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Biomedical subjects

K Iwase

Publications and source records attributed to K Iwase.

At least 109 records · Page 6Linked to original sources

[Clinical and biochemical studies in a case of acute encephalopathy associated with calcium hopanthenate administration].

A case with acute disturbance of consciousness associated with calcium hopanthenate (HOPA) administration was reported. He was a 3-year-old boy with autistic developmental delay, had orally taken 1.5 g of HOPA daily for 3 months. Clinical manifestations consisted of fever, vomiting and coma. Laboratory examination revealed severe hypoglycemia and metabolic acidosis, but there were no hepatic enzyme abnormalities. Analysis of urinary organic acid profile showed that very large amounts of medium and long chain dicarboxylic acids and omega-1 hydroxy-fatty acids were excreted. In particular, 2-hydroxysebacic acid, the accumulation of which has only been reported in the urine of patients with Zellweger syndrome and neonatal adrenoleukodystrophy (NALD), was observed. Analysis of urinary acylcarnitines showed that acetylcarnitine was predominant and C6-C10 dicarboxylic acylcarnitines were also excreted. He was treated with and rapidly responded to intravenous glucose and bicarbonate. After withdrawal of the drug he has had no problems and dicarboxylic aciduria disappeared. A CT scan showed symmetric, low density areas in periventricular white matter, especially around the posterior horns of the lateral ventricles. A T2-weighted MRI scan revealed high-intensity signal in the white matter corresponding to areas of low density on CT scan. We conclude that that a large amount of HOPA administration may cause encephalopathy by the inhibition of both mitochondrial and peroxisomal beta-oxidation.

Acute Disease↗

[PCL implantation in diabetic patients--examination of CME and maculopathy].

We performed posterior chamber lens (PCL) implantation in 287 eyes of 207 diabetic patients, and evaluated postoperative cystoid macular edema (CME) and diabetic maculopathy. The rate of CME was 9.3% and its average period after surgery was 3.6 months. The incidence of diabetic maculopathy was 3.4% and it appeared 8.8 months after operation on average. In both the CME group and diabetic maculopathy group, the duration of diabetes, HbAlc value, the grade of diabetic retinopathy and the conditions of general complications were significantly higher than in those without CME and maculopathy. Only in the diabetic maculopathy group were the pre- and postoperative dilated pupillary diameter significantly smaller. CME patients were treated with oral or subconjunctival injection of corticosteroids, when diabetes was controlled and they had no or mild retinopathy, and good visual acuity was recovered (0.98 on average). The other patients with CME were treated with laser photocoagulation, and they regained a visual acuity of 0.50 on average. All patients with maculopathy were treated with laser photocoagulation, but they regained a visual acuity of 0.36 on average. The postoperative protein concentration in the anterior chamber was significantly higher in the CME group than in the non-CME group at one day and also at three months after operation.

Aqueous Humor↗

Kinetic characteristics of a thioredoxin-activated rat hepatic and renal low-Km iodothyronine 5'-deiodinase.

The properties and kinetic characteristics of a non-GSH NADPH-dependent cofactor system activating rat hepatic and renal 5'-deiodinase (5'-DI), which we have previously demonstrated with partially purified cytosol Fractions A and B [Sawada, Hummel & Walfish (1986) Biochem. J. 234, 391-398], were examined further. Although microsomal fractions prepared from either rat liver or kidneys could be activated by crude cytosol Fractions A and B from those tissues as well as from rat brain and heart, a homologous hepatic or renal system was the most potent in producing 5'-deiodination of reverse tri-iodothyronine (rT3). At nanomolar concentrations both rT3 and thyroxine (T4) were deiodinated but with a much greater substrate preference for rT3 than for T4. However, at micromolar concentrations of these substrates no activation of 5'-DI could be detected. In this deiodinative system, T4 and tri-iodothyronine (T3) competitively inhibited 5'-deiodination of rT3. Dicoumarol, iopanoate, arsenite and diamide were also inhibitory to the activation of hepatic or renal 5'-deiodination by this cofactor system. Purification of cofactor components in hepatic crude cytosolic Fractions A and B to near homogeneity, as assessed by their enzymic and physical properties, indicated that these co-purified with and were therefore identical with thioredoxin reductase and thioredoxin respectively, and accounted almost entirely for the observed activation of rT3 5'-DI. When highly purified liver cytosolic thioredoxin reductase and thioredoxin were utilized to determine the kinetic characteristics of the reaction, evidence for a sequential mechanism operative at nanomolar but not micromolar concentrations of rT3 and T4 was obtained. The Km for rT3 was 1.4 nM. Inhibition by 6-n-propyl-2-thiouracil (Ki 6.7 microM) was competitive with respect to thioredoxin and non-competitive with respect to rT3, whereas inhibition by T4 (Ki 1.3 microM) was competitive. Since rT3 is a potent inhibitor of T4 5'-deiodination, this thioredoxin system activating deiodination of rT3 may play an important role in regulating the rate of intracellular production of T3 from T4.

