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Biomedical subjects

K Okabe

Publications and source records attributed to K Okabe.

At least 91 records · Page 5Linked to original sources

[PCR-RFLP analysis of epithelium in canine cryopreserved tracheal allograft].

In this study, we investigated whether the regenerated epithelia were recipient phenotype or donor phenotype using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. Preoperatively 24 mongrel dogs were classified to 14 types by PCR-RFLP result from peripheral blood. The PCR-RFLP result of peripheral blood agreed to that of recipient epithelia. The cryopreserved tracheal allotransplantation was performed among the five pairs in which we could distinguish donor from recipient by PCR-RFLP. The epithelia of graft at 10 days after transplantation showed donor phenotype, but the epithelia at postoperative 20 days or more showed recipient phenotype. These results showed that allogenic epithelium remained in early post-transplant time and was gradually omitted. The epithelia migrated gradually from the anastomotic site, and the graft was covered with regenerated epithelia showing recipient phenotype within about 50 post-transplant days.

Animals↗

In vivo microautoradiography of [3H]1,24(OH)2D3 (tacalcitol) following topical application to normal rats and in vitro metabolism in human keratinocytes.

This study was conducted to investigate the mechanism of topical absorption of [3H]1,24(OH)2D3 (1,24-dihydroxyvitamin D3; tacalcitol) by applying an ointment containing 4 micrograms2/g [3H]1,24(OH)2D3 to the skin of rats using an occlusion method. Microautoradiography of the skin at the application site 1 h after topical treatment showed a high concentration of radiolabel in the stratum corneum, the epidermis and around the hair follicles. Radiolabel was also seen in the epidermis and hair follicle areas 8 h and 24 h after application. The radiolabel was distributed to a minor extent to the subcutaneous fat layer. Microautoradiography showed two routes of purcutaneous absorption of 1,24(OH)2D3: through the stratum corneum and epidermis into the microvessels, and through hair follicle areas into the bloodstream. After topical application of an ointment containing 4 micrograms/g or 40 micrograms/g [3H]1,24(OH)2D3 to the shaved neck skin of rats, the absorption rate, estimated by excretion in the urine and faeces, was about 30% of the total applied radioactivity. The main excretion route after topical application was in the faeces. Furthermore, 1,24(OH)2D3 added to human adult keratinocytes was not metabolized into other compounds, and only the unchanged compound was detected. These findings strongly suggest that 1,24(OH)2D3 distributed into the epidermis acts on epidermal keratinocytes. Topical application of 1,24(OH)2D3 appears to be a possible approach to the treatment of psoriasis and other skin diseases through its action on the 1,25(OH)2D3 receptor, which reportedly plays a very important role in the regulation of proliferation and differentiation of keratinocytes.

Absorption↗

Effects of calciseptine on unitary barium channel currents in guinea-pig portal vein.

Effects of synthesized calciseptine (CaS), found naturally in the venom of the black mamba, on voltage-dependent Ca2+ channels in smooth muscle cells of the guinea-pig portal vein were investigated. In the whole-cell voltage-clamp configuration, extracellular application of CaS (>/= 10 nM) inhibited the inward current in a concentration- and voltage-dependent manner at a holding potential of -90 mV. The Ca2+ current recorded at a high holding potential (-50 mV) was approximately 8 times more sensitive to CaS than that at a more negative holding potential (-90 mV). CaS (50 nM) shifted to the left the steady-state inactivation curve obtained by using single 8-s conditioning pulses of various amplitudes. When CaS (>/= 200 nM) was present in the pipette, the Ca2+ current remained for the duration of the experiments (more than 60 min) in the whole-cell configuration. Two different Ca2+ channel conductances are present in this tissue (25-pS and 12-pS channels). Both channels are blocked by dihydropyridine (DHP) derivatives, but have different sensitivities. In the cell-attached condition, CaS hardly changed the activity of either unitary Ca2+ channel current. To prevent the "run down" of the Ca2+ channels in cell-free conditions, we added cardiac cytosol, a supernatant from homogenized cardiac cells and an endogenous Ca2+ channel activating factor, in the pipette. The unitary Ca2+ channel currents were then recorded using the outside-out membrane patch configuration. Application of CaS (1 microM) in the bath completely blocked the open events of the 25-pS Ca2+ channel. CaS (10 nM) in the bath reduced the mean open time and channel availability, resulting in a decrease in the open probability of the 25-pS channel currents without affecting the amplitude of the single-channel conductance. CaS also reduced the open probability (though less potently) and channel availability of the 12-pS Ca2+ channel without a change in its amplitude. From these results, we conclude that CaS has inhibitory effects on the voltage-dependent Ca2+ current that are similar to those of DHP derivatives and that it acts from the outside of the membrane.

