Search PubMed⌕ Search

Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 415 records · Page 23Linked to original sources

[Morphological and immunohistochemical study of the placental villi in pregnancy complicated by systemic lupus erythematosus].

In 25 cases of pregnancy complicated by SLE, we examined the relationships between fetal growth and histopathological findings in the placental villi. The following results were obtained. 1. As for histological findings in the placenta, in most cases clear findings of circulatory disorders were obtained. 2. In the light microscopic visual field at x63, no difference was observed among the group in the cross section occupying rate of the villi and cross section area of the terminal villi, but in one case in the IUFD group, the villi were underdeveloped and the cross section occupying rate of the villi was low. 3. The villous/vascular cross section area ratio per single terminal villus became smaller in the following order: full term AFD group, full term SFD group, premature AFD group, and premature SFD group, and a significant difference was observed between the normal controls and the premature SFD group. 4. During immunoglobulin staining by the PAP method, IgG deposits were observed in the villous syncytiotrophoblasts and their periphery, in vascular endothelial cells in the villi, and in the villous interstitium, etc. in both the SLE cases and the normal controls, but deposits of IgM in the same regions were observed only in the premature SFD group of pregnancies complicated by SLE.

Adult↗

Regional localization of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) uptake: mismatch between its uptake and neurotoxic sites.

Three to 24 h following intraventricular injections of radioactive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the rat, accumulations of radiolabel were widely detected, in varying degree, over neuronal perikarya in motor-related structures below the midbrain. Pretreatment with the monoamine oxidase B inhibitor pargyline largely eliminated the perikaryal radiolabeling in the substantia nigra, dorsal raphe and cerebellum, leaving that in the other regions intact. These results indicate that there exists a certain mismatch between MPTP uptake and neurotoxic sites, and that invulnerable cells can accumulate MPTP without being converted to its major active metabolite 1-methyl-4-phenylpyridine (MPP+).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Double immunohistochemical detection of transmitter phenotype of proliferating cells using bromodeoxyuridine.

We describe a new method that can determine transmitter phenotype of proliferating nerve cells at a given age. The procedure is based on indirect sequential double antigen immunofluorescence histochemistry for transmitter-synthesizing enzymes (glutamic acid decarboxylase and tyrosine hydroxylase) and the thymidine analogue, bromodeoxyuridine. The method permits simple, rapid, and effective anatomical detection, and promises to reduce certain limitations inherent in a combination with tritiated thymidine autoradiography. Employing this technique, we observed that many striatal cells expressing gamma-aminobutyric acid (GABA) and nigral cells expressing dopamine undergo the final mitosis at embryonic days 13-14 in the rat.

Animals↗

Cholinergic projections from the globus pallidus to the lateral amygdaloid nucleus in the cat.

Direct projections from the globus pallidus (GP) to the lateral amygdaloid nucleus (A1) were found in the cat by the anterograde and retrograde tracing methods. Pallido-amygdaloid fibers originated mainly from the caudal half of the GP and distributed throughout the entire extent of the A1; most densely in the lateral part of the A1. Choline acetyltransferase immunohistochemistry in combination with retrograde fluorescent tracing indicated that most pallido-amygdaloid neurons were cholinergic.

Amygdala↗

Co-localization of tyrosine hydroxylase and glutamate decarboxylase in a subpopulation of single nigrotectal projection neurons.

The neurotransmitter phenotype(s) of nigral neurons innervating the superior colliculus (SC) in the rat was examined using a combination of immunohistochemical techniques and fluorescent retrograde tracing. After double-immunofluorescent histochemistry for tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD), single cells in the rostral ventrolateral portion of the substantia nigra pars reticulata (SNr) and to a lesser extent the substantia nigra pars lateralis (SN1) displayed immunoreactivity to both antigens. Furthermore, following True blue (TB) injections into the SC and incubation for both TH and GAD immunoreactivity, a considerable number of cells in the SNr retrogradely labeled with TB (approximately 10%) were also immunopositive for both synthetic enzymes. The present study provides evidence for the coexistence of TH and GAD and thus, the coexistence of dopamine and GABA in a subpopulation of single nigrotectal projection cells.

