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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 127 records · Page 7Linked to original sources

[Morphometric study on islet of Langerhans in relation to glucose tolerance in chronic obstructive pancreatitis due to pancreatoduodenal cancer].

Twenty one specimens of the pancreas in the patients who underwent pancreatoduodenectomy or total pancreatectomy for pancreatoduodenal cancer were divided into 4 groups according to the extent of fibrosis (Grade 0-Grade III). Islet cells of serial sections were stained immunohistochemically with calculation of the proportion of B-cells, A-cells, D-cells and PP-cells in the islets of Langerhans. In the pancreatic tissue with the most severe fibrosis (Grade III), B-cell ratio was significantly decreased (p less than 0.01), whereas A-cell ratio was significantly increased (p less than 0.01). Based on the data of oral glucose tolerance test (OGTT) and insulin response test, some indices were calculated (delta IRI/delta BS, sigma IRI/sigma BS, sigma delta IRI/sigma delta BS). In Grade III, sigma delta IRI/sigma delta BS was significantly decreased. A significant positive correlation was observed between B-cell ratio and both delta IRI/delta BS or sigma delta IRI/sigma delta BS, whereas a significant negative correlation was seen between A-cell ratio and sigma delta IRI/sigma delta BS. The present study first demonstrates the significant correlation between the endocrine secretory function of the islets and quantitative changes of the endocrine cells of islets in chronic obstructive pancreatitis due to pancreatoduodenal cancer. The present data strongly suggest that it is possible to estimate the degree of fibrosis and quantitative changes of the islet cells in the patients with pancreatoduodenal cancer by means of calculating the above mentioned indices, especially sigma delta IRI/sigma delta BS.

Blood Glucose

[Phase I and pharmacokinetic study of SM-5887 by 5-day schedule].

Pharmacokinetics of SM-5887, a new totally synthetic anthracycline derivative, was studied in a phase I setting by 5-day schedule. The maximum tolerated dose was 25 mg/m2/d (total dose: 125 mg/m2/body) and the dose-limiting toxicity was myelosuppression which was consistent with the results of the phase I study by a single dose. In terms of subjective side effects, decreased nausea/vomiting and increased stomatitis were observed. In pharmacokinetic study, AUC of active form of SM-5887 increased on day 5 compared to that day 1. This result suggested that 5-day schedule of SM-5887 produced an accumulation of the active form. Five-day treatment schedule of SM-5887 seems to be more tolerable and further clinical study was recommended.

Adult

[MELAS associated with diabetes mellitus and point mutation in mitochondrial DNA].

Point mutation of mitochondrial DNA has been described in the blood from a MELAS patient. The 39-year-old patient developed progressive dementia, stroke-like episodes, heart conduction defect (Lown-Ganong-Levin syndrome) and cortical blindness. CT scan revealed brain atrophy and low density areas in the bilateral occipital lobes. Laboratory tests showed hyperglycemia and lactic acidosis. Muscle biopsy showed ragged red fibers on Gomori trichrome staining. He was clinically diagnosed as having MELAS and insulin-dependent diabetes mellitus. Onset of diabetes mellitus and MELAS was almost same. Family history showed his mother's brother and sisters had also insulin-dependent diabetes mellitus. We amplified the leucine (UUR) tRNA gene from the patient's blood with polymerase chain reaction (PCR) and analysed it by restriction enzyme analysis and sequencing. Genetic analysis showed A-to-G substitution at the nucleotide position 3243 in the leucine (UUR) tRNA gene. This substitution made a new restriction site Apa I. Mutant DNA coexisted with wild type DNA (heteroplasmy). It is shown that in some types of mitochondrial encephalomyopathies, especially patients of Kearns-Sayre syndrome (KSS), diabetes mellitus is often complicated. And in KSS patients insulin receptor in normal, but insulin secretion from beta cells of pancreas is decreased. In MELAS patients, however, has diabetes mellitus been reported to be rarely complicated and relationship between MELAS and diabetes mellitus is not done. As far as we know, two cases, including ours, with genetically diagnosed MELAS have been reported to have diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[A case of the diabetic nephropathy without hyperglycemia].

We report a case of diabetic nephropathy with impaired glucose tolerance. A 52 year obese woman with nephrotic syndrome and hypertension showed severe and remarkable edema, as her legs were elephantiasis. To be clear the etiology of nephrotic syndrome, we performed renal biopsy. The histological findings of the specimen showed glomerulosclerosis. Additionally the examination of ocular fundus revealed microaneurysm and avascular area. We concluded that diagnosis of this case must be non-insulin-dependent diabetes mellitus.