Animals↗

Crystallization and preliminary X-ray diffraction study of recombinant human eukaryotic initiation factor-4E.

Recombinant human eukaryotic initiation factor-4E (eIF-4E), purified by m7GTP-Sepharose 4B affinity chromatography, was used for crystallization. After concentration of the eIF-4E protein (7 mg/ml), the solution was subjected to crystallization by the hanging-drop method. Transparent needle crystals complexed with m7GTP were obtained from 50 mM 2-(N-morpholino)ethanesulfonic acid-KOH buffer (pH 6.5) containing 25% (w/v) polyethylene glycol 6000 and 0.2 M (NH4)2SO4. The crystals belong to tetragonal space group P4(1) or P4(3), of Z = 4, with unit-cell dimensions of a = 89.26, b = 89.26, and c = 38.51 angstrum, and diffract beyond 2.1 angstrum resolution. The Vm value was calculated to be 3.07 angstrum 3/Da, which indicates a solvent content of 59.9%.

Crystallization↗

Spectral properties and quantitative evaluation of hypernasality in vowels.

A new technique for evaluating hypernasality using an acoustic approach is presented. In a preliminary study using this technique, nasal resonance was assessed in 17 normal subjects and 16 subjects judged to be hypernasal. Analyses of the one-third-octave power spectra revealed an increase in power level between the first and second formant, and a reduction in the power level in second and third formant regions among utterances judged to be hypernasal. Factor analysis of the perceptual ratings revealed that the consensus perception of hypernasality accounted for 71% of the total variance. An additional 8% was accounted for by individual differences. Multiple regression analysis revealed a high correlation between the consensus perception of hypernasality and the variance in two acoustic-power levels, these being the power level between the first and second formant and the power level of the second and third formant regions.

Adolescent↗

Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models.

Alendronate is an aminobisphosphonate that acts as a potent inhibitor of osteoclastic bone resorption. To understand the mechanism of action of alendronate in vivo, in this study we investigated the relationship between distribution of [14C]-alendronate in rat bone and its effects on bone resorption in vitro or in rat hypercalcemic models. A single IV dose of 0.05 approximately 1.25 mg/kg inhibited the increase in plasma calcium level induced by bovine PTH or 1 alpha(OH)D3. The minimal effective dose of pamidronate (1.25 mg/kg) and etidronate (over 31.25 mg/kg) were at least 5 times and 25 times, respectively, higher than the dose of alendronate in the rat hypercalcemic model prepared by 1 alpha(OH)D3. The relative potencies of compounds in the hypercalcemic rat models reflected those of inhibitory effects on bone resorption in vitro. We conducted the ivory-slice assay under two conditions: (a) addition of a given bisphosphonate after adherence of the osteoclasts; and (b) preincubation of the ivory slices with a given bisphosphonate. The inhibitory IC50 values of alendronate under condition (b) were similar to those under condition (a). To evaluate the interaction between osteoclasts and alendronate in bone, we investigated the localization of [14C]-alendronate in the tibia of growing rats (4-day-old rats). Alendronate did not distribute uniformly in the tibia. At 1 day after injection (0.05 mg SC), dense labeling was seen primarily under osteoclasts. We injected 0.05 mg/kg of [14C]-alendronate (single i.v.) into rats [14C]-alendronate was rapidly eliminated from plasma, and mainly distributed to the bone in rats. These data suggest that alendronate which distributed on bone surface mainly contributed to the antihypercalcemic action in vivo.

