Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 379 records · Page 21Linked to original sources

PubMed1992

[Determination of vertebral fracture threshold by measuring bone mineral content in the lumbar vertebrae].

Bone mineral density (BMD) in the lumbar vertebrae (L2-L4) was assessed by dual energy X-ray absorptiometry (DEXA: QDR-1000), and the values obtained were compared with the frequency of vertebral fracture as assessed by spinal X-ray photographs. Patients with spondylosis or scoliosis, which affect BMD values, were excluded from the study. An essentially linear correlation was observed between the frequency of vertebral fracture and lumbar BMD values: no vertebral fractures were observed in those whose BMD more than 0.8 g/cm2, whereas the frequency of fracture was 100% in patients whose BMD was less than 0.45 g/cm2. Thus, measurement of lumbar vertebrae by DEXA would be very useful in predicting vertebral fractures.

Absorptiometry, Photon↗

PubMed1992

Direct projections from the globus pallidus to the midbrain and pons in the cat.

Employing the anterograde and retrograde axonal tracing techniques with Phaseolus vulgaris leucoagglutinin and cholera toxin B subunit, we demonstrated direct projections from the globus pallidus (GP) to the midbrain and pons in the cat. Cells of origin of these projections were localized in the caudal 2/3 of the GP, and their major target sites included the peripeduncular region, nucleus of the brachium of the inferior colliculus, para-lateral lemniscal zone, nucleus sagulum, external and pericentral nuclei of the inferior colliculus, and cuneiform nucleus. A combination of retrograde axonal tracing and immunohistochemistry for choline acetyltransferase revealed that GP neurons giving rise to such descending projections were primarily non-cholinergic.

Animals↗

PubMed1992

Ultrastructural localization of calcium in the chick chorioallantoic membrane as revealed by cytochemistry and X-ray microanalysis.

The chorioallantoic membrane (CAM) of the chick embryo actively transports calcium from the egg shell into the embryonic circulation. To investigate the intracellular pathway of calcium transport across the CAM, ultrastructural localization of intracellular calcium in cells of the chorionic ectoderm (CE) was determined using cytochemical methods and X-ray microanalysis. Treatment of the CE with potassium oxalate, potassium ferricyanide or potassium pyroantimonate revealed large numbers of electron-dense granules (EDGs) in the ectodermal cells. These measure 30-40 nm in diameter, and are not membrane-bound. These granules were seen in all three cell types of the CE. The presence of calcium in the EDG was directly confirmed by X-ray microanalysis. When strontium or barium ions were applied to the shell membrane side of the CAM, the cells of the CE incorporated these divalent cations and sequestered them in granules (25-40 nm in diameter) in cytoplasm and mitochondria. This study indicates that calcium enters the CE cells by means other than endocytosis, as the EDGs are not membrane-bound, that all three types of the CE cells appear to function in transport of calcium from shell to embryo during embryogenesis, and that the EDG plays important roles in intracellular accumulation of calcium during the process of calcium transport across the chorioallantoic membrane.

Animals↗

PubMed1992

Sodium-dependent short-circuit current across the yolk sac membrane during embryonic development in normal and shell-less cultured chicks.

The transepithelial electrical characteristics of the isolated yolk sac membrane of normal in ovo or shell-less cultured chick embryos were investigated. In normal chicks the potential difference (blood side positive relative to yolk side) and short-circuit current of the membrane increased during development. Ouabain (10(-4) M) on the blood side (basolateral side, serosal side) significantly decreased potential difference and short-circuit current but was without effect on the yolk side (brush border side, mucosal side). Substitution of choline for Na+ in the bathing solutions abolished the potential difference and the short-circuit current; when Na+ replaced choline this effect was reversed. Amiloride added to both sides of the yolk sac membrane had no effect on potential difference or short-circuit current. Injection of aldosterone (50 micrograms) and T3 (10 microM) into yolk did not induce amiloride sensitivity. The short-circuit current was not altered by addition of either glucose or alanine to the bath. The short-circuit current of the yolk sac membrane of shell-less cultured embryos was significantly lower than that of normal controls. Addition of Ca2+ to the serosal bathing medium did not reverse the foregoing condition, but decreased the short-circuit current. It is concluded that the yolk sac short-circuit current is Na+ dependent and increases with developmental age in the chick embryo.

