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Biomedical subjects

K Kasai

Publications and source records attributed to K Kasai.

At least 163 records · Page 9Linked to original sources

An immunohistochemical study of the 32-kDa galectin (beta-galactoside-binding lectin) in the nematode Caenorhabditis elegans.

The localization of the 32-kDa galectin (beta-galactoside-binding lectin) of the nematode Caenorhabditis elegans, which is the first lectin to be found in a nematode, was examined immunohistochemically using an anti-lectin antiserum. The lectin was found to be localized most abundantly in the adult cuticle and also in the terminal bulb of the pharynx. However, it was difficult to locate the galectin in larval animals, though immunochemical experiments suggested its presence. These results suggest that one of the fundamental roles of the galectin may be as a component of the durable outer barrier, as in the case of the morphogenesis of chick embryonic skin.

Animals↗

Treatment of radioiodine-negative bone metastasis from papillary thyroid carcinoma with percutaneous ethanol injection therapy.

A 62-year-old woman with metastatic papillary thyroid carcinoma in the sternum was successfully treated with percutaneous ethanol injection therapy (PET) when previous radioiodine therapy and external irradiation were ineffective. The patient tolerated the treatment well and the refractory pain in the anterior chest wall that was alleviated with morphine prior to PEIT completely disappeared. No severe complications were observed. PEIT was performed 4 times (2 times with ultrasound guidance and 2 times with CT guidance). The posttreatment CT scan and 201Tl scintigraphy demonstrated significant decrease in the tumor volume. The serum thyroglobulin level fell to less than one-twentieth of the pretreatment value. It is suggested that PEIT has a value in treating bone metastasis from thyroid carcinoma which do not respond to radioiodine.

Bone Neoplasms↗

Up-regulation of rat adrenomedullin gene expression by endotoxin: relation to nitric oxide synthesis.

The effect of bacterial endotoxin (LPS) on adrenomedullin (AM) gene expression was investigated in cultured rat aortic vascular smooth muscle (VSM) cells and in tissues from anesthetized rats. The addition of LPS together with interferon-gamma to VSM cells resulted in a marked increase in the abundance of AM mRNA as well as the appearance of mRNA for the inducible isoform of nitric oxide (NO) synthase (iNOS). Intravenous injection of LPS into rats also increased AM mRNA abundance and induced iNOS mRNA in lung, heart, liver, and kidney. AM significantly enhanced NO synthesis evoked by LPS and interferon-gamma in cultured VSM cells. These data suggest that AM may contribute to circulatory failure during endotoxin shock, in part, by modulating NO synthesis.

Adrenomedullin↗

Nitric oxide inhibits cell growth in cultured human thyrocytes.

Effect of NO induced by interleukin-1 (IL-1) or IL-1/interferon- gamma (IL-1/IFN-gamma) was investigated on cell growth using primary cultures of human thyrocytes. Cytokine-induced NO production was associated not only with an increase in cyclic GMP (cGMP) formation but also with an inhibition of cell growth determined by bromo-deoxyuridine (Br-dU) incorporation into DNA. When NO synthesis was blocked by NG-monomethyl-L-arginine (L-MMA), cGMP formation was prevented in parallel with NO production and inversely a restoration of cell growth was evident. S-nitroso-N-acetyl-penicillamine, a NO donor, but not a cell permeable cGMP analog, 8-bromo-cGMP, inhibited cell growth in a dose-dependent manner. The present findings strongly indicate that endogenous NO produced by the cytokine treatment as well as exogenous NO, has a cGMP-independent inhibitory action on human thyrocyte growth.

Cell Division↗

Cryptogenic localization-related epilepsy of neonatal onset.

We report three patients with localization-related epilepsy of neonatal onset. They exhibited favourable psychomotor development and had no cerebral lesions on neuroimaging studies despite the presence of intractable partial seizures of neonatal onset. Although rare, some cases of epilepsy of neonatal onset may be cryptogenic, i.e. they belong to neither the symptomatic nor the idiopathic group.

Blood Glucose↗

Effect of cycloheximide on the expression of LPS-inducible iNOS, IFN-beta, and IRF-1 genes in J774 macrophages.

The effect of cycloheximide (CHX) on the gene expression for inducible NO synthase (iNOS), interferon (IFN)-beta, and IFN regulatory factor (IRF)-1 was examined in LPS-stimulated J774 macrophages. LPS caused increased expression of mRNAs specific for iNOS, IFN-beta, and IRF-1 with different kinetics. Addition of CHX resulted in inhibition of the LPS-induced iNOS gene expression and parallel decrease in NO production. In contrast, expression of IFN-beta and IRF-1 genes in response to LPS was potentiated in the presence of CHX. These results indicate that de novo protein synthesis is not required for IFN-beta and IRF-1 gene expression and that ongoing protein synthesis including IFN-beta and IRF-1 may be involved in the induction process of iNOS in mouse macrophages.

