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Biomedical subjects

M Isaka

Publications and source records attributed to M Isaka.

16 recordsLinked to original sources

[Acute lymphoblastic leukemia accompanied by severe hypercalcemia; successful treatment with bisphosphonate].

A 62-year-old woman was admitted to the hospital because of bone pain. Laboratory data showed blasts in the peripheral blood, hypercalcemia (corrected calcium 15.1 mg/dl) and an increased level of parathyroid hormone related-protein (PTHrP). Bone marrow aspiration revealed increased lymphoblasts (96.5%), indicating acute lymphoblastic leukemia (ALL, L1). Subsequent radiological examination disclosed bone infiltration of ALL. Although the hypercalcemia was successfully treated with bisphosphonate, the PTHrP level remained high. After chemotherapy, the blasts in the peripheral blood disappeared and the PTHrP level normalized. We hypothesize that in the present case the production of PTHrP by lymphoblasts resulted in the hypercalcemic state. Although ALL is rarely accompanied by hypercalcemia, this case might help us to understand the relationship between ALL and hypercalcemia.

Diphosphonates

[Parathyroid selective venous sampling].

It is important to localize the site of abnormal parathyroid glands in treatment of primary hyperparathyroidism. Selective venous sampling with parathyroid hormone assay is one of the methods for localization of adenoma or hyperplasia in primary hyperparathyroidism. Since Reitz first described it in 1969, it has been improved during the last two decades and there is a high sensitivity (70-80%). Especially in those cases, localization is unknown in imaging methods, the first operation fails or the patients has previously been explored in the neck, venous sampling becomes a very useful method. How to perform, indication, performance, strengths and weakness of selective venous sampling is described here.

Blood Specimen Collection

Transient induction of fatty acid synthase in rat liver after removal of a peroxisome proliferator.

Removal of a peroxisome proliferator from the diet triggered the degradation of peroxisomes and induced the transient expression of a 220 kDa soluble protein in rat liver. The 220 kDa protein was purified by conventional methods and analyzed by amino acid sequencing. A total of 99 amino acid residues in 4 lysylendopeptidase-digested peptides completely matched those in rat fatty acid synthase. The transient induction of fatty acid synthase mRNA during peroxisome degradation was confirmed by Northern blotting.

Amino Acid Sequence

Hemodynamic effects of lipo-PGE1 on peripheral artery in patients with diabetic neuropathy: evaluated by two-dimensional color Doppler echography.

Twenty non-insulin-dependent diabetic patients were studied to evaluate the hemodynamic effects of lipo-PGE1 (prostaglandin E1 incorporated in lipid microspheres). Improvement of diabetic neuropathy was assessed on the basis of subjective symptoms such as pain, coldness, numbness and dysethesia (subjective) after intravenous administration of lipo-PGE1. After lipo-PGE1 treatment, the subjective symptoms were markedly improved. Hemodynamic effects of this drug on the dorsalis pedis artery were examined using new real-time two-dimensional color Doppler echography. After administration of lipo-PGE1, the cross-sectional area of the dorsalis pedis artery significantly increased from 2.6 +/- 0.2 mm2 to 3.5 +/- 0.2 mm2 (P < 0.01). Moreover, the blood flow index significantly increased from 40 +/- 7 to 61 +/- 11 (P < 0.05). The results of this study suggest that lipo-PGE1 may serve as a useful drug in improving diabetic neuropathy.

Adult

High glucose and hyperosmolarity increase platelet-derived growth factor mRNA levels in cultured human vascular endothelial cells.

We investigated the effects of high glucose and hyperosmolality on platelet-derived growth factor (PDGF) production and PDGF-B chain mRNA levels in cultured human umbilical vein endothelial cells. Under an excess of ambient glucose (13.8 and 27.5mM) and a hyperosmolar condition (22.0mOsm/L with mannitol), PDGF concentrations in the culture medium were both significantly increased (10.3 +/- 6.0%, 36.2 +/- 7.2%, 48.5 +/- 9.0% increase respectively compared with 5.5mM glucose). Parallel to protein secretion levels, PDGF-B chain mRNA levels showed a significant increase (57.7%, 103.7%, 210.8% increase), while no change of beta-actin mRNA levels was observed. Thus, elevated PDGF released from endothelium by high glucose may play an important role in the pathogenesis of diabetic angiopathy.

Blotting, Northern

Rat cellular mutants for expression of mRNA from the long terminal repeat of murine retrovirus.

Previously we isolated revertants from a rat cell line transformed by recombinant murine retrovirus containing the v-src gene. These mutant cell lines, R78 and R107, showed low src-kinase activity, but retained wild-type transforming retrovirus, suggesting that a cellular gene involved in viral gene expression was mutated. Southern and Northern hybridization analyses showed that the expression of viral mRNAs from the integrated proviral DNA was reduced in these mutant cells. DNA transfection experiments with various transforming genes and promoters revealed that the mutant cell lines were resistant to transformation by transforming genes expressed under the long terminal repeat (LTR) of Moloney murine leukemia virus (Mo-MuLV). In contrast, these cell lines could be efficiently transformed by the same transforming genes with human metallothionein promoter, polyomavirus promoter-enhancer, and c-H-ras promoter. Transient expression assays using plasmids containing the CAT gene under the LTR of Mo-MuLV also showed that CAT activity expressed under the LTR in these mutant cells was lower than that in the parental cell line, No. 7. These results suggest that cellular mutations of R78 and R107 cells affect specific transcription from the LTR of Mo-MuLV. Studies using various constructs of the LTR CAT indicated that the region responsible for the repression was located in a fragment (-328 to -150) of the LTR containing the 72-bp repeat enhancer. Somatic cell hybridization experiments showed that the mutant phenotype of these mutant cell lines is dominant to that of the parental cell line.

