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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 523 records · Page 29Linked to original sources
PubMed1991

Two patients with insulin resistance due to decreased levels of insulin-receptor mRNA.

Mutations have been identified in the insulin-receptor gene in insulin-resistant patients. We studied two patients with acanthosis nigricans and insulin resistance caused by a decrease in the number of cell surface insulin receptors. Patient 1 was an 11-yr-old boy with a fasting insulin level of 2130 pM; patient 2 was a 14-yr-old girl with hyperandrogenism and a fasting insulin level of 580-740 pM. Based on Southern-blotting studies, the structure of both alleles of the insulin-receptor gene in both patients appeared to be grossly normal. There was no evidence of insertions, deletions, or major rearrangements. Moreover, the nucleotide sequences of all 22 exons of the gene were normal in both patients. Thus, the predicted amino acid sequences of both patients' insulin receptors were normal. In Epstein-Barr virus-transformed lymphoblasts from patient 1, insulin-receptor mRNA levels were so low they could not be detected with an RNase A protection assay, whereas mRNA levels from patient 2 were in the lower half of the normal range. By use of a more sensitive assay based on the polymerase chain reaction, insulin-receptor mRNA could be detected in Epstein-Barr virus-transformed lymphoblasts from both patients. Moreover, because of the existence of silent polymorphisms in the nucleotide sequences, it was possible to differentiate the two alleles of the insulin-receptor gene in both patients. In patient 2, the two alleles were expressed asymmetrically, with 90% of the mRNA molecules having been transcribed from one allele but only 10% transcribed from the second allele. This suggests that there is an unidentified mutation in the underexpressed allele that acts in a cis-dominant fashion to decrease insulin-receptor mRNA levels. However, in patient 1, both alleles were expressed symmetrically in similarly low levels. Although not proven, it seems likely that the mutations that decrease insulin-receptor mRNA levels in patient 1 also map to the insulin-receptor locus.

Adolescent↗
PubMed1991

Renal kinin and kallikrein excretion in cirrhotic patients.

Urinary kinin and urinary kallikrein activity were measured in 33 liver cirrhotics, and the values were correlated with the severity of the liver disease. A significant relationship was observed between urinary kinin excretion and urinary kallikrein excretion (r = 0.53; p less than 0.01). Both urinary kinin and kallikrein excretion were significantly lower in Child's group C than in Child's groups A and B (p less than 0.05) and showed positive correlations with serum albumin (r = 0.47, p less than 0.01 and r = 0.46, p less than 0.01, respectively). Increases in urinary kinin and kallikrein excretion after endoscopic variceal sclerotherapy were observed in 18 patients (p less than 0.01 and p less than 0.05, respectively). These results suggest that the renal kallikrein-kinin system in suppressed in severe liver disease in proportion to the severity of the underlying liver disease. In this study possible activation of this system after sclerotherapy was also demonstrated.

Esophageal and Gastric Varices↗
PubMed1991

Pharmacokinetics of denopamine in hemodialysis patients.

The pharmacokinetics of denopamine on a hemodialysis day and on an interdialysis day was evaluated in 11 hemodialysis patients. Tmax was the only pharmacokinetical parameter that differed significantly between healthy volunteers and hemodialysis patients. It is suggested that denopamine can be administered to hemodialysis both on hemodialysis days and on interdialysis days without dosage adjustments.

Adrenergic beta-Agonists↗
PubMed1991

[Silent cerebral infarction in the patients with essential hypertension].

