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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 667 records · Page 37Linked to original sources

Effects of long-term enalapril treatment on persistent micro-albuminuria in well-controlled hypertensive and normotensive NIDDM patients.

OBJECTIVE: To determine whether long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor has a beneficial effect on the urinary microalbumin excretion and renal function in non-insulin-dependent diabetes mellitus (NIDDM) patients, enalapril (5 mg/day) was administered for 48 months. RESEARCH DESIGN AND METHODS: -Fifty-two patients with NIDDM who had persistent microalbuminuria in the range of 20-300 mg/24 h, serum creatinine < 106.1 microM (1.2 mg/dl), supine systolic blood pressure (BP) < 150 mmHg, supine diastolic BP < 90 mmHg, and HbA1c < 10% were divided into four groups. Twenty-six patients with normotension were divided at random into two groups; one group received enalapril (5 mg/day) (NE group), the other did not receive enalapril (NC group). In the same way, 26 other patients who were already well-controlled with nifedipine (30 mg/day) over a long-term period (4-6 years) were divided at random into two groups; one received enalapril (5 mg/day) (HE group), the other did not receive enalapril (HC group). RESULTS: After 48 months, urinary albumin excretion (UAE) was markedly reduced in group NE from 102.4 x/divided by 1.3 to 55.5 x/divided by 1.3 mg/24 h (P < 0.005), whereas no significant change occurred in group NC. In the well-controlled hypertensive groups, a significant reduction in UAE occurred in group HE (P < 0.05), whereas no significant change occurred in group HC. No changes in creatinine clearance, BP, or blood glucose control were seen during the study. CONCLUSIONS: Treatment with enalapril for 48 months may have a beneficial effect on the decline of microalbumin excretion in NIDDM patients.

Acetylglucosaminidase↗

Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1), CD46 (MCP), and CD55 (DAF), in hematological malignancies.

The distribution and levels of three membrane proteins, CD35, CD46, and CD55, which serve as complement regulators, were examined in normal peripheral blood and hematologically malignant cells. CD35 was negative in most leukemia cells regardless of the type of leukemia, although granulocytes, monocytes, and some populations of lymphocytes were CD35+. CD46 was present in all blood cells except erythrocytes, and levels were 2-8 times higher in most leukemia cells than in their mature counterparts, particularly in CML and CLL cells, except for those of B cell lineage. CD55, a widely-distributed phosphatidyl inositol-anchored protein, was more frequently lost in NHL cells than in other types of hematological malignancies. In this review, we discuss the roles, mechanisms, and clinical applications of cell-associated complement regulatory proteins in hematological malignancies.

Antigens, CD↗

[Thulium-holmium-chromium-doped YAG laser sclerostomy ab externo in uncontrollable glaucoma].

Laser sclerostomy ab externo, using thulium-holmium-chromium-doped YAG laser was performed in 40 eyes with refractory glaucoma. Preoperative intraocular pressure (IOP) ranged from 21 to 50 mmHg (mean +/- SD: 33 +/- 18.6) with maximum tolerable medications. In all cases, a full-thickness sclerostomy was performed and subsequently a filtering bleb was formed. Total energy levels to produce the sclerostomy ranged from 0.2 J to 12.9 J (3.9 +/- 2.4). Follow-up periods varied from 3 to 18 (9 +/- 4) months. IOP control rate calculated by a life-table method at 6 and 12 months after surgery was 54% and 46%, respectively. IOP for successful eyes ranged from 0 to 18 mmHg (12.3 +/- 2.4). As complications, corneal fold formation (all eyes), choroidal detachment (12 eyes), hyphema (10 eyes), and iris incarceration in the sclerostomy site (4 eyes) were found. Astigmatism caused by corneal fold formation disappeared spontaneously within 3 months. Iris incarceration causing IOP elevation was repaired by Nd-YAG laser treatment and IOP control was obtained in 2 of 4 eyes. No other complications were observed.

Chromium↗

[A case of primary hyperparathyroidism associated with marked hypercalcemic crisis].

