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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 19 recordsLinked to original sources

Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa.

Trefoil factor 2 (TFF2) is mucin associated peptide that has a mucosal barrier function in addition to participating in repair and healing. We examined the localization of TFF2 and gastric mucins in gastric mucous cells, the surface mucous gel layer (SMGL) adherent to normal gastric mucosa, and in the mucoid cap covering gastric erosions. Carnoy's solution, or formalin/picric acid-fixed paraffin embedded materials from resected stomachs and formalin-fixed paraffin embedded gastric biopsy materials were used. Sections were immunostained for the TFF2 and histochemically stained for gastric mucins. In addition, thick sectioned gastric mucosa fixed in Carnoy's solution were stained with FITC-labeled GSA-II lectin specific for gland mucous cell mucin and examined for three-dimensional images of the SMGL using a confocal laser scanning microscope. The TFF2 and gland mucous cell mucin were found intermixed together in the gastric gland mucous cells, in the SMGL in laminated layers, and in the mucoid cap. A laminated arrangement of continuous sheets of gland mucous cell mucin in the SMGL was demonstrated in the three-dimensional images. Co-localization of the TFF2 with gland mucous cell mucin suggests a physical interaction between the TFF2 and gland mucous cell mucin. The TFF2 trapped in the adherent mucins may be responsible for mucosal defense, healing, and repair.

Biopsy↗

Pathogenicity of a highly pathogenic avian influenza virus, A/chicken/Yamaguchi/7/04 (H5N1) in different species of birds and mammals.

Outbreaks of highly pathogenic avian influenza (HPAI) have been occurring in domestic poultry in Asia since 1996. In the beginning of 2004, HPAI outbreaks were caused by H5N1 virus in two farms and a group of pet chickens in different areas of Japan. In the present study, the pathogenicity of A/chicken/Yamaguchi/7/04 (H5N1), which had been isolated from a dead chicken during the first outbreak in Japan, was assessed in chickens, quails, budgerigars, ducklings, mice, and miniature pigs by experimental infection. The virus was highly pathogenic to all the birds tested. Mice were susceptible to infection with a low mortality rate and miniature pigs were resistant to infection with the virus.

Animals↗

Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at onset.

Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease.

Antineoplastic Agents↗

Functional characterization of Musca glutamate- and GABA-gated chloride channels expressed independently and coexpressed in Xenopus oocytes.

Ligand-gated chloride channels (LGICs) are important targets for insecticides and parasiticides. Genes encoding subunits of two LGICs, a glutamate-gated chloride channel (MdGluCl-alpha) and a gamma-aminobutyric acid (GABA)-gated chloride channel (MdRdl), were cloned from house-flies (Musca domestica L.). These genes were first expressed independently in Xenopus laevis oocytes by cRNA injection in order to investigate the pharmacology of these ligand-gated channels using two-electrode voltage-clamp electrophysiology. It was found that L-glutamate and GABA activated the MdGluCl-alpha homo-oligomers with an EC(50) value of 30 microM and the MdRdl homo-oligomers with an EC(50) value of 101 microM, respectively. Both channels were chloride ion-permeable, and the MdRdl channel was more sensitive to chloride channel blockers, such as gamma-hexachlorocyclohexane (gamma-HCH), fipronil and picrotoxinin, than the MdGluCl-alpha channel. MdGluCl-alpha required only 1-2 days of incubation after cRNA injection to be expressed in oocytes, whereas 4-7 days of incubation was necessary to achieve MdRdl expression. However, when the cRNA of MdGluCl-alpha was injected at a dose of 1% (w/w) 1 day after the injection of the cRNA of MdRdl, a significant increase in the current amplitude of responses to GABA was observed, and the incubation period necessary for MdRdl expression became shorter. These results suggest that MdGluCl-alpha assists in the expression of MdRdl when the two are coexpressed.

Animals↗

Regulation by orexin of feeding behaviour and locomotor activity in the goldfish.

