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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 523 records · Page 29Linked to original sources
PubMed1984

[Stromal sarcoma of the male breast].

A 63-year-old man who had been aware for 5 years of a tumor near his left nipple was admitted complaining of rapid tumor enlargement. He received standard mastectomy under the diagnosis of breast sarcoma. The regional lymph nodes were not involved and the excised tumor was 12.0 cm in diameter it showed a grayish-white cut surface and a sharp border. Histologically we made a diagnosis of stromal sarcoma of the breast showing diffuse proliferation of spindle shaped cells with high cellularity, moderate atypia and scattered mitosis. Postoperatively, he underwent chemotherapy with cyclophosphamide. Two years and five months after the operation, he is alive and well without any sign of recurrence.

Breast Neoplasms↗
PubMed1983

Specific secretin binding sites in rat pancreas.

The dynamic nature of specific secretin binding sites in the pancreas was studied to simulate the interaction of secretin with its receptors in living organisms using isolated perfused rat pancreas. [125I]Secretin or [125I]-[Tyr1] secretin bound to certain binding sites in the perfused pancreas was displaced only by secretin in a dose-dependent manner, not by glucagon or vasoactive intestinal peptide, and the majority of the displaced radioactivity was demonstrated to be undegraded. On the basis of a secretin binding study with subcellular components, it was considered that the displacement would occur on the plasma membranes. These findings suggest that secretin which is distributed in the pancreas may rapidly and reversibly bind to specific binding sites or receptors on the plasma membranes with high affinity.

Animals↗
PubMed1983

Carrier-mediated transport of amino-cephalosporins by brush border membrane vesicles isolated from rat kidney cortex.

The uptake of cephalosporin antibiotics by brush border membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique, demonstrating a carrier-mediated transport system for amino-cephalosporins such as cephalexin and cephradine. The antibiotics were taken up into an osmotically reactive intravesicular space. The uptake of cephalexin was saturable (apparent Km2.2 mM), was inhibited by structural analogues and sulfhydryl reagents, and was stimulated by the countertransport effect, although the Na+ gradient did not affect the uptake. This transport system was essentially different from the transport system for p-aminohippurate in brush border membranes. The uptake properties for cephradine in brush border membrane vesicles appeared to be similar to those for cephalexin. The present results suggest the existence of a carrier-mediated transport system for amino-cephalosporins in brush border membranes. This system may be a part of the mechanism of tubular reabsorption of these antibiotics.

Animals↗
PubMed1983

Ultrastructural study on nervous system of fetus with GM1-gangliosidosis type 1.

The nervous system of a 22-year-old fetus with GM1-gangliosidosis type 1 was studied by electron microscopy. The tissues thus examined were the cerebral cortex at the parietal region, the cerebellum, the thoracic spinal cord, the Auerbach's myenteric plexus in the large intestine and the radial nerve fibers. In the cerebral cortex, membrane-bound vacuoles, which occasionally contained stacks of fine fibrils, were observed in the large young neurons in the deeper part of the cortical plate. The neurons in the other part of the cerebral cortex carried no storage materials. In the cerebellum, the membrane-bound vacuoles with stacks of fine fibrils were seen only in the Purkinje cells. The neurons in the spinal cord also contained several zebra-like bodies and the above membrane-bound vacuoles. As for the peripheral nervous system (PNS), neurons in the Auerbach's myenteric plexus carried membranous cytoplasmic bodies and zebra-like bodies. Some of the axons in the radial nerve fibers also contained a lot of pleomorphic electron-dense bodies and a few membranous cytoplasmic ones. These results show that the accumulation of storage materials is started in the large neurons which are produced in the early stage of neurogenesis in the central nervous system (CNS). Additionally, the observed membrane-bound vacuoles are considered to be structures which occur before the membranous cytoplasmic bodies and/or the zebra-like bodies. It is also elucidated that the PNS is affected earlier than the cerebral and cerebellar cortices and thoracic spinal cord.

Cerebellum↗
PubMed1983

Immunological evidence for deficiency in an activator protein for sulfatide sulfatase in a variant form of metachromatic leukodystrophy.

Cultured skin fibroblasts from the patient described by Shapiro and co-workers as having a variant form of metachromatic leukodystrophy (MLD) [Shapiro, L.J., Aleck, K. A., Kaback, M.M., Itabashi, H., Desnick, R.J., Brand, N., Stephens, R.L., Fluharty, A.L. & Kihara, H. (1979) Pediatr. Res. 13, 1179-1181] were confirmed to have a partial deficiency (25-40% of controls) of arylsulfatase A activity in vitro and a severe inability to metabolize [14C]stearic acid-labeled sulfatide presented in the medium. When 150 micrograms of purified activator protein for GM1 ganglioside beta-galactosidase and sulfatide sulfatase was added in 4 ml of medium with the 14C-labeled sulfatide, correction of the sulfatide metabolism to the normal range was found. Monospecific antibodies to this activator protein were prepared in rabbits, and they were used to examine cultured cells for the presence of crossreacting material by Ouchterlony double immunodiffusion and rocket immunoelectrophoresis. Cell extracts from controls and from patients with GM1 gangliosidosis and MLD were found to have a single line of identity. By comparison to known concentrations of purified activator protein, cell extracts from controls were found to have 0.76 +/- 0.32 micrograms of activator protein (mean +/- 1 SD, n = 10) per mg of solubilized protein, whereas those from patients with type 1 GM1 gangliosidosis and late infantile MLD had 1.53 and 1.41 micrograms/mg, respectively. Cell extracts from the patient with a variant form of MLD had no visible precipitin line by Ouchterlony double immunodiffusion and only a diffuse nonspecific region of staining by rocket immunoelectrophoresis. These immunologic studies provide evidence for a deficiency in the activator protein required for normal catabolism of sulfatide in the cells from this patient and possibly provide a method for diagnosis of similar patients.