A 41-year-old woman was referred to our hospital with complaints of general fatigue, appetite loss, nausea and vomiting. Blood examination revealed high serum calcium level (21.6 mg/dl) and high serum parathyroid hormone level. Although enlarged parathyroid glands could not be clearly detected via ultrasonography, computed tomography and scintigraphy, we diagnosed her with hypercalcemic crisis due to primary hyperparathyroidism and performed parathyroidectomy after conservative therapy. A parathyroid tumor measuring 1.9 x 1.1 x 1.0 cm, and weighing 1,100 mg was found at the upper right pole of the thyroid gland, and three thyroid tumors were found in the bilateral lobes of the thyroid gland. Histological diagnosis was adenoma of the parathyroid gland and follicular adenomas of the thyroid gland. Following removal of the parathyroid tumor, the serum calcium level rapidly dropped and the symptoms rapidly improved. Hypercalcemic crisis has a high mortality, and the only treatment is surgical removal. Therefore, in patients with hypercalcemic crisis due to primary hyperparathyroidism, surgical removal should be done immediately, unless the serum calcium level has dropped and symptoms of crisis have disappeared after conservative treatment.

Adenoma↗

Effect of thioltransferase on the cystamine-activated fructose 1,6-bisphosphatase by its redox regulation.

Fructose 1,6-bisphosphatase [EC. 3.1.3.11] is activated by the treatment with 0.1 mM cystamine up to about 400% compared to its original activity (dithiothreitol-reduced form). Thiol compounds (0.1 mM of cysteamine and dithiothreitol) can restore its activity effectively. Reduced glutathione, at 0.2 mM, also restores fructose 1,6-bisphosphatase activity only in the presence of cystamine. When excess cystamine is removed, the addition of 1.0 U/ml thioltransferase is able to restore FBPase activity very efficiently coexistence with 0.2 mM reduced glutathione though reduced glutathione alone does not work.

Animals↗

DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa.

DX-9065a is an orally active newly synthesized and specific inhibitor for factor Xa. We have examined the property of DX-9065a in vitro and ex vivo. DX-9065a prolonged human plasma recalcification time, APTT and PT. Its doubling concentrations for clotting times of each coagulation assay were 0.49, 0.97 and 0.52 microM, respectively. Kinetic study revealed that DX-9065a inhibited competitively human factor Xa (Ki value: 41 nM). Ki values (microM) for other human serine proteases were as follows; thrombin > 2000, trypsin 0.62, chymotrypsin > 2000, plasmin 23, t-PA 21, plasma kallikrein 2.3 and tissue kallikrein 1000. DX-9065a up to 100 microM had no effects on human platelet aggregation. After intravenous or oral administration, DX-9065a significantly prolonged APTT and PT with a dose dependent manner. These effects were well correlated with anti-Xa activity in plasma. These results suggest that DX-9065a may become an anticoagulant by means of the specific inhibition of factor Xa.

Adenosine Diphosphate↗

Pterygium surgery using the principle of contact inhibition and a limbal transplanted pedicle conjunctival strip.

We have devised a new type of pterygium surgery, based on the principle of biological contact inhibition, involving the use of a 0.5-millimeter-wide pedicle autoconjunctival strip placed at the corneal limbus. Over a period of 2 years, the procedure has been performed in 56 eyes of 52 patients, 39 to 74 years old (mean, 57 +/- 9 years), with primary pterygium. After an average follow up of 34 +/- 6 months (range, 20 to 40 months), the pterygium recurred in six (10.7%) of the 56 eyes. There were no other significant postoperative complications. Although our method has the disadvantages of being somewhat complicated and involving a fair amount of suturing, the relatively low rate of recurrence achieved is encouraging.

Adult↗

A novel factor Xa inhibitor: structure-activity relationships and selectivity between factor Xa and thrombin.

