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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 181 records · Page 10Linked to original sources

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↗

Unilateral absence of pulmonary artery and ventricular septal defect in an infant.

A 2-month-old boy was diagnosed as having a rare combination of absence of left pulmonary artery and ventricular septal defect. He underwent intracardiac repair at the age of 8 months. Reconstruction of the left pulmonary artery was impossible because it could not be visualized through a median sternotomy. Although his early postoperative course was uneventful, he needed ipsilateral pneumonectomy 3 months later because of unremitting hemoptysis. Hilar left pulmonary artery, which used to exist, was not found even by histologic examination.

Aorta, Thoracic↗

A new technique applicable to pediatric laparoscopic surgery: abdominal wall 'area lifting' with subcutaneous wiring.

BACKGROUND: Recently, the authors developed a unique method of laparoscopic surgery without pneumoperitoneum: "area lifting of the abdominal wall with subcutaneous wiring." METHODS: In this gasless procedure, the anterior abdominal wall is pulled upward by a pair of wires placed subcutaneously and held by thick sutures for "hanger lifting." Simultaneous lifting of a pair of subcutaneous wires across the abdomen, produces a wide, roof-shaped intraabdominal space sufficient for laparoscopic surgical procedures. The practical aspects of this gasless technique, as well as the authors' limited experience with this method in 24 children, ranging from 8 days to 15 years of age is presented. These children have had various pathologies including splenomegaly, rectal prolapse, ovarian cyst, gall stone, adrenal neuroblastoma, and abdominal wall abscess. CONCLUSIONS: Gasless laparoscopic surgery with double subcutaneous wiring is safe for children including neonates and those with respiratory compromise because all operative procedures are performed under normal abdominal pressure. Because of the highly elastic abdominal wall musculature inherent in children, this selective area lifting of abdominal wall creates a relatively larger peritoneal volume than in adults.

Abdominal Muscles↗

Effects of long-term physical exercise on age-related changes of spinal motoneurons and peripheral nerves in rats.

We examined the number and size of motoneurons and myelinated nerve fibers innervating the medial gastrocnemius (MG) muscle in the hindlimb of rats that were subjected to swimming for 10 months (30 min, 3 days/week) from 17 to 27 months of age. The number of MG motoneurons in exercised aged rats was slightly, but not significantly, greater than that in sedentary aged rats, and the number for both aged groups was significantly less compared to that in middle-aged (17-month-old) rats. The size of motoneuronal somata in the exercised aged rats was significantly larger than that in sedentary aged rats. Morphological parameters (fascicular area, fiber density, and axonal diameter) for the MG nerve in the exercised rats showed intermediate values between those for middle-aged and sedentary aged rats, although all of the differences in the means between groups were not significant. Thus, the overall changes seen in the exercised rats seem less compared to the changes in the sedentary rats, suggesting that long-term moderate exercise retards the progressive changes in motoneurons and peripheral nerves that develop in old age.

Aging↗

Change in cerebral glucose metabolism during limbic seizures elicited from lateral septal nucleus.

The roles of the amygdala and hippocampus have been extensively studied in limbic seizures. Although the septal nuclei have a close connection to the hippocampus and affect emotional behavior, the effect on limbic seizures is still unclear. We have reported that characteristic sham-rage seizures were observed in cats, by administering a local injection of kainic acid (KA) into the lateral septal nucleus (LSN). This study investigated the electrophysiological features of KA-induced septal seizures in rats and analyzed the process in relation to the cerebral glucose metabolism using [14C]deoxyglucose autoradiography. On EEG, epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus and the amygdala. Behavioral change was similar to that in limbic seizures induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats. However, the local cerebral glucose metabolism during the seizures increased not only in the limbic structures including the LSN but also in the hypothalamus and periaqueductal grey matter of the midbrain. The findings were distinctive of septal seizures as compared with amygdaloid seizures. The results suggested that sham-rage seizures in cats might be caused by a secondary epileptogenic excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The septal nuclei may play an important role in emotional behavior associated with limbic seizures even if there is a species difference in its function.

Animals↗

Multiple subpial transection in kainic acid-induced focal cortical seizure.

Experimental animal studies on multiple subpial transection (MST) to modify epilepsy have been limited, and its mechanism of therapeutic benefit remains unclear. We examined the effect of MST on the electroencephalogram and cerebral glucose metabolism using a focal cortical epilepsy model in rats. Focal cortical seizures were induced by injecting kainic acid into the left sensorimotor cortex (SMC). Epileptic activity propagated from the focus to neighboring cortex, then to the contralateral SMC. All animals developed right forelimb clonus and/or secondarily generalized convulsions. Sagittal cortical transections on both sides of the focus suppressed the propagation to the ipsilateral hemisphere. However, epileptic activity was not suppressed in the focus and contralateral SMC, and clinical seizures infrequently occurred even following MST. In [14C]2-deoxyglucose autoradiograms, MST did not affect glucose metabolism in naive animals. During focal seizures, MST reduced focal hypermetabolism in the left SMC, although the ipsilateral caudate nucleus, thalamus, and opposite SMC still demonstrated hypermetabolism. These results suggest that MST suppressed focal epileptic activity and its propagation to the neighboring cortical areas. However, clinical seizures were not completely inhibited because vertical interactions between the focus and subcortical areas were preserved. Glucose metabolic changes provided evidence of conserved cortical function following MST.

