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Biomedical subjects

S Ohnuma

Publications and source records attributed to S Ohnuma.

At least 19 recordsLinked to original sources

Cell cycle and cell fate in the nervous system.

Recently, a number of molecules originally thought to have a primary role in cell determination have been shown to affect the cell cycle at specific check points, while other molecules discovered for their roles in the cell cycle progression are known to affect the determination and differentiation of neurons. These discoveries have led to a more detailed investigation of the complex molecular machinery that co-ordinates proliferation and differentiation.

Animals↗

The necessity for dual food intake to provoke food-dependent exercise-induced anaphylaxis (FEIAn): a case report of FEIAn with simultaneous intake of wheat and umeboshi.

BACKGROUND: Food-dependent exercised-induced anaphylaxis (FEIAn) is classified among the physical allergies. Many different food allergens have been reported, but the pathophysiology of FEIAn remains unknown. Furthermore, provocation tests with a suspected food do not always succeed in patients with FEIAn. OBJECTIVE: We sought to clarify and investigate causative foods and mechanisms of FEIAn in a 14-year-old boy. In addition, we tested in vivo and in vitro effects of cromolyn sodium in the same patient. METHODS: We used open challenge tests for the provocation of FEIAn and measured changes in plasma histamine levels and FEV1. In addition, we investigated the mechanism of FEIAn in this case with in vitro histamine release testing. RESULTS: The patient was diagnosed as having FEIAn by provocation testing with a simultaneous intake of wheat and umeboshi, but not when each food was eaten singly, followed by exercise. In addition, his plasma histamine level increased transiently and forced expiratory volume 1, expressed as a percentage change from baseline, decreased significantly. A synergistic effect on in vitro histamine release testing with 2 kinds of the causative foods was shown. Administration of cromolyn sodium proved to be effective on both the in vitro and in vivo tests. CONCLUSION: This is the first report of FEIAn provoked by the test with a simultaneous intake of 2 kinds of food. This case might in part explain negative challenge test results in patients with FEIAn.

Adolescent↗

Glycoside in schizophrenic patients sera affects behavior of mouse forced swimming.

We found a glycoside in sera of schizophrenic patients. This glycoside increased climbing of mouse forced swimming and the climbing was decreased by dopamine D1 receptor antagonist SCH-23390 with a dose dependent manner. This glycoside had much reactivity of GalNAc alpha1-3GalNAc, but not that of polymannoses nor that of Gal beta1-3GlcNAc alpha1-serine or threonine. This strongly suggests that the glycoside is an isolated O-glycoside, but not N-glycoside nor O-glycoside having core 1 or 2. The present findings suggest that schizophrenic patients have the special glycoside affecting the D1 receptor activity in their serum.

Adult↗

Portal and mesenteric vein and inferior vena cava thrombosis associated with antiphospholipid syndrome.

We report a 48-year-old man with thrombosis of the portal and superior mesenteric vein and inferior vena cava associated with primary antiphospholipid syndrome (APS). Primary APS was diagnosed by a positive reaction with anticardiolipin antibody (aCL) and the absence of any evidence suggesting the presence of other disease states known to be associated with aCL. A coeliac angiography showed obstruction of the portal and superior mesenteric vein with prominent collaterals and cavernous transformation. Femoral vein angiography showed total obstruction of the external iliac vein and inferior vena cava, and dilation of the pelvic veins, with contrast medium in the lumbar vein. This case is noteworthy as a report of primary APS accompanied by extensive abdominal and pelvic venous thrombosis.

Antiphospholipid Syndrome↗

An outbreak of allergy-like food poisoning.

Eight cases of allergy-like food poisoning resulting from the ingestion of yellowfin tuna, which had been kept in stock for 10 days prior to being cooked, are described. The main symptoms were headaches, facial flushing and palpitation. Samples of the ingested fish were analyzed for histamine content, and a high level of histamine was confirmed (310 mg/100 g of fish). Corticosteroids were given to 3 patients who exhibited dyspnea or persistent symptoms, while the remaining patients improved without medication. In situations where allergy-like clinical features are present after the ingestion of food, the possibility of allergy-like food poisoning should be recognized and included in a differential diagnosis.

