inhaling at the start of this study was 365 micrograms/day. To determine the effect of discontinuing inhaled corticosteroids, we compared the patients' peak expiratory flow rates and the frequency of beta-agonist use between the 4-week observation period and follow-up periods of varying duration. Only three out of twenty patients enrolled were able to maintain their discontinuation of BDP, while the remaining seventeen patients restarted after a mean period of 30.8 days. Mean peak flow values began to fall during the first week after discontinuation, and decreased morning peak flow values became significant in the 2nd, 3rd and 4th weeks. The mean peak flow value during the observation period was 85.2% of each patient's personal best, but had dropped to 68.8% of this level just before restarting inhaled corticosteroid. The frequency of beta-agonist use during the study period (2.99 +/- 3.39 times a day) was significantly higher than during the observation period (1.94 +/- 2.95 times a day). This finding strongly suggests that the patients' asthmatic conditions had become unstable during the study period. These results suggest that any decision to discontinue the use of inhaled corticosteroid, even in well controlled patients with chronic asthma, should be taken with great care.

Administration, Inhalation↗
PubMed1994

Heterogeneous Mg-containing hydroxyapatites.

Two different Mg-containing hydroxyapatites, H-MgAp and Mg-HAp, were synthesized at 80 degrees C and pH 7.4. For H-MgAp, the calcium solution was supplied in the first half of the synthesis period and the calcium solution containing magnesium was supplied in the second half. For Mg-HAp, the order of supply was reversed. The X-ray diffraction patterns of H-MgAp and Mg-HAp differed slightly from each other. The (002) reflection of both patterns shifted towards a higher angle. The chemical compositions, especially the Mg contents, of the two apatites were almost the same as each other; and the Mg contents were half of that of homogeneous MgHAp synthesized with continuous supply of Mg at the same concentration. However, their crystal shapes were quite different, with H-MgAp appearing plate-like and Mg-HAp needlelike. In a solubility experiment, Mg-HAp was more soluble than H-MgAp. These results suggest that two different heterogeneous Mg-containing hydroxyapatites may be formed: hydroxyapatite covered with Mg-containing hydroxyapatite, and Mg-containing hydroxyapatite covered with hydroxyapatite.

Crystallography, X-Ray↗
PubMed1993

Three new monoclonal antibodies that define a unique antigen associated with prolymphocytic leukemia/non-Hodgkin's lymphoma and are effectively internalized after binding to the cell surface antigen.

Prolymphocytic leukemia (PLL) is closely related to chronic lymphocytic leukemia (CLL), but present with distinctive clinical/laboratory features and associated with much worse prognosis. In this study, we generated three new IgG1-kappa monoclonal antibodies (MoAbs), termed SN8, SN8a and SN8b, by use of an unconventional approach, ie, by using an isolated B PLL antigen preparation to immunize mice. These MoAbs, particularly SN8, showed a highly selective reactivity to B PLL and B non-Hodgkin's lymphoma (NHL) among various human leukemia-lymphoma specimens tested; eg, SN8 was capable of effectively distinguishing B PLL from B CLL as well as from hairy cell leukemia (HCL) cell specimens. The cell surface antigen defined by the three MoAbs was determined to be a covalently linked heterodimeric glycoprotein complex (gp49/40) consisting of a 49,000 dalton (alpha-chain) and a 40,000-dalton component (beta-chain). Epitope comparison showed that the epitope defined by SN8 (SN8 epitope) is in close proximity to SN8a epitope but in a distant position from SN8b epitope. Western blot analysis showed that both SN8 and SN8a epitopes are on the beta-chain, but SN8b epitope was not detected on either the alpha- or the beta-chain of the reduced antigen in the same analysis. Binding of either SN8 or SN8b to the cell surface gp49/40 did not cause significant downregulation of the antigen expression whereas binding of SN8a to the antigen caused small (approximately 20%) decrease in the antigen expression. Among the various normal peripheral blood cells, only a subpopulation (6.0% to 24.2% among different specimens derived from different donors) of B cells reacted with the SN8 series MoAbs; these MoAbs showed no significant reactivity against T cells, granulocytes, monocytes, erythrocytes, and platelets. Minimal or no significant reactivity (0 to 2.6% among different specimens) was detected against normal bone marrow cells. Ricin A-chain conjugates of the three MoAbs are all strongly effective for specific killing of SN8 antigen-expressing leukemia cells in the absence of any potentiators; furthermore, the addition of 10 mmol/L NH4Cl, a potentiator, enhanced strongly the cytotoxic activities of the SN8, SN8a, and SN8b conjugates. Thus, each of the three MoAbs was effectively internalized after binding to the cell surface antigen.

Animals↗
PubMed1993

Angiographic findings of Meckel's diverticulum: the characteristic appearance of the vitelline artery.