Animals

Synthesis and biological activities of cyclopropenone antibiotic penitricin and congeners.

A number of derivatives of the cyclopropenone antibiotic penitricin have been synthesized by the reaction of metalated cyclopropenone acetals with electrophiles. Studies on the antimicrobial structure-activity relationships indicated that the penitricin skeleton, hydroxymethylcyclopropenone, is indispensable for antimicrobial activity. These compounds were also found to display cytotoxic activity.

Bacteria

Simple system for isolation of cellular and viral mutants for transformation by retrovirus.

To investigate the cellular mechanism of transformation by retroviruses, we established a system for isolation of cellular and viral mutants for transformation of a rat cell line. Mutagenized untransformed cells of this line were infected with recombinant murine retrovirus containing the src gene of Rous sarcoma virus and the selective marker gene, neo. After reaching confluence, cells transformed by the src gene tend to overgrow and die. Utilizing this property of src transformed rat cells and the selective marker gene, we could easily select untransformed cell clones containing the retrovirus genome. Expression of the src gene product in the flat clones selected was examined by in vitro assay of src kinase activity. To determine whether the mutations of these flat clones were viral or cellular, the susceptibilities of the clones to transformation were examined after superinfection with the wild-type virus and also characterized the retroviruses recovered from these clones. With this system, two novel clones were isolated. One had a defect in viral information affecting the transformed phenotype, but still retained src kinase activity like fully transformed cells. The other showed low src kinase activity but retained wild-type transforming virus, suggesting that a cellular gene involved in viral gene expression was mutated.

Animals

Increased sympathoadrenomedullary activity and left ventricular hypertrophy in young patients with borderline hypertension.

Echocardiographic dimensions and endocrinological examination were performed in 71 young patients with borderline hypertension (BHT) and 31 age-matched normotensive subjects (NT). Patients with BHT had significantly higher relative wall thickness (RWT) and left ventricular mass index than NT, although all BHT patients showed no asymmetric increase in the ratio of septal to posterior wall thickness. Moreover, these BHT patients demonstrated an increased cardiac output and an augmented mean circumferential fiber shortening rate (mean Vcf), suggesting left ventricular hyperfunction. Overall, there was a positive correlation between RWT and mean Vcf in BHT patients (r = 0.700, P less than 0.001), although there was no significant relationship between RWT and blood pressure. Furthermore, these BHT patients had higher plasma epinephrine (PE) and plasma renin activity compared to NT, suggesting the increased sympathoadrenomedullary activity in BHT. These BHT patients were divided into two groups with regards to PE levels; namely a high PE group (PE greater than or equal to 46 pg/ml) and a normal PE group (PE less than 46 pg/ml). The high PE group had a significantly higher mean Vcf and RWT than the normal PE group. These findings suggest that in young BHT patients left ventricular hypertrophy could be related to abnormalities of the sympathoadrenomedullary systems.

Adolescent

Norepinephrine responsiveness in patients with borderline hypertension under three different sodium balances.

The pressor effects of intravenous norepinephrine (NE) infusion (100 and 200 ng/kg/min for 15 min) were examined in 17 patients with borderline hypertension (BHT) and 15 age-matched normotensive subjects (NT) under three different sodium balances; the regular customary diet, treatment with diuretics, and the high-sodium diet. Treatment with diuretics decreased and high sodium diet increased the pressor response to NE in both groups but there were no significant differences in NE reactivity between the groups. The increments in mean blood pressure after NE infusion (200 ng/kg/min) during the three experimental periods correlated significantly with the preinfusion plasma NE concentration in both BHT and NT: r = -0.58 (p less than 0.01) and r = -0.54 (p less than 0.01), respectively. Neither the slopes nor the intercepts differed between the two groups. Thus, evidence presented indicates that BHT do not have increased pressor responsiveness to NE, and that NE pressor response depends upon basal sympathetic tone.

Adult

Revised assignment for the Bacillus subtilis spo0F gene and its homology with spo0A and with two Escherichia coli genes.

The nucleotide sequences of spo0F mutant genes which block the early sporulation process of Bacillus subtilis were determined. The mutation sites together with the results of complementation tests suggested that an open reading frame for a polypeptide of Mr = 14,229 is the spo0F gene. The deduced amino acid sequence shows striking homology with that of the spo0A gene. In addition, the upstream region involving the rib some binding site of the spo0F coding region is also similar to those of spo0A and spo0B. These homologies suggest that all three genes have a similar function in regulating the initiation of sporulation, and that their expression is controlled by a common mechanism. Clear homology is also seen between the spo0 gene products and the transcriptional control proteins, OmpR and Dye, of Escherichia coli suggesting that the spo0 gene products also are involved in the control of transcription.

Alleles