Adult↗

[Effects of environmental change and others' behavior on cooperative behavior and solution preference in social dilemma].

This study examined how environmental change and others' behavior affected cooperative behavior and solution preference of the person in social dilemma situation. Participants in two experiments played an "environment game," in which gradual pollution in environment and reduction in profit rate were simulated. Information on behavior of other players was manipulated: in "free rider" condition, one person was an extreme free rider, and the others were cooperative; in "loafing" condition, everyone loafed. In both experiments, "Bad Apple Effect" was not observed clearly, and cooperative behavior increased as environmental pollution worsened. In Experiment 2, there was no main effect of others' behavior on solution preference. However, significant correlations were found among solution preference, motivation to control others' behavior, and perceived seriousness of the situation, only when an extreme free rider was among them.

Adult↗

[A case of advanced gastric cancer treated with neoadjuvant chemotherapy of low-dose CPT-11 + CDDP].

Side effects due to administration of anti-cancer drugs often cause the treatment to be abandoned or a decrease in the amount of anti-cancer drugs. Recently, the anti-tumor effects of "low-dose CPT-11", which can be administered at the outpatient clinic, are reported. We performed "low-dose CPT-11 + CDDP" as a neoadjuvant chemotherapy to a patient with advanced gastric cancer. CPT-11 and CDDP combination chemotherapy caused very few side effects, so we could continue the treatment and achieve anti-tumor effects. Consequently, surgery could be performed, but disseminated metastasis was found so that the surgery ended as a non-curative operation. However, it was considered that this method of "low-dose CPT-11 + CDDP" was very effective as the neoadjuvant chemotherapy in a patient with advanced gastric cancer.

Aged↗

[A case of acute pulmonary embolism associated with squatting].

The patient was a 69-year-old man with a 3-year history of diabetes mellitus accompanied by cerebral infarction and arteriosclerosis obliterans of the lower extremities. After squatting to clean a car, the patient began to experience dyspnea. A blood gas analysis was performed upon admission, and the patient's PaCO2 and PaO2 levels were found to be low. Examination of a blood sample revealed elevated FDP, FDP-D dimer and platelet factor 4 levels. A perfusion lung scan showed multiple defects in both lungs, but no abnormal findings were detected on a ventilation scan. A pulmonary angiogram showed an interrupted blood flow in branches A9 + 10 of the left pulmonary artery. Accordingly, a pulmonary embolism was diagnosed. Squatting may have caused a partial obstruction of the venous return from the lower extremities by compression of the inguinal region and may have been a predisposing cause of the thrombosis. To our knowledge, such cases of pulmonary embolism triggered by the act of squatting are very rare.

Acute Disease↗

Isoprenyl diphosphate synthases.

Isoprenyl diphosphate synthases catalyze consecutive condensations of isopentenyl diphosphates with allylic primer substrates to form linear backbones for all isoprenoid compounds including cholesterol. These synthases are classified according to the final chain length of their end products and the stereochemistry of the newly formed double bonds. Mutagenesis and X-ray crystallography data have uncovered the basic catalytic and chain length determination mechanisms of E-isoprenyl diphosphate synthases and shed light on their possible evolutionary course. Although much less is known about the Z-isoprenyl diphosphate synthase family, successful cloning and subsequent crystallizations in the near future will no doubt bring more insight as researchers begin to unravel the essential components and precise reaction mechanisms of this cellular machinery.

Alkyl and Aryl Transferases↗

Mechanism of product chain length determination for heptaprenyl diphosphate synthase from Bacillus stearothermophilus.

