Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 127 records · Page 7Linked to original sources

PubMed1999

[Thermo-chemotherapy using low-dose CPT-11 in a patient with local recurrence of rectal cancer].

We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.

Adenocarcinoma↗

PubMed1999

[Diagnosis of magnetic resonance imaging (MRI) for blowout fracture--three advantages of MRI].

INTRODUCTION: Magnetic resonance imaging (MRI) gives a much more detailed picture of the soft tissue than computerized tomography (CT). In blowout fracture cases, it is very easy to observe the incarcerated orbital tissue. SUBJECTS: We performed MRI in 19 blowout fracture cases. RESULTS: After evaluating the images, we found three advantages of MRI. The first is that even small herniation of the orbital contents can easily be detected because the orbital fatty tissue contrasts well around the other tissues in MRI. The second is that the incarcerated tissues can be clearly differentiated because a clear contrast between the orbital fatty tissue and the extraocular muscle can be seen in MRI. The third is that the running images of the incarcerated muscle belly can be observed because any necessary directional slies can be taken in MRI. CONCLUSION: These advantages are very important in the diagnosis of blowout fractures. MRI should be employed in blowout fracture cases in addition to CT.

Adolescent↗

PubMed1999

[Primary pulmonary cryptococcosis diagnosed by medical examinations in 12 patients].

Primary pulmonary cryptococcosis is thought to be relatively less common than other lung mycoses, but recently there has been an increase in reports of patients with this disease. Our report covers 12 cases of primary pulmonary cryptococcosis in which the diagnosis was based on medical examinations. The patients consisted of 11 men and 1 woman, aged 27 to 58 years. Only 3 exhibited subjective symptoms. Roentgenograms showed cavitating tumor shadows in the lungs of 2 of the patients with subjective symptoms, and nodular shadows with diameters of 1.0 to 2.8 cm in all patients without subjective symptoms, indicating the possibility of lung cancer. The disease was diagnosed in 3 patients on the basis of transbronchial biopsy findings, and in 9 on the basis of needle aspiration biopsy findings. One patient was diabetic, but the others did not exhibit malignancies or other immunocompromised states. Antifungal drugs significantly reduced or eliminated the nodular shadows in 10 patients. Because patients with primary pulmonary cryptococcosis frequently lack subjective symptoms, prompt diagnosis is critical, particularly in view of the need to distinguish the disease from lung cancer.

Adult↗

PubMed1998

Coiled-coil interaction of N-terminal 36 residues of cyclase-associated protein with adenylyl cyclase is sufficient for its function in Saccharomyces cerevisiae ras pathway.

In the budding yeast Saccharomyces cerevisiae, association with the 70-kDa cyclase-associated protein (CAP) is required for proper response of adenylyl cyclase to Ras proteins. We show here that a small segment comprising the N-terminal 36 amino acid residues of CAP is sufficient for association with adenylyl cyclase as well as for its function in the Ras-adenylyl cyclase pathway as assayed by the ability to confer RAS2(Val-19)-dependent heat shock sensitivity to yeast cells. The CAP-binding site of adenylyl cyclase was mapped to a segment of 119 amino acid residues near its C terminus. Both of these regions contained tandem repetitions of a heptad motif alphaXXalphaXXX (where alpha represents a hydrophobic amino acid and X represents any amino acid), suggesting a coiled-coil interaction. When mutants of CAP defective in associating with adenylyl cyclase were isolated by screening of a pool of randomly mutagenized CAP, they were found to carry substitution mutations in one of the key hydrophobic residues in the heptad repeats. Furthermore, mutations of the key hydrophobic residues in the heptad repeats of adenylyl cyclase also resulted in loss of association with CAP. These results indicate the coiled-coil mechanism as a basis of the CAP-adenylyl cyclase interaction.

