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Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 307 records · Page 17Linked to original sources
PubMed1994

Topographic organization of collateral projections from the basolateral amygdaloid nucleus to both the prefrontal cortex and nucleus accumbens in the rat.

The basolateral amygdaloid nucleus, a limbic/autonomic center in the basal forebrain, has been known to send projection fibers to the prelimbic and dorsal agranular insular areas in the prefrontal cortex, as well as to the nucleus accumbens. In the present study, we investigated single basolateral amygdaloid nucleus neurons sending their axons to both the prefrontal cortex and nucleus accumbens. The fluorescent retrograde double-labeling technique was employed in the rat; True Blue was injected into the prelimbic or dorsal agranular insular cortex, and Diamidino Yellow into the medial or lateral part of the nucleus accumbens. The majority of basolateral amygdaloid nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic cortex were located, respectively, in the rostral two-thirds or caudal two-thirds of the nucleus, while those projecting to the medial or lateral part of the nucleus accumbens were diffusely distributed in the nucleus. Almost 50% of basolateral amygdaloid nucleus neurons projecting to the prelimbic cortex sent their axon collaterals to the medial part of the nucleus accumbens. About 30-40% of basolateral amygdaloid nucleus neurons projecting to the dorsal agranular insular cortex or prelimbic cortex issued their axon collaterals to the lateral part of the nucleus accumbens. The axons bifurcating to both the dorsal agranular insular cortex and lateral part of the nucleus accumbens, those bifurcating to both the prelimbic cortex and lateral part of the nucleus accumbens, or those bifurcating to both the prelimbic cortex and medial part of the nucleus accumbens arose preferentially from the rostral, middle or caudal parts of the basolateral amygdaloid nucleus, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗
PubMed1994

Single neurons in the ventral tegmental area that project to both the cerebral and cerebellar cortical areas by way of axon collaterals.

Recently, we have found that the ventral tegmental area of the rat sends dopaminergic and non-dopaminergic axons, respectively, to the cerebellar cortex and deep cerebellar nuclei [Ikai et al. (1992) Neuroscience 51, 719-728]. In the present study, employing fluorescent retrograde double labeling with Fast Blue and Diamidino Yellow, we examined whether individual neurons in the ventral tegmental area of the rat send their axons to both the cerebellum and other brain regions. The neurons projecting to the cerebellar cortex often issued axon collaterals to the cerebral cortical areas, including the prelimbic-anterior cingulate cortices and piriform-entorhinal cortices, but not so frequently to the subcortical regions, including the nucleus accumbens, lateral septum, amygdala, and lateral habenula. On the other hand, the neurons projecting to the deep cerebellar nuclei rarely sent axon collaterals to the cerebral cortical and subcortical regions.

Animals↗
PubMed1994

Topographical organization of subicular neurons projecting to subcortical regions.

Direct projections from the subiculum to the septum, thalamus, and hypothalamus were studied in the rat by the fluorescent retrograde double-labeling technique with Fast blue and Diamidino yellow. The results confirm and extend the previously reported findings. The dorsal subiculum projects primarily to the lateral septum, anterior and midline thalamus, and mammillary complex. The distribution areas of cell bodies of these projection neurons are substantially segregated, depending on their target region, and few single neurons project to two of the target regions by way of axon collaterals. The ventral subiculum projects mainly to the lateral septum, midline thalamus, and ventromedial hypothalamic area. The distribution areas of cell bodies of these projection neurons are considerably overlapped with one another, and a number of single neurons send axon collaterals to two of the lateral septum, midline thalamus, and ventromedial hypothalamic area. It is, thus, indicated that the populations of subicular neurons projecting to each of the subcortical structures examined are more distinctly segregated in the dorsal subiculum than in the ventral subiculum.

Amidines↗
PubMed1994

Measurement of free insulin-like growth factor-I using immunoradiometric assay.

The free Insulin-like growth factor-I (IGF-I) in plasma from normal adults was directly measured with a newly developed highly sensitive immunoradiometric assay (IRMA) for IGF-I. The capture antibody did not crossreact with IGF-I associated binding proteins which exist in plasma, and the assay was designed not to shift the equilibrium of the IGF-I and binding proteins. Total IGF-I concentration was measured using this assay with preliminary acid-ethanol extraction. Approximately 1 percent of total IGF-I existed in the free form. Gel filtration of plasma was also used to separate the free IGF-I from its bound form. The free/total ratio of IGF-I as determined by gel filtration was similar to that determined directly by IRMA with and without acid-ethanol extraction.