A series of 3-amidinoaryl-2-[4-[ [(3S)-3-pyrrolidinyl]oxy]phenyl] propanoic acids have been investigated for development of a novel factor Xa inhibitor, possessing a potent inhibitory activity for factor Xa and a selectivity for factor Xa compared to thrombin. In order to study the structure-activity relationships and the selectivity, models of factors Xa complexes formed with the inhibitors were constructed on the basis of X-ray crystallographic data of a trypsin-inhibitor complex. The models showed that the binding mode of the inhibitors to the S1 pocket of the enzyme accounted for the structure-activity relationships and that the difference between Gln192 of factor Xa and Glu192 of thrombin had a key role in the selectivity.

Amidines↗

Amino acid sequence surrounding the retinal-binding site in retinochrome of the squid, Todarodes pacificus.

Squid (Todarodes pacificus) retinochrome was reduced to N-retinyl protein with borane dimethylamine and cleaved by CNBr. The retinyl peptide was then isolated by chromatography while being monitored for absorbances at 215 and 330 nm, and the N-terminal amino acid sequence was determined to be Ser-Lys-Thr-Gly-X-Ala-Leu-Phe-Pro. This sequence was the same that we had observed at the 7th transmembrane domain of retinochrome whose structure was reported previously. During Edman degradation of the retinyl peptide, the yield of the PTH-lysine at the second cycle was lower than those of the other PTH-amino acids, proving that the lysine residue forms a Schiff's base with retinal (Lys-275 in retinochrome). The amino acid sequence surrounding the retinal-binding lysine in retinochrome greatly differed from those in a variety of known visual pigments. This fact would be associated with the difference in the photoisomerization of chromophore between retinochrome and rhodopsin. The protein structure of retinochrome is also compared with that of rhodopsin in Todarodes.

Amino Acid Sequence↗

Sensory reinnervation of muscle receptor in human.

This report describes sensory reinnervation of muscle receptors in humans. In this study, sensory function was investigated in fourteen patients with brachial plexus injury, whose musculocutaneous nerve was surgically sutured with intercostal nerves for reconstruction of elbow flexion. Tapping the intercostal nerve-reinnervated brachial biceps muscle (IC-biceps) induced somatosensory evoked potentials (IC-biceps SEP) in four patients. Tapping also induced reflex IC-biceps activity in all IC-biceps SEP (+) patients, but not in eight out of nine IC-biceps SEP (-) patients. Results show that muscle afferent fibers in the intercostal nerves reinnervated mechanoreceptors in IC-biceps, and induced both cortical sensory activity and muscle activity that indicated the classical stretch reflex.

Adolescent↗

Rapidly progressive thyroid failure in Graves' disease after painful attack in the thyroid gland.

We studied a new type of Graves' disease: rapidly progressive thyroid failure after painful attack in the thyroid gland. Four women with the mean (+/- SD) age of 51 +/- 3.2 years had newly diagnosed hyperthyroid Graves' disease. A severe painful episode developed in the thyroid glands of two patients and permanent hypothyroidism occurred spontaneously within 2 or 3 months thereafter. Two to three episodes of pain developed in the thyroid glands of the other two patients during antithyroid drug therapy. There was a transient rise in serum thyrotropin level after each painful episode and permanent hypothyroidism developed 6 to 8 months after the initial painful attack. The clinical picture is characterized by moderate to severe pain in the thyroid gland with tenderness. Patients responded to steroid or anti-inflammatory therapy. During painful attack, increased or normal thyroid radioiodine uptake, elevated levels of C-reactive protein, and an elevated erythrocyte sedimentation rate were found, but there was no cytological evidence of subacute thyroiditis. After painful attack, serum thyroid stimulation antibody began to decrease in three of the patients while thyroid stimulation blocking antibody developed in one patient. This is a rapid and self-destructive process of the Graves' thyroid gland, which appears to be associated with painful attack in the thyroid gland.

Autoantibodies↗

Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients.