Adaptor Proteins, Signal Transducing↗

PubMed1998

cDNA cloning and expression during development of Drosophila melanogaster MCM3, MCM6 and MCM7.

cDNAs encoding three Drosophila melanogaster MCM proteins, DmMCM3, DmMCM6 and DmMCM7, candidates of DNA replication-licensing factors, were cloned and sequenced. The deduced amino-acid sequences displayed 60, 59 and 68% identities with the respective Xenopus laevis homologues, XMCM3, XMCM6 and XMCM7. Six members of the D. melanogaster MCM family were found to share 31-36% identities in their amino-acid sequences, and to possess the five common domains carrying conserved amino-acid sequences as reported with X. laevis MCM proteins. DmMCM3, DmMCM6 and DmMCM7 genes were mapped to the 4F region on the X chromosome, the 6B region on the X chromosome and the 66E region on the third chromosome, respectively, by in situ hybridization. Contents of their mRNAs were proved to be high in unfertilized eggs and early embryos (0-4h after fertilization), then decrease gradually by the 12h time point, with only low levels detected at later stages of development except in adult females. This fluctuation pattern is similar to those of genes for proteins involved in DNA replication, such as DNA polymerase alpha and proliferating cell nuclear antigen, suggesting that expression of DmMCM genes is under the regulatory mechanism which regulates expression of other genes involved in DNA replication.

Amino Acid Sequence↗

PubMed1998

Organ and development related difference in tissue norepinephrine concentrations in Dahl rats.

To determine organ and development related differences in tissue norepinephrine concentration (tNE) in Dahl salt-sensitive (S) and -resistant (R) rats, we measured the tNE of 16 organs, including the heart (left ventricle), kidney, cerebrum, brain stem, stomach, jejunum, ileum, colon, spleen, pancreas, liver, aorta, lung, bone, salivary gland, and muscle, at 1, 3, 5, 7, 9, 11 weeks old. Large differences were found in tNE among the organs of both S and R rats, ranging from 4.0 +/- 1.1 ng/g tissue (the bone of S rats) to 1234.8 +/- 32.5 ng/g tissue (the salivary gland of R rats). tNE in R rats increased development-dependently in 12 of 16 organs, but did not significantly change in the other three organs, and decreased in the bone. On the other hand, the development-dependent increase in tNE was suppressed in S rats, and the tNE values of S rats were significantly lower than those of R rats in 14 of 16 organs. To eliminate the baroreflexive effects on tNE, another group of 5-week-old S and R rats were subjected to sinoaortic denervation (SAD) or the sham operation. The tNE was measured in 10 organs in these animals at 9 weeks old. SAD did not alter the tNE in most of the organs in both S and R rats. There was no significant differences in mean arterial pressure (MAP) between S and R rats with baroreceptor intact at 9 weeks old. SAD slightly but significantly increased MAP in S rats, whereas not in R rats. There was no significant differences in plasma NE concentration (pNE) between S and R rats with the baroreceptor intact. SAD did not alter pNE in S or R rats. These results demonstrate that variations of the tNE were dependent on the organ and development. Many organs of S rats had lower tNE than those of R rats. The developmental-dependent increases in tNE in S rats were suppressed, compared with those in R rats. These tNE behaviors in S rats may not be related to blood pressure or baroreflex sensitivity, but might be involved in an abnormal sympathetic nerve activity.

Animals↗

PubMed1998

Role of endogenous endothelin in the development of graft arteriosclerosis in rat cardiac allografts: antiproliferative effects of bosentan, a nonselective endothelin receptor antagonist.

BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET-1) contributes to the development of graft arteriosclerosis and whether the orally active nonpeptide endothelin receptor antagonist bosentan, which blocks both ETA and ETB receptors, can protect against this pathologic damage. METHODS AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1 received heterotopic heart transplantations from Lewis donors and groups 2 and 3 received transplantations from Brown-Norway donors; group 3 recipients also received bosentan orally at the dose of 20 mg/kg per day for 120 days. All recipients were given cyclosporine and were euthanized at examination 120 days after transplantation. Plasma ET-1 levels were significantly higher in group 2 than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1 immunoreactivity was seen in both the thickened neointima and the media of the coronary arteries in group 2 but not in group 1. The mean ratio of the coronary luminal area to the total vascular area in group 2 (19.0+/-11.7%) was significantly lower than that in group 1 (34.2+/-9.9%) and was significantly increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local upregulation of ET-1, mainly in the thickened neointima and the media of the coronary arteries, may play an important role in the pathogenesis of graft arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally active bosentan might be a useful agent for the clinical prevention of graft arteriosclerosis.

