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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 199 records · Page 11Linked to original sources

Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer.

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10-year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20 - 29, 14.5 for those aged 30 - 39, 9.1 for those aged 40 - 49, 3.5 for those aged 50 - 59, and 1.5 for those aged 60 - 69 (trend in odds ratios: P < 0.01). However, there was no such age-dependent trend for early diffuse-type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P = 0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age-class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age-dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age-independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and / or irreversible damage to gastric mucosa in childhood or the teenage years.

Adult↗

Comparison of intertypic antigenicity of Aino virus isolates by dot immunobinding assay using neutralizing monoclonal antibodies.

Neutralizing monoclonal antibodies (MAbs) against the Aino virus were prepared, and the neutralizing epitopes of the virus were defined by competitive binding assay. Seven continuous and overlapping neutralizing epitopes existed on the G1 glycoprotein of the Aino virus. Two antigenic domains were identified and were designated I and II, with domain II consisting of six epitopes. Dot immunobinding assays (DIAs) were performed with MAbs that recognized these seven neutralizing epitopes. DIAs were performed with 1 Australian strain and 21 isolates found in Japan between the years 1964 and 1995. The MAb response patterns of all isolates were divided into four groups. The Japanese isolates did not show large differences in antigenicity, but the antigenicity of the Australian strain collected in 1968 was significantly different from that of the Japanese strains; the Australian strain lacked reactivity to three epitopes and showed only low reactivity to one epitope.

Animals↗

Prevalence of mitochondrial gene mutations among hearing impaired patients.

The frequency of three mitochondrial point mutations, 1555A-->G, 3243A-->G, and 7445A-->G, known to be associated with hearing impairment, was examined using restriction fragment length polymorphism (RFLP) analysis in two Japanese groups: (1) 319 unrelated SNHL outpatients (including 21 with aminoglycoside antibiotic injection history), and (2) 140 cochlear implantation patients (including 22 with aminoglycoside induced hearing loss). Approximately 3% of the outpatients and 10% of the cochlear implantation patients had the 1555A-->G mutation. The frequency was higher in the patients with a history of aminoglycoside injection (outpatient group 33%, cochlear implantation group 59%). One outpatient (0.314%) had the 3243A-->G mutation, but no outpatients had the 7445A-->G mutation and neither were found in the cochlear implantation group. The significance of the 1555A-->G mutation, the most prevalent mitochondrial mutation found in this study of a hearing impaired population in Japan, among subjects with specific backgrounds, such as aminoglycoside induced hearing loss, is evident.

Aminoglycosides↗

Effects of CTGF/Hcs24, a product of a hypertrophic chondrocyte-specific gene, on the proliferation and differentiation of chondrocytes in culture.

Recently, we cloned a messenger RNA (mRNA) predominantly expressed in chondrocytes from a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8, by differential display PCR and found that its gene, named hcs24, was identical with that of connective tissue growth factor (CTGF). Here we investigated CTGF/Hcs24 function in the chondrocytic cell line HCS-2/8 and rabbit growth cartilage (RGC) cells. HCS-2/8 cells transfected with recombinant adenoviruses that generate CTGF/Hcs24 sense RNA (mRNA) proliferated more rapidly than HCS-2/8 cells transfected with control adenoviruses. HCS-2/8 cells transfected with recombinant adenoviruses that generate CTGF/Hcs24 sense RNA expressed more mRNA of aggrecan and type X collagen than the control cells. To elucidate the direct action of CTGF/Hcs24 on the cells, we transfected HeLa cells with CTGF/Hcs24 expression vectors, obtained stable transfectants, and purified recombinant CTGF/Hcs24 protein from conditioned medium of the transfectants. The recombinant CTGF/Hcs24 effectively promoted the proliferation of HCS-2/8 cells and RGC cells in a dose-dependent manner and also dose dependently increased proteoglycan synthesis in these cells. In addition, these stimulatory effects of CTGF/Hcs24 were neutralized by the addition of anti-CTGF antibodies. Furthermore, the recombinant CTGF/Hcs24 effectively increased alkaline phosphatase activity in RGC cells in culture. Moreover, RT-PCR analysis revealed that the recombinant CTGF/Hcs24 stimulated gene expression of aggrecan and collagen types II and X in RGC cells in culture. These results indicate that CTGF/Hcs24 directly promotes the proliferation and differentiation of chondrocytes.

