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Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 397 records · Page 22Linked to original sources

Expression of the cyclooxygenase-2 gene in gastric epithelium.

This study examined the mRNA level of cyclooxygenase-2 (cox-2) in a rat gastric mucosal cell line after growth stimulation in vitro and in rat gastric mucosa before and after acid-induced injury in vivo. RGMI cells were stimulated with fetal calf serum in the in vitro study. Thereafter, the cox-2 mRNA level was examined by Northern analysis. Effects of NS-398, a specific inhibitor of cox-2, and indomethacin on prostaglandin production and cell proliferation were examined in RGM1 cells. In the in vivo study, rats were given 1 ml of 0.6 N hydrochloric acid into the stomach. The level of cox-2 mRNA was examined in rat gastric mucosa after acid administration. Cox-2 mRNA increased 20-60 min after growth stimulation in RGM1 cells. Both NS-398 and indomethacin suppressed prostaglandin production and cell proliferation after growth stimulation. Expression of cox-2 mRNA was observed 40 and 60 min after administration of 0.6 N HCl. Gastric lesions developed within 60 min after HCl administration and healed significantly within 48 h. The present study shows the expression of cox-2 in gastric epithelial cells in vitro and in gastric mucosa after injury in vivo. The results also suggest that cox-2 is involved in de novo synthesis of prostaglandins and cell proliferation in gastric epithelium.

Animals↗

Helicobacter pylori and gastric carcinogenesis.

This article consists of three independent studies regarding Helicobacter pylori-related gastric carcinogenesis. Ammonia, a Helicobacter product, promoted chemically induced gastric carcinogenesis in animals. Moreover, an extract of Helicobacter stimulated inflammatory production of nitric oxide (NO), a potent mutagen that causes G:C-->A:T transition. Meta-analysis of recent studies demonstrated that G:C-->A:T transition is one of the most common mutations in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. Therefore, bacterial factors such as ammonia and host factors, including inflammatory NO production, might play important roles in H. pylori-induced gastric carcinogenesis.

Ammonia↗

Mutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families in Japan.

We analyzed the alteration of BRCA1 in DNA obtained from 83 individuals of 13 Japanese site-specific ovarian cancer families and 6 breast-ovarian cancer families. Six germline mutations were detected in 7 families, which consisted of 4 breast-ovarian cancer and 3 site-specific ovarian cancer families, by single-strand conformation polymorphism analysis, followed by direct sequence determination. The mutations included three frameshifts, two nonsense mutations, and one missense mutation causing loss of a zinc-binding motif. The frequency of loss of heterozygosity at the microsatellite markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, and 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying a mutation of BRCA1 showed deletion of wild-type alleles, implicating BRCA1 as a tumor suppressor gene. These results suggest that germline mutations of the BRCA1 gene play an important role in the carcinogenesis of breast and/or ovarian cancer in a majority of breast-ovarian cancer families and in some site-specific ovarian cancer families.

Adult↗

Possible migration of harderian gland immunoglobulin A bearing lymphocytes into the caecal tonsil in chickens.

This study was designed to evaluate the significance of the Harderian gland (HG) in the chicken IgA-production system by investigating the influence of HG on the increase of surface IgA (sIgA)-positive cells in other lymphoid organs and also the possibility of migration of HG lymphocytes into other organs. Non-contact culture of splenic or caecal tonsil (CT) lymphocytes with HG whole cells did not enhance the expression of sIgA. The experiment of HG lymphocyte transfer showed that the transferred HG lymphocytes migrated mainly into the CT in the 3-week-old recipient, and mainly into the CT and bursa of Fabricius (BF) in the 6-week-old recipient. It was also found that the transferred sIgA-positive HG lymphocytes migrated selectively into CT in both 3-week-old and 6-week-old recipients. These results indicated that chicken HG plays a central role not only in governing the local immunity in the eyes and respiratory tract but also as an organ which supplies precursory IgA-producing cells involved in local immunity in the intestine.

Animals↗

Immunopotentiating activities of polysaccharide fraction from pine seed shell extract.