Evidence of old cerebral infarction of magnetic resonance imaging (MRI) is common in acute stroke patients without a prior history of stroke. This experience led us to investigate the incidence of silent cerebral infarction (SCI) in the patients with essential hypertension, as well-known major predisposing factor for stroke. The incidence, number, size and localization of SCI on MRI (MARK-J, 0.1 T) and the prevalence of risk factors for stroke were investigated both in 66 hypertensive patients (WHO stage I or II; 63 +/- 9 (mean +/- S.D.) years old) and in 42 age-matched normotensive patients (61 +/- 9 years old). Risk factors selected were as follows: diabetes mellitus, hypercholesterolemia, daily alcohol intake, cigarette smoking, obesity, cardiac disease (arrhythmia and ischemic heart disease), hyperuricemia and high hematocrit. In hypertensive patients, the relationships between the incidence of SCI and hypertensive damages in major organs were also investigated. SCI was found in 45 out of the 108 subjects studied and a total of 216 SCI lesions were detected. All of the SCI lesions were localized in the subcortical white matter or in the basal ganglia. All SCI lesions were smaller than 3 cm in diameter and 201 lesions (93%) were smaller than 1 cm. The incidence of SCI tended to be higher in hypertensive patients (47%) than that in normotensives (33%) and increased significantly with advancing age in hypertensives from 26.9% in the 50s to 86.7% in the 70s, while no significant increase was noted in normotensives.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Quantitative determination of hepatic glucose uptake using an innovative approach: effect of strict glycemic regulation and exercise in diabetic subjects.

For perfect glycemic control in diabetics, therapeutic modalities which enhance impaired hepatic glucose uptake seen in diabetics should be utilized. In animal experiments, we demonstrated that factors promoting hepatic glucose uptake are the glucose gradient between the central nervous system and the hepato-portal system, portal hyperinsulinemia and normal premeal glycemia. Therefore, we investigated both the effects of intensified insulin therapy and a single bout of exercise on hepatic glucose uptake by euglycemic hyperinsulinemic clamp combined with oral glucose loading. In 56 out of 77 patients, perfect glycemic normalization was established with mean regular insulin doses of 10, 7, 7 U at breakfast, lunch and dinner, respectively. The ratio of splanchnic glucose disposal to the amount of ingested glucose increased significantly from 19.0 to 42.1%. A single bout of exercise enhanced hepatic glucose uptake from 23.4 to 50.5%. Both strict glycemic regulation and exercise enhance hepatic glucose uptake significantly in non-obese diabetic patients.

Diabetes Mellitus, Type 2↗
PubMed1991

Obesity and liver disease: evaluation of fatty infiltration of the liver using ultrasonic attenuation.

We developed an in vivo ultrasonic attenuation measurement system with which we attempted to evaluate the degree of fatty infiltration in the liver. In an animal study, fatty liver was induced in rabbits, and ultrasonic radiofrequency waveforms from the liver were obtained using a 10 MHz A mode transducer. Frequency-dependent attenuation of the ultrasound, which was correlated with total lipid content, was calculated using a spectral difference method. In a human study, ultrasonic waveforms were obtained using a 3.5 MHz transducer. Frequency-dependent attenuation also showed a significant correlation with the grading of fatty infiltration of the liver. These results suggested that fatty infiltration of the liver could be evaluated quantitatively and noninvasively using frequency-dependent attenuation of the ultrasound.

Animals↗
PubMed1991

Organ assimilation of peptides.

Dipeptides injected intravenously or added to liver perfusion medium were hydrolyzed rapidly to amino acids. The clearance volumes per min of plasma Gly-Phe and Gly-Lys were 63% and 224%, respectively, of the total plasma volume. These values far exceed the blood flow in any single organ, suggesting that several organs must be involved in peptide assimilation. Intravenous administration of peptides increased the levels of their constituent amino acids in organs. Two possible explanations for this were assimilation of the peptides by the organs, and transport into the organs of the amino acids generated by extracellular hydrolysis of the peptides. The former possibility was tested by eliminating plasma lysine by enzymic degradation, so that the amino acid would accumulate only in the organs that assimilate lysine-containing peptides. Results showed that all organs tested, except the brain, had an intrinsic ability to assimilate peptides.

Animals↗
PubMed1991

[Detection of hepatitis C virus RNA in serum during treatment of chronic hepatitis C with interferon alpha].

