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Biomedical subjects

T Suwa

Publications and source records attributed to T Suwa.

At least 91 records · Page 5Linked to original sources

Determination of protein binding of a highly lipophilic drug, isocarbacyclin methyl ester (TEI-9090), using a polydimethylsiloxane-coated glass beads assay.

An adsorption technique with polydimethylsiloxane-coated glass beads (PDMS-GB) was developed to determine the protein binding of a highly lipophilic and hydrophobic drug. The present assay method is based on the quantitative adsorption of unbound drug to the PDMS-GB. This method of batch separation in a glass assay tube has an advantage of simplicity and rapidity. To evaluate the reliability of PDMS-GB assay, we compared the protein binding of diazepam in serum in-vitro measured by ultrafiltration and PDMS-GB assay. There was no significant difference between the extent of binding measured by each method. Using PDMS-GB assay, we determined the protein binding of the prostaglandin I2 (PGI2) analogue isocarbacyclin methyl ester (TEI-9090), whose binding cannot be measured by commonly employed techniques (equilibrium dialysis, ultrafiltration, gel filtration or ultracentrifugation) because of a high degree of adsorption to membranes, resins or tubes. The percentage of TEI-9090 bound in human serum, 4% human serum albumin (HSA, fatty acid-free) and dog serum were approximately 98, approximately 87 and approximately 95%, respectively, and these values were independent of TEI-9090 concentration up to 10 ng mL-1. The binding of isocarbacyclin (TEI-7165) to serum protein in man, dogs, rabbits and rats, determined by ultrafiltration, was also high (> 90%). While the displacement of TEI-9090 and TEI-7165 binding to HSA by aspirin, salicylic acid and indomethacin was not observed, clofibric acid and free fatty acids significantly inhibited the protein binding of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Radiological study of symptomatic Rathke's cleft cysts.

We investigated the relationship between radiological findings and the nature of the cyst fluid and histological findings of six Rathke's cleft cysts. The results show that the majority (five of six cases) of symptomatic Rathke's cleft cysts exhibit no enlargement of the sella turcica on plain x-rays, which may be helpful in differentiating cystic pituitary adenoma in the radiological diagnostic process. Three cases with large cysts showing high-intensity T1-weighted magnetic resonance images harbored abundances of cholesterol crystal and hemosiderin pigment in the cyst walls. The high signal intensity in magnetic resonance images of Rathke's cleft cysts may be explained by hemorrhage and a deposition of cholesterol crystal and may be considered in certain cases of Rathke's cleft cyst, especially when they are large.

Adult↗

Possible gliclazide-induced water retention with azotemia.

An 80-year-old woman with diabetes mellitus was treated with gliclazide. Prior to the gliclazide administration, her urinary excretion of albumin, serum urea nitrogen and serum creatinine were normal. After the medication, oliguria, edema and azotemia developed. On the twenty-fourth day when the edema was severe and generalized, gliclazide administration was terminated. On the following day urinary volume increased suddenly (5,740 ml/day). Polyuria persisted for five days. Edema improved and urea nitrogen and creatinine were normalized thereafter. Though the mechanism is not known, the clinical course suggests that gliclazide is the principal causative factor in the water retention and azotemia in this patient.

Aged↗

[Intracranial extracerebral glioma].

A case of solitary leptomeningeal extracerebral glioma is reported. A 75-year-old man was admitted to our hospital because of headache and right hemiparesis. CT scan and carotid angiography revealed a tumor in the left convexity. At operation, the tumor was located between the dura mater and the arachnoid membrane and adhered to the brain surface only in a limited area. Histological study including immunostain and electron microscopy showed the tumor as anaplastic oligo-astrocytoma. We speculate that our case may originate from a heterotopic glial nest in the dural border cell layer of dura mater. This explanation seems likely because the tumor was located mostly in the subdural space.

Aged↗

[An early phase II clinical study of RP56976 (docetaxel) in patients with breast cancer].