Animals↗

Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance.

Aged↗

A randomized study of cisplatin versus cisplatin plus vindesine for non-small cell lung carcinoma.

Between August 1983 and March 1985, a randomized study was conducted that compared cisplatin (CDDP) (80 mg/m2 on day 1) alone with CDDP plus vindesine (VDS) (3 mg/m2 on days 1, 8, and 15) in 160 consecutive patients with inoperable non-small cell lung cancer (NSCLC). There were no complete responses. The response rate for CDDP plus VDS (22 of 77 patients, 29%) was significantly higher than that for CDDP alone (9 of 78 patients, 12%) (P less than 0.05). However, no difference existed in the median duration of response (20 weeks for CDDP plus VDS versus 20 weeks for CDDP alone) or the median survival time (45 weeks for CDDP plus VDS versus 39 weeks for CDDP alone). No significant differences in toxicity were detected between the two arms; myelosuppression, alopecia, and peripheral neuropathy occurred more frequently with CDDP plus VDS and there was one lethal episode of hepatorenal syndrome in the CDDP plus VDS arm. Among the variables Eastern Cooperative Oncology Group (ECOG) performance status (PS), age, sex, stage, weight loss, serum lactate dehydrogenase (LDH) level, albumin level, histologic cell type, and chemotherapy arm, only chemotherapy arm was a significant factor leading to a major response (P = 0.019, multiple logistic regression analysis). The significant predictors of survival were PS (P = 0.000), sex (P = 0.000), and stage (P = 0.002) (Cox's proportional hazards model), with a PS of 0 or 1, female sex, and lower stage yielding the best survival. Although a significantly higher response rate was obtained in the combination arm than in the single agent arm, the survival benefit to patients receiving such combination chemotherapy was not determined and more effective chemotherapy regimens are required.

Adult↗

A phase I study of chronic daily dosing of oral etoposide in combination with cisplatin for patients with advanced cancer.

A dose escalation study of daily oral etoposide and cisplatin was carried out on 22 patients with advanced cancer using starting doses of 20 mg/m2/d of etoposide given orally for 21 days and 80 mg/m2 of cisplatin given intravenously (IV) on day 1. A total of 40 courses were given. Myelosuppression was the major dose-limiting toxicity, with a maximum tolerated dose of 50 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. Doses of 40 mg/m2/d of etoposide for 21 days plus 80 mg/m2 of cisplatin for 1 day in four of eight courses (50%) were associated with Grade 3 or worse leukopenia that occurred between days 18 and 26. However, no Grade 3 or worse thrombocytopenia occurred at this dose level. Nausea and vomiting occurred in most patients at each dose level but were mild and could be controlled by antiemetics. Alopecia also occurred frequently. Significant mucositis (Grade 4) occurred in one patient, but no other toxicities were observed. Four partial responses that lasted from 1.3 to 5.8+ months were observed in patients with cervical (one patient), small cell lung (one patient), and squamous cell lung cancer (two patients); one of them had been heavily pretreated with platin analogue-containing regimens. The recommended doses for Phase II studies on this schedule are 40 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. A combination regimen on this schedule seems particularly effective in patients with etoposide-sensitive malignancies.

Adult↗

Single dopaminergic nigrostriatal neurons form two chemically distinct synaptic types: possible transmitter segregation within neurons.

