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Biomedical subjects

M Kishimoto

Publications and source records attributed to M Kishimoto.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Prediction of postoperative visual acuity in retinal detachment with macular involvement].

We used laser interferometry (LI) and a potential acuity meter (PAM) to predict visual acuity after surgery for patients with rhegmatogenous retinal detachment with macular involvement. Thirty one eyes of 31 patients with retinal detachment were treated with scleral buckling procedures. Postoperative visual acuity was correlated with preoperative measurements of the LI and PAM, preoperative visual acuity by Landort's ring, and the estimated duration of macular detachment. The correlation between the duration of macular detachment and the postoperative visual acuity was not good (r = 0.55, p < 0.01). Although the preoperative visual acuity showed a relatively good correlation with postoperative visual acuity (r = 0.62, p < 0.01), the results of the LI and PAM provided a better correlation (LI; r = 0.73, PAM; r = 0.71). Our results suggest that the LI and PAM are useful to predict the visual acuity after retinal reattachment in patients with preoperative macular detachment.

Humans↗
PubMed1994

Substitution of glutamine for arginine 1131. A newly identified mutation in the catalytic loop of the tyrosine kinase domain of the human insulin receptor.

We studied a patient with severe insulin resistance and a remarkable decrease in the in vivo autophosphorylation of the insulin receptor. Using a polymerase chain reaction-single strand conformation polymorphism method and direct sequencing, we identified a heterozygous mutation substituting Gln for Arg1131 in the putative "catalytic loop" of the tyrosine kinase domain of the insulin receptor gene. The Gln1131 mutant receptor was expressed by transfection in Chinese hamster ovary cells and compared with cells expressing the wild-type insulin receptor. Both mutant and wild-type receptors were expressed on the cell surface and displayed similar insulin-binding affinity. The Gln1131 mutation impaired the activity of the receptor tyrosine kinase and inhibited the ability of insulin to phosphorylate the endogenous substrate insulin receptor substrate-I. In addition, the Gln1131 mutant receptor exhibited diminished tyrosine-phosphorylated phosphatidylinositol 3-kinase and myelin basic protein kinase activities compared with the wild-type cells. It also demonstrated a defective mediation of the insulin signal stimulating 2-deoxy-D-glucose transport and thymidine incorporation, resistance to endocytosis, and insulin-induced down-regulation. Unlike a previously described mutation in the putative catalytic loop of the receptor that substituted Glu for Ala1135, the Gln1131 mutation retained proteolytic cleavage of the proreceptor into separate subunits. Our results demonstrate that a naturally occurring mutation (R1131Q) in the putative catalytic loop of the insulin receptor results in severe impairment of the tyrosine kinase function in our patient. In addition, our results indicate that Arg1131 is important for receptor-mediated insulin action in vivo and suggest that the amino acids constituting the catalytic loop of protein kinases may possess different modes in order to retain kinase function.

Amino Acid Sequence↗
PubMed1994

Effect of strict metabolic control on glucose handling by the liver and peripheral tissues in non-insulin-dependent diabetes mellitus.

To examine the effect of strict glycemic control on the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM), we applied euglycemic hyperinsulinemic clamp combined with an oral glucose load (OGL) to nine non-obese subjects with NIDDM and quantitated insulin-mediated glucose uptake by the liver (HGU) and peripheral tissues (PGU) simultaneously before and after 3 to 4 weeks of intimate glycemic control by preprandial regular insulin injections 3 times a day. The glucose infusion rate (GIR) required to maintain euglycemia during the clamp before OGL was considered as PGU. After OGL, the fraction of ingested glucose that is not extracted by the liver enters the systemic circulation and reduces the GIR required for the clamp. HGU was calculated from the difference between the amount of OGL and the cumulative decrements in GIR after OGL and was expressed as the ratio to the amount of OGL (%). Three to 4 weeks after initiation of strict metabolic control, FPG and HbA1c levels significantly improved (9.1 +/- 0.5 vs. 6.4 +/- 0.4 mmol/l, and 11.2 +/- 0.8 vs. 8.3 +/- 0.3%, P < 0.05). HGU significantly increased to 33.1 +/- 9.5 from 14.5 +/- 4.8%, while PGU did not change (38.2 +/- 5.2 vs. 37.4 +/- 3.9 mumol/kg.min). These data suggest that short-term strict metabolic control ameliorates insulin resistance in NIDDM mainly at the hepatic level.

Adult↗
PubMed1994

Enzyme-linked immunosorbent assay method for human autophosphorylated insulin receptor. Applicability to insulin-resistant states.

