Biomedical subjects

A Sakurai

Publications and source records attributed to A Sakurai.

At least 109 records · Page 6Linked to original sources

PubMed1997

Alopecia universalis with remission during pregnancy and prednisolone therapy.

In a 32-year-old woman, alopecia universalis went into unequivocal remission during pregnancy and prednisolone therapy. A skin biopsy specimen showed intense infiltration of the lymphocyte around the hair follicle without immunoglobulin and complement deposition. Autoantibody test results were negative except for the antithyroid and anti-nuclear antibodies. Human leukocyte antigen haplotypes common in Japanese patients with insulin-dependent diabetes were found in this patient. However, thyroid function and glucose tolerance were normal, and other clinical evidence of collagen vascular disorders was not found. In this patient, alopecia was considered to have been caused by autoimmune abnormalities. This is the first documentation of remission of autoimmune alopecia universalis during pregnancy.

Adult↗

PubMed1997

Lupus vulgaris of the earlobe.

Cutaneous tuberculosis is rare today and is often confused with other granulomatous lesions. Its diagnosis remains bothersome, because detecting mycobacteria in skin lesions using a conventional laboratory examination remains difficult. A 59-year-old woman presented with lupus vulgaris of the earlobe. Surgical treatment was employed, with an initial diagnosis of hemangioma. After the operation the condition was diagnosed correctly and preventive antituberculous drugs were prescribed. The incidence of tuberculosis has increased since the mid-1980s chiefly due to the expansion of the HIV-infected, immunocompromised population. Thus the diagnosis and treatment of cutaneous tuberculosis has become once again important.

Antitubercular Agents↗

PubMed1997

The Arabidopsis deetiolated2 mutant is blocked early in brassinosteroid biosynthesis.

The Arabidopsis DEETIOLATED2 (DET2) gene has been cloned and shown to encode a protein that shares significant sequence identity with mammalian steroid 5 alpha-reductases. Loss of DET2 function causes many defects in Arabidopsis development that can be rescued by the application of brassinolide; therefore, we propose that DET2 encodes a reductase that acts at the first step of the proposed biosynthetic pathway--in the conversion of campesterol to campestanol. Here, we used biochemical measurements and biological assays to determine the precise biochemical defect in det2 mutants. We show that DET2 actually acts at the second step in brassinolide biosynthesis in the 5 alpha-reduction of (24R)-24-methylcholest-4-en-3-one, which is further modified to form campestanol. In feeding experiments using 2H6-labeled campesterol, no significant level of 2H6-labeled campestanol was detected in det2, whereas the wild type accumulated substantial levels. Using gas chromatography-selected ion monitoring analysis, we show that several presumed null alleles of det2 accumulated only 8 to 15% of the wild-type levels of campestanol. Moreover, in det2 mutants, the endogenous levels of (24R)-24-methylcholest-4-en-3-one increased by threefold, whereas the levels of all other measured brassinosteroids accumulated to < 10% of wild-type levels. Exogenously applied biosynthetic intermediates of brassinolide were found to rescue both the dark- and light-grown defects of det2 mutants. Together, these results refine the original proposed pathway for brassinolide and indicate that mutations in DET2 block the second step in brassinosteroid biosynthesis. These results reinforce the utility of combining genetic and biochemical analyses to studies of biosynthetic pathways and strengthen the argument that brassinosteroids play an essential role in Arabidopsis development.

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

PubMed1997

Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity.

Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness to thyroid hormone caused by mutations in the thyroid hormone receptor beta (TRbeta) gene. Mutant TRbetas exhibit variable degrees of impaired T3 binding resulting in reduced T3-mediated function. The dominant mode of inheritance is attributed to the ability of mutant TRbetas to interfere with the function of the wild-type (WT) TR, a phenomenon known as dominant negative effect (DNE). We recently identified two families with RTH having mutations in amino acid 243 (R243Q and R243W) in whom the mechanism of RTH appears to be distinct from that of other natural TRbeta mutations. These mutations, which are located in the hinge domain of the TRbeta, do not significantly alter the binding affinity for T3, measured in vitro. The present study was undertaken to characterize the properties of these mutant TRbetas to understand the molecular basis of the RTH phenotype. Two other mutant TRbeta producing RTH with mild (320H) and severe (345R) impairment of T3 binding were studied in parallel. The results demonstrate that TRbetas 243Q and 243W could be translocated into the nucleus where they exerted normal ligand-independent repression of positively regulated thyroid hormone response elements. Yet, the addition of 10 nmol/L T3 failed to normalize the transactivation (16-13% of WT) and revert the DNE exerted by the two TRbeta mutants. In contrast, at this T3 concentration, the transactivation function of 320H was significantly higher (50% of WT), and the DNE was completely abolished, in keeping with the mild clinical form of RTH. Formation of 243Q and 243W homodimers on thyroid hormone response elements could not be as readily prevented by T3 as those formed by the WT and 320H TRbetas. These results suggest that the substitution of R243 in TRbeta produces RTH by increasing the propensity for the formation of tightly bound homodimers or by reduction of the receptor affinity for T3 only after it binds to DNA.

