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Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

514 records · Page 29Linked to original sources

Prevention and treatment of linear scar formation in the scalp: basic principles of the mechanism of scar formation.

Linear scar formation in the scalp after suturing an incision has been considered unavoidable. It was not known why scars formed even if the hair bulb was left intact. The authors developed a subcutaneous tissue-shaving method for radical treatment of bromidrosis and studied the process of hair regeneration by using thick-tissue specimens. They suggest that stem cells (lower) are located not only in the lower end of the telogen hair follicles but also in the sebaceous isthmus at the secretory opening of the sebaceous gland (upper stem cells). They found that linear scars can be prevented and existing linear scars can be surgically treated by using a relaxed suture on a scalp incision to avoid excessive pressure on the upper stem cells.

Adult↗

Increased biological potency of hexafluorinated analogs of 1,25-dihydroxyvitamin D3 on bovine parathyroid cells.

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is known to be involved in regulating the proliferation of parathyroid cells and PTH synthesis through reactions involving its nuclear receptor. We evaluated the effects of 1,25-(OH)2D3 and its hexafluorinated analog, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3), on parathyroid cells. The 1,25-(OH)2D3 and 26,27-F6-1,25-(OH)2D3 each inhibited [3H]thymidine incorporation and ornithine decarboxylase (ODC) activity, which is important in cell proliferation, in primary cultured bovine parathyroid cells. The inhibitory effect of 26,27-F6-1,25-(OH)2D3 on PTH secretion from parathyroid cells was significantly more potent than that of 1,25-(OH)2D3 between 10(-11) M and 10(-8) M. Study of 26,27-F6-1,25-(OH)2D3 metabolism in parathyroid cells in vitro elucidated its slower degradation than that of 1,25-(OH)2D3. After 48 h of incubation with [1beta-3H]26,27-F6-1,25-(OH)2D3, two HPLC peaks, one for [1beta-3H]26,27-F6-1,25-(OH)2D3, and a second larger peak for [1beta-3H]26,27-F6-1,23(S),25-(OH)3D3, were detected. No metabolites were detected after the same period of incubation with 1,25-(OH)2[26,27-3H]D3. We observed that 26,27-F6-1,23(S),25-(OH)3D3 was as potent as 1,25-(OH)2D3 in inhibiting the proliferation of parathyroid cells. Data suggest that the greater biological activity of 26,27-F6-1,25-(OH)2D3 is explained by its slower metabolisms and by the retention of the biological potency of 26,27-F6-1,25-(OH)2D3 even after 23(S)-hydroxylation.

Animals↗

In vitro-in vivo correlation in anticancer drug sensitivity test using AUC-based concentrations and collagen gel droplet-embedded culture.

To improve the ability of an in vitro drug sensitivity test to predict in vivo effects, we applied a drug concentration that was pharmacokinetically equivalent to plasma levels and collagen gel droplet-embedded culture with a high cloning efficiency. We reported that the cell-killing effect of cell cycle phase-nonspecific drugs such as mitomycin C, cisplatin and Adriamycin depends on the area under the drug concentration-time curve (AUC). The plasma AUC values of these drugs were estimated after an injection into nude mice at the maximal tolerated doses (MTD). Tumor cells isolated from human tumor xenografts implanted into nude mice and cultured in collagen gel droplets were exposed to drugs under conditions that can reproduce the plasma AUC in vitro. The in vitro sensitivity to a drug was compared with the in vivo response of the same tumor treated with the MTD of the drug. When the criterion of sensitivity was taken as 50% or less of the growth inhibition (growth rate of treated group/that of control group, T/C), the correlation between the in vitro and in vivo growth inhibition of all 3 drugs tested was relatively high (86% of the true-positive rate, 82% of the true-negative rate and 83% of the correlation rate).

Animals↗

Anticancer activities of orally administered menogaril against human stomach and breast cancers implanted in nude mice.

The therapeutic effects of orally administered menogaril, a semisynthetic analog of the anthracycline antibiotic nogalamycin, were studied on a panel of human stomach and breast cancer xenografts. The maximum tolerated dose (200 mg/kg) of menogaril was administered 3 times every 4 days and its growth-inhibitory effects on subcutaneously implanted tumors in nude mice were evaluated. Menogaril significantly retarded the growth of 3 out of 7 stomach cancers, SC-2, SC-9 and 4-1ST, and 3 out of 4 breast cancers, H-31, MC-2 and MX-1, with overall response rates of 43 and 75% for stomach and breast cancers, respectively. Some of these relatively responsive cancers were also treated by daily oral administration for 5 consecutive days, but the anticancer effects of the intermittent administration seemed to be better. These results suggest that menogaril may be effective against stomach and breast cancers when orally administered.