Adult↗
PubMed1994

pH-sensitive dissociation and association of beta-N-acetylhexosaminidase from boar sperm acrosome.

beta-N-Acetylhexosaminidase (beta-Hex, EC, 3.2.1.52) was released from cauda epididymal boar sperm by treatment with ionophore A23187, indicating that this enzyme is localized in the acrosome. beta-Hex was extracted on a large scale, with 2% acetic acid containing 0.2% Brij 35, from washed ejaculated sperm. By gel filtration chromatography, beta-Hex was separated into a high-molecular-weight fraction (beta-Hex I) and a low-molecular-weight fraction (beta-Hex I). beta-Hex I, which is predominant under acidic conditions (pH 6.5), dissociated into beta-Hex II under alkaline conditions (pH 7.4). beta-Hex II, converted from beta-Hex I, associated again to form beta-Hex I under acidic conditions. By sequential chromatography on ion-exchange, lectin, gel filtration, and ion-exchange HPLC columns, beta-Hex I and II were purified 1200-fold and 4000-fold, respectively, with a combined recovery of 23% as measured with synthetic substrate. An inhibitor of beta-Hex, O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl-carbamate (PUGNAC), reduced the in vitro fertilization rate in porcine cumulus-enclosed eggs, but barely changed the rate when cumulus-free eggs were used. beta-Hex I was shown to possess cumulus dispersion activity, suggesting that beta-Hex plays a role in the passing by sperm through cumulus cells before they bind to the zona pellucida.

Acetylglucosamine↗
PubMed1994

The significance of CD44 in human pancreatic cancer: I. High expression of CD44 in human pancreatic adenocarcinoma.

The CD44 cell surface glycoprotein, which is the adhesion molecule of lymphocytes, has been suggested to be an important factor for the metastatic potential and invasive ability of cancer. We demonstrated the expression of CD44 in human pancreatic adenocarcinoma cells and normal cells by using flow cytometry (FACS-can) and immunohistological staining. CD44 was highly expressed in human pancreatic adenocarcinoma cells, while it was little expressed in normal human pancreas cells. These results indicate that the quantitative analysis of CD44 expression may be a useful diagnostic tool for pancreatic cancer.

Adenocarcinoma↗
PubMed1994

The significance of CD44 in human pancreatic cancer: II. The role of CD44 in human pancreatic adenocarcinoma invasion.

In our previous report (1), we showed the high expression of CD44 in human pancreatic adenocarcinomas cells. Pancreatic cancer aggressively invades surrounding tissues by penetrating basement membrane barriers. To examine the relation between the biological characteristics of human pancreatic adenocarcinoma cells and CD44 expression, we studied the function of CD44 in cell proliferation and cell invasion using a Matrigel basement membrane. The proliferation of human pancreatic adenocarcinoma cells was not affected by anti-CD44 antibody. On the contrary, invasion of the cells was suppressed by anti-CD44 antibody. This result suggests that the CD44 molecule plays an important role in pancreatic cancer cell invasion of the basement membrane.

Adenocarcinoma↗
PubMed1994

The stimulative effect of diffusion potential on enoxacin uptake across rat intestinal brush-border membranes.

Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal brush-border membrane vesicles has been found. The transient overshooting uptake of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in the presence of an outward H(+)-gradient. Momentary dissipation of the H(+)-gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed by an interior positive K(+)-diffusion potential induced by valinomycin. Furthermore, not only the outward H(+)-gradient but also an inward Cl(-)-gradient caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl(-)-gradient was dissipated by using voltage-clamped membrane vesicles. These results indicate that enoxacin transportation across the brush-border membrane is dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the presence of an inward (for Gly-Gly) or outward (for guanidine) H(+)-gradient as a driving force for each transport system. Therefore, it seems that enoxacin transport through the intestinal epithelia does not participate in the carrier-mediated transport systems for Gly-Gly and guanidine.

Animals↗
PubMed1994

Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer.

