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Biomedical subjects

T Kadowaki

Publications and source records attributed to T Kadowaki.

At least 307 records · Page 17Linked to original sources

Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins.

Two high molecular weight heat shock proteins, HSP90 (Mr, 90,000) and HSP100 (Mr, 100,000), were separately purified from extracts of cultured cells of a mouse lymphoma cell line, L5178Y. Both of the HSPs exist in homodimeric form under physiological conditions. Their physicochemical properties are quite similar to each other. Each of the purified HSPs was shown to coprecipitate with rabbit skeletal muscle actin under actin-polymerizing conditions. Both HSP90 and HSP100 increased the low-shear viscosity of filamentous actin solutions in a dose-dependent manner, which suggests that these HSPs cross-link actin filaments. Although some molecular properties and the effects described above on actin solution of HSP90 and HSP100 resemble those of alpha-actinin, the HSPs were distinguished from alpha-actinin by various means, including visualization of molecular shapes by electron microscopy with the aid of the low-angle rotary shadowing technique. Immunofluorescence staining by specific antisera against HSP90 revealed that HSP90 was localized in ruffling membranes in addition to the cytoplasmic space.

Actins↗

Characteristics of human erythrocyte insulin-like growth factor I receptors.

The scarcity of purified materials has prevented studies of the mechanism of insulin-like growth factor I (IGF-I) action. Recently, an IGF-I analog, Thr59-IGF-I, was synthesized by recombinant DNA technology. We found that this analog had binding characteristics similar to those of natural IGF-I in the radioreceptor assay system. We used this analog to characterize human erythrocyte IGF-I receptors as follows. Erythrocytes from 33 normal subjects specifically bound 6.9 +/- 0.7% (mean +/- SD)/2.8 X 10(9) cells/ml. Scatchard analysis of the binding data showed that the total number of receptors per erythrocyte was 13, and the affinity constant was 1.26 X 10(9) M-1, similar to that of other human IGF-I receptors previously reported. We also examined IGF-I receptors in patients with insulin receptor abnormalities. Although the specific values of IGF-I binding to erythrocytes were decreased or increased in parallel with those of insulin, the degrees of decrease or increase were much smaller. This suggests that the expression of insulin receptors and that of IGF-I receptors are discordant.

Adolescent↗

Familial disorder with increased number of insulin receptors: a new category of insulin receptor abnormality.

We found a family in which 6 of 13 family members had extremely high insulin binding to their erythrocytes. The specific binding values of these patients were 3- to 4-fold higher (22.8-28.6% of added [125I]insulin) than normal (mean +/- SD, 7.1 +/- 0.8%; r = 44). Scatchard analysis revealed that in each patient increased insulin binding was due to increased binding capacity, with little change in affinity. In all patients, reticulocyte counts were within the normal range. From the pedigree analysis, the pattern of inheritance was considered to be autosomal dominant. The propositus was more extensively studied. His mononuclear leukocytes and Triton X-100-solubilized preparations of erythrocyte ghosts also had high (approximately 3-fold) insulin-binding capacity compared to that of normal subjects. In contrast, the number of ouabain-binding sites and kinetics of sugar transport were normal. From these findings, we propose a new type of inherited abnormality of the insulin receptor.

Adult↗

[The management of bleeding following transurethral prostatic resection by local irrigation with a thrombin solution].

The clinical value of local irrigation of thrombin was studied in 30 patients with urethral bleeding following transurethral prostatic resection. A thrombin solution consisting of 25,000 units of thrombin in 500 ml of saline was irrigated in 20 patients through the especially designed three-way balloon catheter at a speed of 8.3 ml/min for five hours after the operation while sterile saline was irrigated in the same manner in 10 patients as a control. The hemostatic effect of thrombin solution was evaluated as excellent in 2 patients (10%), good in 5 (25%), moderate in 6 (30%), and poor in 2 (10%) with 5 drop outs (25%) in the thrombin irrigating group. In the control group, the effect of irrigation was evaluated as good in 1 patient (10%), moderate in 4 (40%), poor in 2 (20%), and unable to be estimated in 2 (20%) with 1 drop out (10%). Therefore the rate of overall effectiveness was 65% in the thrombin irrigating group and 50% in the control group and volume of postoperative blood loss was 0.58 ml/g X hour and 0.62 ml/g X hour, respectively. Though almost all of the patients in both groups showed a moderate elevation of fibrinogen in serum, there was no adverse effect considered to be caused by thrombin irrigation. The local irrigation of the thrombin solution is a useful method and safe in the management of bleeding following transurethral prostatic resection.