The function of polysaccharide (PSE) extracted from pine seed shells as a immunopotentiator was investigated. The phagocytosis and chemotaxis of mouse peritoneal macrophages (MP) were augmented by oral administration of PSE. The incorporation of 3H-thymidine by Con A-stimulated mouse splenic cells was significantly intensified by administration of PSE but the adherent-cells (MP)-eliminated splenic lymphocytes was not increased. It is shown that the existence of activated MP is needed for the activation (proliferation) of T lymphocytes. The responsiveness of mouse T cells to alloantigen was also augmented by administration of PSE. The number of anti-SRBC plaque-forming cells in the spleen of mouse and chicken was also significantly increased. The results indicate that MP are first activated by oral administration of PSE and that the activation of T cells is then initiated indirectly by humoral factors (cytokines) produced by activated MP.

Adjuvants, Immunologic↗

Relationship between interleukin-8 levels and myeloperoxidase activity in human gastric mucosa.

Although interleukin (IL)-8 is well known as a chemotactic agent for neutrophil migration in vitro, the relationship between IL-8 activity and the degree of neutrophil infiltration in gastric mucosa is still unclear. In the present study, we investigated IL-8 and myeloperoxidase activity, a marker of neutrophil infiltration, in gastric antral mucosa using biopsy samples in 23 patients with no gastric lesions. The results indicate that there is a good correlation between IL-8 and myeloperoxidase activity (y = 0.173x + 13.9; r = 0.49, P < 0.01). Furthermore, IL-8 and myeloperoxidase activity are significantly higher in Helicobacter pylori-positive patients than in H. pylori-negative patients. In conclusion, an increase of IL-8 activity in the gastric mucosa causes increased neutrophil infiltration in human gastric mucosa and H. pylori infection accelerates these reactions in the mucosa.

Aged↗

Dedifferentiated liposarcoma with an inflammatory malignant fibrous histiocytoma-like component presenting a leukemoid reaction.

A rare case of dedifferentiated liposarcoma (well-differentiated liposarcoma with an inflammatory malignant fibrous histiocytoma (MFH)-like anaplastic component) occurring in a 69-year-old male is presented. The patient had noticed a dull pain in his left loin and thigh for about 1 month. Computed tomography examination revealed a low-density mass lesion, measuring about 6 cm in diameter, in the left iliopsoas muscle, and it was surgically removed. Grossly, the lesion was composed of an encapsulated, soft, whitish mass and an adjacent, well-demarcated, yellowish hard nodule, measuring about 2.5 cm in diameter. Microscopically, both lesions showed features of an inflammatory variant of MFH and a sclerosing type of well-differentiated liposarcoma, respectively. To our knowledge, only two cases of dedifferentiated liposarcoma combined with inflammatory MFH as a dedifferentiated component have been recorded in the literature. The salient feature of the present case is a systemic inflammatory reaction, as shown by prominent leukocytosis (up to 73,900/mm3) and the elevated serum value of C reactive protein (up to 26.0 mg/dL), which were transiently reduced after surgery. The inflammatory reaction was suggested to be induced by cytokines, such as granulocyte colony-stimulating factor and interleukin-6, which were probably produced by the tumor cells in the present case, because the elevated serum values of those cytokines were decreased after surgery.

Aged↗

Clinical features of familial diffuse Lewy body disease.

We present 5 patients from two families with familial autosomal dominant diffuse Lewy body disease. All 5 patients initially showed parkinsonian symptoms that responded well to levodopa therapy; however, dementia followed and later progressed. In 3 patients, the disease was manifested before age 40 years, exhibiting wearing-off phenomenon and choreic limb dyskinesia. One patient was examined neuropathologically, and brain stem lesions compatible with Parkinson's disease were revealed, and Lewy bodies and senile plaques were found in the cerebral cortex. Familial cases of diffuse Lewy body disease may provide some explanation of the pathogenesis of this disease.

Adult↗

Slowly progressive limb-kinetic apraxia.

The case of a 69-year-old female with slowly progressive limb-kinetic apraxia (LKA) of the right hand over 3.5 years is reported. She did not show any other neurological or neuropsychological symptoms except for a defect in two-point discrimination, and 3.5 years after onset she developed a slight cogwheel-like muscle tone in the right wrist. Brain MRI revealed atrophic changes in the left central region including the precentral and postcentral gyri and the superior parietal region, and among them, most strikingly at the postcentral gyrus. 123I-IMP SPECT revealed decreased 123I uptake in the atrophic lesion as revealed by MRI. We should suspect corticobasal degeneration as the etiology for this patient taking her symptoms and findings on MRI and SPECT into consideration. However, her symptoms and course were quite unique among the case reports of patients with slowly progressive LKA as she had only LKA and a defect in two-point discrimination for more than 3.5 years without any other symptoms. This characteristic also indicated that the simultaneous appearance of LKA and a defect in two-point discrimination may suggest a mechanism of LKA in the present patient.