Animals↗

Differential induction by methyl jasmonate of genes encoding ornithine decarboxylase and other enzymes involved in nicotine biosynthesis in tobacco cell cultures.

A cDNA of tobacco BY-2 cells corresponding to an mRNA species which was rapidly induced by methyl jasmonate (MeJA) in the presence of cycloheximide (CHX) was found to encode ornithine decarboxylase (ODC). Another cDNA from a MeJA-inducible mRNA encoded S-adenosylmethionine synthase (SAMS). Although these enzymes could be involved in the biosynthesis of polyamines, the level of putrescine, a reaction product of ODC, increased slowly and while the levels of spermidine and spermine did not change following treatment of cells with MeJA. However, N-methylputrescine, which is a precursor of pyrrolidine ring of nicotine, started to increase shortly after MeJA-treatment of cells and the production of nicotine occured thereafter. The levels of mRNA for arginine decarboxylase (ADC), an alternative enzyme for putrescine synthesis, and that for S-adenosylmethionine decarboxylase (SAMDC), required for polyamine synthesis, were not affected by MeJA. In addition to mRNAs for ODC and SAMS, mRNA for putrescine N-methyltransferase (PMT) was also induced by MeJA. Unlike the MeJA-induction of ODC mRNA, MeJA-induction of SAMS and PMT mRNAs were blocked by CHX. The level of ODC mRNA declined after 1 to 4 h following MeJA treatment, while the levels of mRNAs for SAMS and PMT continued to increase. Auxin significantly reduced the MeJA-inducible accumulation of mRNAs for ODC, SAMS and PMT. These results indicate that MeJA sequentially induces expression of a series of genes involved in nicotine biosynthesis by multiple regulatory mechanisms.

Acetates↗

Radiation-induced painless thyrotoxic thyroiditis followed by hypothyroidism: a case report and literature review.

A 68-year-old woman presented with a small painless goiter and thyrotoxic symptoms immediately after 50-Gy external radiation for mucoepidermoid carcinoma of the submandibular gland. Elevated serum thyroid hormone and thyroglobulin levels, and undetectable serum thyrotropin level, together with extremely low thyroidal radioiodine uptake established the diagnosis of painless thyrotoxic thyroiditis. Thyroidal autoantibodies were negative. At follow-up without medication, all the symptoms disappeared, and laboratory abnormalities normalized within 6 months. One year later, the patient developed compensated hypothyroidism as indicated by elevated serum thyrotropin level with low normal serum thyroid hormone levels.

Aged↗

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↗

An mRNA of tobacco cell, which is rapidly inducible by methyl jasmonate in the presence of cycloheximide, codes for a putative glycosyltransferase.

Two-dimensional gel electrophoretic display of polypeptides labeled in vivo and those synthesized in vitro from poly(A)(+)-RNA indicated that treatment of cultured cells of tobacco (Nicotiana tabacum) BY-2 with methyl jasmonate (MeJA) induces accumulation of a limited number of specific mRNAs within a few hours. The MeJA-induction of most of these mRNAs was inhibited by cycloheximide (CHX). Six MeJA-inducible cDNAs identified by differential screening were classified into three groups based on the sensitivity of their induction to CHX. Induction of group I mRNAs by MeJA occurred earlier than the induction of other mRNAs and it was not inhibited by CHX. The induction of group II mRNAs by MeJA was blocked by CHX, while group III mRNAs were induced by CHX alone. One group I cDNA was found to encode a putative protein, JIGT, homologous to UDP-sugar glycosyltransferases previously characterized from several plant species. JIGT was structurally different from a putative glycosyltransferase that is rapidly inducible by salycylic acid (SA) in BY-2 cells. JIGT mRNA was not induced by SA. In addition to MeJA, as little as 10(-9) M coronatine induced JIGT mRNA. A sequence highly homologous to JIGT is present as a single copy in the genomes of Nicotiana sylvestris and N. tomentosiformis. The MeJA-inducible production of JIGT may be involved in sugar-conjugation of an unknown substrate in a defensive response and expression of the gene for JIGT in BY-2 cells might serve as a good model system for disecting molecular events occurring in JA-inducible gene expression.

Acetates↗