Alendronate↗

Factors affecting the occurrence of bacteremia associated with tooth extraction.

This study examined the factors that affect the occurrence of bacteremia associated with tooth extraction and the kinds of bacteria causing this bacteremia. Bacteremia was found in 132 (72.1%) of 183 patients who had one or more teeth extracted for various reasons. Bacteremia occurred more frequently when teeth were extracted because of inflammatory dental diseases. The occurrence of bacteremia also increased with the number of teeth extracted and the age of the patients. When the volume of blood lost during surgery was > 50 ml and the time required for the operation exceeded 100 min, the occurrence of bacteremia was also higher. Anaerobes were isolated from 104 (78.8%) of the 132 cases of bacteremia. Of the 187 isolates obtained, three (1.6%) were aerobes, 51 (27.3%) were facultative anaerobes (including microaerophils), and 133 (71.1%) were anaerobes. Among facultative anaerobes and microaerophils, the most frequently isolated bacterial genera were Lactobacillus (n = 15), Streptococcus (n = 13), and Staphylococcus (n = 12); and among anaerobes, Eubacterium (n = 40), Peptostreptococcus (n = 40), and Propionibacterium (n = 20).

Adolescent↗

Effects of time stress on psychophysiological responses during data entry tasks.

Six male and six female students (19-23 yrs) volunteered as subjects in the present experiment. Subjects performed the data entry tasks. A hundred and twenty single digit numbers 12 by 10 lines matrix were displayed in a random sequence on the left side of monitor. Subjects input the same numeral as these numbers one by one with clicking of the mouse on the ten keys displayed on the right side of the monitor. Each task consists of the following conditions: 1) system response time is fast or slow; 2) delete the input numerals from 120 numbers or not; 3) button flashes after input or not; and 4) the remaining time is displayed or not during performing the tasks. These tasks are programmed to be finished automatically after 200 seconds independent of the rate of completing all inputs. We measured heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), skin blood flow (SBF), skin potential level (SPL), number of errors (Es), total number of input and subjective ratings concerning the degree of irritation (SR1), difficulty of input (SR2) and unpleasantness in operation (SR3). It was shown that when system response time was slow, even the average of heart rate and blood pressure were lower than fast system response time, however, the subjects felt greater emotional irritation, difficulty of input and unpleasantness in operation hence making more errors.

Adult↗

[Clear cell sarcoma extending into the inferior vena cava].

A 6-year-old boy who had been diagnosed as having Wilms tumor at the prior hospital was admitted to our hospital for investigation of a right flank mass and macrohematuria in October 1990. Magnetic resonance imaging showed Wilms tumor of the right kidney extending into the inferior vena cava. Right radical nephrectomy, lymphadenectomy and thrombectomy were done on October 30th, 1990. Pathological findings indicated clear cell sarcoma of the kidney. One week after the operation, radiotherapy and chemotherapy with actinomycin D (ACTD), vincristine sulfate (VCR), doxorubicin hydrochloride (DXR) and cyclophosphamide (CPM)) were started according to the protocol by National Wilms Tumor Study (NWTS) III. However, he died of bone metastases and pneumomycosis on October 13th, 1992. Clear cell sarcoma of the kidney (CCSK) is a rare tumor accounting for about 4-5% of Wilms tumors. This is the first report on CCSK with tumor thrombus in Japan.

Child↗

[Development of the monoclonal antibody to cultured uterine endometrial adenocarcinoma cells (EI)].

