Biomedical subjects

A Sakurai

Publications and source records attributed to A Sakurai.

At least 19 recordsLinked to original sources

PubMed1998

Novel V184E MEN1 germline mutation in a Japanese kindred with familial hyperparathyroidism.

We studied the MEN1 gene in a kindred where three patients (the proposita and two of her sons) were affected with hyperparathyroidism. By polymerase chain reaction (PCR)-based direct sequencing of 10 exons of MEN1, a novel germline mutation was identified in the proposita. This mutation, a T-to-A transition at codon 184 in exon 3, predicts an amino acid change from valine to glutamine (V184E). PCR-single-strand conformational polymorphism (PCR-SSCP) analysis of exon 3 followed by sequencing showed the same mutation in the two sons, and in two clinically normal granddaughters of an affected son. Since the T-to-A substitution segregated with the disorder in the kindred except for the granddaughters and it was not detected in 100 alleles from 50 normal individuals, the change observed in MEN1 is not a polymorphism, but causes familial hyperparathyroidism. Thus the two grandchildren with the mutation were diagnosed as presymptomatic carriers.

Adolescent↗

PubMed1998

Glutamatergic neuromuscular transmission in the heart of the isopod crustacean Ligia exotica.

Neuromuscular transmission between the cardiac ganglion (CG) and the myocardium was examined in the adult heart of the isopod crustacean Ligia exotica. Intracellular injection of neurobiotin into the CG neurones revealed that all six CG neurones send their axons onto the cardiac muscle, where they form axon terminals bearing varicosities. All the CG neurones and their processes exhibited glutamate-like immunoreactivity. The cardiac muscle showed depolarizing membrane potential responses to glutamate applied focally to sites close to axon terminals bearing varicosities. Both the glutamate-induced response and the excitatory junctional potential (EJP) showed desensitization in response to the repeated application of glutamate. Under voltage-clamp conditions, the cardiac muscle produced inward current responses to focally applied glutamate. The reversal potential for the glutamate-induced current estimated from extrapolation of the linear current/voltage relationship was similar to that of the excitatory junctional current evoked by ganglionic nerve stimulation. Both the glutamate-induced response and the EJP were blocked by a glutamate-specific antagonist, Joro spider toxin. These results led us to conclude that the CG neurones of Ligia exotica are glutamatergic motoneurones.

Journal Article↗

PubMed1998

Novel MEN1 gene mutations in familial multiple endocrine neoplasia type 1.

The recent isolation of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1) has enabled direct genetic diagnosis for people with endocrine tumors and family members of affected patients. Although MEN 1 is rarely recognized in the Japanese population compared to its prevalence in Caucasians, we have previously reported a high prevalence of this disease in a limited area (Nagano Prefecture; population, 2.15 million). In this communication, we report mutations of the MEN1 gene in kindreds living in Nagano Prefecture. The absence of a common mutation among these kindreds indicates that the high prevalence of MEN 1 in this area is not due to a regional accumulation of patients descended from a common ancestor. This result implies that the prevalence of MEN 1 in other areas of Japan could also be higher than had been thought.

Frameshift Mutation↗

PubMed1998

Transcription of the Arabidopsis CPD gene, encoding a steroidogenic cytochrome P450, is negatively controlled by brassinosteroids.

The Arabidopsis CPD gene encodes a cytochrome P450 steroid side-chain hydroxylase (CYP90) that plays an essential role in the biosynthesis of the plant hormone brassinolide. Expression of the CPD gene is confined to cotyledons and leaf primordia in etiolated seedlings and detectable in the adaxial parenchyma of expanding leaves in light-grown plants. Transcription of the CPD gene is not affected by the plant growth factors auxin, ethylene, gibberellin, cytokinin, jasmonic acid and salicylic acid, but is specifically down-regulated by brassinolide in both dark and light. Steady-state mRNA levels of a CPD promoter-driven uidA reporter gene correlate with the expression of resident CPD gene in transgenic plants. Intermediates of the early and late C-6 oxidation pathways of brassinolide, carrying C-22 and C-23 side-chain hydroxyls, efficiently inhibit the activity of the CPD promoter. Repression of CPD transcription by brassinosteroids is sensitive to the protein synthesis inhibitor cycloheximide, indicating a requirement for de novo synthesis of a regulatory factor.

Arabidopsis↗

PubMed1998

Reconstruction of skull defects with vascularized omentum transfer and split calvarial bone graft: two case reports.