Actins↗

PubMed1998

Timed markers for the differentiation of the cuticular plate and stereocilia in hair cells from the mouse inner ear.

The differentiation of the cuticular plate and stereocilia in cochleovestibular hair cells from the mouse was traced with monoclonal antibodies raised by in vitro immunization. The cuticular plate is detected first from embryonic days 14-15 (E14-E15), before cell differentiation is apparent, either with scanning electron microscopy or with actin filament labeling. A flat disc of material forms beneath the apical membrane and subsequently expands, forming a fully shaped cuticular plate at postnatal stages 3-5 (P3-P5). A second antibody labels stereocilia from stage E16 to E18. In the cochlea, the label initially appears as a punctate disc on the cell apex and then follows the development of the stereocilia until the adult shape of the bundle forms at P4-P6. Additional antibodies label stereocilia from P4 to P6 and are apparently specific for the inner ear. They do not label the cuticular plate at any stage and do not cross react with tissues of muscle, kidney, eye, tongue, gut, skin, or brain. At stage P12-P14, coinciding with the functional maturity of the ear, they label the apical regions of Deiter's cells. The temporally overlapping sequence of antibody labeling sheds new light on the development of the hair cell apex and allows us to monitor the differentiation of hair cells from their last mitotic division to the initiation of organ function, a period of over 2 weeks.

Actins↗

PubMed1998

Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells.

The pleiotropic biological activities of interleukin-18 (IL-18) are mediated by IL-18 receptor (IL-18R). When the ligand binds to the IL-18R, IL-18R initiates a signaling cascade that results in the activation of nuclear factor kappa B (NF-kappa B). When mouse EL-4 cells were exposed to IL-18, IL-1 receptor-associated kinase (IRAK) was recruited to IL-18R and was phosphorylated. In addition, tumor necrosis factor receptor-associated factor-6 (TRAF6) was associated with IRAK. Therefore, we concluded that IL-18/IL-18R-mediated signaling may share the IRAK/TRAF6 pathway through NF-kappa B activation with the IL-1/IL-1 receptor system.

Animals↗

PubMed1998

Sinoaortic denervation produces sodium retention in Dahl salt-sensitive rats.

The role of the arterial baroafferent signals in sodium (Na) homeostasis was examined in salt-sensitive rats. Sodium balances, water balances, and systolic arterial pressure (SAP) were measured for 3 weeks in sinoaortic denervated (SAD) or sham denervated (Sham) Dahl salt-sensitive (S) and salt-resistant (R) rats fed a standard-salt diet (0.4% NaCl). In R rats, there was no significant difference in Na balance, water balance, or SAP between the SAD and Sham animals. In the S rats, urinary Na excretion was suppressed in the SAD but not in the Sham animals, resulting in Na retention. SAD significantly increased SAP and mean arterial pressure. High salt challenge (8% NaCl diet) markedly increased SAP and Na and water balances in both S-SAD and S-Sham rats. However, no significant difference was found in SAP or cumulative Na and water balances between S-SAD and S-Sham rats. These results suggest that the baroafferent signals may have some role on the regulation of Na balance in salt-sensitive animals under a standard-salt condition, although a high-salt load masked the baroafferent-dependent sodium excretion.

Animals↗

PubMed1998

The gain of the hepatorenal reflex in anesthetized dogs.

To determine the overall gain of the hepatorenal reflex, hypertonic NaCl solutions were infused into the portal vein or inferior vena cava of anesthetized dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36 +/- 16 or 40 +/- 17 microeq/kg/30 min, respectively, while inferior vena caval infusion had no effect. With 13.5% NaCl infusion, a significant increase in the natriuretic response was seen with portal venous infusion, with no significant difference between portal venous and inferior vena caval infusion. Thus, the difference in the natriuretic response between portal venous and inferior vena caval infusion was dependent on the degree of input; when an appropriate input was given, natriuresis was induced only by portal venous infusion, probably mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was calculated from the output divided by the input. When 4.5% or 9% NaCl was infused into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38 +/- 0.15 or 0.34 +/- 0.14, respectively.