Orexin is a hypothalamic neuropeptide that is implicated in the regulation of feeding behaviour and the sleep-wakefulness cycle in mammals. However, in spite of a growing body of knowledge concerning orexin in mammals, the orexin system and its function have not been well studied in lower vertebrates. In the present study, we first examined the effect of feeding status on the orexin-like immunoreactivity (orexin-LI) and the expression of orexin mRNA in the goldfish brain. The number of cells showing orexin-LI in the hypothalamus of goldfish brain showed a significant increase in fasted fish and a significant decrease in glucose-injected fish. The expression level of orexin mRNA in the brains of fasted fish increased compared to that of fed fish. We also examined the effect of an i.c.v. injection of orexin or an anti-orexin serum on food intake and locomotor activity in the goldfish. Administration of orexin by i.c.v. injection induced a significant increase of food intake and locomotor activity, whereas i.p. injection of glucose or i.c.v. injection of anti-orexin serum decreased food consumption. These results indicate that the orexin functions as an orexigenic factor in the goldfish brain.

Animals↗

Association of candidal activity with denture use and salivary flow in symptom-free adults over 60 years.

The purpose of this study was to examine the amount of palatal mucosa Candida species associated with denture use and stimulated salivary flow in symptom-free adults over 60 years. The subjects were 351 (189 men and 162 women) independently living elderly people with a mean age of 66.7 +/- 4.3 (SD) years. Candidal activity of palatal mucosa was evaluated by the pH change in the medium that was associated with the acid production of the yeast. Subjects whose stimulated salivary flow rate was less than 0.5 ml/min were placed in the hyposalivation group. A multiple logistic regression analysis was used to determine if an independent variable was statistically significant after controlling for other variables. Candidal activity of the palatal mucosa was significantly associated with the dental status of the maxillae (Kruskal-Wallis test, P < 0.001), but was not significantly associated with age or drug intake. In maxillary denture wearers, Candidal activity of palatal mucosa had a significantly positive correlation with candidal activity of tissue fitting surfaces of maxillary dentures (r = 0.806, P < 0.001). A multiple logistic regression analysis showed that high candidal activity of the palate was significantly associated with being male and wearing maxillary removable dentures. Stimulated salivary flow rate was likely to be negatively related to high candidal activity (P = 0.07). This study suggests that the activity of Candida species in the oral cavity is associated with the wearing of removable dentures and stimulated salivary flow, independent of age or gender even in the relatively healthy elderly.

Aged↗

Medullary sponge kidney in a 10-year-old Shih Tzu dog.

Medullary sponge kidney was diagnosed in a 10-year-old male Shih Tzu dog with a long history of hyposthenuria, but with no other findings indicating renal failure or hormonal aberration. At the dog's death from heart failure, an autopsy was performed. On gross morphology, bilateral kidneys were normal size and had many cysts ranging from the corticomedullary junction to renal papillae. Histopathologic findings showed that almost all of the cysts were lined by monolayered or multilayered and columnar or cuboidal epithelium with chilium similar to epididymis. Immunohistochemically, all of these cells were strongly positive for AE1/AE3 and negative for vimentin. Many of these cells were positive for cytokeratin 7 (CK7), and only a few cells were positive for desmin. The results of staining are the same as those for epithelium of the collecting duct of normal canine kidney. This is the first report of this pathologic entity in the canine kidney.

Animals↗

[Impending rupture of aneurysm of Salmonella-infected aortic arch].

We report a case of a 67-year-old man with Salmonella infected aortic arch aneurysm. The patient presented with persistent high fever, chest pain, back pain and hoarseness. Laboratory studies showed the presence of severe inflammation. Both impending rupture and saccular aneurysm were suspected by preoperative computed tomography (CT), magnetic resonance imaging (MRI) and angiography and diagnosis was, therefore difficult to make. We conducted semi-emergency total aortic arch replacement, under deep hypothermic circulatory arrest and retrograde cerebral perfusion. Salmonella was identified in the aneurysmal wall and antibiotics were administered for 6 weeks until CRP was normalized, when they were replaced by oral antibiotics. Postoperative course was uneventful. The patient was discharged on the 60th postoperative day. He continues to take oral antibiotics.