PURPOSE: For patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC), radiotherapy (RT) has been used conventionally for many years. Few prospective trials have determined the role of RT. Recently, chemotherapy (CT) has been shown to produce excellent responses in regionally advanced disease. We therefore conducted a randomized trial using cisplatin (P)-based CT regimens with or without thoracic irradiation. PATIENTS AND METHODS: We randomly assigned 92 patients with locally advanced NSCLC to receive one of three arms of P-based combination chemotherapy: vindesine (V) plus P, mitomycin (M) plus V plus P, or etoposide (E) plus P alternating with V plus M. After two cycles of CT, patients were reevaluated and those with stage III were again randomized to receive RT or not. RT consisted of 50 to 60 Gy in 5 to 6 weeks; 2 Gy was delivered once daily in conventional fractions. RESULTS: Sixty-three patients were included in the second randomization. The patients in the CT/RT group (n = 32) and CT-alone group (n = 31) were comparable in terms of age, sex, performance status, histologic features, stage of disease, and induction CT regimen. The median durations of survival were similar for the two groups (461 days in CT/RT group and 447 days in CT-alone group). The survival rate in the CT/RT group was 58% at 1 year, 36% at 2 years, and 29% at 3 years, as compared with 66%, 9%, and 3% at 1, 2, and 3 years, respectively, in the CT-alone group. One patient in the CT/RT group died of pneumonitis, but there were no CT-related deaths. CONCLUSION: In locally advanced NSCLC, P-based combination CT followed by chest irradiation significantly increases the number of long-term survivors as compared with CT alone. RT to bulky disease in the thorax is thus an important part of combined modality therapy, and a necessary part of further studies in locally advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase I and pharmacologic study of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor support for advanced lung cancer.

PURPOSE: We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) support because of the overlapping neutrophil toxicity of both drugs. The aim was to determine the maximum-tolerated dose of CPT-11 combined with a fixed dose of etoposide in patients with advanced lung cancer, as well as the dose-limiting toxicities of this combination. PATIENTS AND METHODS: Twenty-five patients with stage III or IV lung cancer, 15 (60%) with prior chemotherapy, were treated at 4-week intervals using CPT-11 (90-minute intravenous infusion on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3). In addition, rhG-CSF (2 micrograms/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. The starting dose of CPT-11 was 60 mg/m2, and it was escalated in 10-mg/m2 increments until the maximum-tolerated dose was reached. RESULTS: The maximum-tolerated dose of CPT-11 was 90 mg/m2, since two of the three patients developed grade 3 to 4 leukopenia or grade 3 to 4 diarrhea during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the dose-limiting toxicities, while thrombocytopenia was only a moderate problem. Elimination of CPT-11 was biphasic, with a mean +/- SD beta half-life of 18.17 +/- 9.09 hours. The mean terminal half-life of 7-ethyl-10-hydroxycamptothecin (SN-38; the major metabolite of CPT-11) was 43.40 +/- 37.84 hours. There was one complete response (5%) and eight partial responses (38%) among 21 assessable patients, for an overall response rate of 43%. The response rates for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) were 58% (seven of 12 patients) and 22% (two of nine patients), respectively. CONCLUSION: The combination of CPT-11 and etoposide with rhG-CSF support seems to be active against lung cancer, especially SCLC, with acceptable toxicity. The recommended dose for phase II studies in previously untreated patients is 80 mg/m2 of CPT-11 (days 1, 8, and 15) and 80 mg/m2 of etoposide (days 1 to 3) plus 2 micrograms/kg of rhG-CSF (days 4 to 21, except when CPT-11 is given). In addition, 70 mg/m2 of CPT-11 appears to be the appropriate dose for previously treated patients receiving this regimen.

Adult↗
PubMed1994

Urinary levels of gamma-carboxyglutamic acid and its clinical significance.

Urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in healthy subjects of all ages. The urinary gamma-Gla levels were highest in infants (0-1 years), then fell in an age-dependent manner, again in subjects reaching a minimum value in adults, then gradually increased over 60 years of age. Urinary gamma-Gla levels therefore change markedly with aging. The relationships between the urinary gamma-Gla excretion and plasma levels of prothrombin and protein C in patients with various hepatic diseases or diabetes mellitus were examined and compared with those in healthy adults. Both plasma prothrombin and protein C levels were decreased in all patients with liver disease compared with healthy adults. In patients with hepatitis and liver cirrhosis, the decrease did not, however, affect the gamma-Gla excretion. In addition, in patients with hepatoma or carcinoma with liver metastases, the urinary gamma-Gla levels were increased. In patients with diabetes mellitus, the urinary gamma-Gla levels and plasma levels of prothrombin and protein C tended to increase, but this was not significant. The present results indicate that simultaneous measurement of the levels of urinary gamma-Gla and plasma prothrombin and protein C is a useful tool for the diagnosis of liver diseases and diabetes mellitus.

1-Carboxyglutamic Acid↗
PubMed1994

Sustained release of phenytoin following the oral administration of phenytoin sodium/ethylcellulose microcapsules in human subjects and rabbits.