We estimated HCV RNA in serum of 20 patients with chronic hepatitis C during interferon therapy using a combination assay of reverse transcription and polymerase chain reaction (RT-PCR). RNA was extracted from 200 microliters of serum. The primers were chosen from the NS3 region of prototype HCV RNA sequence. After 40 cycles of PCR, the products were analyzed by Southern hybridization. HCV RNA was detected in 18 of 20 (90%) patients before therapy. In cases with improvement of serum GPT level, HCV RNA became undetectable at 4 weeks of the therapy. However, HCV RNA reappeared within 4 weeks after the therapy in cases with relapse. In the no response group, HCV RNA did not disappear during the therapy. Interferon therapy is beneficial in improvement of viremia of HCV, and the detection of HCV RNA in serum is useful to evaluate the antiviral effect of interferon.

Adult↗
PubMed1991

Auditory evoked potentials in the Japanese monkey.

Auditory sensitivity based on auditory brain stem response (ABR), whole nerve action potential (AP), and cochlear microphonics (CM) to tone bursts of 0.5-8 kHz were compared with behavioral audiometry in the Japanese monkeys. Although sensitivity loss at 4-6 kHz was observed in these potentials, an increase in sensitivity at 8 kHz was obtained only in the ABR. Thus the sensitivity loss at 4-6 kHz originates at the peripheral system and the increased sensitivity at 8 kHz originates at the central.

Action Potentials↗
PubMed1991

Cepstral analysis of ultrasound in chronic liver disease--a preliminary study in the non-invasive evaluation of structural change.

To evaluate the morphological changes in chronic liver disease non-invasively we used the frequency-domain analysis of ultrasound. We assumed that liver tissue is a collection of semi-regularly arrayed small scatterers of ultrasound. We applied cepstral analysis to ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum, caused by an interference effect among liver scatterers of a given spacing. In a phantom experiment, we could correctly measure the space among scatterers of a phantom consisting of a regularly spaced distribution of nylon filaments. In an experiment involving a freshly excised porcine liver, the distribution of the space among scatterers (SAS) determined on cepstral analysis reflected the size distribution of the hepatic lobules. In a human study, two statistical parameters, mode and kurtosis, were determined from the distribution of the SAS for each patient. In a previous study, we collected ultrasonic data during peritoneoscopy with a 10 MHz transducer directly contacting the liver and showed that we could evaluate morphological changes in chronic liver disease using cepstral analysis. In the present study, we obtained data in two ways: with a 3.5 MHz transducer through the abdominal wall and with a 10 MHz transducer directly contacting the liver during peritoneoscopy. The mode and kurtosis of the SAS obtained with the 3.5 MHz transducer were both well correlated with the mode and kurtosis of the SAS obtained with the 10 MHz transducer. These results suggest that we can evaluate morphological changes in chronic liver disease non-invasively.

Animals↗
PubMed1991

Dephosphorylation of the insulin receptor partially restores the decreased autophosphorylation in streptozotocin induced diabetic rats.

The insulin resistance seen in diabetes mellitus has been attributed partly to impaired autophosphorylation of the insulin receptor. It has been suggested that the phosphorylation of serine and/or threonine residues of the insulin receptor may reduce tyrosine autophosphorylation in streptozotocin-induced diabetic rats (STZ-D rats). To elucidate the mechanisms of decreased autophosphorylation of the insulin receptor in diabetic rats, we have investigated the effect of dephosphorylation of the insulin receptor by alkaline phosphatase on the insulin- and protein kinase-stimulating incorporation of 32P into the receptor of the liver from STZ-D rats. Both basal and insulin-stimulated autophosphorylations of the insulin receptor from STZ-D rats were significantly impaired to those from normal rats. Dephosphorylation of the insulin receptor by alkaline phosphatase resulted in an increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats (43 +/- 13% to 66 +/- 14%, P less than 0.05), but not from normal rats (100% to 109 +/- 12%, NS). Although maximal autophosphorylation of the dephosphorylated insulin receptor was still lower in STZ-D rats than in normal rats, the increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats by dephosphorylation was higher than that from normal (159.2 +/- 27.2% vs 108.0 +/- 12.4%, p less than 0.01), supporting the idea that the residues of the insulin receptor of STZ-D rats was highly phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
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

High dose rate intracavitary radiation therapy of carcinoma of the cervix using a linear source.