Diabetes Mellitus, Type 2

[A case of allergic bronchopulmonary candidiasis treated with amphotericin B inhalation].

A 77-year-old man underwent emergency admission for nocturnal asthmatic attack. Although his asthmatic attack improved within a few days with treatment including systemic corticosteroid, bilateral recurrent infiltrative shadows developed in his chest roentgenogram in association with a further exacerbation of dyspnea. Various antibiotic agents were given; however, the pulmonary infiltration did not improve. He was transferred to our department with the diagnosis of intractable pneumonia. C. albicans was detected in the sputum, and both IgE antibody and precipitating antibody specific for C. albicans were positive. Immediate cutaneous reactivity to C. albicans was positive even with a million-fold dilution of antigen extract C. albicans was also detected in bronchoalveolar lavage fluid. A diagnosis of allergic bronchopulmonary candidiasis was made. Chest roentgenographic findings as well as clinical symptoms improved with inhalation of 50 mg of amphotericin B.

Administration, Inhalation

[An autopsy case of Degos disease with neurological symptoms--neuropathological observations and increased platelet aggregation].

We reported clinical and neuropathological observations of a 41-year-old man with Degos disease. He first noted painless skin lesions over the upper extremities in January, 1982. Three years later he was diagnosed as Degos disease by skin biopsy, and treatment with aspirin was started. In September, 1985, he complained of paresthesia on his right arm, followed by a series of new neurological manifestations suggesting multifocal spinal cord lesions. On October 28, examination of admission showed papules with central umblication over the whole body except the head, face, palms, soles and scrotum. Neurological examination revealed no weakness, diminished right biceps reflex, exaggerated patellar reflexes and Achilles reflexes, left extensor plantar reflex, hypesthesia and hypalgesia to the level of Th8, mild left spastic gait, and retention of urine. In November, he had paraparesis, loss of vibration sense of lower extremities, hypesthesia and hypalgesia to the level of TH4, and weakness of right upper extremity. In December, he showed tetraplegia, left-sided facial palsy, and hypesthesia and hypalgesia to the level of C5. In January, 1986, he showed right facial palsy, left facial hypesthesia, pseudobulbar palsy. In February, he had bilateral abducens nerve palsy and hiccups. On February 18, he died of intracranial hemorrhages. He had episodic abdominal pain several times during admission. His condition deteriorated progressively in four months after the first manifestation of neurological symptoms, despite the therapy with heparin, urokinase, ticlopidine, dipyridamole, and prednisolone. Laboratory studies showed gradual increase of CSF proteins (from 156 mg/dl to 602 mg/dl) and extremely increased platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Intraoperative radiation therapy of carcinoma of the pancreas].

From May 1978 to December 1989, 54 patients with pancreatic carcinoma underwent electron beam intraoperative radiotherapy (IORT). Three died of preoperative complications within a month. In 19 patients, liver metastasis and/or peritoneal dissemination became obvious at laparotomy. They therefore underwent IORT with palliative intent. Relief of pain was obtained in 12 of the 14 patients with pain (85.7%), although three of them were treated in combination with splanchnic nerve block. Thirty-two patients with localized carcinoma underwent IORT with curative intent (total tumor resection in 6, partial resection in 6, and no tumor resection in 20). With additional IORT treatment, their survival was significantly (p less than 0.05 during the 18th month) longer than that of 40 patients without IORT (total tumor resection in 13, partial resection in 9, and no tumor resection in 18). Among the patients without tumor resection, the 20 patients who underwent IORT survived significantly (p less than 0.05 during the 7th month) longer than the 18 patients who did not. Twelve patients who underwent total pancreatectomy died earlier than the 23 patients treated with IORT in combination with partial tumor resection or no tumor resection (not significant). In 26 patients with partial tumor resection or no tumor resection, either additional external irradiation or IORT using a small field within a large field significantly (p less than 0.05 during the 7th and 8th month) improved survival compared with IORT using a single field. Of the 20 patients without tumor resection, relief from pain was obtained in 18 of 19 patients with pain (94.7%), although two of them were treated in combination with splanchnic nerve block. In terms of adverse effects possibly caused by IORT in 26 patients who survived longer than 6 months, gastrointestinal problems were serious in several (gastric ulcer in 2, duodenal stenosis in 1, gastric ulcer and duodenal stenosis in 1, and duodenal perforation and duodenal ulcer in 1). In conclusion, our experience suggests that IORT can relieve patients of serious pain and improve survival in patients with localized pancreatic carcinoma.

