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Biomedical subjects

M Izumi

Publications and source records attributed to M Izumi.

At least 19 recordsLinked to original sources

Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript.

In the present study, we report the molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor (hTSHR) mRNA transcript, which has previously been detected on Northern blot analysis of human thyroid cells. The smaller hTSHR cDNA, designated hTSHR cDNA-I, is approximately 1 kb in size and encodes a protein of 253 amino acids. Comparison of the nucleotide sequence of hTSHR cDNA-I with available hTSHR genomic sequence data reveals that the cDNA-I contains exons 1-8 and unidentified DNA tract, presumably an intron. Thus, the hTSHR cDNA-I encodes for the N-terminal half of the extracellular domain of the hTSHR (approximately 60%). The truncated TSHR-I may be secreted and function as a TSH binding protein.

Alternative Splicing

Multiple endocrine neoplasia type 2 with malignant pheochromocytoma--long term follow-up of a case by 131I-meta-iodobenzylguanidine scintigraphy.

The case of a 33-year-old Japanese man, who has Multiple Endocrine Neoplasia Type 2 (MEN IIa) (Sipple's syndrome) with malignant pheochromocytoma, is reported. He had survived for twelve years since the initial diagnosis of malignant pheochromocytoma. Within this period, he had undergone 131I-meta-iodobenzylguanidine scintigraphy twice, in 1983 and 1990. This is the first case in Japan of a longterm surviving patient with malignant pheochromocytoma followed up by 131I-MIBG scintigraphy. Although he had no exacerbation of clinical symptoms or urinary catecholamine levels, second scintigraphy clearly showed an increase in the tumor size, new metastasis of the malignant pheochromocytoma and exacerbation of the medullary thyroid carcinoma. Compared with any other roentgenological device and hormonal data, 131I-MIBG scintigraphy was seen to be a good tool for evaluating the localization and the progression of tumors. 131I-MIBG scintigraphy is a useful procedure not only for initial diagnosis but also for judging progression in a case of advanced malignant pheochromocytoma.

3-Iodobenzylguanidine

Impairment of the TSH signal transduction system in human thyroid carcinoma cells.

In order to further evaluate the role of TSH in the proliferation and the differentiation of human thyroid carcinoma cells, we have analyzed the function of the TSH receptor in the established thyroid carcinoma cell lines NPA and WRO. The TSH signal transduction system in the carcinoma cells was also compared with that in normal thyroid cells. Although unresponsiveness to bovine and human TSH was demonstrated by measurement of cAMP production and [3H]thymidine incorporation after treatment of TSH, cAMP production was induced after stimulation of these cells by forskolin, cholera toxin, and isoproterenol. Specific binding to 125I-TSH was demonstrated in both NPA and WRO cells in addition to the existence of a TSH receptor mRNA and thyroglobulin mRNA species, although thyroid-specific gene expression in these cells was not regulated by TSH. These findings suggest that the unresponsiveness to TSH in these cells may be due to an abnormality of TSH receptor-G protein coupling rather than to a decreased level of TSH-receptor expression or a Gs protein abnormality.

Base Sequence

Protein binding of four antiepileptic drugs in maternal and umbilical cord serum.

The total and protein free levels of 4 antiepileptic drugs (AEDs) in serum from 35 maternity patients who had been treated with AED monotherapy throughout pregnancy were studied. Results were compared with those in the umbilical cord serum at the time of delivery, and the placental transfer of AEDs was evaluated from the viewpoint of the protein binding capacity of the drug. The materials consisted of 35 samples of maternal and umbilical cord serum in total and included 13 patients on phenobarbital (PB), 7 on phenytoin (PHT), 7 on carbamazepine (CBZ) and 8 on valproic acid (VPA). The mean fetal/maternal total concentration ratios were 0.86, 0.91, 0.73 and 1.59 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being above 1. On the other hand, the mean fetal/maternal free fraction ratios were 1.13, 1.10, 1.42 and 0.50 for PB, PHT, CBZ and VPA, respectively, only the VPA ratio being less than 1. Correlation of the 2 ratios showed a reciprocal proportion with a correlation coefficient of -0.90 (P < 0.005). It was considered that the fetal/maternal total concentration ratio of 4 AEDs was regulated by the fetal/maternal free fraction ratio of the corresponding AEDs and that the difference in fetal/maternal free fraction ratio depended on the type of drug being administered.