One hundred patients with carcinoma of the cervix stages 1B to 4A were treated with intracavitary high dose rate radiation using a linear cobalt source. All cases have received external beam pelvic irradiation to 4500cGy mid plane in twenty fractions over four weeks. The results in terms of patient compliance and convenience were good while acute and late morbidities were comparable to standard Manchester technique of low dose rate intracavitary therapy as practised in the Institute of Radiotherapy and Oncology General Hospital Kuala Lumpur. The four year actuarial survival rate is 76% for stage II and 48% for stage III. All three stage IV patients died within 1 year. Four out of seven stage I patients are alive (minimum follow-up 18 months, longest 43 months). One died of systemic spread at 33 months while one is lost to follow up.

Adult↗
PubMed1991

[Quantification of mitral regurgitation by Doppler color flow mapping: comparison of mitral regurgitant fraction and volume with Doppler measurements].

Color flow imaging of the regurgitant areas has been used to quantitate the severity of valvular regurgitation, however, the exact relationship between color flow areas and regurgitant volumes or fraction has not been clarified. This study was designed to determine whether measurements of jet flow areas and distances using color flow imaging are closely related to the regurgitant volume (MRV:ml/beat) and fraction (MRF: %). Doppler examinations were performed in 29 patients with mitral regurgitation (MR). The MR jet was depicted as the largest clearly definable flow disturbance on the echo images, and the maximal jet area (cm2) and length (cm) were measured. The MRV and MRF were obtained from the Doppler measurements of the transmitral flow (TMF) and the aortic flow (AF) as follows: MRV = TMF-AF, MRF = MRV/TMF x 100. The maximal jet area showed significant correlations with the MRV and MRF (r = 0.75 and 0.75, p < 0.01), and the maximal jet length showed even better correlations with the MRV and MRF (r = 0.82 and 0.80, p < 0.01), irrespective of the etiology of MR. Thus, both the maximal jet area and length obtained from color flow imaging can be simple and useful measurement methods for predicting the MRV and MRF.

Blood Flow Velocity↗
PubMed1991

Endothelin-1 stimulates prostaglandin E2 production in an extracellular calcium-independent manner in cultured rat mesangial cells.

To study a possible role of endothelin-1 (ET-1) in the regulation of glomerular function, we examined the presence of receptors for, and the biological action of, ET-1 in cultured rat mesangial (M) cells. The first-subcultured M cells prepared from isolated glomeruli of Sprague-Dawley rats were used. ET-1 binding was assayed by using 125I-ET-1. Inositol 1,4,5-trisphosphate (IP3) was determined by IP3-specific binding assay. Intracellular calcium (iCa2+) was measured in fura-2 loaded cells. Prostaglandin E2 (PGE2) was measured by radioimmunoassay. In M cells there existed two classes of binding sites specific for ET-1 (Kd was 0.24 and 4.4 nmol/L, Bmax was 130 and 1070 fmol/mg, respectively). ET-1 (10(-7) mol/L) induced a rapid and transient increase in IP3, followed by transient and sustained increases in iCa2+. Nicardipine (10(-6) mol/L) inhibited only the sustained increase in iCa2+. ET-1 (10(-9) mol/L to 10(-7) mol/L) significantly stimulated PGE2 production with the concentration dependency. Nicardipine (10(-6) mol/L) and diltiazem (10(-6) mol/L) did not inhibit the PGE2 production. We conclude that M cells have specific ET-1 receptors linked to phosphoinositide turnover and PGE2 production, and PGE2 production by ET-1 may be through an extra-cellular calcium-independent mechanism. Our results suggest that ET-1 plays an important role in the regulation of glomerular functions by modulating PGE2 production in M cells.

Animals↗