These experiments were designed to examine a paradox present in the literature with regard to the fine structure of nigrostriatal dopamine terminals within the rat striatum. Previous studies have shown that anterograde transport of tritiated labeled proteins from the substantia nigra to the striatum over short survival times primarily labels asymmetric synapses (and that these asymmetric synapses are preferentially vulnerable to selective dopaminergic neurotoxins such as 6-hydroxydopamine). In contrast, fine structural immunohistochemical studies with antibodies to tyrosine hydroxylase and dopamine have consistently labeled primarily symmetric synapses en passant within the striatum. We have now confirmed that these two seemingly contradictory types of labeled synapses (radio- and immuno-labeled) can both be present, but most often separate from one another, in single ultrathin sections. However, we also found that radiolabeled unmyelinated axons were usually double-labeled by tyrosine hydroxylase immunohistochemistry. Employing longer survival times (10 days after the nigral isotope injections) in order to enhance the ratio of "en passant" to terminal labeling produced a large increase in the occurrence of radiolabeled striatal axonal varicosities with the result that many symmetric synapses en passant were double-labeled with both the autoradiographic and the immunohistochemical markers. Given that more than 95% of the nigrostriatal projection arises from dopamine fluorescent neurons, it would appear that both the asymmetric and symmetric terminals belong to the same type of neuron. Thus, we suggest that single dopaminergic neurons in the substantia nigra make two types of synaptic contact with striatal cells: 1) symmetric synapses en passant, which can be stained with tyrosine hydroxylase and dopamine and which contact dendritic spine necks, and 2) asymmetric terminal boutons of unknown chemical nature which end on dendritic spine heads. We conclude that both the asymmetric terminal and symmetric en passant synapses take origin from a single nigrostriatal dopaminergic neuronal population and that dopaminergic transmitter markers occur only in one of these synaptic types in the rat striatum.

Animals↗

Surgical treatment of cavernous angioma involving the brainstem and review of the literature.

Five cases of symptomatic cavernous angioma involving the brainstem are reported. Magnetic resonance (MR) imaging is of greatest value in the diagnosis and for surgical indication. All cases were treated by radical extirpation. All of them improved postoperatively. The surgical indications for this lesion of the brainstem are briefly discussed with a review of the literature, including 28 previous cases, operated on directly.

Adolescent↗

Relationship between metabolic acidosis and calcium phosphate urinary stone formation in women.

The relationship between the degree of metabolic acidosis and calcium phosphate stone formation was studied. Furthermore, the reasons why renal tubular acidosis (RTA) and primary hyperparathyroidism (PHPT) dominantly occur in women, and female stone formers more often produce calcium phosphate stone are discussed. Blood was slightly more acidotic in women than in men in both the urolithiasis and the control groups. Likewise, blood was significantly more acidotic and urinary pH significantly higher in patients with PHPT. Patients with RTA had severe metabolic acidosis, and urinary pH was highest among all groups. Calcium phosphate concentration was significantly higher in women than in men, and was also higher in patients with PHPT than in those with urolithiasis. All patients with RTA had pure calcium phosphate stones. The reasons why females are more acidotic and have more calcium phosphate in stones are suspected to be related to progesterone and urinary tract infection.

Acidosis, Renal Tubular↗

Morphological changes of striatal dopaminergic presynaptic boutons following intrastriatal kainate injection.

Bouton-sparing properties of kainic acid were re-investigated at the fine structural level. Two to 42 days after kainic acid (2.2-5.0 nmol) injection into the rat striatum, nigrostriatal dopaminergic boutons were examined at the injection site using tyrosine hydroxylase immunohistochemistry. Injection of the toxin produced marked dilatations of intensely tyrosine hydroxylase-positive boutons with tremendous amounts of vacuoles. Active astroglial processes reacted with those enlarged, immunoreactive boutons. Thus these boutons, if not all, are interpreted as being in the process of degeneration. Such enlarged boutons were observed more frequently at longer survival times than at shorter ones, suggesting an indirect effect of kainic acid resulting from severe loss of postsynaptic neuronal elements. Morphological changes described here may explain biochemical features that tyrosine hydroxylase level of the kainic acid affected striatum, following initial elevation, gradually decreases at a later stage.

Animals↗

Redevelopment of small-cell lung cancer nine years after the start of therapy. A case report and review of the literature.

Most patients with small-cell lung cancer usually relapse within 1 to 2 years. Relapses after a 5-year disease-free interval occur extremely rarely. This report describes a patient with limited-stage small-cell lung cancer who had achieved a complete response to combination chemotherapy followed by chest irradiation but developed small-cell lung cancer 9.4 years after the beginning of therapy. Small-cell lung cancer recurred in the same side of the lung, in the mediastinal nodes, and in the liver. The pattern of development of small-cell lung cancer suggests that the patient had a relapse rather than a metachronous lung cancer. To our knowledge, this is the second-latest relapse of small-cell lung cancer in the literature.