Angiographic findings of the vitelline artery in five patients with surgically proven Meckel's diverticulum were reviewed retrospectively. Superselective vitelline arteriography was performed in two patients and superior mesenteric arteriography in three. Arteriography showed the elongated artery without branching originating from the distal ileal artery and a group of tortuous vessels at the distal portion of this artery in all patients. A dense capillary staining of the vitelline artery was exclusively shown in patients with ectopic gastric mucosa. In one patient, injection of methylene blue intraoperatively through a previously placed angiographic catheter into the vitelline artery stained only the vitelline artery and Meckel's diverticulum in blue but neither the mesentery nor the ileum. Demonstration of a nonbranching artery from the ileal artery and a group of dilated tortuous vessels at the distal portion of this artery should suggest the possibility of Meckel's diverticulum and can be confirmed by selective injection of the artery. It should be emphasized that angiography can detect Meckel's diverticulum even in the absence of acute bleeding.

Adolescent↗
PubMed1993

Cronkhite-Canada syndrome associated with colon cancer: report of a case.

A 68-year-old man with the clinical features of Cronkhite-Canada syndrome developed cancer of the ascending colon. Although Cronkhite-Canada syndrome has always been considered a benign condition, it may be a premalignant disorder, as suggested by the clinical course of the patient whose case is described herein.

Adenocarcinoma, Mucinous↗
PubMed1993

Biodistribution and in vivo antitumor efficacy of the systemically administered anti-human T-leukemia immunotoxins and potentiation of their efficacy by alpha-interferon.

In this study, the systemically administered anti-human T-leukemia immunotoxins (ITs) are shown to be effective for tumor suppression in Ichikawa T-leukemia-bearing nude mice. In addition, their antitumor efficacy was markedly potentiated by recombinant human IFN-alpha. The combination of ITs and IFN-alpha effectively killed the tumor in the majority of the treated mice; 9 of the 12 treated mice survived tumor-free for as long as they were followed, i.e. for 140 days. Two different ITs, SN1-ricin A chain (RA) and SN2-RA, were used together to minimize the problem of tumor heterogeneity; monoclonal antibodies SN1 and SN2 are directed toward two different human T-leukemia associated cell surface antigens. In the biodistribution experiments, the paired label technique was used to include a reliable internal control. In an experiment, equal amounts of 125I-SN1-RA and 131I-labelled isotype-matching control IgG (IgG1-kappa)-RA were mixed and administered i.v. into tumor-bearing nude mice. In a separate experiment, a mixture of equal amounts of 125I-SN2-RA and 131I-control IgG-RA was administered i.v. This technique allowed us to distinguish the immunospecific uptake from the non-immunospecific uptake of ITs into individual organs. The present results clearly show that both SN1-RA and SN2-RA are specifically localized in tumors after systemic administration. For instance, 24 h after the administration of a radiolabelled mixture, the ratio of 125I/131I in the tumor was 7.0 and 23.5, respectively, for the SN1-RA/control IgG-RA mixture and the SN2-RA/control IgG-RA mixture. Such high ratios of 125I/131I were detected in the tumors throughout the experiments between 30 min and 24 h after the administration of the paired label mixture.

Animals↗
PubMed1993

Establishment and characterization of the tumors of chronic lymphocytic leukemia cell line in nude and SCID mice.

A new cell line, designated MO1043, was established from the peripheral blood (PB) of a patient with B-cell chronic lymphocytic leukemia (CLL). Both the PB leukemia cells and MO1043 were found to have an abnormal cytogenetic marker of trisomy 12, the most common cytogenetic abnormality in CLL. In addition, both the PB cells and MO1043 expressed a cell surface phenotype of typical B-CLLs. The MO1043 was efficiently transplanted into X-irradiated athymic nude mice by i.p. inoculation after it was subjected to serial passages in new born (1 week old) and irradiated adult nude mice. The tumor of a CLL cell line (termed CLL tumor) was also generated in the nude mice by s.c. inoculation of the cells. The MO1043 was inoculated i.p. into mice with severe combined immunodeficiency (SCID) which had not been subject to any preconditionings. The CLL tumor in the non-conditioned SCID mice was disseminated to various tissues in a manner more analogous to CLL tumors in patients as compared with nude mice, where the CLL tumors were not as widely disseminated. At each of four different tumor doses, i.e. 2 x 10(6), 6 x 10(6), 1.8 x 10(7) and 5.4 +/- 10(7) cells of MO1043, the transplantability was 100%. Titration experiments revealed a reciprocal relationship between survival and the number of tumor cells inoculated. FACS analysis showed that several cell surface markers of the parental MO1043 were maintained in CLL tumors from nude and SCID mice. Fluorescence in situ hybridization with novel DNA probes demonstrated that CLL tumors of both nude and SCID mice maintained trisomy 12. The CLL tumor models developed here, particularly the SCID mouse model, may be very useful for therapeutic studies of CLL.

Aged↗