Adenoviridae↗

Protein kinase C modulates Ca2+-activated K+ channels in cultured rat mesenteric artery smooth muscle cells.

The electrical and pharmacological properties of protein kinase C (PKC) and its effect on the single Ca2+-activated K+ channel (Kca-channel) in the cultured smooth muscle cells of rat mesenteric artery were studied using a patch-clamp technique. The Kca-channel had a slope conductance of 151+/-7 pS (mean+/-S.E.) in symmetrical 142 mm K solutions. The high conductance K+ channel, applied to the outer side of membrane patches, was potently inhibited by charybdotoxin (0.1 microM) and tetraethylammonium (0.5 microM), but not by apamin (0.4 microM). In cell-attached patches, bath application of phorbol 12-myristate 13-acetate (PMA, 2 microM), a PKC activator, inhibited the activity of the Kca-channel in the presence of the Ca2+ ionophore, A 23187 (10 microM). This inhibition was reversed by subsequent application of staurosporine (1 nM), a PKC inhibitor. Application of 1-oleoyl-2-acetylglycerol (OAG, 30 microM), another PKC activator, also inhibited the A 23187-induced activation of the K+ channel, and this inhibition was reversed by staurosporine. In inside-out patches, bath application of PKC (0.2 munits), in the presence of ATP (1 mM) and PMA (1 microM), inhibited the K+ channel. These results indicate that protein kinase C inhibits the Ca2+-activated K+ channel of mesenteric artery smooth muscle cells in the rat.

Adenosine Triphosphate↗

[Molecular cloning of cDNAs coding Sarcophaga diptericin family].

We purified an antibacterial protein named sarcotoxin III from the hemolymph of injured larvae of Sarcophaga peregrina (Baba K., et al., J. Biochem., 102, 69-74 (1987)). In this report we determined the partial amino acid sequence of sarcotoxin III and tried to conduct the cloning of sarcotoxin III cDNA. As a result we obtained two clones coding a protein similar to sarcotoxin III in sequence. Their primary structures are highly homologous to N-terminal sequences of an antibacterial protein from Phormia, diptericin, and another 8 kD antibacterial protein purified from Sarcophaga peregrina. These results suggested that sarcotoxin III is one of the proteins forming a diptericin family in Sarcophaga peregrina as well as newly obtained clone-coded products and 8 kD protein.

Amino Acid Sequence↗

[Development and evaluation of a local area network system to make drug information paper for inpatient--adaptation to characteristics of diseases, and expansibility to other hospitals and the Internet].

We developed and evaluated a local area network system to make drug information papers. Because pharmacists should explain drug information both orally and using papers to patients in response to their understanding and characteristics of their diseases. The merit of this system is as follows: pharmacists can use it without any education for its operation; most data can be inputted by selection from the lists and automatic reference; the data are adjustable for individuals; different contents are available for different wards; multiple users can access the same data file. Input data in this system are available for making explanation papers on the medical examination of outpatients, and making a plan for pharmaceutical care and guidance services. This system is also available in other hospitals, and on the internet. First, we surveyed the time required for preparing drug information papers. Making a hand written paper for typical patient takes 395 sec. for manuscript, 160 sec. with the system using text data only, and 178 sec. with the system using text and picture data. Next, we surveyed 27 patients' views on the addition of drug pictures to drug information papers, and with the result that 19 patients thought it very good. Last, we surveyed 13 ward pharmacists about their usage of this system. We found that 8 pharmacists used frequently this system, and 3 pharmacists used the same file in the same hours at the maximum.

Aged↗

[Neurotoxicity of beta-amyloid].

Recent observations on the neurotoxicity of beta-amyloid have been reviewed and possible roles of racemization of beta-amyloid are discussed. beta 1-40, beta 25-35 and D-Ser26 beta 25-35 (all HCl salt forms), but not commercially available beta 1-40 (TFA salt form), take the beta-structure within few hours in PBS, form fibrils, exert toxic effects on hippocampal cultured neurons and suppresses MTT reduction activity of non-neuronal HeLa cells without cytotoxicity. D-Ser26 beta 1-40 is soluble and non-toxic in vitro but is converted by brain proteinases to D-Ser26 beta 25-35, a potent toxic and proteinase-resistant fragment. The co-injection of beta 1-40, D-Ser26 beta 25-35 or D-Ser26 beta 1-40 with ibotenic acid, but not beta-amyloid alone or ibotenic acid alone, into rat brains produce drastic neuronal loss in the hippocampal CA1 area. The in vivo degeneration activity of beta-amyloids is well correlated with their having beta-structure and activity to suppress the MTT reduction activity. A specific antibody against D-Ser26 beta 25-35 strongly reacts with hippocampal degenerated-CA1 neurons in AD but not control brains. These results suggest that D-Ser26 beta 25-35 and related peptides possibly generated from insoluble beta 1-40 due to aging exert toxic effects on the hippocampal CA1 pyramidal neurons by enhancing the susceptibility to excitatory amino acids.