Anticonvulsants

Long-term effectiveness of antiepileptic drug treatment and seizure recurrence in patients with epilepsy.

We studied the rate of seizure recurrence in 334 patients with epilepsy who had received antiepileptic drug (AED) therapy for at least eight years. During the three-year "observation period" (April 1985-March 1988), 163 or 48.8% of the 334 patients were considered to be seizure-free. Seizures were absent in 53 or 81.5% of 65 patients with idiopathic generalized epilepsy, 48 or 40% of 120 with temporal lobe epilepsy, 39 or 39.4% of 99 with partial epilepsy other than those involving the temporal lobe, 2 or 8.3% of 24 with symptomatic generalized epilepsy and 21 or 80.8% of 26 with other epilepsies. Of the 163 patients, 15 or 9.2% suffered seizure(s) during the three-year "follow-up period" (April 1988-March 1991). There was no difference among the different types of epilepsy with respect to seizure recurrence rates. Compared with the 15 patients whose seizures recurred, more of the 148 patients with nonrecurring seizures received AED monotherapy (p < 0.05). However, no significant differences were seen between the two groups for other background factors.

Adult

Interleukin-1 inhibits human thyroid carcinoma cell growth.

In order to further clarify the growth regulating effect of cytokines on thyroid cell proliferation, the effect of interleukin-1 (IL-1) was tested on growth of human papillary and follicular thyroid carcinoma cells (NPA and WRO). Although fetal bovine serum stimulated DNA synthesis, TSH did not affect cell growth and the level of thyroglobulin messenger RNA (mRNA) in NPA. Eight-bromo-cAMP and forskolin, however, significantly suppressed DNA synthesis, suggesting the impairment of TSH receptor signal transduction in NPA cells despite of the presence of [125I]TSH binding. Both IL-1 alpha and beta inhibited [3H] thymidine uptake into NPA cell DNA in a dose- and time-dependent manner at concentrations ranging from 5 x 10(2) to 10(5) U/L; 10(5) U/L of IL-1 suppressed DNA synthesis by more than 40% of control. The suppressive activity of IL-1 beta was more potent than that of IL-1 alpha in spite of the same lymphocytes activating factor (LAF) activity. Steady state levels of c-myc mRNA transcripts were also inhibited by both IL-1 alpha and beta, respectively. On the other hand, IL-1 alpha and beta did not affect the WRO cell growth. Although forskolin stimulated cAMP production in NPA cells, IL-1 did not induce cAMP generation. Indomethacin (1.0 approximately 10 mg/L) did not alter the suppressive activity of IL-1. Neither IL-1 alpha and beta caused a cytotoxic effect on the NPA cells. Although changes in c-myc mRNA content may just be an epiphenomenon of the decrease in proliferative activity in response to IL-1, and not a direct target of action of the peptide, these results demonstrate the inhibitory effect of IL-1 on cell growth of NPA. IL-1 may have an aspect of antitumorigenic action in some human thyroid carcinoma differentiation and replication.

Adenocarcinoma

Dihydrotestosterone accumulation in genital skin fibroblasts derived from elderly men with prostatic hyperplasia.