Animals↗

PubMed1997

Antitumor agents. 169 Dysoxylum cumingianum. V. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum.

Detailed chemical studies on the cytotoxic fraction from the leaves of Dysoxylum cumingianum have resulted in the isolation of two new triterpene glucosides, cumingianosides P (18) and Q (19), with an apotirucallane-type skeleton. The structures of 18 and 19 were determined by spectral examinations, and by conversion of cumingianosides C (3) and A (1) into 18 and 19, respectively. The cytotoxicities of cumingianosides P and Q against over 50 human cancer cell lines were evaluated. Cumingianoside P exhibited significant (EC50 < 4 microM) cytotoxicity against 37 human cancer cell lines. Among them, the UO-31 (renal cancer) cell line was the most sensitive to this compound (EC50 0.267 microM). In contrast, cumingianoside Q showed selective cytotoxicity against NCI-H522 (non-small cell lung cancer) cells with an EC50 value of 1.67 microM, and exhibited no cytotoxicity (EC50 > 10 microM) against most of the remaining cancer cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines.

Nine new triterpene glucosides, named cumingianosides G-O (4-7, 9, 12-15), containing a 14,18-cycloapotirucallane-type skeleton were isolated from a cytotoxic fraction of the leaves of Dysoxylum cumingianum. The structures of the new compounds were established on the basis of chemical and spectral examinations. Evaluation of the cytotoxic activity of cumingianosides G-O showed that cumingianoside M exhibited significant (< 4 microM) cytotoxicity, especially against leukemia and melanoma cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Studies on biosynthesis of brassinosteroids.

Biosynthesis of steroidal plant hormones, brassinosteroids, was studied using the cell culture system of Catharanthus roseus. Feeding labeled compounds of possible intermediates to the cultured cells, followed by analyzing the metabolites by gas chromatography-mass spectrometry disclosed the pathways from a plant sterol, campesterol, to brassinolide. There are two pathways, named the early C6-oxidation pathway and late C6-oxidation pathway, both of which would be operating in a wide variety of plants. Recent findings of brassinosteroid-deficient mutants of Arabidopsis and the garden pea by several groups, and the possible blocked steps of the mutants in the biosynthetic pathways are also introduced.

Brassinosteroids↗

PubMed1997

Insulinoma in a patient with non-insulin-dependent diabetes mellitus.

Insulinoma in a patient with pre-existing diabetes is exceedingly rare. Only a small number of well-documented cases have been reported in the world during the last 40 years. We describe a case with non-insulin-dependent diabetes mellitus who after seven years of sulfonylurea treatment experienced recurrent episodes of hypoglycemia. Endogenous hyperinsulinism was found and radiographical examination and transhepatic venous sampling confirmed an insulin secreting pancreatic tumor. After surgical excision of the tumor, patient was relieved from hypoglycemic attacks but required to initiate insulin injection for the treatment of hyperglycemia.

Aged↗

PubMed1997

Multiple endocrine neoplasia type 1 is not rare in Japan.

Multiple endocrine neoplasia type 1 (MEN 1) is rarely reported in Japanese and other oriental populations. To examine if there is a racial difference in the prevalence of MEN 1, we initiated extensive work on patients with endocrine tumors for additional lesions, and annual screening of family members of affected patients. In a four-year study, eleven asymptomatic patients were found by family screening, and the number of patients with MEN 1 in our clinics increased from 16 to 38. Estimated prevalence of MEN 1 was no less than 0.018/1000. MEN 1 may not be as rare as had been thought in Japanese, and the prevalence of MEN 1 in Japanese would not be significantly different from that of Caucasians. Systemic surveillance and extensive screening of family members are required for early detection and management of patients.