Cells, Cultured↗
PubMed1983

Concentrations of an activator protein for sphingolipid hydrolysis in liver and brain samples from patients with lysosomal storage diseases.

The hydrolysis of sphingolipids by lysosomal enzymes requires the presence of additional proteins, which have been called activator proteins. The number of activator proteins, their specificity, exact mechanism of action, and response to a storage process all remain to be determined. In this study, antibodies to an activator protein known to bind sphingolipids and activate the enzymatic hydrolysis of GM1 ganglioside and sulfatide were used to estimate the concentration of this activator protein in small samples of liver and brain from patients with lysosomal storage diseases. By using rocket immunoelectrophoresis, the concentration of cross-reacting material (CRM) was determined. Control livers had an average of 0.95 +/- 0.18 (mean +/- 1 SD) microgram CRM/mg protein in the extracts, and control brains had an average of 0.25 +/- 0.14 microgram CRM/mg protein. Extremely high levels of CRM were found in extracts of livers from patients with type 1 GM1 gangliosidosis (15.1 and 16.9), and type A Niemann-Pick disease (10.7). Extracts of brain samples revealed a large amount of CRM in type 1 GM1 gangliosidosis (14.8), Tay-Sachs disease (5.3 and 8.7), and Sandhoff disease (13.5). Significantly elevated CRM was also measured in brain samples from patients with type 2 GM1 gangliosidosis, type A Niemann-Pick disease, metachromatic leukodystrophy, and Krabbe disease. The highest levels are found in those genetic diseases where the lipids stored, primarily or secondarily to the genetic defect, bind to this activator protein. This activator protein may have an important function in regulating intralysosomal lipid catabolism, and changes in its concentration in certain genetic diseases may be the cause of clinical, biochemical, and pathological heterogeneity found in the patients.

Adolescent↗
PubMed1983

Juvenile GM2 gangliosidosis (AMB variant): inability to activate hexosaminidase A by activator protein.

Two sibling from a consanguineous Puerto Rican marriage were found to have a juvenile-onset type of lipidosis first noted at age 2 1/2 by expressing difficulties with motor function and developmental delay. They continued to deteriorate, showing muscle atrophy, spasticity, and loss of speech, and death occurred at ages 7 and 8. Examination of the brains from these patients revealed that the concentration of GM2 ganglioside was about 56% of the total gangliosides. Hexosaminidase and percent hexosaminidase A (HEX A) and other lysosomal enzymes were normal in cultured skin fibroblasts, liver, and brain. The concentration of the activator protein required for the enzymatic hydrolysis of GM2 ganglioside was in high normal levels in the brain of the patient available. However, the HEX A from the patient's brain and liver as well as from skin fibroblast lysates could not be activated to hydrolyze GM2 ganglioside by the activator protein from a control or himself. The HEX A from a control could be activated by the activator protein from controls or this patient. These patients appear to have a defect in HEX A, which does not affect it heat stability, electrophoretic migration, and activity toward fluorogenic substrates, but may affect the binding of the activator protein required for GM2 ganglioside hydrolysis. We propose to call these patients the AMB variant of GM2 gangliosidosis to denote the mutation in HEX A but with normal levels of HEX A and B with synthetic substrates. This is to distinguish these patients from those missing the activator protein and normal HEX A and B levels.

Brain↗
PubMed1983

[Non-epitherial malignant neoplasms of the breast--a clinicopathological study of 4 cases].

Between 1972 and 1981, 4 women with breast sarcoma underwent treatment at our department; they accounted for 1.1% (4 of 355) of all female breast malignancies. There was one case of malignant lymphoma and liposarcoma each, and 2 cases of malignant cystosarcoma phyllodes. The patients averaged 31.0 years of age. Of the two cases of cystosarcoma phyllodes, one had coexisting lobular carcinoma in situ arising in a fibroadenoma of the contralateral breast, the other had a coexisting lung cancer. Mastectomy was performed in 3 cases, irradiation in one (malignant lymphoma). All patients received concurrent chemotherapy. The regional lymph nodes were not involved, and 2 patients are alive and well without recurrence.

Adolescent↗
PubMed1983

[Intraoperative dual-mode independent lung ventilation for open-chest surgery: conventional volume-set ventilation in healthy lung and high frequency jet ventilation in diseased lung].