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-Androstane-3 alpha,17 beta-diol (3 alpha-diol) by 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 15 prepubertal boys (2-10 yr), 17 young men (20-40 yr), 13 elderly men (60-78 yr) without clinically evident prostatic pathology, and 17 elderly men (61-88 yr) with benign prostatic hyperplasia (BPH). Respective DHT formations from testosterone (5 alpha-reduction) and 3 alpha-diol (3 alpha-HSOR oxidation) were not different among genital skin fibroblasts of the 4 groups. However, DHT degradation to 3 alpha-diol (3 alpha-HSOR reduction) was significantly lower in fibroblasts from elderly men with BPH than in those from the prepubertal boys (P less than 0.01), the young men (P less than 0.01), and the elderly men without BPH (P less than 0.05). 3 beta-HSOR reduction in fibroblasts of the BPH group was significantly lower (P less than 0.05) than in those of the elderly men without BPH; however, it did not differ from values for the prepubertal boys and the young men. (3 alpha + 3 beta)-HSOR reduction was also significantly lower (P less than 0.05) in the BPH group than respective values of the three other groups. These results indicate that DHT accumulation may occur in genital skin fibroblasts from elderly men with BPH, resulting from a shift in the overall balance of androgen metabolism, which favors the net formation of DHT.

Aged

Acute adrenal insufficiency due to symptomatic Rathke's cleft cyst.

A 65-year-old Japanese man who suffered from secondary hypopituitarism due to Rathke's cleft cyst is reported. Although computed tomography failed to detect any pituitary abnormality, magnetic resonance imaging demonstrated the presence of a cystic intrasellar mass, initially suggesting craniopharyngioma or abscess. Operative findings revealed Rathke's cleft cysts within the pituitary fossa which resulted in secondary hypopituitarism. Among cases of secondary hypopituitarism with abnormal findings in the pituitary, symptomatic Rathke's cleft cysts should be included in the differential diagnosis of adrenal insufficiency.

Adrenal Insufficiency

Evaluation of hemodialysis efficiency by an edema fluid model.

The concentrations of urea, creatinine, and uric acid were measured in edema fluid and plasma during hemodialysis and 18 h after hemodialysis. The concentrations of these solutes in plasma were 15-17% lower than in the edema fluid after hemodialysis. Eighteen hours after hemodialysis, however, the concentrations in plasma were almost the same as those in edema fluid. These data suggest that the removal of these solutes from the extracellular space is delayed during hemodialysis. The plasma concentrations obtained at 18 h after hemodialysis are better indicators of hemodialysis efficiency.

Adult

Mesangial cell growth in genetically hypertensive rats and effect of calcium antagonists upon this growth.

Mesangial cells play an important role in physiological and pathophysiological regulation of glomerular functions. To explore the involvement of deranged mesangial cell functions in the pathogenesis of hypertension, the growth activity of mesangial cells was compared in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Upon exposure to fetal calf serum, the growth rate was significantly higher in mesangial cells cultured from glomeruli of 4-week old SHRSP than in those of age-matched WKY. This abnormally high growth of SHRSP mesangial cells was significantly inhibited by dihydropyridine calcium antagonists. Of the three antagonists tested, manidipine was the most potent inhibitor. Significant growth inhibition occurred at a concentration as low as 10(-12) M; inhibition as high as 65% was found at 10(-6) M. Calcium antagonists, particularly manidipine, may prevent or delay the development of hypertension not only through vasodilation but also through inhibition of mesangial cell growth. By slowing mesangial cell proliferation, calcium antagonists also may slow the progression of hypertension-induced glomerular sclerosis.

Animals

Effects of macrolide antibiotics on gastrointestinal motility in fasting and digestive states.

The effect of macrolide antibiotics on gastrointestinal motility was studied in unanaesthetized dogs by using strain-gauge transducers. Midecamycin acetate, leucomycin, josamycin and acetylspiramycin, which are 16-membered macrolides, did not affect the gastrointestinal motility and no symptoms of gastrointestinal disorder were observed. On the other hand, erythromycin, roxithromycin, clarithromycin and oleandomycin, which are 14-membered macrolides, caused giant contraction and disorder symptoms. Moreover, it was found that the glycosidic linkages of the lactone ring were necessary for a structure to exert strong contractile activity.