Autogenous calvarial bone grafts have been widely used in craniofacial reconstruction following trauma, congenital anomalies, and head and neck tumors. In cases of late restoration of a collapsed cranial vault, an extradural dead space is occasionally observed which might cause infection and grafted bone absorption. The combined use of a split calvarial bone graft and an omental flap has been an effective technique for treating complicated cranial defects. The omental flap eliminates the extradural dead space between the grafted calvarial bone and the scarred dura, and provides an acceptable vascular bed for grafted bone. The authors report this technique for complex cranioplasties in two cases, with good cosmetic results.

Aged↗

PubMed1998

Skeletal analysis of craniofacial asymmetries in plagiocephaly (unilateral coronal synostosis).

Why do the craniofacial bones grow asymmetrically in patients with plagiocephaly (unilateral coronal synostosis)? We obtained three-dimensional skeletal replicas of two patients with the condition and analysed the deformities of the facial bones. From this analysis we deduced that the asymmetric deformation of the facial bones in these patients was caused by a combination of three rotations: rotation of the calvaria toward the affected side because of premature synostosis of the coronal and sphenofrontal sutures; rotation of the facial bones on the horizontal plane toward the unaffected side caused by anterior displacement of the TM (temporomandibular)-joint on the affected side; and downward rotation of the facial bones toward the unaffected side caused by inferior displacement of the TM-joint on the affected side.

Cephalometry↗

PubMed1998

Ligand- and nuclear factor-dependent change in hydrophobicity of thyroid hormone beta1 receptor.

An aqueous two-phase partitioning assay was performed using in vitro translated human thyroid hormone beta1 receptor (TRbeta1). Wild-type TRbeta1 was less hydrophobic in the presence of both triiodothyronine (T3) and nuclear extract. This reflects a conformational change, or change in electrostatic properties, of the TRbeta1-nuclear factor complex as a result of T3 binding. Mutant TRbeta1s with reduced T3 binding affinity required a higher concentration of T3 for the shift of hydrophobicity, and a mutant without T3 binding activity did not show any shift, even in the presence of 1 mM T3. The unique mutant receptor, R243Q, has impaired transcriptional function despite virtually normal binding affinity for T3. When this mutant was examined in this assay, the shift of hydrophobicity was significantly impaired even in the presence of both nuclear extract and a high concentration of T3. Nuclear extract of COS1 cells did not affect the T3-binding affinity of R243Q. These results indicate that the R243Q mutant has impaired a ligand-dependent conformational change and interaction with nuclear factor(s). Inability of R243Q to interact normally with nuclear factor(s) may explain, in part, the molecular mechanism of discordance between ligand binding and transactivation function of this mutant.

Animals↗

PubMed1998

Craniofacial fibrous dysplasia with rapidly increasing proptosis due to a mucocele behind the globe.

A 16-year-old male with fibrous dysplasia, in which rapidly increasing proptosis of the left eye was induced by a mucocele behind the globe, is reported. The mucocele was removed and the expanded bone was completely recontoured back to normal dimensions with the aid of an acrylic skull replica fabricated preoperatively by laser lithography on the basis of computed tomographic data. The result was satisfactory and no recurrence of bony swelling or proptosis has been detected for 2 years and 9 months.

Adolescent↗

PubMed1998

Gradual cranial vault expansion for the treatment of craniofacial synostosis: a preliminary report.

To treat craniosynostosis, skull reshaping (such as fronto-orbital advancement) is widely performed. Surgical techniques have improved, however several problems still remain, such as postoperative relapse, late resorption, and infection. The main reason for this is probably (1) that the "craniotomized" bone for changing skull contour is used as free bone grafts and (2) that dead space between the reshaped bone and dura is created. We have developed a new method in which cranial bone is expanded gradually, together with the dura, using expansion devices. With this approach there is no extradural dead space postoperatively and the cranial bone segment remains vascularized. We have performed this procedure in 2 patients with Crouzon's disease and in 1 patient with sagittal synostosis. In the Crouzon's patients, osteotomies were performed to form a one-piece fronto-orbital bony complex without detaching the bone from the dura, and three expansion devices were applied. In the patient with sagittal synostosis, bilateral temporoparietal osteotomies were done in the same fashion and two expansion devices were applied. Expansion was started on the fourth postoperative day at a rate of about 1 mm per day. After obtaining the proper expansion, the devices were removed and the bone segments were fixed with miniplates and screws. All patients showed good results without any complications.

Cephalometry↗

PubMed1998

Clinical value of computer-generated acrylic skull replicas produced by laser lithography.