Animals↗

Galectins: a family of animal lectins that decipher glycocodes.

Galectins, animal lectins exhibiting specificity for galactosides, are now known to be widely distributed from lower invertebrates, such as sponges and nematodes, to higher vertebrates. The origin of the family can be traced back to the Precambrian era. They are classified into proto-, chimera-, and tandem-repeat types on the basis of protein architecture. The molecular functions of these types should be different because they can cross-link pairs of biomolecules of different combinations. Their biological significance, however, is not yet fully understood because they are involved in too many phenomena, such as differentiation, morphogenesis, metastasis, etc., and too many problems remain unsolved, such as those regarding their controversial cellular localization, mechanism of externalization, etc. Nevertheless, such difficulties seem to indicate their importance as household equipment and their common roles throughout the animal kingdom. They are likely to be responsible for recognizing the N-acetyllactosamine (LacNAc) structure, which is included in various glycoconjugates and considered to be an important glycocode, and then carry out appropriate tasks under given circumstances. Recently, crystallographic studies revealed that galectins and legume lectins such as concanavalin A have a common topology in spite of the absence of sequence homology. This suggests a possible relationship between animal and plant lectins, and the existence of a lectin super family. Studies on the galectin family are becoming increasingly important for glycobiology.

Amino Sugars↗

Determination of the affinity constants of pea lectin for neutral sugars by capillary affinophoresis with a monoligand affinophore.

Affinophoresis is a type of affinity electrophoresis in which an affinophore, a conjugate of an affinity ligand and a multiply charged soluble matrix, causes a change in migration velocity of proteins which have a specific affinity for the ligand. A monoligand affinophore bearing a mannoside was prepared by coupling iodoacetylated p-aminophenyl alpha-D-mannoside to the free thiol group of N-succinylated glutathione, and used for the affinophoresis of pea lectin in a capillary. The electrophoretic mobility of pea lectin towards the anode increased in the presence of the affinophore as a function of its concentration in a manner that is described by the equation for affinity electrophoresis. Analysis of the suppression of the affinophoresis on the addition of neutral sugars to the system allowed the determination of the dissociation constants of the lectin for these neutral sugars. The dissociation constants obtained on affinophoresis agreed well with the values in the literature. The preparation of a monoligand affinophore for ligands bearing an amino group should facilitate the application of this type of microscale analysis (0.14 ng of protein for each run) to protein ligand interactions.

Affinity Labels↗

The role of the phrenic nerves in stress response in upper abdominal surgery.

Previous studies have failed to demonstrate a block of the endocrine response to upper abdominal surgery by thoracic epidural analgesia. To clarify the bases for this failure, we compared the effects of epidural analgesia of different dermatome levels up to C8-T2 or C3-4. The patients who received general anesthesia alone showed significant increases of adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) immediately after skin incision. The patients with C8-T2 blocked developed significant increases in these hormones, not after the skin incision, but after the intraabdominal procedure. Of the eight patients with C3-4 block, six developed no such responses throughout the study period. The responses of oxytocin (OXT) and prolactin (PRL) were more susceptible to epidural analgesia and were blocked at the C8-T2 level. Growth hormone (GH) showed no correlation with surgical procedures and epidural block. These findings indicate that the nociceptive neural information during upper abdominal surgery is conveyed by the sensory fibers included in both the thoracic and lumbar spinal nerves that innervate the abdominal wall and the intraabdominal viscera, and by the phrenic nerves that innervate the diaphragm. The rationale for postulating the involvement of the phrenic nerves can be referred to the embryonal descent of the diaphragm from the C3-5 myotomes that serves as the upper wall of the abdominal cavity.

Abdomen↗

Increased cell proliferation and transforming growth factor-alpha (TGF alpha) in the gall-bladder epithelium of patients with pancreaticobiliary maljunction.