Animals↗

PubMed1992

A new method for determination of urinary citrate.

We have developed a new assay technique using high-performance liquid chromatography. The assay was performed at a flow rate of 0.7 ml/min, a temperature of 60 degrees C and an ultraviolet absorption of 214 nm. Comparison of the results of the new assay with the results obtained for identical samples using the conventional fluorometric method demonstrated a very high correlation coefficient of 0.931.

Adult↗

PubMed1992

The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer.

We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Direct projections from the central amygdaloid nucleus to the globus pallidus and substantia nigra in the cat.

Employing both anterograde and retrograde axonal tracing, we investigated direct projections from the central amygdaloid nucleus to the basal ganglia in the cat. The anterograde axonal tracing of Phaseolus vulgaris-leucoagglutinin revealed that projection fibers from the central amygdaloid nucleus to the basal ganglia ended in the globus pallidus (the feline homolog to the external segment of the globus pallidus of primates) and substantia nigra. The amygdalopallidal fibers terminated chiefly in the medial most part of the globus pallidus at its caudal level. The amygdalonigral fibers terminated densely in the substantia nigra pars lateralis, and moderately in the dorsolateral part of the substantia nigra pars reticulata; none of them were found to end in the substantia nigra pars compacta. Both of the amygdalopallidal and amygdalonigral projections were ipsilateral. These neuronal connections were confirmed by retrograde axonal tracing of cholera toxin B subunit in the second set of the experiments: The cells of origin of the amygdalopallidal and amygdalonigral projections were located predominantly in the lateral part of the central amygdaloid nucleus, and additionally in the intercalated cell islands of the amygdala. Most of them were of small bipolar or multipolar type. The cells projecting to the globus pallidus were preferentially distributed at the rostral levels of the central nucleus and intercalated cell islands of the amygdaloid complex, while those projecting to the substantia nigra were mainly located at the caudal levels of these amygdaloid subdivisions. In the third set of the experiments, sequential double-antigen immunofluorescence histochemistry for transported cholera toxin B subunit and horseradish peroxidase showed that some single neurons in the lateral part of the central amygdaloid nucleus, particularly at its middle level, issued axon collaterals to both the globus pallidus and substantia nigra pars lateralis. The results of the present study indicate that the central amygdaloid nucleus sends projection fibers to the globus pallidus and substantia nigra possibly to exert a limbic influence upon forebrain motor mechanisms.

Amygdala↗

PubMed1992

Dopaminergic and non-dopaminergic neurons in the ventral tegmental area of the rat project, respectively, to the cerebellar cortex and deep cerebellar nuclei.

It has been suggested recently that dopamine in the cerebellum not only acts as a precursor for noradrenaline in afferent fibers supplied by locus coeruleus neurons, but also subserves an independent transmitter role in a separate neural system. The present study was initiated to investigate the possible sources for dopaminergic innervation of the cerebellum. Employing anterograde and retrograde axonal tracing with cholera toxin and a combination of fluorescent retrograde axonal tracing with Fluoro-Gold and tyrosine hydroxylase immunofluorescence histochemistry, we found in the rat that the ventral tegmental area, containing the A10 dopaminergic cell group, sends projection fibers to the cerebellum bilaterally with a slight contralateral predominance. The projections from the ventral tegmental area to the cerebellum were segregated into the dopaminergic one to the cerebellar cortex and the non-dopaminergic one to the deep cerebellar nuclei. Dopaminergic fibers projecting from the ventral tegmental area to the cerebellar cortex terminated mainly in the granular layer, additionally in the Purkinje cell layer, but not at all in the molecular layer. They were distributed predominantly in the crus I ansiform lobule and paraflocculus, and to a lesser extent in the crus II ansiform lobule. On the other hand, non-dopaminergic fibers projecting from the ventral tegmental area to the deep cerebellar nuclei were seen to terminate mainly in the lateral nucleus, to a lesser extent in the interpositus nucleus, but not at all in the medial nucleus. The ventral tegmental area was also observed to receive projection fibers from the lateral and interpositus cerebellar nuclei bilaterally with a contralateral predominance. The projections from the ventral tegmental area to the cerebellum revealed in the present study might exert limbic influences upon the cerebro-cerebellar loops subserving the execution and co-ordination of voluntary movements.