Animals↗

Rat hepatic and renal 5'-deiodination of rT3 during fasting: supportive role of intermediate Mr cytosolic non-glutathione thiol cofactor and NADPH.

The roles of subcellular components and, in particular, cytosol fractions and beta-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), in the regulation of rat hepatic and renal 5'-deiodination during fasting were assessed. 5'-deiodinase (5'-DI) activities in reaction mixtures were measured by using outer ring 125I-radiolabelled reverse triiodothyronine (rT3) as a substrate in the presence of 200 mumol/L NADPH. Subcellular components from rats fed ad libitum or fasted for 24, 48 or 72 hours were prepared by standard differential centrifugation. Cytosol was chromatographed on a Sephadex G-50 column to obtain Fraction A of molecular weight (Mr) greater than 60,000 and Fraction B of Mr approximately 13,000 and to exclude reduced glutathione (GSH) (Mr less than 400). 5'-DI activity in liver homogenates was reduced by 42% at 24 hours and by 59% at 48 hours of fasting. In reconstitution experiments, liver microsomes showed a progressive loss of 5'-DI activity, reaching a maximal reduction of 46% at 72 hours of fasting. Activation of microsomal deiodinase by whole liver cytosol was also significantly reduced at 24 hours of fasting and achieved a maximal reduction of 5'-DI activation of 42% at 48 hours before substantial but incomplete recovery at 72 hours. Cytosolic Fraction A and B were assessed in combination with fed microsomes and NADPH. A close correlation was demonstrated between the loss of hepatic 5'-DI supportive activity in whole cytosol and that of Fraction B but not A during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cytosol components from human placenta and rat liver in iodothyronine 5- and 5'-deiodination.

Using either human placental microsomal 5-deiodinase as enzyme (5-DI) and thyroxine as substrate or rat liver (RL) microsomal 5'-deiodinase (5'DI) as enzyme and reverse [(3'- or 5'-)-125I]triiodo-L-thyronine ([125I]rT3) as substrate, activation of 5'-DI in the presence of NADPH was observed using either human placental or rat liver cytosolic components, but there was no activation of 5-DI. Both could be activated by DTT, with higher concentrations being required for 5-DI than for 5'-DI. Iopanoic acid, dicumarol, and sodium arsenite inhibited 5'-DI and 5-DI activated by DTT. In the presence of DTT, 1 mM 6-propyl-2-thiouracil had no effect on 5-DI but inhibited 5'DI. Thus, human placental and rat liver cytosolic components are interchangeable in activating hepatic 5'-DI in the presence of NADPH. However, if an endogenous cofactor system involved in the activation of human placental 5-DI exists, it probably differs from the activator of liver 5'-DI.

Animals↗

[A case of secretory carcinoma of the breast in a elderly Japanese woman].

We report a case of a secretory carcinoma of the breast in a 72-year-old woman with a long history of a left breast mass. Rapid growth and skin invasion of the tumor was noticed three months before a radical mastectomy was performed and a lung metastasis was found one month after the operation. A metastasis to the axillary nodes was noted in 6 of 9 resected specimens and a receptor assay of the estrogen and progesterone proved to be negative. This patient is the oldest case of a secretory carcinoma of the breast reported in Japan.

Adenocarcinoma↗

[Quantitative assessment of aqueous flare intensity and cell count in uveitis].

In an attempt to evaluate the validity of the laser flare-cell meter in in iridocyclitis, we conducted a comparative study of slit-lamp examination and flare-cell meter measurements in 251 eyes of uveitis patients. A significant correlation was observed between the two methods both in the measurement of flare intensity (Kendall tau = 0.580, p less than 0.001) and cell count (tau = 0.390, p less than 0.001). However, there were wide variations in grading within groups and large overlaps in scores between groups. These results were thought to be attributable to differences in the two examination methods. Flare-cell meter demonstrated high sensitivity for flare measurements, while there were some cases where low numbers of cells, which could be observed by a slit-lamp, were undetectable by the flare-cell meter. Patients with Behçet's disease were divided into three groups based on the interval from an ocular attack episode. Flare-cell meter examination revealed that flare intensity values remained abnormally high even in patients free from an attack episode for more than six months prior to the examination (p less than 0.001). It was considered that disruption of the blood-aqueous barrier exists permanently in patients with Behçet's disease.