Adult

[Clinical application of asialoglycoprotein receptor-mediated liver scintigraphy using 99mTc-DTPA-galactosyl-human serum albumin].

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptors on the hepatocytes. Studies were performed in three normal volunteers and 19 patients with chronic liver diseases. Serial scintigrams and time-activity curves of heart and lever were obtained for 60 min following a single intravenous injection of 99mTc-GSA (1 mg/185 MBq). % Injected dose (%ID) in the blood at 60 min after injection and that in the liver were determined. Excellent hepatic images were obtained for 60 min in normal subjects, and neither blood pool image nor extrahepatic uptake was recognized. In the studies of patients, however, blood pools were also visualized in various degrees suggesting altered receptor quantity, although the livers were visualized clearly. The %ID in the blood at 60 min after the injection showed significant correlations with serum albumin levels (r = -0.741, p less than 0.0001), retention rates of ICG at 15 min (r = 0.855, p less than 0.0001), plasma disappearance rates of ICG (r = -0.760, p less than 0.0005), prothrombin times (r = -0.696, p less than 0.002), hepaplastin tests (r = -0.575, p less than 0.05), total bilirubin levels (r = 0.689, p less than 0.001) and Child Turcotte scores (r = 0.769, p less than 0.0001). Significant differences of %ID in both blood and liver were observed between normal subjects and patients in accordance with severities of the hepatic disorders. These results suggest that 99mTc-GSA liver scintigraphy is useful in evaluating the liver function.

Adult

Group II phospholipase A2 inhibitors suppressed lysophosphatidylserine-dependent degranulation of rat peritoneal mast cells.

Rat peritoneal mast cells were sensitized with IgE and challenged with the specific antigen in the presence of lysophosphatidylserine (lysoPS), an essential co-factor for rodent connective tissue mast cell degranulation, and the effects of phospholipase A2 inhibitors were examined. Mepacrine, a known inhibitor of phospholipase A2, at concentrations below 10(-5) M and anti-rat 14-kDa group II phospholipase A2 antibody inhibited histamine release, while they did not affect the prostaglandin generation. Like histamine release, prostaglandin generation in IgE- and antigen- challenged rat peritoneal mast cells was dependent on the presence of lysoPS. These results indicate that 14-kDa group II phospholipase A2 may play an essential role in IgE-, antigen-, and lysoPS-dependent degranulation process of rat peritoneal mast cells and that the mechanism whereby it participates may not be due to the production of lysoPS from PS in mast cell membranes.

Animals

Flow cytometric analysis of the nuclear DNA content of hepatoblastoma.

The nuclear DNA content of 15 hepatoblastoma cases was determined in paraffin-embedded tissues by flow cytometry. The DNA index (DI) was calculated, and the ploidy pattern of nuclear DNA was estimated. The correlation between the ploidy pattern and clinicopathologic findings was studied, and the prognostic significance of the ploidy pattern was investigated. An aneuploid pattern was seen in 50% of the lesions with histologic embryonal and anaplastic types. It was not seen in the fetal type. In the tumors with combined epithelial components, the fetal-type component had a diploid pattern in all five cases. The embryonal-type component was associated with aneuploidy in two of five cases. In aneuploid tumors, vascular invasion (tumor emboli in the vessels) was observed more frequently. The prognosis of the patients with an aneuploid tumor was significantly poorer. These results indicate that nuclear DNA ploidy pattern analysis might be useful in investigating the prognosis of hepatoblastoma.

Carcinoma, Hepatocellular

Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2.

The extracellular form of 14-kDa group II phospholipase A2 has been found to accumulate at various types of inflammatory sites. In the present paper, we have studied the possible role of the extracellular 14-kDa group II phospholipase A2 in the process of prostaglandin production in activated rat mast cells. When mast cells obtained from the peritoneal cavity of rats were sensitized with IgE, challenged with antigen and then exposed to extracellular 14-kDa group II phospholipase A2, appreciable release of prostaglandin D2 was observed. Generation of prostaglandin D2 was dependent on the concentration of the phospholipase A2 as well as that of the antigen, while no appreciable prostaglandin D2 generation was observed with cells in the absence of the antigen. No histamine release was observed under the same conditions. Phosphatidylcholine in mast cell membranes was appreciably hydrolyzed to liberate free arachidonic acid when mast cells were incubated with 14-kDa group II phospholipase A2 added exogenously in the presence of the antigen. Both the generation of prostaglandin D2 and the release of arachidonic acid were retarded by inhibitors specific to 14-kDa group II phospholipase A2. Thus, 14-kDa group II phospholipase A2 may function in the process of inflammation by acting on IgE-antigen-primed mast cells, which are not fully activated, to generate eicosanoids.