Pancreaticobiliary maljunction is associated frequently with gall-bladder carcinoma. Although increased turnover of the gall-bladder epithelium in patients with pancreaticobiliary maljunction is thought to predispose to carcinogenesis, there is little data to confirm this hypothesis. In addition, no previously published study has addressed the process underlying cell proliferation. In this study, cell kinetics were first evaluated using two methods, proliferating cell nuclear antigen (PCNA) immunohistochemical staining and argyrophilic nucleolar organizer region (AgNOR) staining. Second, immunohistochemistry was used to investigate the expression of transforming growth factor-alpha (TGF alpha), a potential regulator of cell proliferation in the gall-bladder. The gall-bladders of 11 patients with pancreaticobiliary maljunction were studied, and 11 gall-bladders removed from patients during other surgery were used as controls. The number of PCNA-positive cells and the number of AgNOR per nucleus were significantly greater in the gall-bladders of patients with pancreaticobiliary maljunction than in the control gall-bladders. The expression of TGF alpha was also significantly greater in the gallbladders of patients with pancreaticobiliary maljunction than in the control gall-bladders. In conclusion, these results suggest that the increased TGF alpha expression induced by pancreaticobiliary maljunction promotes proliferation of the gall-bladder epithelium, which may lead to carcinogenesis.

Adolescent↗

Cortical hypometabolism and delayed myelination in West syndrome.

PURPOSE: We examined the relation between cortical hypometabolism and delayed myelination in patients with West syndrome (WS). METHODS: Serial positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG) and magnetic resonance imaging (MRI) were performed in 18 patients with WS, first at the onset of epileptic spasms and later at age 10 months. The age at onset of seizures ranged from 2 to 7 months. Ten patients were diagnosed as having cryptogenic WS and 8 as having symptomatic WS. RESULTS: Cortical hypometabolism was detected in many patients at onset of epilepsy, but disappeared later, whereas delayed myelination tended to become evident with age. PET showed diffuse or focal cortical hypometabolism in 12 patients at onset, but in only 6 patients at age 10 months. MRI showed delayed myelination in only 2 patients at onset of epilepsy, but the number of patients with delayed myelination increased to 12 at age 10 months. Delayed myelination was more often present in patients with cortical hypometabolism. Delayed myelination was noted in 11 (85%) of 13 patients with cortical hypometabolism on first or second PET scans, but in only 1 (20%) of 5 patients who did not show PET abnormalities. Hypometabolism on the first or second PET scan was positively correlated with delayed myelination at age 10 months. CONCLUSIONS: In patients with WS, assessing myelination with MRI again at age 8-10 months is important even when MRI at the onset of epilepsy appears normal. Serial MRI and PET scans disclose more detailed pathophysiology of WS.

Age of Onset↗

Tetrahydrobiopterin and GTP cyclohydrolase I in a rat model of endotoxic shock: relation to nitric oxide synthesis.

Induction of the inducible isoform of nitric oxide synthase (iNOS) in various types of cells is implicated as the cause of septic shock. We evaluated the concentration of tetrahydrobiopterin (BH4), a cofactor of NOS, in plasma and various other tissues of rats treated with lipopolysaccharide (LPS; 10 mg/kg I.V.). The activity of GTP cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in the de novo synthesis of BH4, in rat tissues was also determined. Three hours after administration of LPS, rats showed plasma levels of BH4 and NOx (NO3- and NO2-) that were elevated by 137 and 206%, respectively. GTPCH was expressed in liver and, to a lesser extent, in the lung, heart and kidney of control rats. In control rats, although a high concentration of BH4 was detected in the liver, its level was lower in lung, heart, kidney and aorta. Three hours after LPS administration, a significant increase in BH4 concentration and/or GTPCH activity was observed in all tissues examined except the liver. Our results demonstrate that the de novo synthesis of BH4 is upregulated by LPS in the rat in vivo, which may, at least in part, account for the increases in plasma level and tissue concentration of BH4 after the administration of LPS.

Anesthesia, General↗

[A novel RNA capture method for the extraction of HCV-RNA].

A novel method for the extraction of HCV-RNA by using DNA probe coated-latex microparticle (AmpliTex) was developed. This high density particle, with a large surface area, could be dispersed uniformly in a guanidium lysate of the serum. The DNA probe on the particles could hybridize with a few copies of HCV-RNA in the lysate. The RNA thus extracted on the particle can be subjected to the reverse-transcription and PCR reaction. Analytical sensitivity to detect HCV in serum was approximately 20 copies per ml. AmpliTex and the conventional organic extraction gave the same sensitivity and specificity (both 100%) to detect the HCV-RNA from fifty clinical specimens. It was also possible to extract the HCV-RNA from heparinated plasma.

DNA Probes↗

Successful vitrification of stroke-prone spontaneously hypertensive and normal Wistar rat 2-cell embryos.