Aged↗

Wischnevsky's gastric lesions in accidental hypothermia.

We examine the pathogenesis of Wischnevsky's lesions. These gastric lesions were found in 15 of 17 deaths due to accidental hypothermia. Deaths occurred at various minimum temperatures (-2.4-20.4 degrees C); gastric lesions did not always reflect exposure temperatures. However, all victims exposed to temperatures greater than 10 degrees C had severe lesions. At temperatures less than 5 degrees C, on the other hand, severe gastric lesions were seen in victims younger (43.2 years old) than those with mild lesions (61.0 years old). These findings suggest that gastric lesions develop by exposure to temperatures at which the body's response to cold stress continues, or as result of a strong response to short-term stress. Histopathologic examination demonstrated a characteristic finding of cystic dilatation of the capillaries, presumably due to massive reperfusion after functional collapse of the microcirculation in the gastric mucosa.

Accidents↗

External control of drug release and penetration: enhancement of the transdermal absorption of indomethacin by ultrasound irradiation.

The effect of ultrasound (1 MHz) on transdermal absorption of indomethacin from an ointment has been studied in rats. Ultrasound energy was supplied for 10 min at a range of intensities (0.25, 0.5 and 0.75 W cm-2), energy levels commonly used for therapeutic purposes. The pronounced effect of ultrasound on transdermal absorption of indomethacin was observed for all three intensities studied. The mean AUC value (33.22 micrograms h mL-1) after irradiation at 0.75 W cm-2 was 3.4 times the control value (9.70 micrograms h mL-1).

Administration, Cutaneous↗

Immunofluorescent study on the interaction between collagen and calcium oxalate crystals in the renal tubules.

The interaction of calcium oxalate crystals and renal tubular cells was studied. Rat renal collecting tubular cells were cultured and immunologically stained with anti-type-IV collagen antiserum (type-IV collagen exists in renal tubular basement membrane). When renal tubular cells and calcium oxalate crystals were mixed, clumps were formed. These clumps were examined by immunological staining with anti-type-IV collagen antiserum. In another series of experiments, calcium-containing crystals were found to be adsorbed onto mucous threads and cast-like materials, although no such adsorption was observed on squamous cells. These absorbed materials interacted with anti-type-IV collagen antiserum. These results suggest that collagen in the renal tubular basement membrane may act as matrix in urinary stone formation.

Animals↗

A randomized trial in inoperable non-small-cell lung cancer: vindesine and cisplatin versus mitomycin, vindesine, and cisplatin versus etoposide and cisplatin alternating with vindesine and mitomycin.

Patients with inoperable non-small-cell lung cancer (NSCLC) were randomly assigned to receive one of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine, and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). In 199 assessable patients, the response rates were VP, 33%; MVP, 43%; and EP/VM, 19%. The addition of mitomycin to the VP regimen did not significantly improve the response rate. The response rate was significantly lower with the EP/VM regimen than with the MVP regimen (P less than .01). The median survival times were VP, 50 weeks; MVP, 42 weeks; and EP/VM, 40 weeks. These differences were not significant. Grade III or IV thrombocytopenia was significantly greater (P less than .01) in MVP patients (22%) than in the VP (5%). Other toxicities were similar in the three groups. Analyses of prognostic factors showed that treatment with MVP, sex, and histologic classification (squamous cell carcinoma) were predictive of improved response. Important factors for improved survival, according to the Cox regression analysis, were the stage of disease, performance status, sex, weight loss before diagnosis, and hemoglobin concentration.

Adult↗

[Effect of inclusion complexation of decanoic acid with alpha-cyclodextrin on rectal absorption of cefmetazole sodium suppository in rabbits].

Inclusion complex of decanoic acid (DA) with alpha-cyclodextrin (alpha-CyD) was prepared as an additive of cefmetazole sodium (CMZ) suppository and rectally administered to rabbits. The resulting complexation was examined by the phase solubility method, differential scanning calorimetry (DSC) and X-ray diffractometry. Plasma concentration and AUC of CMZ after rectal administration of a suppository containing DA/alpha-CyD complex to rabbits increased more significantly than those with none additive.

Adjuvants, Pharmaceutic↗