Animals

[Efficacy and limitations of antiepileptic drug monotherapy for temporal lobe epilepsy].

To evaluate the efficacy of antiepileptic drug (AED) monotherapy, we studied 147 patients with temporal lobe epilepsy (TLE) aged 15 or older who had been undergoing treatment at our hospital for at least five consecutive years. We divided the treatment time into Period I which included one year beginning six months after the initial diagnosis, and Period II which was the two years from January, 1987 to December, 1989. The efficacy of therapy was evaluated for the two periods based on the following standards: effective, if seizures had been controlled, and ineffective, if at least one seizure had occurred during each period. Patients in whom monotherapy was effective increased by a factor of 1.7 over the period of observation, from 38 cases (28%) in Period I to 65 cases (44%) in Period II. The total number of effectively treated cases (including those on polytherapy) also rose from 58 cases (40%) in Period I to 79 cases (54%) in Period II. The average number of AEDs used was reduced from 3.0 +/- 1.3 at the time of initial diagnosis to 1.8 +/- 0.8 in Period I and 1.6 +/- 0.8 in Period II. When compared with the 68 ineffectively treated cases, significant background factors for the 65 effectively treated cases on monotherapy included: higher age at ictal onset, fewer histories of any previous treatment at initial diagnosis, or of encephalitis or febrile seizures, fewer psychological impairments such as cognitive degeneration or personality disorders, lower frequency of seizures, fewer histories of secondary generalization or automatism, and a higher rate of normal findings of background EEG and cerebral CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Isolation and characterization of alpha 1-acid glycoprotein from horses, and its evaluation as an acute-phase reactive protein in horses.

Equine alpha 1-acid glycoprotein (alpha 1AG) was isolated from equine serum by successive ammonium precipitation, anion- and cation-exchange chromatographies, and gel filtration. Purified equine alpha 1AG had a molecular weight of 46,000 +/- 1,000, and contained 31.4% carbohydrate. Gel isoelectric focusing revealed an isoelectric point range of 2.8 to 3.7. With immunoelectrophoresis, it was found that alpha 1AG migrated to the alpha 1-globulin region. Single radial immunodiffusion was used for quantitative measurement of alpha 1AG in equine serum. In clinically normal foals, serum alpha 1AG was undetectable (less than or equal to 20 micrograms/ml) in less than or equal to 7-day-old foals, but was detected by 14 days. The alpha 1AG concentration (mean +/- SD) increased to reach mean adult values of 99.23 +/- 26.90 micrograms/ml by 1 year of age. The alpha 1AG concentration in pregnant mares decreased at 2 to 3 months before parturition, then gradually increased until 1 day after parturition, when a brief decrease was observed. The concentration increased again at 2 weeks after foaling, then a decrease was observed, after which the alpha 1AG concentration increased again by 2 to 4 months after parturition. The concentration of serum alpha 1AG quickly rose to peak values 2 to 3 days after castration and jejunojejunostomy in adult horses, returning to baseline values by 14 to 28 days after surgery. The alpha 1AG was concluded to be an acute-phase reactive protein in horses.

Acute-Phase Reaction

Lithium carbonate in the preoperative preparation of Graves' disease.

Lithium carbonate was given in the preoperative preparation of 12 patients with Graves' disease, the reasons for its use being side effects of thionamide in 9 patients, insufficient control by thionamide in 1 and psychic symptoms in 2. Lithium carbonate was often used in combination with other drugs, namely; thionamide in 4 patients, beta-adrenergic blockades in 5, reserpine in 5 and glucocorticoid in 1. This preoperative control significantly decreased the mean serum T2 and T4 levels from 656 +/- 55 ng/dl to 180 +/- 16 ng/dl and from 25.9 +/- 2.1 micrograms/dl to 9.7 +/- 1.5 micrograms/dl, respectively. The only adverse effect of lithium carbonate was pollakisuria observed in one patient. All patients underwent subtotal thyroidectomy uneventfully. It is concluded that the administration of lithium carbonate alone or in combination with other drugs is an effective method of preoperatively controlling hyperthyroidism when conventional antithyroid drugs show adverse effects.