Animals↗

PubMed1992

Mitomycin C, vindesine, and cisplatin in advanced non-small-cell lung cancer. A phase II study.

Between August 1985 and June 1986, 49 previously untreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) were treated with the combination of cisplatin 80 mg/m2 i.v. on day 1, vindesine 3 mg/m2 i.v. on days 1 and 8, and mitomycin-C 8 mg/m2 i.v. on day 1 (MVP), repeating after an interval of 4 weeks, and thereafter every 6 weeks. The median age for all patients was 62 years, with a range of 21 to 77 years. All patients had a performance status of 0, 1, or 2 (ECOG scale) and measurable disease. Histologic types included squamous cell carcinoma (22 patients), adenocarcinoma (22 patients), and large-cell carcinoma (6 patients). Forty-eight patients were evaluable for response. Out of 48 patients, one (2%) achieved a complete response and 24 patients (50%) achieved a partial response, resulting in an overall response rate of 52% (95% confidence interval, 38-68%). The response rates were 52% for squamous cell carcinoma, 45% for adenocarcinoma, and 80% for large-cell carcinoma, respectively. The median duration of response was 4.2 months and the median duration of survival for all patients was 10.6 months. The major toxicity was myelosuppression. Leukopenia and thrombocytopenia of grade 3 or 4 occurred in 85% and 33%, respectively. One patient died of sepsis associated with leukopenia. Other toxicities were manageable and reversible. In conclusion, the MVP regimen was active and tolerable in patients with advanced NSCLC. Prospective randomized study comparing the MVP regimen with the two-drug combination of vindesine and cisplatin is warranted.

Adult↗

PubMed1992

The pH dependent uptake of enoxacin by rat intestinal brush-border membrane vesicles.

The mechanism of the intestinal transport of enoxacin, an orally active fluoroquinolone antibiotic, has been investigated using brush-border membrane vesicles isolated from rat small intestine. The initial rate and time-course of enoxacin uptake were considerably dependent upon the medium pH (pH 5.5 greater than pH 7.5) and upon the percent ionization of the carboxyl group (pKa 6.2, anionic charge), namely, the degree of uptake of cationic form was higher than that of the zwitterionic form. There was evidence of transport into the intravesicular space as shown by the effect of extravesicular medium osmolarity on enoxacin uptake at steady state (30 min). This transport across the brush-border membrane was stimulated by the valinomycin-induced K(+)-diffusion potential (interior negative) and an outward H(+)-diffusion potential. Furthermore, changing the pH of the medium from 5.5 to 7.5 significantly decreased the effect of valinomycin-induced K(+)-diffusion potential on the enoxacin uptake. These results suggest that the uptake behaviour of the cationic form of enoxacin plays an important role in the intestinal absorption process of enoxacin.

Animals↗

PubMed1992

[Colonization rates of Mobiluncus spp. in female lower genital tract and its relationship with bacterial vaginosis].

To clarify the colonization rate of Mobiluncus spp., 889 specimens were collected from the vagina and 688 specimens from the cervical canal in three groups of women, namely, non-pregnant women, pregnant women, and patients fulfilling the criteria of bacterial vaginosis. On screening, this organism was detected from the vagina in 18/576 cases (3.2%) in non-pregnant women and in 2/280 cases (0.7%) in pregnant women, and it was detected from the cervical canal in 12/410 cases (2.9%) in non-pregnant women, and 3/278 (1.1%) in pregnant women. Although the positive rates were slightly higher in non-pregnant women from both the vagina and cervical canal, they were not significant. However, in cases of bacterial vaginosis, the positive rate of Mobiluncus spp. was 9/33 cases (27.3%), so that it was significantly higher than in the other two groups. Although the role of Mobiluncus spp. in bacterial vaginosis has not been clarified, our results indicate that the presence of Mobiluncus spp. is abnormal, since its colonization rate in healthy women is too small to be regarded as a member of normal flora. G. vaqinalis and anaerobes (other than Mobiluncus spp.) are also closely connected to bacterial vaginosis. G. vaginalis alone was seen in 7/33 cases (21.3%), anaerobes alone in 7/33 (21.3%), and Mobiluncus spp. alone in 3/33 cases (9.1%). Multiple infections including 2 or 3 of the above organisms were seen in 13/33 cases (39.3%), and all cases had anaerobes. On the other band, only three cases were infected by none of the above organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Isolation rates and pathogenicity of enterococci in obstetric and gynecological operations.