Animals↗

PubMed1998

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Age of Onset↗

PubMed1998

"Physiological" age as an outcome predictor for abdominal surgery in elderly patients.

It would seem that a large discrepancy exists between the "chronological" age and "apparent" age of elderly patients, and we often observe that the latter reflects the results of surgical procedures very well. In the present study, we reviewed 258 patients aged 70 years or older who underwent elective abdominal operations under general anesthesia, to evaluate an outcome predictor representing their "physiological" age. A total of 24 preoperative variables were compared between patients who left the hospital in a satisfactory condition, being survivors, and those who died in hospital despite the operative procedure performed, being nonsurvivors. In the group of patients aged between 70 and 79 years, there was no significant difference between the survivor and nonsurvivor groups for any of the variables examined; however, in the group of patients aged over 80 years old, the oldest of whom was 93 years, there were significant differences in the total lymphocyte count (TLC) and the performance status (PS), as well as in age, between the survivor and nonsurvivor groups. Utilizing the three variables of age, PS, and TLC, a computer-generated discriminant function analysis yielded an equation which discriminated survival with 97% accuracy, and mortality with 83% accuracy. These findings indicate that the PS and TLC scores added to the chronological age should be considered when deciding whether a surgical procedure is appropriate for an elderly patient.

Age Factors↗

PubMed1998

Role of Helicobacter pylori in residual gastritis after distal partial gastrectomy.

We studied the relation between Helicobacter pylori and residual gastritis in 28 patients with gastric cancer on whom distal partial gastrectomy with Billroth I reconstruction was performed over a 13-month period. They were subjected to serologic testing along with endoscopic and histologic examinations before operation and at 3, 6, and 12 months after operation. Anti-H. pylori immunoglobulin G (IgG) and serum gastrin levels were measured by serologic tests. The presence or absence of gastritis was determined endoscopically, and gastric mucosal hexosamine levels were determined. Gastritis was measured quantitatively by histologic examination in specimens taken from the gastric mucosa using Rauws' score. After the initial histologic evaluation we divided the H. pylori-positive patients into two groups: those with a Rauws' score of 0 to 3 ("weak" gastritis group), and those with a Rauws' score of 4 to 10 ("strong" gastritis group), allowing us to compare the results of our three postoperative histologic examinations of the two groups for possible significant differences. Our endoscopic examinations showed gastric mucosal inflammatory changes in both H. pylori-positive and H. pylori-negative patients at 3, 6, and 12 months after operation, but there was no significant difference between these two groups at any point. During the histologic examinations, however, anti-H. pylori IgG assay had become negative in several patients in the "weak" gastritis group at 3 months after operation and was found to have become negative in 78% of all patients in that group 12 months after operation. In contrast, in the "strong" gastritis group H. pylori infection was still evident in the patients 12 months after operation, suggesting that "strong" histologic gastritis may have some connection to H. pylori infection, whereas "weak" histologic gastritis has no such connection. The gastric mucosal hexosamine level was higher in the "weak" gastritis group than in the "strong" gastritis group both before operation and at 6 and 12 months, indicating some relation between gastric inflammatory changes and hexosamine levels in gastric mucosa. It further suggested the possibility that H. pylori plays a role in destroying gastric mucosa by depleting mucin, thus acting as one (though not the only) cause of residual gastritis after distal partial gastrectomy. In conclusion, we found evidence that there is a relation between residual gastritis and H. pylori infection, but H. pylori is not the sole cause of residual gastritis after gastric surgery. A causal relation is difficult to detect by simple analysis of histologic findings or by endoscopic observation or clinical symptoms alone.

Female↗

PubMed1998

Developmental expression of the tight junction protein, occludin, in the gastrointestinal tract of the chick embryo.