Aged↗

Phosphorylation of tubulin and microtubule-associated proteins by the purified insulin receptor kinase.

The purified insulin receptor kinase catalyzed the phosphorylation of native tubulin and microtubule-associated proteins (MAPs; MAP2, tau) on tyrosine residues. Insulin (10(-7) M) stimulated the reaction by 4-10-fold by increasing Vmax with little change in Km. alpha-Tubulin was preferred as a substrate for the kinase compared to beta-tubulin. MAP2 was found to be the best substrate among the cytoskeletal proteins tested; in the presence of insulin, the Vmax for MAP2 was 6.3 nmol/min/mg, its Km was 5.1 microM, and 1.7 mol of phosphate were incorporated per mol of MAP2. Under the same conditions used for this phosphorylation of tubulin and MAPs, actin and tropomyosin were very poorly phosphorylated. These data, coupled with previous evidence for potential functional relationships between insulin action and microtubules, raise the possibility that microtubule proteins may be cellular targets for the insulin receptor kinase.

Humans↗

Phosphorylation of fodrin (nonerythroid spectrin) by the purified insulin receptor kinase.

Fodrin (nonerythroid spectrin) from porcine brain was found to be phosphorylated on tyrosine residues by the purified insulin receptor kinase. The phosphorylation occurred in an insulin-sensitive manner with a physiologically relevant km. The beta(235 K) subunit of fodrin, but not the alpha(240 K) subunit, was phosphorylated by the kinase. Neither the alpha(240 K) subunit nor the beta(220 K) subunit of erythrocyte spectrin was phosphorylated under the same conditions. Fodrin phosphorylation by the purified insulin receptor kinase was markedly inhibited by F-actin. These data raise the possibility that tyrosine phosphorylation of fodrin plays some roles in the regulation of plasma membrane-microfilament interaction.

Actins↗

Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats.

It has been documented that streptozotocin-induced diabetes in rats is associated with diminished effects of insulin despite increased insulin binding to its receptor. This paradox led us to examine whether any alterations of insulin receptor-kinase activities occur in this type of insulin resistance. Insulin binding capacity/mg of protein of solubilized, wheat germ agglutinin-purified preparations from livers was increased by 1.8-fold in the streptozotocin (65 mg/kg) diabetic rats. This increase was associated with a parallel increase in receptor protein as measured by an immunoblotting method using anti-insulin receptor antibody. Moreover, no apparent change was observed in the stoichiometry of alpha and beta subunits of the insulin receptor between diabetic and control rats. Insulin-stimulated (10(-7) M) phosphorylation of the beta subunit of the insulin receptor was decreased by 40% in diabetic rats when equal quantities of insulin binding capacity were compared. Phosphorylation of an exogenously added synthetic peptide (similar in sequence to the tyrosine phosphorylation site in pp60src) by the insulin receptor-kinase was also decreased by 25% in diabetic rats. These abnormalities were partially restored by in vivo insulin treatment. These data suggest that diminished insulin receptor autophosphorylation and kinase activity could provide a possible mechanism for the "post-binding insulin resistance" in diabetic rats.

Animals↗

Risk factors for worsening to diabetes in subjects with impaired glucose tolerance.

In a 5-12 year follow-up study of 288 subjects with impaired glucose tolerance after a 100-g glucose load, 48 worsened to overt Type 2 (non-insulin-dependent) diabetes with the elevation of fasting blood glucose. The initial level of blood glucose was a major predictor of subsequent worsening to diabetes. In addition, subjects with a lower insulin response to glucose showed a higher incidence of worsening to the disease, irrespective of blood glucose levels. Multivariate analysis indicated that a diminished insulin response and a high maximal body weight index, as well as a high level of fasting and 2-h glucose values at the initial 100-g oral glucose tolerance test were significant independent risk factors for the development of diabetes in Japanese subjects.

Adult↗

Adrenal myelolipoma: report of a case with CT and angiographic evaluation.

A case of adrenal myelolipoma which was diagnosed preoperatively based on the combined examinations of computed tomography and angiography is presented. Computed tomography revealed a large suprarenal fatty tumor with increased density areas secondary to hemorrhage. Angiography demonstrated that the tumor originated from the adrenal gland.