Adolescent↗

PubMed1997

[Day to day changes in SAA (serum amyloid A) values of healthy subjects and the effect of dexamethasone administration].

Serum amyloid A (SAA) is a sensitive acute phase reactant; its serum level increases up to 1,000 fold of the healthy level (less than 10 micrograms/ml). Recently, the diagnostic usefulness of this protein in comparison with C-reactive protein (CRP) has been discussed in disorders or situations which show slight elevation of these protein levels, especially, in subjects receiving glucocorticoid therapies. To clarify physiological changes of this protein, day to day variations in SAA values of 23 healthy individuals were investigated and it was shown that majority (91%) had dynamic ranges of less than 3.0 micrograms/ml. Effect of dexamethasone administration on SAA and CRP values was studied in 10 subjects who received a dexamethasone suppression test. Changes in SAA values were within the physiological variation, and discrepancy in the changes between SAA and CRP as previously described in subjects with glucocorticoid therapies was not shown.

Acute-Phase Proteins↗

PubMed1996

Uniaxial tension inhibits tendon collagen degradation by collagenase in vitro.

Tendon structure is governed largely by factors regulating the anabolic and catabolic phases of tenocyte metabolism. Little is known about the mechanisms that regulate the synthesis, activation, and action of metalloproteinases, which are key enzymes in a multifactorial cascade controlling homeostasis of the extracellular matrix. In the present study, we investigated the effect of tension on collagenase-induced degradation of the tendon in vitro by assessing changes in structural and material properties measured during tensile failure tests. Devitalized right-left pairs of rabbit patella-patellar tendon-tibia units were maintained under culture conditions in the presence of 60 U/ml highly purified collagenase for 20 hours. One randomly selected unit from each animal was subjected to a tension that produced a constant 4% elongation or strain (n = 10); the contralateral unit served as a slack comparison (n = 10). In one series of experiments (immediate, n = 5), the tension was applied immediately prior to collagenase exposure. In a second series (delayed, n = 5), it was delayed for 4 hours to allow time for the collagenase to diffuse into the tendon. Additional devitalized and nonincubated units (n = 6) were used as normal controls. Collagenase exposure caused large decreases in stiffness and elongation to failure in slack units. This resulted in greater than 80% reductions in both maximum failure force and energy to failure. In contrast, the loaded unit in both experimental protocols had significantly greater stiffness than control units. In both the immediate and the delayed protocols, the loaded tendons had significantly higher stiffness and failed at significantly higher elongations and maximum forces than the slack tendons. Diffusion studies with and without tension showed the tension did not inhibit diffusion of collagenase into the tendon but did significantly decrease the water content from 64.6 to 57.8%. The data suggest that stresses and strains of the extracellular matrix may modify the kinetics of the bacterial collagenase-collagen interaction. Matrix stress and strain may be an important and overlooked factor that modulates the susceptibility of collagen to proteolytic degradation.

Animals↗

PubMed1996

Partial characterization of a 17 kDa acidic protein, EFP, induced by thiocarbamate in the early flowering phase in Asparagus seedlings.

Asparagus officinalis seedlings treated with either thiocarbamates or carbamates are induced to flower within 2-3 weeks of application. SDS-PAGE and 2-D PAGE resolutions of total soluble proteins of treated seedlings showed the accumulation of an acidic 17 kDa polypeptide. Partial amino acid sequence of the acidic protein showed homology to the wound-responsive A. officinalis PR 1, AoPR1. We named this protein EFP, early flowering protein, owing to its advanced appearance during the early transition from vegetative to floral phase. Carbamates and thiocarbamates that induced more than 80% flowering rates corresponded with increased level of EFP while compounds that are weak flower inducers showed reduced amount of EFP. The observation thus defined the correlationship of EFP to variable flowering rates.

Amino Acid Sequence↗

PubMed1996

Identification of castasterone, 6-deoxocastasterone, typhasterol and 6-deoxotyphasterol from the shoots of Arabidopsis thaliana.

Endogenous brassinosteroids in the shoots of Arabidopsis thaliana were investigated. Castasterone, 6-deoxocastasterone, typhasterol and 6-deoxotyphasterol were identified by GC-MS. The co-occurrence of 6-deoxo-brassinosteroids and 6-oxo-brassinosteroids suggests that there are both early and late C6-oxidation pathways of brassinosteroids in A. thaliana.