The developmental expression of occludin was studied biochemically in whole chick embryos to determine when intercellular tight junctions develop. Occludin mRNA was first detected after 3 days of incubation by the reverse transcriptase-polymerase chain reaction. On northern blot analysis, although occludin mRNA was not discernible in 3-day-old embryos, weak but clear expression was noted on day 4 of incubation and increased dramatically in 5-day-old embryos. Occludin was not detectable on days 3 or 4 of incubation by western blot analysis, and was first detected in 5-day-old embryos. In addition, the expression of occludin was examined immunohistochemically in the gastrointestinal tract of 3- to 21-day-old embryos. Immunoreactivity for occludin was not expressed on day 3 of incubation. On day 4 of incubation, weak immunoreactivity was demonstrated in the gastrointestinal tract, and gradually became stronger with development. By day 11 of incubation, a positive immunoreaction was obtained only on the apical surfaces of the epithelial cells, i.e., at the junctional complexes, while weak immunoreactivity was diffusely distributed throughout the epithelial cells. The possible roles of occludin in the developing gastrointestinal tract are discussed.

Animals↗

PubMed1998

Fatal rupture of the brachiocephalic artery in a dog.

A case of arterial rupture that caused sudden death in a 3-year-old dog is presented. Rupture of the brachiocephalic artery was located just distal to the origin of the left common carotid artery. Histological examination of the vessel wall revealed necrosis of the media.

Animals↗

PubMed1998

A novel Drosophila nuclear protein serine/threonine kinase expressed in the germline during its establishment.

Nuclear protein kinases are believed to play important roles in regulating gene expression. We report here the identification and developmental expression of Dmnk (Drosophila maternal nuclear kinase), a Drosophila gene encoding a putative nuclear protein serine/threonine kinase with no apparent homology to previously identified protein kinases and located at 38B on the second chromosome. Dmnk mRNAs are transcribed in nurse cells and are subsequently localized in the anterior of oocytes during oogenesis, in a manner similar to several maternal transcripts regulating oogenesis and early embryogenesis. At early cleavage-stages Dmnk transcripts are transiently present throughout the embryo, but become restricted to the posterior pole and then to the newly-formed primordial germ cells (pole cells) by the blastoderm stage. The transcripts are sustained in the pole cells during gastrulation until they pass through the midgut pocket wall into the body cavity. Immunostaining with specific antibodies revealed that Dmnk proteins are localized to the nuclei in a speckled pattern. Dmnk proteins become detectable in both somatic and germ line cell nuclei upon their arrival at the periplasm of the syncytial embryo, but then disappear from the somatic cell nuclei. Consistent with mRNA expression, Dmnk proteins in pole cell nuclei are sustained during gastrulation. Taken together, Dmnk represents a novel class of nuclear protein kinases and the dynamic expression of Dmnk suggests a role in germ line establishment. The results are discussed in the light of recent findings concerning germ line establishment in Caenorhabditis and Drosophila.

Alternative Splicing↗

PubMed1998

Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.

alpha-Mannosidosis is an autosomal recessive lysosomal-storage disorder caused by a deficiency of lysosomal alpha-mannosidase activity. This disease shows a wide range of clinical phenotypes, from a severe, infantile form (type I), which is fatal at <3-8 years of age, to a less severe, late-onset form (type II), which ultimately may involve hearing loss, coarse face, mental retardation, and hepatosplenomegaly. To elucidate the molecular mechanism underlying this disease in both types of patients, we have used PCR, followed by either SSCP analysis or direct sequencing, to analyze the 24 exons and intron/exon boundaries of the alpha-mannosidase gene (MANB) from five patients. Two amino acid substitutions-H72L and R750W, in exons 2 and 18, respectively-and two nonsense mutations-Q639X and R760X, in exons 15 and 19, respectively-were identified in four type II patients. One amino acid substitution, P356R, was identified in exon 8 from a type I patient. This patient and three of the type II patients were homozygous for their mutations (H72L, P356R, R750W, and R760X) and one type II patient was heterozygous for the Q639X and R750W mutations. Transfection experiments of COS 7 cells, using the alpha-mannosidase cDNA containing one of the missense mutations-H72L, P356R, or R750W-revealed that each of these mutations dramatically reduces the enzymatic activity of alpha-mannosidase. These data demonstrate that widely heterogeneous missense or nonsense mutations of the MANB gene are the molecular basis underlying alpha-mannosidosis.

Child↗