Animals

A unique vacuolar processing enzyme responsible for conversion of several proprotein precursors into the mature forms.

Proprotein precursors of vacuolar components are transported from the endoplasmic reticulum into vacuoles, where they are proteolytically processed into their mature forms. However, the processing mechanism in plant vacuoles is very obscure. Characterization of a purified processing enzyme is required to determine whether a single enzyme is responsible for processing many vacuolar proteins with a large variability of molecular structure. If this is true, how can it recognize the numerous varieties of processing sites? We have now purified a processing enzyme (Mr = 37,000) from castor bean seeds. Our results show that the purified enzyme can process 3 different proproteins isolated from either the endoplasmic reticulum or transport vesicles in cotyledon cells to produce the mature forms of these proteins which are found at different suborganellar locations in the vacuole: the 2S protein found in the soluble matrix, the 11S globulin found in the insoluble crystalloid and the 51 kDa protein associated with the membrane. Thus a single vacuolar processing enzyme is capable of converting several proprotein precursors into their respective mature forms.

Amino Acid Sequence

The intracortical position of pyramidal tract neurons in the motor cortex of the reeler changes from postnatal day 10 to adulthood.

To determine whether or not the intracortical distribution pattern of pyramidal tract (PT) neurons in the motor cortex (hindlimb area) of normal and reeler mutant mice changes during early postnatal development of the cortex, we injected HRP into the pyramidal decussation of postnatal day (P) 8 and adult animals of the normal and reeler strains, and killed the animals 2 days later. In the normal P10 and adult mice, such an injection resulted in a band of labelled neurons confined to the layer of large pyramids (LP), suggesting that the intracortical localization of PT neurons does not change from P10 to adulthood in the normal strain. In the P10 and adult reeler mice, labelled PT neurons were scattered radially from the deepest zone to the superficial zone of the motor cortex. However, while the HRP-labelled PT neurons are located bilaminarly in both the deepest zone and the superficial zone of the motor cortex of the P10 reeler mouse, the majority of PT neurons were found in the upper third of the motor cortex of the adult reeler mouse. Thus, the intracortical distribution pattern of PT neurons of the reeler mouse changes during the postnatal period.

Animals

Liquid chromatographic-mass spectrometric analysis for screening of patients with cystinuria, and identification of cystine stone.

Analyses of amino acids in the urine of a normal human and of patients with heterozygous and homozygous cystinuria have been carried out, using liquid chromatography-mass spectrometry with an atmospheric pressure ionization interface system. A kidney cystine stone was also analysed by this system. Very intense quasi-molecular ions ([M + H]+) of standard cystine, arginine, lysine and ornithine were observed on mass chromatograms as base peaks. Mass chromatograms of the urine samples from a normal human and from patients with heterozygous and homozygous cystinuria were easily distinguishable. The retention times in the mass chromatogram and mass spectrum of kidney stone cystine was almost the same as that of authentic cystine.

Arginine

Purification and characterization of the alpha-tocopherol transfer protein from rat liver.

alpha-Tocopherol transfer protein was purified from the 10,000 x g supernatant of rat liver. Two isoforms of the transfer protein exist, of which the isoelectric points are 5.0 and 5.1 as determined by chromatofocusing. These two isoforms have the same molecular weight; both showed molecular weight of approx. 30,500 on SDS-polyacrylamide gel electrophoresis. They cannot be distinguished from each other by amino acid composition or substrate specificity.

Amino Acids

Detection of 14-kDa group II phospholipase A2 in human seminal plasma.

About 90% of phospholipase A2 activity detected in human seminal plasma reacted with monoclonal antibodies raised against human synovial fluid phospholipase A2. The crude seminal plasma yielded a pure immuno-cross-reactive phospholipase A2 preparation in a single purification step using immuno-affinity chromatography. The amino acid sequence of the N-terminal 20 residues of this seminal enzyme was determined and found to be identical with that of human synovial phospholipase A2. Thus, it is suggested that human seminal plasma contains phospholipase A2, belonging to the 14-kDa group II enzyme family, as the major isoenzyme.

Amino Acid Sequence