An effort by the anesthesiologist to maintain adequate ventilation during thoracic surgery is sometimes disturbing for the operative procedures of the surgeon. Unilateral ventilation with a large tidal volume, leaving the operative site unventilated, may provide an adequate and quiet operative field, but is opposed by the problem of disturbance in pulmonary gas exchange. The application of high frequency jet ventilation has recently been introduced to solve these problems. However, the disadvantage inherent to this technique is the tendency to produce carbon dioxide retention although it provides adequate oxygenation. In the present study, using a double lumen endobronchial tube, the large-tidal volume ventilation of the non-operative site and the high frequency jet ventilation with small tidal volume of the operative site were performed simultaneously. This technique provided the satisfactory condition of operative field, i.e., "quiet lung". Also, the serial gas analysis of the arterial and mixed venous blood samples indicated the satisfactory condition of pulmonary gas exchange.

Aged↗
PubMed1982

Mechanisms of p-aminohippurate transport by brush-border and basolateral membrane vesicles isolated from rat kidney cortex.

The uptake of [3H]-labeled p-aminohippurate by brush-border and basolateral membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique. Some characteristics of carrier-mediated transport for p-aminohippurate were demonstrated in basolateral membrane vesicles: the uptake was inhibited by probenecid or 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), was saturable, was stimulated by the countertransport effect, and showed discontinuity in the Arrhenius plot. In contrast, brush-border membrane vesicles failed to display saturability of p-aminohippurate uptake and stimulation by the countertransport effect, although probenecid and DIDS reduced the uptake. Furthermore, p-aminohippurate uptake by brush-border membrane vesicles was influenced more sensitively by alteration in the membrane potential compared with that by basolateral membrane vesicles.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1982

Normalization of intracellular lysosomal hydrolases in I-cell disease fibroblasts with sucrose loading.

I-cell disease (ICD) is an hereditary inborn error of metabolism by lysosomal storage due to the multiple lysosomal hydrolases deficiency. Many inclusion materials are seen by phase contrast microscopy in cultured skin fibroblasts from the patients with ICD. We recently reported that the addition of 88 mM sucrose to the medium of cultured human skin fibroblasts from normal subjects induced several lysosomal hydrolases, but did not induce deficient hydrolases in lysosomal enzyme deficiencies (Kato, T., Okada, S., Ohshima, T., Inui, K., Yutaka, T., and Yabuuchi, H. (1981) Biochem. Int. 3, 551-556). This time sucrose loading was applied to the cultured skin fibroblasts from the patients with ICD. Incubation with 88 mM sucrose for more than 10 days exhibited significant effects. Biochemically, the activities of deficient hydrolases reached their normal levels, and morphologically, typical inclusion materials disappeared. These results indicate that sucrose enhanced synthesis of normal lysosomal enzymes and lysosome functions were normalized in ICD fibroblasts.

Cells, Cultured↗
PubMed1982

The interaction of cephalosporin antibiotics with renal cortex of rats: accumulation to cortical slices and binding to purified plasma membranes.

The interaction of cephalosporin antibiotics with renal cortex of rats has been examined in vitro by means of cortical slice uptake and binding assay to plasma membranes and other subcellular fractions, including the comparative study with p-aminohippurate. The uptakes of cephalexin and cephaloridine by cortical slices were concentrative, and were strongly inhibited in the presence of 2,4-dinitrophenol, ouabain, nitrogen gas and probenecid. In the case of cefazolin, the degree of concentrative uptake and influence of inhibitors were low. Cephalexin, cephaloridine and p-aminohippurate specifically bound to the basolateral membranes, compared to brush border membranes and other subcellular fractions. Cefazolin binding to basolateral membranes was relatively small. These results suggest that the specificity of cephalexin and cephaloridine bindings to the basolateral membranes could be related to the interaction with the organic acid transport system at the antiluminal side. Thus, an examination of cephalosporin interaction with plasma membranes from renal cortex could offer an appropriate in vitro model system to study the renal transport of these antibiotics.

Animals↗
PubMed1982

Galactose 6-sulfate sulfatase activity in Morquio syndrome.

We have prepared a new substrate (o-beta-D-sulfo-galactosyl-(1-4)-beta-D-6-sulfo-2-acetamido-2-deoxyglucosyl- (1-4)-D-[1-3H]galactitol), from shark cartilage keratan sulfate, for the assay of galactose 6-sulfate sulfatase activity. Using this substrate, we found there was a striking deficiency of galactose 6-sulfate sulfatase activity, in addition to the known deficiency of N-acetylgalactosamine 6-sulfate sulfatase, in the cultured skin fibroblasts of patients with Morquio syndrome. Our results could be explained by the hypothesis that accumulation of keratan sulfate and chondroitin 6-sulfate in Morquio syndrome is due to a deficiency of galactose 6-sulfate sulfatase and N-acetylgalactosamine 6-sulfate sulfatase activity, which are necessary for the degradation of these two mucopolysaccharides.

Animals↗