Phenytoin sodium was microencapsulated with ethylcellulose (EC) by a coacervation-phase separation method from ethyl acetate solution to develop a prolonged release dosage form of phenytoin. Release of phenytoin from the microcapsules (phenytoin sodium/EC) was evaluated by the JP dissolution test in JP disintegration media No. 1 and No. 2. The release rates of phenytoin from phenytoin sodium powders were extremely rapid in both media, however, the release rates from the microcapsules were much more retarded. Following the oral administration of microcapsules to rabbits, prolonged plasma concentrations of phenytoin were obtained, while microcapsules orally administered to human subjects showed prolonged urinary excretion of phenytoin metabolites.

Administration, Oral↗
PubMed1994

Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery.

Bioadhesive tablets for intraoral drug delivery were prepared by directly compressing the drug with a mixture of chitosan and sodium alginate in weight ratios of 4:1, 1:1 and 1:4, and the adhesion and release characteristics of the prepared systems were evaluated in vitro and in vivo. Ketoprofen was used as a model drug. The magnitudes of the adhesion force of chitosan/alginate tablets were observed to be comparable to that of Aftach, which is a typical commercial preparation of an oral mucosal adhesive tablet. Increasing the chitosan content in the tablets resulted in a decrease in the release rate of ketoprofen. When the tablets were administered to the sublingual site of rabbits, ketoprofen from the tablets with chitosan/alginate was rapidly absorbed without an initial sharp peak. Furthermore, the plasma concentration curves for the tablet with a 1:4 chitosan/alginate ratio showed a sustained release 3 h after administration. The data presented suggest that tablets prepared from chitosan and alginate are potential candidates for intraoral drug delivery.

Adhesiveness↗
PubMed1994

Effects of microsphere suspension agents on systemic hemodynamics in rats. Comparison of nonradioactive colored and radioactive microspheres.

The systemic hemodynamic effects of different microsphere suspension agents were evaluated in 22 Sprague-Dawley male rats. Rats were divided into three groups, and three different solutions (distilled water; n = 7, 10% dextran; n = 8, and 70% glucose; n = 7) were injected through the left atrium respectively. 0.2 ml of each solution was injected repeatedly until significant hemodynamic changes developed. During four sequential injections, distilled water had no significant effects on cardiac output, mean arterial pressure, and heart rate. However, the 10% dextran (mol wt 70,000) solution produced significant decreases in both cardiac output and mean arterial blood pressure during and after the third injection. The 70% glucose solution also decreased, cardiac output significantly during the third injection. Although microspheres itself must cause some hemodynamic changes, our results indicated that the hemodynamic disturbances observed during a large dose injection of microspheres might have been at least in part due to the use of high-density suspending solutions. The doses of radioactive microsphere solution in many previous rat studies were usually less than 0.6 ml. However, in the case of large dose injection of microspheres, these results indicate that the suspending solutions can affect hemodynamic parameters in various ways.

Animals↗
PubMed1994

[Therapy-related acute non-lymphocytic leukemia (M2) with 7;11 chromosome translocation induced into complete remission by low dose cytosine arabinoside and cytarabine ocfosfate therapy].

A case of therapy-related acute non-lymphocytic leukemia (t-ANLL) in a 70-year-old female patient is reported. An operation for lung cancer was performed in February 1991, and she was treated with etoposide (VP-16), a topoisomerase II inhibitor. Nineteen months after the start of chemotherapy, she complained of palpitations, and anemia and thrombocytopenia developed. The myelogram revealed 41.2% leukemic cells, and a diagnosis of t-ANLL induced by VP-16 was made. The karyotype of bone marrow cells showed 46, XX, t(7;11) (p13;p15), 16p+. She obtained complete remission (CR) by treatment with low dose cytosine arabinoside (Ara-C) and cytarabine ocfosfate (SPAC). Karyotype with t-ANLL induced by alkylate agents frequently shows unbalanced abnormalities. The difference of cytogenetic findings suggest the difference of mechanisms. Detailed chromosomal analysis make clear the oncogenesis of t-ANLL. It is reported that the prognosis of patients with t-ANLL treated by conventional chemotherapy is poor. Considering that elderly cases of acute leukemia have a lower probability of achieving CR than non-elderly cases, because of complications and side effects of chemotherapy such as bone marrow suppression, treatment with low dose Ara-C and SPAC is thought to be indicated in elderly patients with t-ANLL.

Aged↗