The insulin receptors from erythrocytes of 50 patients with non-insulin-dependent diabetes mellitus were tested for their ability to autophosphorylate. The assay was performed by a new enzyme-linked immunosorbent assay system that used monoclonal anti-insulin receptor antibodies absorbed to microtiter plates as a first antibody and polyclonal antiphosphotyrosine antibody as a labeled second antibody. By this assay, 3 patients were identified with defects in their insulin receptor kinase, although their defects appeared heterogeneous. Patient 1 had 85% less maximal autophosphorylation with a normal ED50 (1.6 x 10(-9) M insulin). Patient 2, who had polycystic ovary disease, had a 49.2% decrease in maximal autophosphorylation of insulin receptors, and the ED50 was shifted to the right (5.6 x 10(-8) M). Patient 3 with acanthosis nigricans had a normal maximal autophosphorylation, but the ED50 shifted to the right (2.9 x 10(-8) M). The mechanisms for the diversity detected in this assay is not known, but this technique has sufficient specificity and sensitivity to be used to screen for insulin-resistant patients who have a lack of kinase activity.

Adult↗
PubMed1994

[The structure function relationship in the human insulin receptor].

The human insulin receptor gene is composed of 22 exons and spans in excess of 130 kb, on chromosome 19. The basic structure of the insulin receptor is a disulfide-linked tetramer, composed of the alpha subunit (135 kDa), which is extracellular and provides the binding site for insulin, and the beta subunit (95 kDa), contains the transmembrane domain, tyrosine kinase domain and C-terminal domain. Insulin binding to the alpha subunit causes the activation of the receptor tyrosine kinase activity that plays a critical role in mediating insulin signal transduction. Site-directed mutagenesis or the gene analysis of the patients with insulin resistant diabetes mellitus has revealed the structure and functional relationship of the insulin receptor to some extent but further investigations required.

Amino Acid Sequence↗
PubMed1993

The presence of Ca(2+)-independent phospholipase A1 highly specific for phosphatidylinositol in bovine brain.

EDTA-insensitive phospholipase A activity hydrolyzing phosphatidylinositol was detected in a bovine brain soluble fraction. This phospholipase A was purified 25-fold by sequential chromatographies of DEAE-Toyopearl, Phenyl-Toyopearl, and Ultrahydrogel 1000. The partially purified EDTA-insensitive phospholipase A showed an apparent molecular mass of 230kDa on an Ultrahydrogel 1000 column in the presence of 0.05% Triton X-100 and a pH optimum at 7.0. The enzyme was highly specific for phosphatidylinositol; phosphatidylethanolamine and phosphatidylcholine were not hydrolyzed significantly. The enzyme activity was characterized as phospholipase A1, and Ca2+ and Mg2+ were not required for its activity. These results indicate the existence of Ca(2+)-independent, phosphatidylinositol-specific metabolism besides those catalyzed by Ca(2+)-dependent phospholipase A2 and Ca(2+)-dependent, phosphatidylinositol-specific phospholipase C.

Animals↗
PubMed1993

EDTA-insensitive deacylation of phosphatidylinositol in porcine platelet membranes.

Pathways for EDTA-insensitive degradation of phosphatidylinositol (PI) were investigated in porcine platelet membranes and cytosol. The incubation of platelet membranes with [3H]glycerol-labeled PI in the presence of 2mM EDTA produced [3H]lysoPI and aqueous radioactive products, but not radioactive neutral lipids. The degradation in the membranes was optimal at pH8.0-9.0, while EDTA-insensitive hydrolysis was also observed in cytosol with optimal pH at pH7.0-9.0. The major water-soluble product was identified as glycerophosphoinositol. Under the conditions, [14C]arachidonate was released from 1-stearoyl-2-[14C]arachidonyl PI without accumulation of [14C]lysoPI. The deacylation activity preferred PI to phosphatidylcholine and phosphatidylethanolamine. Collectively, these results suggest that PI can be converted to lysoPI by phospholipase A2 in the absence of free Ca2+, providing the substrates for lysoPI-specific phospholipase C characterized earlier in porcine platelet membranes (Murase and Okuyama (1985) J.Biol.Chem. 260, 262-265).

Animals↗
PubMed1993

Submandibular hemangioma as the initial manifestation of Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome (thrombocytopenia, consumption coagulopathy and occasional hemolysis) is an infrequent but often fatal complication of rapidly growing hemangiomas in infants. We describe a 1-month-old infant with a huge hemangioma involving the left submandibular region associated with a severe consumptive coagulopathy, who was successfully treated with transfusion of blood products, prednisone and radiation therapy. It is stressed that pediatric otorhinolaryngologists should always be aware of the lethal status of this condition in infants.

Combined Modality Therapy↗
PubMed1993

Clinical usefulness of a non-wiping type glucose meter in diabetic patients.