Isolation of enterococci in patients undergoing obstetric and gynecological operations was studied as well as reviewing the postoperative infection due to this organism during the period from 1985 to 1990. 1) In 126 cases undergoing abdominal total hysterectomy, vaginal specimens were obtained before and after (3rd day) the operation. The isolation rates increased after the operation (before 16.7%, after 35.7%). They increased not only in the group using PIPC, CEZ, CEPR, CMZ, and LMOX by drip infusion but also in the group without prophylactic use of antibiotics. On the other hand in the group using CP vaginal suppositories, the isolation rate decreased. However no statistical proof was obtained as to antibiotics especially in regard to cephem drugs as the reason for the increase. 2) Enterococci were isolated from the surgical field during abdominal total hysterectomy in only 2.0% (n = 88). 3) Isolation rates of enterococci inside the transvaginal drain following radical hysterectomy (n = 30) reached 86.7%. 4) E. faecalis was isolated in 20.0% of the cases with wound infection (n = 25). However isolated Enterococcus strains were not regarded to be the causative organism. 5) There was one case of postoperative enterococcal septicemia in treating stage Ib adenocarcinoma of the uterine cervix.

Anti-Bacterial Agents↗

PubMed1992

Influence of morphologic factors on calcium-containing stone formation.

Pathogenesis of urolithiasis cannot be explained only by metabolic disorder. In the present study, morphologic differences of the renal pelvic-caliceal system (PCS) were examined on both the stone and normal sides in calcium-containing stone formers. The results indicated that as compared to the normal side, the urine flow in the PCS was stagnant or not straight on the stone side even in the same individual, showing unfavorable conditions for stone formation. It is therefore considered that morphologic disorders of the urinary tract may be one of the causes for stone formation.

Adult↗

PubMed1992

Renal damages after extracorporeal shock wave lithotripsy evaluated by Gd-DTPA-enhanced dynamic magnetic resonance imaging.

Renal damages after extracorporeal shock wave lithotripsy (ESWL) were evaluated by magnetic resonance imaging (MRI) including Gd-DTPA-enhanced dynamic MRI in 37 patients with renal stone by spin echo methods (T1 and T2-weighted scan) and small tip angle gradient echo method (T2-weighted scan). Sixty-eight percent of the patients had changes in the MRI findings after ESWL. The frequently observed findings were perirenal fluid collection (38%), loss of corticomedullary junction (35%), and increased signal intensity of muscle and other adjacent tissue (34%). Preoperative Gd-DTPA-enhanced dynamic MRI showed low intensity band which suggests Gd-DTPA secretion from the glomerulus into the renal tubulus. In all cases the low intensity band became unclear after ESWL because of renal contusion due to ESWL. MRI, including Gd-DTPA-enhanced dynamic MRI, is considered to be a good procedure for evaluation of renal damages due to ESWL.

Contrast Media↗

PubMed1992

CPT-11 in combination with cisplatin for advanced non-small-cell lung cancer.