Aged↗

Developmental changes in the expression of growth-associated protein-43 mRNA in the monkey thalamus: northern blot and in situ hybridization studies.

The expression of growth-associated protein-43 has been related to axonal elongation and synaptic sprouting. Using the Northern blot analysis, we investigated the developmental changes of growth-associated protein-43 mRNA in the thalamus of macaque monkeys. The amount of growth-associated protein-43 mRNA was high at embryonic day 125, and decreased at postnatal day 1. It increased again at postnatal day 8, reached its peak value at postnatal days 50-70, and then decreased gradually until postnatal year 1. We previously reported that the amount of growth-associated protein-43 mRNA in the cerebral cortex decreased roughly exponentially during perinatal and postnatal periods and that it approached the asymptote by postnatal day 70 [Oishi T, Higo N, Umino Y, Matsuda K, Hayashi M (1998) Development of GAP-43 mRNA in the macaque cerebral cortex. Dev Brain Res 109:87-97]. The present findings may indicate that extensive synaptic growth of thalamic neurons continues even after that of cortical neurons has finished. We then performed in situ hybridization to investigate whether the expression level of growth-associated protein-43 mRNA was different among various thalamic nuclei. In the infant thalamus (postnatal days 70-90), moderate to intense expression of growth-associated protein-43 mRNA was detected in all thalamic nuclei. Quantitative analysis in the infant thalamus indicated that the expression levels were different between the nuclear groups that are defined by the origin of their afferents. The expression in the first order nuclei, which receive their primary afferent fibers from ascending pathways [Guillery RW (1995) Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review. J Anat 187 (Pt 3):583-592], was significantly higher than that in the higher order nuclei. While moderate expression was also detected in the adult dorsal thalamus, the expression in the first order nuclei was almost the same as that in the higher order nuclei. Thus, the in situ hybridization experiments indicated that the transient postnatal increase in the amount of growth-associated protein-43 mRNA, which was shown by the Northern blot analysis, was mainly attributed to enhanced expression in the first order nuclei during the postnatal period. This may be a molecular basis for environmentally induced modification of thalamocortical synapses.

Animals↗

Three-dimensional computer-aided design based design sensitivity analysis and shape optimization of the stem using adaptive p-method.

The number of stem designs for total hip arthroplasty is increasing, and occasionally design changes have yielded unexpected clinical results. At present, we are not able to clearly identify which parameter of the stem is most important, and the optimum value of many parameters. The goals of this study were to identify which parameter is most important, to understand the effect of design change, and to find the optimum stem shape. For this purpose, we used adaptive p-method together with three-dimensional computer-aided design software program for the design sensitivity analysis (DSA) and shape optimization of the stem. The results suggested that increasing the lateral and medial width of the distal cross-section together with decreasing the medial-lateral width and the medial radius of the distal cross-section from the default value would lead to a decrease in the largest maximum principal stress of the distal cement. The medial width of middle cross-section, however, was not so simple. The result of DSA suggested that decreasing this parameter from the default value decreased the stress in the distal cement, but the optimum shape was obtained by increasing this parameter. The method used in this study will assist our engineers and surgeons in the process of modifying and optimizing the stem design.

Arthroplasty, Replacement, Hip↗

Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA).

Gefitinib (IRESSA), an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor, has antitumour activity in the advanced non-small-cell lung cancer (NSCLC) setting. However, in chemotherapy-naïve patients with advanced NSCLC, the addition of gefitinib to standard chemotherapy regimens failed to increase survival. These results suggest the need for improved patient selection and combination rationales for targeted therapies. We have identified subpopulations of an adenocarcinoma cell line that are naturally resistant to gefitinib, and have analysed the cDNA expression profiles, genomic status of EGFR gene and the effect of gefitinib on signalling pathways in these cell lines in order to identify key mechanisms for naturally acquired resistance to gefitinib. Gefitinib-resistant subpopulations demonstrated increased Akt phosphorylation (not inhibited by gefitinib), reduced PTEN protein expression and loss of the EGFR gene mutation when compared with parental cell lines. These differences in Akt and PTEN protein expression were not evident from the cDNA array profiles. These data suggests that (1) the EGFR gene mutation may be possibly lost in some cancer cells with other additional mechanisms for activating Akt, (2) reintroduction of PTEN or pharmacological downregulation of the constitutive PI3K-Akt-pathway activity may be an attractive therapeutic strategy in cancers with gefitinib resistance.