A non-wiping type glucose meter using electrochemistry was developed. The glucose sensor strip has a sophisticated micro-structure for aspirating blood automatically. The meter compensates for drift of sensor output due to temperature change of the atmosphere. Mounting blood on the sensing site and wiping blood and precise time are no longer required. Range of measurement is 40-500 mg/dl. Reading of the meter for standard solutions of 90 or 360 mg/dl glucose showed negligible drift of measurement from 10.5 degrees C to 38.5 degrees C. The correlation between plasma glucose concentrations as determined by the meter and that by a Glucose Analyzer 2 was 0.995 with a slope of 1.00 and intercept of -0.65 (n = 48). In the case of blood glucose concentration (Y), the values were Y = 1.06X-0.91, r = 0.987, n = 62. This meter is quite easy to use and is highly accurate for glucose monitoring in patients regardless of operation skill. It should thus be readily applicable to diabetic patients.

Blood Glucose↗
PubMed1993

A possible pathway of phosphoinositide metabolism through EDTA-insensitive phospholipase A1 followed by lysophosphoinositide-specific phospholipase C in rat brain.

Incubation of [2-3H]glycerol-labeled phosphatidylinositol with a crude cytosol fraction of rat brain in the presence of EDTA yielded [3H]lysophosphatidylinositol predominantly without accumulation of labeled monoacylglycerol and diacylglycerol. The pH optimum of this phospholipase A activity was 8.0. The activity for phosphatidylinositol was twofold higher than for phosphatidylethanolamine, whereas phosphatidylcholine, phosphatidylserine, and phosphatidic acid were not hydrolyzed significantly under the conditions used. The phospholipase A activity for phosphatidylethanolamine was resolved in part from that for phosphatidylinositol by ammonium sulfate fractionation of the cytosol, indicating the existence of at least two forms of EDTA-insensitive phospholipase A. The positional specificity of the phosphatidylinositol-hydrolyzing activity was found to be that of a phospholipase A1, as radioactive lysophosphatidylinositol was produced from 1-stearoyl-2-[1-14C]arachidonyl-sn-glycero-3-phosphoinositol without release of free arachidonate. A phospholipase C activity specific for lysophosphoinositides was found in a membrane fraction from rat brain, which was similar to that characterized in porcine platelets. The phospholipase C was demonstrated to hydrolyze the 2-acyl isomer as well as the 1-acyl isomer of lysophosphatidylinositol. Taken together, our results suggest a possible pathway through which phosphatidylinositol is selectively degraded to the 2-acyl isomer of lysophosphatidylinositol in a Ca(2+)-independent manner, and subsequently converted to a 2-monoacylglycerol in rat brain.

Animals↗
PubMed1992

Detection of mutations in the human insulin gene by single strand conformation polymorphisms.

Single strand conformation polymorphisms (SSCP) is the method by which mutations can be detected in DNA amplified by the polymerase chain reaction (PCR). This method utilizes the fact that the electrophoretic mobility of single stranded DNA under nondenaturing condition depends not only on its size but also on its conformation. We examined whether this technique could detect five mutations that had previously been identified in the insulin genes of patients with abnormal insulin or familial hyperproinsulinemia. Five mutant insulin genes were constructed by site directed mutagenesis, and the cloned mutant insulin genes were amplified by PCR. All five mutations were detected because they were associated with shifts in the electrophoretic mobility of the DNA fragments. In addition, we analyzed amplified genomic DNA from a patient who is heterozygotes for the Insulin Wakayama mutation A3(Val----Leu). This mutation was also detected by the SSCP technique. We conclude that PCR-SSCP method is a simple, fast, and efficient method for detection of mutations in the human insulin gene.

Base Sequence↗
PubMed1992

A case of cleft palate in a Kuril seal (Phoca vitulina stejnegeri), from Hokkaido, Japan.

A male pup Kuril seal (Phoca vitulina stejnegeri) from Hokkaido, Japan, was observed with a unilateral and total cleft of the primary palate. Complications included a supernumerary tooth, hypoplasia and asymmetry of the face, and deformation of the eyeball and external auditory meatus. An accompanying pneumonia may have resulted from water flowing into the respiratory system due to imperfect closure of the nostril by the cleft. No other abnormalities were found.

Abnormalities, Multiple↗
PubMed1992

[Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes].

A novel mutation Arg1131-->Gln in the catalytic loop of insulin receptor (IR) associated with insulin resistant diabetes was detected. A 56-year-old male with hyperinsulinemia (fasting IRI 92 microU/ml) showed moderate impairment in glucose tolerance (HbAlc 7.0%, fructosamine 258 mumol/l, fasting glucose 119 mg/dl, maximum value of blood glucose during 75 g OGTT 220 mg/dl). While insulin binding to erythrocytes IR was normal, the insulin-induced autophosphorylation of the patient's erythrocytes IR in vivo showed marked decrease, suggesting this patient had some defect in the kinase domain (exon 17-21) of IR. PCR-SSCP analysis of kinase domain with a genomic DNA obtained from the patient's leucocytes indicated the presence of some mutations in exon 19. Sequencing analysis in M13 revealed a heterozygous mutation at a position 1131 (CGG-->CAG) substituting Gln for Arg. Four people of patient's family analyzed are revealed to have an identical missense mutation at the same position with the patient.