A member of the medium-chain prenyl diphosphate synthases, Bacillus stearothermophilus heptaprenyl diphosphate synthase, catalyzes the consecutive condensation of isopentenyl diphosphate with allylic diphosphate to produce (all-E)-C35 prenyl diphosphate as the ultimate product. We previously showed that the product specificity of short-chain prenyl diphosphate synthases is regulated by the structure around the first aspartate-rich motif (FARM). The FARM is also conserved in a subunit of heptaprenyl diphosphate synthase, component II', which suggests that the structure around the FARM of component II' regulates the elongation. To determine whether component II' regulates the product chain length by a mode similar to that of the short-chain prenyl diphosphate synthases, we replaced a bulky amino acid at the eighth position before the FARM of component II', isoleucine 76, by glycine and analyzed the product specificity. The mutated enzyme, I76G, can catalyze condensations of isopentenyl diphosphate beyond the native chain length of C35. Moreover, two mutated enzymes of A79Y and S80F, which have a single replacement to the aromatic residue at the fourth or the fifth position before the FARM, mainly yielded a C20 product. These results strongly suggest that a common mechanism controls the product chain length of both short-chain and medium-chain prenyl diphosphate synthases and that, in wild-type heptaprenyl diphosphate synthase, the prenyl chain can grow on the surface of the small residues at positions 79 and 80, and the elongation is precisely blocked at the length of C35 by isoleucine 76.

Alkyl and Aryl Transferases↗

Relationship between antidepressants and glycolipids in the forced swimming test in mice.

GalNAc alpha 1-3GalNAc-lipids induce an antidepressive-like effect in mice in the forced swimming test. In the present study, the relationship between the effects of several antidepressants and serum glycolipid reactivities were investigated. The antidepressants imipramine, maprotiline, paroxetine, trazodone and mianserin induced an effect in forced swimming in mice after 1 or 6 h but not 15 min after treatment. The GalNAc alpha 1-3GalNAc-lipid globopentaosylceramide dose-dependently induced the effect only 15 min after treatment, and the glycolipid reactivities were found in the serum dose-dependently at the period that the mice showed the antidepressive-like climbing behavior. The results strongly suggest that glycolipid production, and not the central neurological activities of the antidepressants, induce the antidepressive effect in mice.

Animals↗

Use of cultured tubular cells isolated from human urine for investigation of renal transporter.

AIM: To facilitate the understanding of the transporter function of human renal tubular cells, we have developed a simple method using primary cultured proximal tubule (PT) cells isolated from voided urine. METHODS: PT cells grown to confluence on glass coverslips could be identified by parallel arrays of spindle cells and hemicyst formation. Brush-border gamma-glutamyl transpeptidase (gammaGTP) activity was histochemically identified. Apical membrane Na+/H+ exchanger (NHE) activity was measured by monitoring changes in intracellular pH (pHi) after an acid load in a single cell level using the pH-sensitive dye 2'7'-bis-(2-carboxyethyl)-5.6'carboxyfluorescein (BCECF). RESULTS: Amiloride and 5-(N-ethyl-N-isopropyl) amiloride (EIPA) inhibited the NHE activity with half-maximal inhibition values (IC50) of 15.3 and 4.0 microM, respectively. NHE-3 mRNA was detected by the RT-PCR technique in clonally proliferated PT cells. CONCLUSION: These results suggest that cultured PT cells isolated from human urine express amiloride-resistant NHE-3 activity on the apical membranes, which can be compared to functional properties of PT in vivo. Our experimental strategy offers a useful experimental approach to investigating human renal tubular transport function in vitro.

Adult↗

p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina.

p27Xic1, a member of the Cip/Kip family of Cdk inhibitors, besides its known function of inhibiting cell division, induces Müller glia from retinoblasts. This novel gliogenic function of p27Xic1 is mediated by part of the N-terminal domain near but distinct from the region that inhibits cyclin-dependent kinases. Cotransfections with dominant-negative and constitutively active Delta and Notch constructs indicate that the gliogenic effects of p27Xic1 work within the context of an active Notch pathway. The gradual increase of p27Xic1 in the developing retina thus not only limits the number of retinal cells but also increasingly favors the fate of the last cell type to be born in the retina, the Müller glia.

Animals↗

The neuronal architecture of Xenopus retinal ganglion cells is sculpted by rho-family GTPases in vivo.