Administration, Oral↗

Responsiveness of subcutaneous human glioma xenografts to various antitumor agents.

Responsiveness of seven human glioma xenografts to seven antitumor agents was investigated by an sc-iv system and the efficacies of these agents against human glioma were evaluated in terms of response rate. When their maximum tolerated doses were used, experimental response rates of nimustine (ACNU), vincristine (VCR), adriamycin (ADR) and vinblastine (VLB) were as high as 86-100%, while that of mitomycin (MMC) was 57%, and those of 5-fluorouracil (5-FU) and methotrexate (MTX) were 0%. On the other hand, when the doses pharmacokinetically equivalent to their clinical doses were employed, the response rate of ADR was the highest, followed by VCR and ACNU in this order. These results suggest that gliomas are significantly responsive to various antitumor agents in this sc-iv system.

Adult↗

Early clinical results of the modified human umbilical cord vein homograft (Dardik Biograft).

Fifty-six reconstructions using Biograft were performed in 45 cases with peripheral arterial occlusion. These consisted of 11 femoro-popliteal bypasses above the knee, 19 femoro-popliteal below the knee, 10 femoro-tibial or peroneal and 16 other miscellaneous procedures including aorto-femoral and extra-anatomic bypasses. Overall patency rates for each type of procedure were 81.8%, 78.9%, 30.0%, and 93.8%, respectively. The cumulative patency rate (calculated by the life table method) for the total group was 70.5% at 56 months. Early failure was thought to relate to technical factors in most instances. The majority of late failures was due to intimal hyperplasia at the distal anastomotic site. One of 9 late failures was successfully treated by patch angioplasty at 23 months following initial operation. Therefore, in order to attain better late results, early discovery of developing stenosis by noninvasive examination techniques and arteriography is important.

Aged↗

Pharmacokinetic correlation between experimental and clinical effects on human non-small cell lung cancers of cis-diammineglycolatoplatinum (254-S) and cis-diamminedichloroplatinum.

We attempted to correlate the in vitro and in vivo antitumor activities of cis-diammineglycolatoplatinum (254-S), a novel platinum complex, and cis-diamminedichloro-platinum (CDDP) against the established culture cell lines and xenografts of human non-small cell lung cancer (NSCLC) with their clinical effects, based on the previous finding that the cytotoxicity of CDDP depends on the area under the curve (AUC). The concentration of 254-S and CDDP inhibiting the in vitro growth of 4 cultured NSCLC lines by 50% (IC50) was 0.82-7.8 and 0.53-4.2 micrograms/ml, respectively, showing a similar level. Of the 4 cell lines, only the most sensitive line, RERF-LC-AI, showed an IC50 close to a specific concentration (0.50 for 254-S and 0.32 micrograms/ml for CDDP) that reproduces in vitro the clinical AUCfree (24.8 and 5.34 micrograms-hr/ml) of the respective drugs. We treated 6 lines of human NSCLC xenografts implanted in nude mice with 254-S and CDDP at a particular dose (13.2 and 3.7 mg/kg) that is equivalent to the clinical doses with respect to the plasma AUCfree. 254-S and CDDP exhibited significant antitumor effects on 2 and 1 of the 6 lines, respectively. These in vitro and in vivo findings were considered to be relatively well correlated with the reported clinical response rates of 15-19% for 254-S and 14-15% for CDDP.

Adenocarcinoma↗

Diabetes mellitus increases the severity of anemia in non-dialyzed patients with renal failure.

We investigated whether the presence of diabetes mellitus (DM) was related to the severity of the anemia observed in patients with renal failure who were not receiving dialysis. Forty patients were examined, (19 with long-term type II DM (DM-CRF), 21 with renal failure due to other causes (non-DM-CRF)). The two groups did not differ significantly as to age, sex, serum creatinine or erythropoietin. Hemoglobin was significantly (p < 0.005) lower in the DM-CRF patients (9.5 +/- 2.1 g/dl) than in the non-DM-CRF patients (11.2 +/- 2.0 g/dl). Multiple regression analysis indicated that higher serum creatinine levels and the presence of DM were independent risk factors for anemia (R2 = 0.494, p < 0.001). DM appeared to be a risk factor for the severity of anemia in patients with renal failure who were not receiving dialysis.

Adult↗