Adenocarcinoma↗

Pathogenicity of H5 influenza viruses for ducks.

Four H5N1 highly pathogenic avian influenza (HPAI) viruses and an avirulent reassortant H5N1 virus were tested for their pathogenicity in domestic ducks. A/chicken/Yamaguchi/7/04 (H5N1) (Ck/Yamaguchi/04) isolated from a dead bird during the HPAI outbreak in Japan and A/duck/Yokohama/aq-10/03 (H5N1) (Dk/Yokohama/03) isolated from duck meat at a quarantine inspection for importation from China replicated in multiple organs including the brain of ducks. The ducks infected with Ck/Yamaguchi/04 did not show any clinical signs, while those infected with Dk/Yokohama/03 showed neurological signs. The ducks infected either with A/Hong Kong/483/97 (H5N1) or A/tern/South Africa/61 (H5N3), or with an avirulent H5N1 reassortant, did not show any clinical signs. Virus-specific antibodies were detected in the sera of the ducks infected with each of the five strains tested, indicating that all of the viral strains infected and replicated in the birds. Dk/Yokohama/03 grew in multiple organs more rapidly than did Ck/Yamaguchi/04. Considerable titers of virus were detected in the brain of the ducks infected with Dk/Yokohama/03 and these birds showed neurological signs. The present results demonstrate that the pathogenicity of influenza viruses for ducks does not correlate with that for chickens and that replication of the virus in the brain is critical for ducks to show neurological signs.

Animals↗

Edit, cut and paste in the nicotinic acetylcholine receptor gene family of Drosophila melanogaster.

Nicotinic acetylcholine receptors (nAChRs) are important for fast synaptic cholinergic transmission. They are targets of drugs/chemicals for human and animal health as well as for pest control. With the advent of genome sequencing, entire nAChR gene families have now been described for vertebrates and invertebrates. Mostly, these are extensive with a large number of distinct subunits, making possible many nAChR subtypes differing in transmitter affinity, channel conductance, ion selectivity, desensitization, modulation and pharmacology. The smallest nAChR gene family to date is that of the fruit fly, Drosophila melanogaster, with only 10 members. This apparently compact family belies its true diversity as 4 of the 10 subunits show alternative splicing. Also, using Drosophila, A-to-I pre-mRNA editing has been demonstrated for the first time in nAChRs. Such is the extent of this variation, that one subunit alone (Dalpha6) can potentially generate far more isoforms than seen in entire gene families from other species. We present here three-dimensional models constructed for insect nAChRs, which show that many variations introduced by alternative splicing and RNA editing may influence receptor function.

Alternative Splicing↗

Fast sound in expanded fluid Hg accompanying the metal-nonmetal transition.

The dynamic structure factor S(Q,omega) of expanded fluid Hg has been measured up to the metal-nonmetal transition region at 9.0 g cm(-3) (1723 K and 1940 bars) using high-resolution inelastic x-ray scattering, at momentum transfers, Q, from 0.2 to 4.8 A(-1). Analysis in the framework of generalized hydrodynamics reveals that the frequencies of the collective excitations increase faster with Q than estimated from the macroscopic speed of sound. The effective sound velocity at 9.0 g cm(-3) estimated from the dispersion relation is triple the ultrasonic sound velocity. The present result suggests the existence of fast sound in expanded fluid Hg accompanying the metal-nonmetal transition.

Mercury↗

Mini-incision posterior approach for total hip arthroplasty.