DNA↗
PubMed1991

[The examination of DNA strand breaks induced by peplomycin-using non-radioactive in situ nick translation method].

In situ nick translation (ISNT) is a method to detect DNA single strand break (nick) at each cellular level. In this study, peplomycin (PEP)-induced DNA strand breaks and its repair were examined using non-radioactive ISNT method. Human fibroblasts were cultured with various concentrations of PEP for different durations, and then DNA strand breaks were evaluated by ISNT method. The signal intensity of DNA strand breaks of the PEP-treated fibroblasts was increased in a dose dependent manner. At the fixed concentration of PEP, it reached to a maximum level after 10 min. of culture and remained unchanged for at least 24 hours. In addition, DNA strand breaks induced by PEP was rapidly repaired in 10 min. after washing. Thus, the non-radioactive ISNT is thought to be a quick, sensitive and specific method not only to detect DNA strand breaks but also to observe its repair.

Bleomycin↗
PubMed1991

Assessment of early stage autonomic nerve dysfunction in diabetic subjects--application of power spectral analysis of heart rate variability.

To assess early stage autonomic nerve dysfunction, power spectral analyses were conducted on the consecutive RR records of healthy subjects (N/C, n = 21) and age-matched diabetic patients without neuropathy (DNN, n = 11), with peripheral neuropathy alone (DPN, n = 14), and with autonomic neuropathy (DAN, n = 13) during resting, deep breathing, and tilting. From the analyses, power spectral densities of low frequency (0.05-0.1 Hz) component (LF; msec2) and of high frequency (0.2-0.35 Hz) component (HF; msec2) were calculated as expressing sympathetic activity and parasympathetic activity, respectively. In N/C, LF and HF were 466 +/- 332 and 251 +/- 151, respectively. Deep breathing significantly (p less than 0.05 by paired t-test) increased HF to 403 +/- 305 and tilting increased LF significantly to 593 +/- 375. In diabetics as a group, both LF and HF were significantly smaller than those in N/C. DNN showed significantly smaller HFs than N/C. DPN showed a significantly smaller HF during deep breathing (135 +/- 93) and a significant smaller LF during tilting (122 +/- 119) than N/C. DAN showed a significantly smaller HF during deep breathing (49 +/- 49) and a significantly smaller LF during tilting (54 +/- 52) than DPN. Tilting increased LF significantly (p less than 0.001) in N/C but not in diabetics. Deep breathing increased HF significantly (p less than 0.001) in N/C and DNN. HF in diabetics highly correlated with known duration of diabetes. LF in diabetics did not correlate with known duration of diabetes nor level of hemoglobin A1c.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Enhanced rectal and nasal absorption of human epidermal growth factor by combined use of the absorption promoter and the synthetic polymer in rats.

Previously, the presence of sodium carboxymethylcellulose (CMC Na) in addition to an absorption promoter, sodium caprate (C10 Na), in the dosing solution was found to be necessary for the enhancement of the rectal absorption of human epidermal growth factor (hEGF). In the present study, other synthetic polymers and absorption promoters were examined for their ability to enhance the rectal and nasal absorption of hEGF in rats. The effect of polymers in combined use with 100 mM C10 Na on the rectal absorption of hEGF was in the following order: 1% methylcellulose 1% hydroxypropylmethylcellulose 0.1% polyacrylic acid 1% CMC Na. Other absorption promoters such as N-lauroyl-alanine (C12-A) and dihydroxy-bile salts also enhanced the rectal absorption of hEGF in combined use with CMC Na. In order to confirm the increased rectal absorption of hEGF, the disappearance of hEGF from the rectal loop was examined. When hEGF in a 1% CMC Na solution (200 ug/kg) was administered in the rectal loop, the disappearance percent of hEGF during 60 min was 13.9% of the dose, although hEGF was not detected in the plasma. The presence of promoters such as 10 mM C10 Na or 15 mM C12-A in 1% CMC Na increased the disappearance percent to about 50% in a dosing range of hEGF from 100 to 500 ug/kg. On the other hand, a markedly enhanced nasal absorption of hEGF by 100 mM C10 Na was observed even in the absence of any polymer in a dising solution. However, addition of CMC Na into the dosing solution accelerated the rate of nasal absorption of hEGF in early phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