To determine for what deformity and utility the computer-generated acrylic (CGA) skull replica has the greatest value, we analyzed retrospectively a consecutive series of patients with craniomaxillofacial deformities (N = 54) whose treatment involved the utilization of CGA skull replicas. Application of the CGA skull replica was divided retrospectively into four groups: (1) use as an aid for preoperative analysis of osseous deformity, (2) use as material for preoperative surgical simulation, (3) use as a navigational aid during an operation, and (4) use as a negative template. Based on the aspects of these utilizations, we evaluated for what deformity the CGA skull replica was useful. Analysis of the data led us to conclude the following. First, the CGA skull replica is a valuable tool in craniomaxillofacial surgery, especially for patients with asymmetrical deformities and delicate convexities and concavities of the skull surface. Second, the largest function that CGA skull replicas can satisfy is standardization of craniomaxillofacial surgery. In carrying out preoperative surgical simulation utilizing a replica, drawing osteotomy lines on it, sterilizing it, and then bringing it to the operating table for consultation whenever required during an operation, we are able to proceed with greater precision and speed than if it was not available.

Acrylic Resins↗

PubMed1998

The DWF4 gene of Arabidopsis encodes a cytochrome P450 that mediates multiple 22alpha-hydroxylation steps in brassinosteroid biosynthesis.

dwarf4 (dwf4) mutants of Arabidopsis display a dwarfed phenotype due to a lack of cell elongation. Dwarfism could be rescued by the application of brassinolide, suggesting that DWF4 plays a role in brassinosteroid (BR) biosynthesis. The DWF4 locus is defined by four mutant alleles. One of these is the result of a T-DNA insertion. Plant DNA flanking the insertion site was cloned and used as a probe to isolate the entire DWF4 gene. Sequence analysis revealed that DWF4 encodes a cytochrome P450 monooxygenase with 43% identity to the putative Arabidopsis steroid hydroxylating enzyme CONSTITUTIVE PHOTOMORPHOGENESIS AND DWARFISM. Sequence analysis of two other mutant alleles revealed deletions or a premature stop codon, confirming that DWF4 had been cloned. This sequence similarity suggests that DWF4 functions in specific hydroxylation steps during BR biosynthesis. In fact, feeding studies utilizing BR intermediates showed that only 22alpha-hydroxylated BRs rescued the dwf4 phenotype, confirming that DWF4 acts as a 22alpha-hydroxylase.

Alleles↗

PubMed1998

Identification of two novel mutations in the OCRL1 gene in Japanese families with Lowe syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder with features of congenital cataracts, Fanconi syndrome of the renal tubule, and mental retardation. The OCRL1 gene has been positionally cloned and shown to encode a phosphatidylinositol 4,5-biphosphate-5-phosphatase. OCRL is thus thought to be an inborn error of inositol polyphosphate metabolism. We analyzed the gene in two Japanese OCRL patients and their families by DNA sequencing and mismatch polymerase chain reaction (PCR) followed by restriction digestion. A novel nonsense mutation (C1399T) replacing the glutamine of codon 391 (Gln 391 Stop) was identified in exon 12 in 1 patient and also in his mother. A novel missense mutation (C1743G) was identified in exon 15 in the second patient. his mother and maternal grandmother. The missense mutation predicts a substitution of serine for arginine (Ser 505 Arg) in a domain highly conserved among the inositol-5-phosphatase family. Our observations expand the range of OCRL1 mutations that cause Lowe syndrome, and will be useful for genetic counseling in these two families.

Amino Acid Sequence↗

PubMed1998

Changes of ischemic heart disease in Utsunomiya, Japan, over 10 years: a survey of primary care physicians.

A total of 502 patients presenting in Utsunomiya city and its suburbs during a 10-year period were studied to determine the clinical features of ischemic heart disease and to identify coronary risk factors. The male/female ratio was 1.21, but the ratio decreased with increasing age. The duration of chest pain showed a continuous spectrum between angina and infarction, with a short duration of chest pain not being useful for excluding the diagnosis of myocardial infarction. Hypertension was more common than hypercholesterolemia in this study, although the prevalence of the latter increased slightly with time, along with the shift towards a modernized occupational pattern. Smoking was a more important risk factor for ischemic heart disease in younger individuals than in the elderly, and diabetes mellitus was highly associated with the development of myocardial infarction. The incidence of radiologically diagnosed cardiac hypertrophy and aortic calcification decreased over time. These changes may have resulted in part from improved blood pressure control and the development of new anti-hypertensive and cholesterol-lowering agents.

Age Factors↗

PubMed1998

Pheochromocytoma arising from an accessory adrenal gland in a patient with multiple endocrine neoplasia type 2A: transient development of clinical manifestations after hemorrhagic necrosis.