We compared the short-term outcomes of 50 total hip arthroplasties performed through a mini-incision posterior approach with those of 42 arthroplasties performed through a conventional posterior approach. There were no significant differences in age, gender, and bodymass index between groups. The mean operative time was shorter (99+/-26 versus 123+/-30 min), and the peroperative mean blood loss was smaller with the mini-incision (339+/-210 versus 422+/-177 ml). There was no significant difference between groups in post-operative mean blood loss, mean inclination angle of acetabular components, percentage of hips with good inclination angle, and mean hip score at 6 months after surgery. There was one infection in the conventional group but none in the mini group. There were no dislocations or symptomatic pulmonary embolism in either group. With the mini-incision posterior approach, surgical invasion was reduced, and short-term outcome was as good as with a conventional posterior approach.

Arthroplasty, Replacement, Hip↗

Combination of transconjunctival and endonasal-transantral approach in the repair of blowout fractures involving the orbital floor.

In the repair of orbital blowout fractures through eyelid or conjunctival incision, it is difficult to see the posterior edge of the fracture and the condition of the herniated tissue before reduction of the orbital contents. Prolapsed orbital tissue or infraorbital nerve and vessels may therefore be damaged in the reduction. The recently advocated combination of traditional transconjunctival approach and endoscopic transantral approach allows reduction and reconstruction under clear endoscopic vision without a facial skin incision. We modified this technique to make it less invasive and applied it to the repair of orbital blowout fractures involving the orbital floor. The use of a 70-degree straight endoscope through an enlarged ostium as for functional sinus surgery allowed clear sight of the roof of the antrum. During the repair of the orbital floor through a transconjunctival approach, reduction and reconstruction was assisted from the antrum. Twelve cases of fresh blowout fractures were treated with this approach. There were seven male and five female patients. Mean age was 23.5 years. Causes of injuries were fights, motor vehicle or bicycle accidents, and sports. Patients with concomitant fractures involving the orbital rim were excluded. Persistent diplopia was present in eight cases and enophthalmos of more than 2 mm was detected in five cases preoperatively. The average intervals from injury to surgery was 22.8 days.Exploration, reduction and reconstruction of the orbital floor fractures were precisely performed with this procedure. Large orbital floor defects were reconstructed with silicone sheets, thin iliac bone grafts or nasal septal cartilage. In all eight cases that showed diplopia, ocular movement recovered and symptomatic diplopia disappeared after surgery. Enophthalmos of more than 2 mm was also improved in all five cases. One early case showed temporary entropion. Transient numbness of the cheek appeared in five cases and temporary maxillary sinusitis recovered in one case. Postoperative infection was not observed.This method provides visualisation of posterior edge of the fracture and the condition of herniated orbital contents before initiation of reduction. Dual manipulation by two surgeons is also possible in reduction and reconstruction of the orbital floor.

Adolescent↗

Northern blot and in situ hybridization analyses for the development of myristoylated alanine-rich c-kinase substrate mRNA in the monkey cerebral cortex.

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major neuron-specific substrate for protein kinase C, and is involved in both neurite outgrowth and synaptic plasticity. Using both Northern blot and in situ hybridization techniques, we investigated whether the expression of MARCKS mRNA in the monkey cerebral neocortex and hippocampus changed during the developmental period. In each of four neocortical areas examined, i.e. the prefrontal area (area FD of [Illinois Monographs in the Medical Sciences (1947) 1]), the temporal association area (TE), the primary somatosensory area (PB), and the primary visual area (OC), the Northern blot analysis showed that the amount of MARCKS mRNA was high during the fetal and early postnatal periods, and decreased sharply between postnatal day 70 and postnatal month 6. The in situ hybridization experiments showed that the expression of MARCKS mRNA was decreased in every layer of neocortical areas at postnatal month 6 or later. In the primary sensory areas (areas PB and OC), the degree of decrease was higher in the supragranular layers (layers II and III) than in the infragranular layers (layers V and VI). In the hippocampus, the developmental change in the amount of MARCKS mRNA was small, but the in situ hybridization revealed a prominent decrease in Ammon's horn in monkeys on postnatal month 8 and later. These findings indicate that region-specific expression of MARCKS mRNA is established around postnatal month 6. We suggest that the extensive expression of MARCKS mRNA is one of the molecular bases of high plasticity in the infant cerebral cortex.

Animals↗