CYP11B2, the gene coding for steroid 18-hydroxylase (P-450C18), has been recently shown to be the same gene as that for corticosterone methyl oxidase type I and type II (CMO I & II) which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of CYP11B2 of three patients affected with CMO I deficiency has revealed that deletion of 5 nucleotides occurs exclusively in exon 1, resulting in a frameshift to form a stop codon in the same exon. Thus, P-450C18 is not produced at all due to the mutation, causing a complete lack of aldosterone biosynthesis in the patients. Restriction fragment length polymorphism analysis has demonstrated that the patients are homozygous and the unaffected parent is heterozygous as for the mutation, indicating that CMO I deficiency is inherited in an autosomal recessive manner. These results provide the molecular genetic basis for the characteristic biochemical phenotype of CMO I deficient patients.

Aldosterone↗

Cloning and nucleotide sequence of cDNA for rhodopsin of the squid Todarodes pacificus.

A cDNA for rhodopsin was isolated from a library constructed from poly(A)+RNA of the squid (Todarodes pacificus) retina. One positive clone with the longest insert of cDNA (3.1 kb) was selected by employing a PCR-amplified cDNA fragment as a probe. The nucleotide sequence of the cDNA revealed a single open reading frame of 1,344 bp encoding a polypeptide (M(r)49,833), which covered a complete sequence for the squid opsin. This clone had a very long 3'-non-coding region (1.7 kb) including multiple polyadenylation signals, AATAAA, resembling the clones for Todarodes retinochrome and retinal-binding protein (RALBP). The analysis of hydropathicity demonstrated the presence of seven transmembrane spanning domains, and a possible retinal-binding site, Lys-305, was found in the 7th domain. Todarodes rhodopsin contained characteristic sequences of PPQGY repeated in the C-terminal region, as reported in Loligo and octopus rhodopsins. Structural comparison of those cephalopod rhodopsins is also discussed.

Amino Acid Sequence↗

Membrane cofactor protein (MCP, CD46) in seminal plasma and on spermatozoa in normal and "sterile" subjects.

A sperm protein of molecular mass 43 kDa (the spermatozoa membrane cofactor protein, smMCP) and a seminal plasma protein of 60 kDa (ssMCP) were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting with four monoclonal antibodies (mAb) against membrane cofactor protein (MCP, CD46). These proteins served as factor I cofactors for the cleavage of methylamine-treated C3 (C3ma), the activity of which was blocked by M75, an MCP cofactor-activity-blocking mAb. Thus, these semen proteins are antigenic and functional homologous of MCP. On SDS-PAGE analysis these MCP migrated as single-band proteins which differed from the two-band forms of MCP expressed on other cells. smMCP was N-glycosylated but not O-glycosylated, while ssMCP was O-glycosylated: after deglycosylation of these proteins bands were detected at 38-40 kDa and 43 kDa on SDS-PAGE, respectively. These semen MCP are therefore, structurally different from the conventional MCP. ssMCP in both normal and "sterile" subject groups was determined by sandwich enzyme-linked immunosorbent assay. Seminal plasma in the two groups contained 250-700 ng/ml ssMCP. The difference between the two groups was marginal, although samples from normal subjects tended to show higher concentrations of ssMCP than samples from "sterile" subjects. No molecular difference was observed with ssMCP and smMCP in the two groups by SDS-PAGE/immunoblotting analysis. Immunohistochemical analysis suggested that MCP was positive in glandular epithelial cells and the lumen of the prostate, and in most intra-lumen cells of the testis. Using antibody M177, solubilized prostate and testis were analyzed by immunoblotting and compared with other cell MCP. The major band of MCP in the testis, but not in the prostate, was of 60 kDa, which aligned with ssMCP. No band of testis or prostate MCP, however, aligned with smMCP. ssMCP may be produced in the testis, while the origin of smMCP remains unknown. We hypothesize that ssMCP is important in the survival of spermatozoa, protecting them against local secretion of immunoglobulin and complement in the female genital tract, and that smMCP, which is expressed on acrosome-reacted spermatozoa, plays an essential role in the interaction of spermatozoa with oocytes.

Antigens, CD↗