An early phase II clinical study of RP56976 (docetaxel), a new anticancer agent of plant origin, was conducted in patients with breast cancer at 20 Japanese collaborative institutions. Docetaxel was administered at two or more doses of 60 mg/m2 by intravenous infusion with dose-free intervals of 3-4 weeks, and the efficacy and safety was evaluated. Of the 51 patients enrolled, 50 patients completed the scheduled course of treatment. Two patients showed a complete response (CR) and 19 showed a partial response (PR) with a response rate of 42.0%. The response rates based on the efficacy for metastatic lesions in soft tissue, liver and lung, were 46.2% (18/39), 37.5% (3/8), and 38.5% (5/13), respectively. Of the 50 patients who completed the study, 48 patients had previously been treated for the present malignancy. Forty-seven patients had previously been treated with chemotherapy and showed a response rate of 40.4% (19/47). The response rate in those who had received chemotherapy composed of anthracyclines and other agents was 44.1% (15/34). Grade 3 or more severe leukopenia and neutropenia developed in 43 patients (84.3%) and 48 patients (94.1%), respectively. Other adverse reactions which occurred in a Grade 3 or more severe form included nausea/vomiting (1 patient), anorexia (5 patients), diarrhea (4 patients), fatigue (2 patients), and alopecia (20 patients). Except for alopecia, most adverse reactions were generally transient and reversible without any specific treatment.

Adult↗

[Recurrent meningioma with malignant transformation: a case which changed from meningothelial type to papillary type].

We report here a case with meningioma showing malignant transformation in its course of multiple recurrences. A 59-year-old woman developed a right-sided hemiparesis in June, 1982 and CT scan disclosed a parasagittal well-enhanced mass. The tumor was subtotally removed (Simpson grade III) by an operation in September, 1982. Histological findings of the tumor were consistent with a meningothelial meningioma but showed no malignant features, such as high cellularity, necrotic foci, high mitotic rate, or nuclear pleomorphism. However, the tumor did invade the underlying cerebral cortex. In August, 1986, a recurrent tumor was detected by CT scan and was removed (Simpson grade III). The tumor tissue at the second operation showed the same histological features as the first specimen. In September, 1990, the patient developed multiple intracranial recurrences. There were three tumor nodules, all of which were removed. Histologically, significant histological differences between the second and the third operative specimens were found. In the last tumor tissue, one nodule showed a papillary pattern. In the other tumor nodules, each tumor cell had proliferated separately instead of adhering to other tumor cells to form a syncytium. This histological pattern was consistent with an epithelial meningioma described by Cushing and Eisenhardt in 1938. The papillary portion of the tumor was stained with monoclonal antibody Ki-67 in frozen section. The labelling index was 9.7%, which was as high as malignant meningioma. Electron microscopic examination of the papillary portion of the tumor showed that the tumor cells had irregular nuclei, interdigitations between the adjacent plasma membranes and a few ill-developed desmosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Simultaneous high-performance liquid chromatographic determination of lornoxicam and its 5'-hydroxy metabolite in human plasma using electrochemical detection.

A selective and sensitive high-performance liquid chromatographic method with coulometric detection is described for the simultaneous quantitation of lornoxicam, a new oxicam class drug, and its 5'-hydroxy metabolite in human plasma. The two analytes and the internal standard are extracted from plasma at pH 4.0 by liquid-liquid extraction and separated on a C18 column. Absolute detection limits using 100 microliters of plasma are found to be 5 and 10 ng/ml for lornoxicam and 5'-hydroxylornoxicam, respectively. The assay described has been successfully applied to samples from clinical studies.

Anti-Inflammatory Agents, Non-Steroidal↗

Case report: silent thyroiditis developed during alpha-interferon therapy.