Adolescent

Blasticidin S-resistance gene (bsr): a novel selectable marker for mammalian cells.

Blasticidin S is a microbial antibiotic that inhibits protein synthesis in both prokaryotes and eukaryotes. The blasticidin S-resistance gene (bsr), isolated from Bacillus cereus K55-S1 strain, was inserted into pSV2 plasmid vector and introduced into cultured mammalian cells by transfection. The bsr gene was integrated into the genome and conferred blasticidin S resistance on HeLa cells. The transfection frequency of the bsr gene was as high as that of the aminoglycoside phosphotransferase gene, the so-called neo gene, which is a representative selectable marker for mammalian cells. Transfectants in which several copies of bsr had been integrated into the genome were highly resistant to blasticidin S. Furthermore, blasticidin S killed the cells more rapidly than G418, which is conventionally used as a selective drug for the neo gene. Thus bsr is concluded to be useful as a drug-resistance marker for mammalian cells.

Anti-Bacterial Agents

DHT formation and degradation in cultured human skin fibroblasts: DHT accumulation in the genital skin.

The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase and the interconversion between DHT and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) by 3 alpha-hydroxy-steroid oxidoreductase (3 alpha-HSOR) were studied in fibroblasts derived from the genital skin of 22 males and 6 females, and from the nongenital skin of 19 males and 9 females with normal gonadal function. The formation of DHT from testosterone (5 alpha-reduction) was significantly greater in fibroblasts from genital skin than in those from nongenital skin in both males (2.15 +/- 1.43 vs 0.81 +/- 0.46 pmol/mg protein/h, mean +/- SD, P less than 0.001) and females (2.52 +/- 1.99 vs 0.69 +/- 0.18, P less than 0.01). Furthermore, DHT formation from 3 alpha-diol (3 alpha-HSOR oxidation) was also significantly greater in genital skin fibroblasts than in nongenital skin fibroblasts of males (5.47 +/- 3.37 vs 2.52 +/- 1.74 pmol/mg protein/h, P less than 0.01). However, the degradation of DHT to 3 alpha- and/or 3 beta-diol (3 alpha- and/or 3 beta-HSOR reductions) was not different between genital and nongenital skin fibroblasts of either males or females. Respective ratios of DHT formation to DHT degradation (5 alpha-reduction/3 alpha-HSOR reduction, 3 alpha-HSOR oxidation/3 alpha-HSOR reduction) were also significantly greater (P less than 0.002) in genital skin fibroblasts than in nongenital skin fibroblasts of males. On the other hand, both DHT formation and degradation were not different between male and female genital skin fibroblasts. These results suggest that the increased production of DHT in genital compared to nongenital skin results from increased 5 alpha-reduction and 3 alpha-HSOR oxidation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States.

In three separate studies, members of the American Thyroid Association (ATA), the European Thyroid Association (ETA), and the Japan Thyroid Association (JTA) were surveyed by questionnaire on their management of Graves' disease. The aim was to determine how expert clinical thyroidologists employ diagnostic procedures and the three different therapies that are available for this disorder. In this report, we identify, summarize, compare, and contrast similarities and differences in the results of these surveys in these three different regions of the world. In general, ATA members used fewer diagnostic tests than did their European or Japanese colleagues. For the index patient, radioiodine was the therapy of choice for 69% of ATA respondents but only 22% and 11% of ETA and JTA respondents, respectively. In contrast, only 30.5% of ATA respondents chose antithyroid drugs as first-line therapy compared to 77% of ETA and 88% of JTA respondents. There was consensus on the relative lack of a role for thyroidectomy except for narrow indications. The implications of these differing approaches for the diagnosis and treatment of hyperthyroidism due to Graves' disease are discussed.

Adolescent