Adult↗

Quantitative assessment of aqueous flare and cells in uveitis.

Validity of the laser flare-cell meter in uveitis was evaluated. A comparative study of slit-lamp examination and flare-cell meter measurements was carried out in the evaluation of iridocyclitis in a total of 251 measurements in patients with uveitis of various etiologies, including Behçet's disease, Vogt-Koyanagi-Harada's disease and sarcoidosis. The data obtained by these two methods showed a significant overall correlation both in the measurement of flare intensity (Kendall tau = 0.580, P less than 0.001) and cell count (tau = 0.390, P less than 0.001). Problems inherent to the slit-lamp examination were marked in terms of wide variations in grading within groups and large overlaps in scores between groups. The flare-cell meter was highly reliable in the measurement of flare intensity; whereas it could not detect low numbers of cells in some cases. Ninety-one eyes of patients with Behçet's disease were divided into three groups based on the interval from the last ocular attack episode. The flare-cell meter examination revealed that values for flare intensity remained abnormally high even in patients free from an attack episode for more than six months prior to the examination. It was considered that deterioration or breakdown of the blood-aqueous barrier function persists in patients with Behçet's disease.

Aqueous Humor↗

[Clinical study of penetrating thoracic injuries].

During the 13-year period ending in December 1987, 39 patients (pts) of penetrating thoracic injuries were treated. Thirty-five pts (89.7%) were male, and the age range was 21 to 56 years with average of 38.7 years. Thirty-one pts (79.5%) sustained stab wounds and eight (20.5%) had gun-shot wounds. 5 pts died in all (2 pts with stab wounds, 3 with gun-shot wounds). The wounds were limited on chest wall in 14 pts, and penetrated to thorax in 25. In these pts with penetrating wounds, lung injuries were found in 18, heart in 7 and esophagus in 1, respectively. Twenty-one pts had multiple injuries, and abdominal injuries were found in 20 pts (95.2%), limbs in 7 (33.3%), and neck in 2 (9.5%). All 5 dead pts had multiple injuries. Prognoses were fair in cases of simple chest wall injuries or lung injuries. In the cases of lung injuries, thoracotomy was performed in 8 pts (44.4%) and tube thoracostomy in 10 (55.6%). Thoracotomy was performed for massive bleeding (over 600 ml/1-2 hours) (6 cases) and the sites of the injuries suspecting of heart injuries (2 cases). Two pts undergoing tube thoracostomy and one pt done thoracotomy died, but the causes of the death were not related to lung injuries. Regarding the heart injuries, the injured sites were left ventricle in 1, right ventricle in 1, right atrium in 2, and pericardium in 3. All the 7 pts were in shock on arrival. In these pts with heart injuries, all the wounds were in and near the Sauer's danger zone. In all pts, emergent thoracotomy was performed, and 5 pts could be saved (mortality 28.6%). As the risk factors, heart injuries, multiple injuries, and gunshot injuries were noticed with mortality of 28.6%, 23.8%, and 37.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

DNA polymerase beta in human thyroid of Graves' disease and thyroid tumors.

We have shown that the level of DNA polymerase beta of rat adrenal cortex is regulated by pituitary trophic hormones and may correlate with their endocrine function. Here we measured DNA polymerase beta activity in human thyroid tissues of various benign and malignant thyroid disorders in order to verify the correlation between DNA polymerase beta activity and endocrine function. In Graves' disease (hyperfunction), the level of DNA polymerase beta per cell was three times higher than in normal thyroid, while in undifferentiated thyroid carcinomas this enzyme level was lower than normal. Furthermore, DNA polymerase beta in the crude extracts of cancer cells showed larger molecular forms, ranging from five to 12S, upon sucrose gradient sedimentation. These observations further support the hypothesis that the activity of DNA polymerase beta correlates, in part, with the functional level of the endocrine organ and with cell differentiation.

Adenoma↗

Hormonal regulation of DNA polymerase-beta activity in the rat thyroid gland.