A case of pheochromocytoma arising from an accessory adrenal gland in a patient with multiple endocrine neoplasia type 2A (MEN 2A) is reported. This tumor resulted in autonecrosis which caused transient expression of clinical symptoms. Scintigraphy of the abdomen identified the existence of an additional accessory adrenal gland because of which the patient did not require a supplement of hydrocortisone after bilateral total adrenalectomy. Pheochromocytoma arising from an accessory adrenal gland is rarely reported, and spontaneous remission of clinical symptoms due to necrosis of the pheochromocytoma without a clinical emergency is also unusual. Accessory adrenal glands can be the cellular basis for pheochromocytoma, and the importance of continual follow up for pheochromocytoma in subjects with MEN 2A should be emphasized.

Adrenal Gland Neoplasms↗

PubMed1998

Hyperfunctioning thyroid adenoma concomitant with papillary thyroid carcinoma, follicular thyroid adenoma and primary hyperparathyroidism.

A case of 67-year-old woman with hyperthyroidism due to functioning thyroid adenoma is reported. The patient had concomitant follicular thyroid adenoma and primary hyperparathyroidism in addition to functioning adenoma. Histological examination of the excised thyroid tissue revealed occult papillary carcinoma within a functioning adenoma. Genetic analysis of such tumors indicated that functioning adenoma and papillary carcinoma may be etiologically independent. There have been a number of case reports on the coexistence of functioning thyroid adenoma and thyroid cancer or hyperparathyroidism, but none of the studies had examined the etiologic relationship of these lesions on a genetic basis. Furthermore, to our knowledge, this is the first report of the concurrence of four tumors in the neck, functioning thyroid adenoma, papillary thyroid carcinoma, follicular thyroid adenoma and parathyroid adenoma.

Adenoma↗

PubMed1998

Antibody to hepatitis B e positive hepatitis induced by withdrawal of steroid therapy for polymyositis: response to interferon-alpha and cyclosporin A.

A 57-year-old woman was admitted with symmetrical proximal muscle weakness, liver dysfunction, abnormal muscle enzymes, and she was an antibody to hepatitis B e (anti-HBe) positive hepatitis B virus (HBV) carrier. Biopsy of her left quadriceps femoris showed myositis, so prednisolone was started at 40 mg/day. However, her hepatic function deteriorated and liver biopsy after 4 months showed acute hepatitis with partial submassive necrosis. Treatment with interferon-alpha and cyclosporin A progressively reduced the transaminase and HBV-DNA levels. Early treatment with interferon-alpha plus cyclosporin A can control exacerbation of hepatitis B.

Alanine Transaminase↗

PubMed1998

Frontoorbital advancement by gradual distraction. Technical note.

A substantial number of patients with coronal synostosis who undergo frontoorbital advancement still require additional surgical treatment to correct increased intracranial pressure or unsatisfactory craniofacial structure. However, frontoorbital advancement currently requires elevation of the frontal as well as the orbital bone, which can result in a fragile dura mater and partial resorption of the advanced bone. Thus the dura is easily torn by dissection and the advanced bone is further resorbed and deformed during repeated craniofacial operations. To avoid these drawbacks and to create an easier second surgical treatment via the intracranial approach, a new technique for frontoorbital advancement is presented. In this technique frontoorbital bone is advanced as a single unit, without elevation from the underlying dura, by means of gradual distraction. The details of the technique and an illustrative case are reported.

Cranial Sutures↗

PubMed1997

Differanisole A, a novel antitumor antibiotic, enhances growth inhibition and differentiation of human myeloid leukemia cells induced by 9-cis retinoic acid.

Differanisole A, 3,5-dichloro-2-hydroxy-4-methoxy-6-n-propylbenzoic acid, inhibited growth of human myeloid leukemia cells. The compound induced G1 arrest and granulocytic differentiation of HL-60 cells, although the differentiation-inducing effect was modest. Differanisole A and 9-cis retinoic acid (9cisRA) synergistically inhibited the growth and induced functional and morphologic differentiation of HL-60 and NB4 cells, whereas the combined treatment with differanisole A and all-trans retinoic acid or 1alpha,25-dihydroxyvitamin D3 was less effective. Similar results were obtained in primary culture of leukemia cells from a patient with acute promyelocytic leukemia. The synergistic effect on growth inhibition and induction of differentiation required simultaneous treatment with differanisole A and 9cisRA. Differanisole A and an RXR-specific ligand (Ro47-5944) cooperatively inhibited the cell growth, while the combined effect of differanisole A and an RAR-specific ligand Am80 was just additive. Differanisole A in combination with 9cisRA may have implications for therapy of acute promyelocytic leukemia patients.

Alitretinoin↗