Arabidopsis↗

PubMed1996

A spheno-orbital encephalocele with unilateral exophthalmos.

Encephaloceles are rare congenital defects in the skull, through which the meninges and brain tissue have herilated. We report a case of an 11-year-old boy with a spheno-orbital encephalocele that presented with pulsatile exophthalmos. A two-stage operation resulted in a good outcome.

Child, Preschool↗

PubMed1996

Genetic screening in hereditary multiple endocrine neoplasia type 1: absence of a founder effect among Japanese families.

Ten Japanese families with hereditary multiple endocrine neoplasia type 1 (MEN1) were examined. Five DNA polymorphic markers on the long arm of chromosome 11 were analyzed for genetic screening of MEN1 in members of affected families, and disease carriers were identified before clinical manifestations. Unlike MEN1 families in Newfoundland or in Tasmania, no consistent haplotypes were segregated with the disease in the Japanese families when defined by 5 nearby markers. The identification of asymptomatic disease carriers is of substantial clinical importance for early management, genetic counseling and to avoid unnecessary screening for non-disease carriers. However, genetic screening of family members by polymorphic markers could be useful only to each family, and no generally applicable markers were found for Japanese subjects with MEN1.

Adult↗

PubMed1996

Gs alpha mutation may be uncommon in patients with multiple endocrine neoplasia type 1.

Activating mutations of the Gs alpha gene, termed gsp, have been identified in various endocrine tumors. Recently, a high frequency of gsp mutation in patients with multiple endocrinopathies was reported, and a family with both McCune-Albright syndrome and multiple endocrine neoplasia type 1 was described. Each suggests that the oncogenic mutations of Gs alpha may play an important role in tumorigenesis in patients with multiple neoplastic endocrinopathies, and a search for the gsp mutation in multiple endocrine neoplasia type 1 (MEN1) should be undertaken. We, therefore, reevaluated the frequency of gsp mutations in endocrine tumors of patients with MEN1. Of 18 tumors from 13 patients with MEN1, we found no gsp mutations regardless of heredity. We conclude that the gsp mutation may be uncommon in endocrine tumors of MEN1 patients, and thus, this mutation plays little, if any, role in their tumorigenesis.

Adult↗

PubMed1996

Acromegaly associated with Chiari-I malformation and polycystic ovary syndrome.

We report a 19-year-old female case of acromegaly associated with Chiari-I malformation and polycystic ovary syndrome. She also had syringomyelia and thoracic scoliosis. Although the association of acromegaly and Chiari-I malformation was by chance, exaggerated secretion of growth hormone may have aggravated the scoliosis. The incidence of polycystic ovary in acromegalic patients remains to be elucidated. However, elevation of plasma insulin and insulin-like growth factor, that is usually observed in patients with acromegaly, could stimulate androgen production in the ovaries. The patient was successfully treated with transsphenoidal adenomectomy for pituitary tumor and correction surgery for thoracic scoliosis.

Acromegaly↗

PubMed1995

Transcriptional regulation of human thyroid hormone receptor beta 1 gene expression: effect of human retinoid X receptor and identification of a transcriptional silencer region.

Effects of human retinoid X receptor alpha (hRXR alpha) and its ligand, 9-cis-retinoic acid, on T3-mediated auto-regulation of hTR beta 1 gene expression were examined using a chloramphenicol acetyltransferase (CAT) reporter system, and a deletional analysis of the promoter. hRXR alpha enhanced T3-dependent CAT induction mediated through the proximal (p) TRE in a ligand (9-cis-retinoic acid) independent manner. In a gel mobility shift assay, hRXR alpha enhanced the binding of hTR beta 1 to the pTRE by the formation of hRXR alpha-hTR beta 1 heterodimers. On the other hand, hRXR alpha and 9-cis-retinoic acid did not show any effects on T3-dependent CAT induction mediated through the distal (d) TRE or the binding of hTR beta 1 to the dTRE. A four hundred-base pair (bp) fragment adjacent upstream of the dTRE showed a T3 independent suppressor effect on the function of the pTRE and dTRE. Thus, this region may be an important regulator of the T3 dependent up-regulation of the TR beta 1 gene expression which is observed only under specific conditions.

Base Sequence↗