A new monoclonal antibody (Moab), 3H2, was produced by immunizing Balb/C mouse with EI, a newly established human cell line from moderately differentiated endometrial adenocarcinoma of the uterus. The molecular weight of the Moab 3H2-defined antigen was 36,000 daltons, and suggests that the epitope of the Moab 3H2-defined antigen was protein moiety. Moab 3H2 was of the IgG1, subclass. Using formalin-fixed, paraffin-embedded human tissues and immunohistochemical techniques (ABC method), Moab 3H2 has demonstrated reactivity, Moab 3H2 reacted with well and moderately differentiated endometrial adenocarcinoma of the uterus, but did not react with poorly differentiated endometrial adenocarcinoma of the uterus, Moab 3H2 did not react with other tissues, malignant or normal, except ovarian clear cell adenocarcinoma, suggesting that Moab 3H2 reacts with well and moderately differentiated endometrial adenocarcinoma of the uterus with high specificity. To analyze the epitope of the Moab 3H2-defined antigen, it should be useful to make clear the function of carcinogenesis, differentiation and growth of endometrial adenocarcinoma of the uterus.

Adenocarcinoma↗

[Establishment and characterization of the new cell line (EI) from a human endometrial adenocarcinoma].

A moderately-differentiated endometrial adenocarcinoma cell line(EI) was established from a surgical specimens obtained from a 55-year-old woman with endometrial carcinoma. This cell line could be transplanted to nude mice, where the cells showed the same histological type as the primary tumor. The doubling time of the cell line was 50.5 hours; the saturation density was 7.5 x 104 cells/cm2; the plating efficiency was 46%. This cell line was determined to produce TPA, but not other tumor markers, such as CA125 or CEA. Neither estrogen receptor, nor progesterone receptor was detected from the culture cell or the primary tumor. Chromosome analysis revealed that cells examined were all 46,XX, + 8,t(14q14q), and only cells with this karyotype were thought to be able to grow. From these results, it was suggested that a gene on No. 8 chromosome would be involved in the carcinogenesis of endometrial adenocarcinoma. Thus this cell line was thought to be useful for the clarification of gene conversion during the process of development of endometrial adenocarcinoma.

Adenocarcinoma↗

[Treatment of 11 cases of pulmonary arteriovenous fistula].

We have experienced a total of 11 patients operated for pulmonary arteriovernous fistula (PAVF) from 1976 to 1993 consisting of three males and eight females with the average age of 35 years. To reserve the pulmonary function, limited resections were applied for all cases (partial resection in 8, fistula excision in 2, and segmentectomy in one case). The most recent case, a 36-year-old female who had two abnormal shadows on her routine chest X-ray, was diagnosed as PAVF by pulmonary arteriogram. She was treated by fistula excision in the right S8 lesion and embolization in the left S1 + 2 lesion. Because of its unsatisfactory natural course, PAVF should be treated aggressively by surgery and/or by embolization according to the size, shape and localization.

Adolescent↗

[Clinical analysis of lung cancer in patients with chondromatous hamartoma].

Between 1978 and 1993, 776 patients with lung cancer and 18 patients with chondromatous hamartoma were operated on in the department of Surgery II in Okayama University Hospital. 3 patients had both lung cancers and chondromatous hamartomas. They were all men. Two patients were 65 years old and the other was 82 years old. They all pointed out them by a medical examination of chest X-ray. 2 patients had lung cancers and chondromatous hamartomas in the same lobe, the other had them in other lobe of the same side. Lung cancer and chondromatous hamartoma localized in near area. It was difficult to discriminate chondromatous hamartoma between pulmonary metastasis of lung cancer before an operation.

Adenocarcinoma↗

Formulation optimization of indomethacin gels containing a combination of three kinds of cyclic monoterpenes as percutaneous penetration enhancers.