PURPOSE: The purpose of this study was to determine the maximum-tolerated dose and the dose-limiting toxicities of CPT-11, a new derivative of camptothecin, in combination with a fixed dose of cisplatin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-seven previously untreated patients with stage IIIB or IV NSCLC were assessable for toxicity, and 26 were assessable for response. The initial dose of CPT-11 was 30 mg/m2 given as a 90-minute intravenous (IV) infusion on days 1, 8, and 15 in combination with cisplatin (80 mg/m2 IV on day 1) given every 4 weeks. The dose of CPT-11 was escalated in increments of 10 mg/m2 until severe or life-threatening toxic effects were observed. RESULTS: Significant toxicity was infrequent up to 60 mg/m2 of CPT-11. The maximum-tolerated toxicity was reached at a dose of 70 mg/m2. Three of six patients either had leukocyte count nadirs of less than 2,000/microL or experienced grade 4 diarrhea during the first cycle of therapy at 70 mg/m2. The major toxic effects were leukopenia and diarrhea. There were 14 partial responses (54%) among the 26 patients. CONCLUSIONS: A combination of CPT-11 and cisplatin seems to be effective against NSCLC with acceptable toxicities. The recommended dose for phase II studies is 60 mg/m2 of CPT-11 on days 1, 8, and 15, and 80 mg/m2 of cisplatin on day 1 every 4 weeks.

Adult↗

PubMed1992

CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To evaluate the activity of CPT-11, which is a new derivative of camptothecin, against refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Sixteen patients with refractory or relapsed SCLC were entered onto a prospective, non-randomized, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Five patients had received previous chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide (CODE) as an induction therapy. Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous (IV) infusion every week with subsequent doses based on toxicity. Fifteen patients were assessable for toxicity, response, and survival. RESULTS: Seven patients (47%; 95% confidence limits for an overall response rate, 21.4% to 71.9%) responded to CPT-11 with a median duration of response of 58 days. The major toxicities were myelosuppression (predominantly leukopenia), diarrhea, and pulmonary toxicity. CONCLUSION: CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SCLC.

Adult↗

PubMed1992

Antitumor effect of pluronic F-127 gel containing mitomycin C on sarcoma-180 ascites tumor in mice.

Pluronic F-127 (PLF-127) gels were evaluated as a sustained-release vehicle for intraperitoneal administration of mitomycin C (MMC) in order to enhance the therapeutic effects of MMC against a Sarcoma-180 ascites tumor in mice. Tumor cell injections were made on day 0 and injections of MMC in 25% (w/w) PLF-127 on day 1, both intraperitoneally. A prolongation of the life span of tumor-bearing mice following injection of therapeutic PLF-127 was noted, and PLF-127 containing MMC was therapeutically more active than free drug. The high chemotherapeutic efficiency of MMC in PLF-127 was striking at high doses, which would be toxic in the case of the drug alone. PLF-127 gels exhibit reverse thermal behavior and are fluid at refrigerator temperature, but are soft gels at body temperature. The in vitro release experiments indicated that Pluronic gel might serve as a rate-controlling barrier and be useful as a vehicle for sustained-release preparations of MMC to be administered intraperitoneally. These results suggest that sustained-release occurs in the peritoneum and that effective drug concentrations can be maintained by the preparation.

Animals↗

PubMed1992

External control of drug release and penetration. VI. Enhancing effect of ultrasound on the transdermal absorption of indomethacin from an ointment in rats.

The effect of an ultrasound (1 MHz) on transdermal absorption of indomethacin from an ointment was studied in rats. Ultrasound energy was supplied for between 5 and 20 min at a range of intensities (0.25, 0.5, 0.75, and 1 W cm-2), energy levels commonly used for therapeutic purposes. For evaluating skin penetration of indomethacin, the change of plasma concentration was measured. The pronounced effect of ultrasound on the transdermal absorption of indomethacin was observed at all ultrasound energy levels studied. The intensity and the time of application were found to play an important role in the transdermal phonophoretic delivery system of indomethacin; 0.75 W cm-2 appeared to be the most effective intensity in improving the transdermal absorption of indomethacin, while the 10 min ultrasound treatment was the most effective. Although the highest penetration was observed at an intensity of 0.75 W cm-2, 0.5 W cm-2 was preferred because intensities of less than 0.5 W cm-2 of ultrasound for 10 min did not result in any significant skin temperature rise nor did it have any destructive effect on rat skin. Progressively more skin damage was noted as the intensity and the time of application of ultrasound increased. When used at a proper intensity and time of application, ultrasound appears to be a safe technique for enhancing the passage of various drug molecules through human skin.

Administration, Cutaneous↗