Adrenal Gland Neoplasms↗

Erythrocyte ouabain binding capacity as a possible cellular index of hyperthyroid status.

The maximum ouabain binding capacity in erythrocytes from 8 normal subjects and 14 patients with hyperthyroidism was assessed by measuring [3H]-ouabain binding. The mean value for maximum ouabain binding capacity was significantly lower in the patients than in normals (0.422 +/- 0.084 vs 0.671 +/- 0.095 pmol per 10(9) cells, p less than 0.001). Furthermore, a close inverse correlation was found between the ouabain binding capacity and serum T3 (r = 0.766; p less than 0.01) or T4 (r = -0.870; p less than 0.001) levels. These results suggest that the maximum ouabain binding capacity in erythrocytes may provide a useful index of the peripheral effect of thyroid hormone.

Adult↗

[Simultaneous determination of multiple elements in airborne particulate samples by X-ray fluorescence spectrometry].

An energy dispersive X-ray fluorescence spectrometer (EDX) has been applied to determine multielements in the workplace air. The standards for X-ray fluorescence analysis were prepared by the chelate precipitation method on polyvinyl chloride (PVC) membrane filter. And, the specimens were prepared to deposit various metal compounds of different chemical forms by the suspension method on PVC membrane filter, and they were determined with EDX and atomic absorption spectrometer (AAS). The results obtained were as follows. Though there is a difference by each element, an amount less than 3 microgram/cm2 per unit area makes it possible to undergo multielement analysis, that is, is has no influence on fine particle effect (particle size; under 5 microns). Then, effects of the X-ray intensity by different chemical forms are negligible. At the presence the neighboring element and other elements this technique showed greater precision by carrying out on corrective treatment, etc. The coefficient of variation of this technique was in the range of 2.5-6.5% at DDTC-Cu of 0.5-5.0 micrograms/cm2, with the limit of detection for As : 0.002 microgram/cm2, Zn : 0.003 microgram/cm2, Pb : 0.003 microgram/cm2, Cu : 0.004 microgram/cm2, Ni : 0.003 microgram/cm2, Fe : 0.005 microgram/cm2, Mn : 0.008 microgram/cm2, Cr : 0.013 microgram/cm2, respectively. Aerosols collected at the workplace were analyzed with EDX and AAS, and the obtained results showed good agreement with such regression line as y = 1.04 chi + 0.04, the coefficient of correlation being r = 0.995. From these results, this technique was found to be a very excellent method for monitoring of multielements in the workplace air.

Aerosols↗

On the pathogenesis of type II diabetes with special reference to diminished insulin response and obesity: a 5-12 year follow-up study of subjects with borderline glucose tolerance.

In a 5-12 year follow-up study of 288 subjects with borderline glucose tolerance, 56 of them worsened to overt noninsulin dependent diabetes mellitus (NIDDM). Multivariate analysis indicated that a high level of fasting and 2-hour blood glucose values at the initial 100 g oral glucose tolerance test, a large maximal body weight index (Max. BWI) and a diminished insulin response to glucose load were significant independent risk factors for worsening to diabetes. Deterioration to diabetes was observed 4.5 times, 6.1 times and 2.1 times more frequently in subjects with fasting blood glucose greater than or equal to 100 mg/100 ml, 2-hour blood glucose greater than or equal to 180 mg/100 ml and Max. BWI greater than or equal to 130%, respectively, as compared with those having lower values of each variable. Diabetes developed almost exclusively from low insulin responders in 253 non- or mildly obese subjects, while in 35 severely obese subjects a certain number of 'normal or high' insulin responders did develop diabetes. In conclusion, the majority of cases of NIDDM develop on the basis of low insulin secretion, with an additional precipitating factor of obesity, and, in some with higher insulin responses diabetes develops when extreme obesity exists, though these cases form a minor group in Japan today.

Blood Glucose↗

[Neurofibrosarcoma of the perineum associated with von Recklinghausen's disease: a case report and review of the literature].

A case of perineal neurofibrosarcoma associated with von Recklinghausen's disease is reported. The patient was a 30-year-old man, who complained of a mass between the scrotum and anus. The mass was asymptomatic. On Jan. 13, 1981, simple excision was performed. Histological examination revealed neurofibrosarcoma. After 3 months he had recurrence of the perineal tumor. Combined chemotherapy and radiation therapy were performed. But, his condition became worse due to general metastasis and he died 12 months after operation. A total of 22 cases of perineal neoplasms are reviewed.

Adult↗