Alpha-interferon (IFN-alpha) was used for the treatment of chronic active hepatitis C in a 30-year-old woman who was euthyroid but had low titers of antithyroid antibodies before treatment. Two months after the initiation of IFN-alpha therapy she became thyrotoxic. She had nontender diffuse goiter. A laboratory examination revealed elevated levels of serum free thyroid hormones and a suppressed concentration of serum thyrotropin. Titers of antimicrosomal antibodies increased. The anti-thyrotropin receptor antibody was negative. A 99mTcO- scintigram of the thyroid showed reduced uptake. During the IFN therapy free thyroid-hormone levels started to decline. The IFN-alpha therapy was completed 1 month after the onset of thyrotoxicosis. Two months after the completion of the therapy the patient became euthyroid and 99mTcO- uptake was normalized. It is likely that preexisting chronic thyroiditis was exacerbated to cause silent thyroiditis during IFN-alpha therapy. None of the other 11 patients with chronic hepatitis C who had had no anti-thyroid antibodies and were treated with IFN-alpha showed anti-thyroid antibodies and thyroid dysfunction after the therapy. It is advisable to assess anti-thyroid antibodies and thyroid function in patients who are going to receive IFN-alpha treatment.

Adult↗

Metabolic fate of a new dihydropyridine calcium antagonist, CD-349, in rat and dog.

1. The metabolic fate of 14C-CD-349, a new calcium antagonist, was studied in rat and dog. 2. After oral administration of 14C-labelled drug in both species, the plasma levels of radioactivity reached maxima at 1-2 h and declined with elimination half-lives of 6-7 h. In both species, 71-85% of radioactivity was excreted in faeces and 17-27% in urine in 120 h. Biliary excretion in rat after oral doses amounted to 33%. 3. The low ratio of unchanged drug to total radioactivity in plasma suggested that CD-349 underwent rapid metabolism in both species. 4. Twenty-two metabolites were isolated and identified from dog urine and an incubation mixture with 9000 g rat liver supernatant. Principal routes of biotransformation of CD-349 were similar in both species, and involved: (1) oxidation of the dihydropyridine ring to the corresponding pyridine ring; (2) denitration of the nitrate ester; (3) hydrolysis of the carboxy ester to the carboxylic acid; and/or (4) oxidation of the side chain, although quantitative interspecies differences were observed.

Animals↗

[Hepatic protein synthesis in regenerating liver after partial hepatectomy].

The process of hepatic protein synthesis was studied in the regenerating liver after partial hepatectomy (HTX). Hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were determined in the regenerating liver of rats after 68% HTX. The serum levels of the following items were determined in 10 patients before and after HTX: interleukin-6 (IL-6), acute-phase proteins (APP), and negative acute-phase proteins (NAPP). HPS has markedly increased after HTX, with the peak occurring at 48 hours. The regenerating rat liver showed an increase of 80% over normal livers in HPS and 200% in SPS 48 hours after HTX. A remarkable increase in IL-6 levels occurred on the first day after HTX. In all patients transient falls in APP levels occurred on the first day. Values appeared to return rapidly toward preoperative values by 3 or 5 days after HTX but failed to show any significant increase compared to preoperative values. In contrast to APP, prolonged decreases in NAPP levels occurred after HTX. Values declined to a nadir on the first or third day after HTX and remained suppressed for 14 days. These results suggest that the production of APP is activated at an early stage of liver regeneration after partial hepatectomy.

Acute-Phase Proteins↗

Invasive meningiomas in relation to high proliferating potential.

We conducted a study to investigate whether an association exists among histologic findings, labeling index determined by the labeling index (LI) of proliferating cell nuclear antigen (PCNA) and recurrence in a population of 30 meningioma patients. All of 6 patients (invasive meningioma) with brain invasion had a PCNA LI in excess of 5%. Recurrence was found in 4 of these patients. In 24 patients who did not have brain invasion, PCNA LI was 4% or less and only 1 case had recurrence. Recurrence occurred in 3 of 25 patients who underwent macroscopic total resection and all of these 3 cases had brain invasion and a PCNA LI in excess of 5%. The findings of this study indicated the existence of a close correlation between peripheral invasiveness of meningioma and its biological behavior.

Adolescent↗

Origin of craniopharyngioma: an electron microscopic study.

To investigate the possibility that the two subtypes of craniopharyngioma, adamantinous type and squamous papillary type, are tumors arising from different origins, the authors conducted an electron microscopic study in 10 cases of craniopharyngioma. Light microscopic study revealed distinct differences between the two subtypes, but their ultrastructure was fundamentally similar. In this report, the authors propose an explanation of the origin of these subtypes to account for the findings.