Stroke-prone spontaneously hypertensive rats (SHRSPs) have been widely used as models of hypertension and cerebral apoplexy. They were obtained by selective sib-breeding of Wistar Kyoto rats with higher blood pressure than rats of the original Wistar Kyoto strain. For vitrification of SHRSP 2-cell embryos, DPS solution containing 2.75 M dimethylsulfoxide, 2.75 M propylene glycol and 1.0 M sucrose was prepared and diluted in a modified phosphate-buffered saline, PB1, containing 0.3% bovine serum albumin. Embryos were exposed to the resulting solution in one step at room temperature, kept in the solution for 15 s, vitrified in liquid nitrogen, and warmed rapidly. The post-warming survival rate as morphologically assessed was 70% (148/210), which was comparable (P > 0.05) to the rate of 88% (78/89) for the solution control. After vitrification, the embryos were transferred into recipient animals, and 62% (48/78) were normally delivered, comparable (P > 0.05) to the percentage for the solution control (68%, 57/84). These was no significant difference between pups from vitrified embryos and those from unvitrified control embryos in either the growth curve or degree of blood pressure increase. These findings demonstrate the effectiveness of the simple vitrification method we used for cryopreservation of SHRSP and Wistar rat 2-cell embryos, and also demonstrate that vitrification-mediated cryopreservation does not affect the phenotypic characteristics of SHRSPs.

Animals↗

Lip form responses to changes in maxillary incisor position.

A study was conducted to assess the measurement accuracy of a laser three-dimensional measurement system for measuring facial profile and to investigate the changes in lower facial morphology caused by experimental protrusion of the upper incisors, and also to examine the relationship between the changes in lip form and lip thickness. The study subjects were 24 Japanese male dental students attending Nihon University School of Dentistry at Matsudo, who had normal overbite, overjet, and normal occlusion, and a good facial profile. The mean age was 23.2 years with a range of 21.5 to 25.8 years. Three-dimensional measurements obtained by a computerized 3D laser scanning system were used to evaluate facial morphology. The measurement error of this system was less than 0.5 mm in any three-dimensional linear measurements. The stability and reproducibility of the recording procedure were evaluated. The changes in facial morphology caused by orthodontic treatment and orthognathic surgery were visualized in any direction by this three-dimensional graphic system. Lip thickness was not associated with changes in lip form. However, a relationship between the right and left corners of lip and lip thickness was noted. With regard to the ratio of changes in hard tissue and lips, the value of the original position for a 4 mm protrusion was not the same as that for a 4-8 mm protrusion. Also, the correlation of the changes in both groups was very low. The changes in lip thickness were associated with changes in stomion position, which in turn were related to the vertical change in the upper lip.

Adult↗

A second mutant allele of furin in the processing-incompetent cell line, LoVo. Evidence for involvement of the homo B domain in autocatalytic activation.

Furin is a Golgi membrane-associated endoprotease that is involved in cleavage of various precursor proteins predominantly at Arg-X-Lys/Arg-Arg sites. Furin itself is synthesized as an inactive precursor, which is activated through intramolecular autocatalytic cleavage at an Arg-X-Lys-Arg site. We previously found that human colon carcinoma LoVo cells have a frameshift mutation within the homo B domain of furin and thereby lack processing activity toward Arg-X-Lys/Arg-Arg sites. In this study, however, we identified a second furin mutation in this cell line. The mutation, a replacement of a conserved Trp residue within the homo B domain with Arg, results in lack of processing activity of the mutant furin. The combination of both mutations can account for the recessive nature of the processing incompetence of LoVo cells. Immunofluorescence analysis with three distinct anti-furin monoclonal antibodies revealed that neither furin mutant underwent the autocatalytic activation or left the endoplasmic reticulum for the Golgi. These data indicate that the homo B domain as well as the catalytic domain is required for autocatalytic activation of furin.

Amino Acid Sequence↗

Lipopolysaccharide treatment in vivo induces tissue expression of GTP cyclohydrolase I mRNA.

A significant induction of GTP cyclohydrolase I (GTPCH) mRNA was observed in lung, heart and kidney of rats treated with lipopolysaccharide (LPS; 10 mg/kg i.v.). GTPCH mRNA levels in liver were high even in untreated rats, and remained elevated after LPS treatment. Parallel induction of nitric oxide synthase (NOS) mRNA was observed in these tissues of LPS-treated rats. Our results demonstrate induction of GTPCH mRNA after LPS treatment in vivo and provide molecular evidence for the increased GTPCH activity which may up-regulate NOS activity in vivo.

Amino Acid Oxidoreductases↗