Dendritogenesis, axonogenesis, pathfinding, and target recognition are all affected in distinct ways when Xenopus retinal ganglion cells (RGCs) are transfected with constitutively active (ca), wild-type (wt), and dominant negative (dn) Rho-family GTPases in vivo. Dendritogenesis required Rac1 and Cdc42 activity. Moreover, ca-Rac1 caused dendrite hyperproliferation. Axonogenesis, in contrast, was inhibited by ca-Rac1. This phenotype was partially rescued by the coexpression of dn cyclin-dependent kinase (Cdk5), a proposed effector of Rac1, suggesting that Rac1 activity must be regulated tightly for normal axonogenesis. Growth cone morphology was particularly sensitive to dn-RhoA and wt-Cdc42 constructs. These also caused targeting errors, such as tectal bypass, suggesting that cytoskeletal rearrangements are involved in target recognition and are transduced by these pathways.

Animals↗

Cauda equina syndrome complicating pneumococcal meningitis.

A 14-month-old female with pneumococcal meningitis presented with flaccid paraplegia, saddle anesthesia, and bladder and bowel dysfunction. Magnetic resonance imaging of the spine demonstrated intense gadolinium enhancement of the cauda equina, whereas the conus medullaris appeared normal. This finding indicated that lumbosacral polyradiculopathy caused her symptoms.

Cauda Equina↗

Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution.

In the synthesis of isoprenoids, isoprenyl diphosphate synthases catalyze the consecutive condensation of isopentenyl diphosphate with allylic diphosphates to produce a variety of prenyl diphosphates with well-defined chain lengths. Site-directed mutagenesis in conjunction with X-ray crystallographic studies have identified specific amino acid residues responsible for chain-length determination. Simple combinations of these residues within a characteristic motif are not only sufficient to confer product specificities to all isoprenyl diphosphate synthases but represent structural features that reflect the enzyme family's evolutionary course.

Alkyl and Aryl Transferases↗

Protein design of geranyl diphosphate synthase. Structural features that define the product specificities of prenyltransferases.

Geranyl diphosphate synthase catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give a C(10) compound, geranyl diphosphate, which is a precursor of all monoterpenoids. However, the gene has not been isolated from any organisms. To examine the possibility that geranyl diphosphate synthase has evolved from a common ancestor of the prenyltransferase family and to predict the active site structure, we tried to convert Bacillus stearothermophilus farnesyl diphosphate synthase to geranyl diphosphate synthase, according to our previous findings. Several mutated farnesyl diphosphate synthases that have single amino acid substitutions before the first aspartate-rich motif were constructed. A mutated enzyme that has the replacement of serine by phenylalanine at the fourth position before the motif exclusively produced geranyl diphosphate when dimethylallyl diphosphate was used as the primer, and hardly accepted geranyl diphosphate as a primer, indicating that this mutation causes the conversion to geranyl diphosphate synthase. This result supports the idea that the product specificities of all members of the E-prenyltransferase family are mainly defined by a few structural features: the amino acids at the fourth position and the fifth position before the first aspartate-rich motif, and the insertion of two amino acids in the motif. This suggests that natural geranyl diphosphate synthases might have an active site structure similar to that of the mutated enzyme.

Amino Acid Sequence↗

[A case of type 4 gastric cancer with peritoneal dissemination treated with intra-aortic chemotherapy].

A 45-year-old woman was admitted to our hospital because of lower abdominal pain and anorexia. A barium gastrography and gastroscopy showed a type 4 gastric cancer in the upper gastric body. Histologic study on biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Computed tomography revealed bilateral hydronephrosis, and barium enema showed diffuse stenosis of the sigmoid colon because of peritoneal dissemination. This patient was treated by intra-aortic infusion therapy with sequential MTX and 5-FU. After five courses of the administration, barium enema revealed reexpansion of the lumen of sigmoid colon with normalization of the tumor markers. The patient was discharged without symptoms. Intra-aortic infusion therapy with sequential MTX and 5-FU was considered an effective treatment for unresectable gastric cancer.

Adenocarcinoma↗