Alzheimer Disease↗

Association of p53 expression with second primary tumour development in hypopharyngeal carcinoma.

Abnormalities of p53 tumour suppressor gene are detected in a diversity of malignancies and play an important role in their pathogenesis. Hypopharyngeal carcinoma is the most morbid among head and neck squamous cell carcinomas because of the high incidence of treatment failures and because a biological marker predictive of the treatment failures remains elusive. The expression of p53 protein in 46 hypopharyngeal squamous cell carcinomas was examined histochemically and p53 immunoreactivity was found in 19 of 46 cases (41.3 per cent). The rate of second primary tumour development was significantly higher in the p53-positive group than in the p53-negative group (p = 0.039), whereas that of tumour recurrence was not significantly different between the two. Moreover, there was no statistically significant difference in either overall or disease-free survival between the p53-positive and -negative groups. These results indicate that although p53 expression significantly correlates with second primary tumour development in patients with hypopharyngeal squamous cell carcinomas, it is not predictive of the clinical outcome.

Biomarkers, Tumor↗

Blockade of angiotensin receptors in the anterior hypothalamic preoptic area lowers blood pressure in DOCA-salt hypertensive rats.

It has been established that deoxycorticosterone acetate (DOCA)-salt hypertensive rats have an overactive brain angiotensin-system. The purpose of the present study was to identify the brain sites showing enhanced angiotensin-system activity responsible for the pathogenesis of hypertension in DOCA-salt hypertensive rats. The angiotensin receptor antagonist, losartan, was injected into brain ventricles or into tissues around the rostral parts of the third ventricle in conscious DOCA-salt hypertensive rats. Losartan (1 microg) injection into the lateral ventricle or into the rostral parts of the third ventricle produced a depressor response, whereas the agent did not affect blood pressure when injected into the caudal parts of the third ventricle or into the fourth ventricle. Losartan (0.1 microg) injection into the anterior hypothalamic preoptic area, anterior (AHA) produced a depressor response. Angiotensin II (0.1-1 ng) injection into the AHA produced a pressor response in sham-operated and DOCA-salt hypertensive rats, and the pressor response to angiotensin II (1 ng) was greater in DOCA-salt hypertensive rats than that in sham-operated rats. Release of angiotensin peptides in the AHA was greater in DOCA-salt hypertensive rats than that in sham-operated rats. These findings suggest that the angiotensin-system in the AHA is enhanced, and that this enhancement is involved in the maintenance of hypertension in DOCA-salt hypertensive rats. Both increased pressor reactivity to angiotensin II and increased release of angiotensin peptides in the AHA appear to be related to this enhancement of the angiotensin-system in DOCA-salt hypertensive rats.

Angiotensin II↗

Radial MRI of the hip with moderate osteoarthritis.

We carried out radial MRI in 30 hips with moderate osteoarthritis and in ten normal hips. On a scout view containing the entire acetabular rim, 12 vertical radial slices were set at 15 degrees intervals. Different appearances were observed in different parts of the joint. In the weight-bearing portion, from 45 degrees anterosuperior to 45 degrees posterosuperior, 'attenuation' (n = 16) and 'disappearance' (n = 25) were observed as abnormalities of the labrum with 'capsular stripping' (n = 29) and 'extraosseous high signal lesion' (n = 27) as capsular abnormalities, seen more often in the anterosuperior portion. In all 12 planes there were osteophytes on the acetabular edge (n = 24), femoral head (n = 22) and/or at the central acetabulum (n = 6), a bone cyst on the acetabulum (n = 18) and/or the femoral head (n = 9), irregularity of the articular cartilage (n = 30), and an effusion (n = 28). Our findings indicate that radial MRI may be a useful non-invasive diagnostic method for demonstrating pathology in moderate osteoarthritis of the hip.

Adult↗

Thyroid-stimulating antibody in a patient with euthyroid Graves' disease.

We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positive for anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.

Antithyroid Agents↗