A computer optimization technique based on response surface methodology was applied for the optimization of a hydrogel formulation containing indomethacin as a model drug. As the penetration enhancer, a combination of three cyclic monoterpenes, limonene, menthol, and cineole, was employed. Pharmacokinetic parameters, from an in vivo percutaneous absorption study on rats of model formulations prepared according to the composite experimental design for five factors, were determined as prime response variables. The skin damage evoked by each formulation was microscopically judged and graded as the response variable concerning skin safety. The response variables were predicted by multiple regression equations comprising combinations of the five formulation factors. The regression equations for the response variables assembled as a simultaneous optimization problem based on the generalized distance function. The simultaneous optimum was predicted as a function of individual optima within a 95% confidence region. The predicted response values for the optimum formulation have been successfully validated in a repeated in vivo percutaneous absorption study.

Administration, Topical↗

Total synthesis of a frog poison, (+/-)-epibatidine, a potent non-opioid analgesic.

A non-opioid analgesic, epibatidine (1), isolated from Ecuadoran poison frogs was synthesized in the racemic form starting from a readily available compound 2. A partial Curtius rearrangement product 5 of 2 was converted into 12c by way of the ketone 3 and its condensation product with the pyridine moiety 9c, and catalytic hydrogenation of 12c was specifically conducted in hydrochloric acid-containing 2-propanol for the preferential formation of an exo-product 15b. Conversion of the substituent from 15b to 15a in a single operation using the Vilsmeier reagent, followed by deprotection of the p-toluenesulfonyl group with hydrobromic acid completed an eight-step synthesis of (+/-)-1 from 2.

Analgesics↗

Improvement of multiple coronary risk factors in obese hypertensives by reduction of intra-abdominal visceral fat.

The association of obesity and hypertension is well documented, and the combination is important as a coronary risk factor, but its non-pharmacological management is very difficult. Japanese hypertensive obese subjects (HO, n = 95) selected from 321 non-medicated obese subjects with a body mass index > 25 kg/m2 were characterized by the clinical features of significant diaphragmatic elevation, higher heart rate (HR), fasting blood glucose (FBS), total cholesterol (Tch), uric acid and gamma GTP values and lower vital capacity (VC) compared to those of normotensive-obese subjects (NO, n = 226) (p < 0.01). During a diet therapy program (about 1,200 kcal/day) for HO (n = 55), 25 subjects were treated with a non-drug-dependent pulse-synchronized transpercutaneous electric abdominal muscle stimulator (PEM) (ca. 30,000 muscle contractions/day) for 4 weeks. These subjects showed significant improvement with reduction in body weight (9.4%, 7.4 kg), intra-abdominal visceral fat (VF) CT scan area (29%), abdominal subcutaneous area (10%) at the level of the umbilicus, blood pressure (BP), HR, FBS, gamma GTP, Tch, plasma norepinephrine, plasma renin activity and plasma insulin, an increase of VC and lowering of the diaphragm (p < 0.05). The reductions in weight, BP, FBS and Tch in the diet group (n = 30, 1,200 kcal/day for 4 weeks) were smaller than those in the PEM-diet group (p < 0.05). The Japanese hypertensive obese patients had complications of many other coronary risk factors, and the reduction in weight and VF with PEM-diet therapy seems to be effective for improving these risk factors.

Abdominal Muscles↗

[Surgical treatment of pulmonary aspergillosis].

There is controversy about the optimal treatment for pulmonary aspergillosis. Eight patients with pulmonary aspergilloma underwent surgical treatment. Three patients had tuberculosis, one Sjögren syndrome, one aortitis syndrome, one malignant lymphoma. Lobectomy was performed in five patients, segmentectomy in three patients. All patients are alive and have no recurrence. We have obtained excellent results from surgery and advocate early surgery for localized lesions to prevent life-threatening hemoptysis. This will allow patients to continue with further treatment for the underlying disease. We encountered a granulocytopenic patient with rapidly progressive aspergillus infection resulting in occlusion of main pulmonary artery leading to death. Surgical intervention could not prevent this fatal outcome. The selection of the patients with diffuse lesions should be made carefully.

Adult↗