Aged↗

Machado-Joseph disease in four Chinese pedigrees: molecular analysis of 15 patients including two juvenile cases and clinical correlations.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder associated with the expansion of a (CAG)n array in the MJD1 gene. We analyzed the sizes of the (CAG)n array using DNA samples from 61 members of four Chinese MJD families and 18 Chinese normal control subjects and confirmed that the (CAG)n array in 15 MJD chromosomes was expanded to 72-86 repeat units. There were no subjects with (CAG)n array sizes intermediate between those of normal and MJD affected groups. Meanwhile, we found a significant negative correlation between the age of onset of symptoms and (CAG)n array size. The largest (CAG)n array of 86 repeat units was in the youngest patient, whose age of onset was 5 years. The intergenerational increase in number of CAG repeat units was associated with the clinical phenomenon of anticipation.

Adolescent↗

The beta APP717 Alzheimer mutation increases the percentage of plasma amyloid-beta protein ending at A beta42(43).

We measured plasma levels of amyloid beta protein (A beta) ending at positions 40 (A beta40) and 42(43) [A beta42(43)] in six carriers of beta APP717 (Val to Ile) mutation linked to familial Alzheimer's disease (FAD) as well as in patients with sporadic AD (sAD) and controls. The percentage and the level of A beta42(43) were significantly higher in carriers of beta APP717 mutation relative to sAD, whereas A beta40 levels were decreased. In contrast, A beta levels and ratios were at similar levels in sAD, regardless of the stage of the disease, compared with non-AD neurologic disease controls and nondemented control individuals. These results suggest that the reported increase in the percentage of A beta42(43) secretion in transfected cells with beta APP717 mutant genes actually takes place in the bodies of carriers of beta APP717 mutation, and that plasma A beta could be used as an indicator of the alterations of beta APP/A beta metabolism in subtypes of AD.

Adult↗

Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.

To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units > or = 66; group 2, number of CAG repeat units < or = 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.

Adolescent↗

Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A.

Charcot-Marie-Tooth disease type 2 (CMT2) is characterized by a motor conduction velocity of the median nerve of > 38 m/sec and is a genetically heterogeneous disorder with at least three loci identified: CMT2A (1p35-36), CMT2B (3q13-22), CMT2C (not linked to any known loci), and CMT2D (7p14). In this study, we performed linkage analysis of two Japanese CMT2 families using markers flanking the CMT2A, CMT2B, and CMT2D loci. The highest cumulative multipoint lod score of 3.69 was obtained at D1S244. The CMT2B and CMT2D loci were excluded by the results of linkage analysis performed using markers D3S1551, D3S1290, and D7S484. The clinical features of the CMT2A affecting the two families include similar levels of muscle weakness of the posterior and anterior tibial muscles, tendon reflexes preserved in upper extremities but reduced or absent in lower extremities, no enlargement of the peripheral nerves, and mild sensory disturbance in only 20% of affected individuals.

Charcot-Marie-Tooth Disease↗

Evoked potentials in patients with chronic respiratory insufficiency.

P300, somatosensory evoked potential (SEP) and brainstem auditory evoked potential (BAEP) are widely used neurophysiological methods for objectively evaluating cognitive, somatosensory and brainstem auditory functions. We studied the P300, SEP and BAEP in 17 patients with chronic respiratory insufficiency (PaO2:58.2 +/- 7.0 mmHg; mean +/- SD) and 15 age-matched healthy subjects (PaO2: 84.4 +/- 11.3 mmHg). The latency and amplitude of P300, the N9 latency, N9-N13 and N13-N20 interpeak latencies (IPL) in SEP, wave I latency and I-V IPL in BAEP were compared between the patients and controls. The P300 latency, N9-N13 and N13-N20 IPLs in SEP in the patients were significantly prolonged compared to the controls. In contrast, the amplitude of P300, N9 latency in SEP, wave I latency and I-V IPL in BAEP were not significantly different between the patients and controls. These results suggest that chronic respiratory insufficiency influences the cognitive and somatosensory functions, and indicate that there is a selective vulnerability of evoked potentials to this condition.

Aged↗