Using hypophysectomized rats, it has been shown that DNA polymerase-beta activity in the adrenal gland and testis is largely influenced by pituitary trophic hormones. Sucrose gradient centrifugation of thyroid extracts revealed three peaks of DNA polymerase-beta activity sedimenting at 3.3S, 7.3S and 12S. Of these, hypophysectomy induced a decrease in the 3.3S DNA polymerase-beta, whereas other molecular forms were affected only slightly. DNA polymerase-alpha and -gamma activities were unaffected by hypophysectomy. These changes in DNA polymerase-beta caused by hypophysectomy were reversed by daily i.p. injection of TSH. Furthermore, stimulation of the thyroid by excess TSH induced by the administration of 1-methyl-2-mercaptoimidazole resulted in an increase of all forms of thyroid DNA polymerase-beta. These results show that the level of DNA polymerase is relatively constant after hypophysectomy but that DNA polymerase-beta in the rat thyroid gland is also modulated by TSH mainly through the change of activity of the polymerase-beta which sediments at 3.3S.

Animals↗

[Change in serum thyroid hormone levels in patients with acute myocardial infarction].

It has been reported that there is a decrease in the serum concentration of thyroid hormones in non-thyroidal illness. In the present study we made serial measurements of serum concentration of thyroid hormones [triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), reverse triiodothyronine (rT3)], thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG) in 10 patients with acute myocardial infarction (AMI, Grade I, according to the classification of Killip & Forrester) during 14 days after onset. In the early phase of AMI, serum T3, T4, FT3 and FT4 levels decreased while rT3 increased. TSH and TBG levels, however, were unchanged. In the patients with a high peak creatine phosphokinase activity (greater than or equal to 400 mU/ml), the decrease in thyroid hormone and increase in serum rT3 levels were greater than in patients with a low peak value (less than 400 mU/ml), suggesting a correlation between severity of AMI and changes in serum thyroid hormone levels. Especially, serum FT3 levels fell below the lower limit of controls within 14 days, with the lowest levels and the rT3 peak on the third day after onset. These data suggest that in AMI peripheral conversion of T4 favours rT3 production and that low levels of serum FT3 and T3 protect the infarcted heart muscle against thyroid hormone action.

Aged↗

Increase in S-100b protein content in thyroid carcinoma.

S-100b protein was detectable in the soluble fraction of thyroid tissue. The concentration of S-100b protein in thyroid carcinoma tissue was three to five times higher than in normal thyroid tissue and thyroid adenoma. It is, however, not higher in the thyroid tissue of Graves' disease. The increase of S-100b protein concentration was not remarkable in carcinomatous tissue of the stomach and other digestive organs. The calmodulin content in the thyroid carcinoma tissue increased but the increment was low compared to that of S-100b protein. These data suggest that S-100b protein may play a significant role in cell maturation or differentiation.

Adenoma↗

Long-term prognosis of tuberous sclerosis with epilepsy in children.

A follow-up study was performed on 40 children with tuberous sclerosis and epilepsy. In 68% of the patients with infantile spasms and 73% of those without them, complex partial seizures were observed. Thus, patients with tuberous sclerosis are subject to not only infantile spasms but also complex partial seizures. Patients with infantile spasms showed mental retardation more often than those without. Seizures which had evolved from infantile spasms were more difficult to control than those which had not. The prognosis of infantile spasms associated with tuberous sclerosis was better than that of prenatal group other than tuberous sclerosis. Forty percent of the 40 cases showed asymmetry on EEG, and the asymmetry tended to disappear as the patients grew up.

Adolescent↗

Crohn's disease associated with giant inflammatory polyposis.

We found shallow serpiginous, longitudinal ulcerations in the descending colon at the first examination of a 17-year-old female patient with Crohn's disease. Four months later at the second examination, we observed that a polypoid lesion had formed longitudinally in the region of the healed ulcers. The third examination, one year later, showed the presence of pedunculated and semi-pedunculated giant polyps in the descending colon. The lesion of the descending colon was removed surgically to cure the crampy abdominal pain caused by colonic obstruction. The segmental colectomy specimen showed longitudinally aligned pedunculated polyps of various sizes. The pathological diagnosis was inflammatory polyposis. To the best of our knowledge, there have been very few reports on the appearance of a number of pedunculated polyps such as in this case. This reports shows, through endoscopic pictures, the evolution of the polyp and discusses its formation.

Adolescent↗