Adolescent↗

A continuous cell line (KK-2) from a supratentorial primitive neuroectodermal tumor.

Tumor tissue located in the occipital lobe with hemorrhage was obtained from a 19-year-old patient. Histological examination indicated it to consist of undifferentiated small, round cells without neuronal or glial differentiation, and possibly to be a type of primitive neuroectodermal tumor. The tumor cells were cultured for 3 years and a continuous cell line (KK-2) was established. KK-2 was transplantable to nude mice. With immunocytochemistry, neuron-specific enolase, protein gene product 9.5, vimentin, TUJ1 (a monoclonal antibody specific for neuron-associated class III beta-tubulin isotype) and 6H7 (a monoclonal antibody to NCAM produced by us) were detected. None of the following could be found: glial fibrillary acidic protein, S-100 protein, neurofilament and synaptophysin, calcitonin gene-related peptide, gastrin releasing peptide corticotropin-releasing factor, substance P, somatostatin, chromogranin, aromatic L-amino acid decarboxylase and tyrosine hydroxylase. The original tumor and KK-2 cells obtained after 3 years of culture and transplants in nude mice displayed essentially the same ultrastructural and immunohistochemical characteristics. KK-2 cells showed no differentiation to mature neuronal, glial or ependymal cells. This cell line may possibly serve as a useful model for studying cellular differentiation of human neuroectodermal tumors and normal neuronal development.

Adult↗

Selected ion monitoring for the determination of bromovalerylurea in human plasma.

A gas chromatography-selected ion monitoring procedure with chemical ionization is described for the determination of bromovalerylurea (BVU) in human plasma. BVU was extracted with ether after addition of 2-bromo-2-methylpropylurea as an internal standard. The lower limit of BVU quantification by this method was 2 ng/0.1 ml plasma volume. This procedure was used to determine the sequential plasma levels of BVU in a human volunteer following a single oral dose of a commercial analgesic.

Administration, Oral↗

[Hepatic protein synthesis and cytokines in obstructive jaundice].

UNLABELLED: To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). THE RESULTS: (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.

Acute-Phase Proteins↗

[Intramedullary neurofibroma in the cervical spinal cord; a case report].

A 62-year-old woman was admitted complaining of clumsiness in both hands. On neurological examination, bilateral hand muscles were weak, both legs were spastic and hyperreflexic, all the extremities were hypoesthetic. Urological examination revealed detruser sphincter dyssynergia. Spinal CT scan demonstrated an iso density mass lesion in the cervical spinal cord, and it was markedly enhanced. On MRI, it was also markedly enhanced by Gd-DTPA. The operative finding was that an oval shaped tumor was buried in the spinal cord and was totally removed. Its histological diagnosis was neurofibroma. Intramedullary neurofibroma is rare and only 18 cases have been reported. In this case the tumor seemed to have arisen at the root entry zone and to have grown sub-pially.

Female↗

Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report.

A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM.

Cerebral Hemorrhage↗

Analysis of the protective effect of the haemagglutinin-neuraminidase protein in Newcastle disease virus infection.

The role of immune responses to haemagglutinin-neuraminidase (HN) protein in protection against a Newcastle disease virus (NDV) infection was investigated using a recombinant vaccinia virus expressing HN (HN-RVV). Live HN-RVV replicated in chickens and completely protected them from lethal infection with virulent NDV. Inactivated HN-RVV also protected chickens when administered with adjuvant but not when administered without adjuvant. However, large amounts of the inactivated HN-RVV (100-fold excess) without adjuvant provided protection. Specific antibodies against the HN protein of NDV were detected in sera from survivors but not from dying birds. However, the kinetics of antibody responses in chickens inoculated with live HN-RVV and inactivated HN-RVV were considerably different. These results clearly confirm that immune response(s) solely to the HN protein of NDV can provide chickens with protection against NDV challenge, and show that the presence of antibodies to the HN protein correlates significantly with the protection from NDV infection at least in HN-immunized chickens.

Animals↗