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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 505 records · Page 28Linked to original sources

Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer.

Although epidemiological studies strongly suggest an association between gastric cancer and Helicobacter pylori infection, there has been no clinical report indicating that cure of the infection prevents cancer. We conducted a nonrandomized H. pylori eradication trial in patients whose gastric cancer was removed by endoscopic resection (ER). We investigated the effect of treatment on the histopathology of the gastric mucosa, as well as on the incidence of metachronous gastric cancer during the long-term clinical and endoscopic follow-up. One hundred and thirty-two patients with early gastric cancer underwent ER and had H. pylori infection. Sixty-five (group A) were treated with omeprazole and antibiotics to eradicate the infection, and 67 (group B) were not. All patients were followed for 2 years post ER. After eradication treatment in group A, the disappearance of neutrophil infiltration in the antrum and body of the stomach was observed as was a decrease of the severity of intestinal metaplasia. Endoscopy after ER detected no new gastric cancers in these patients. After 3 years of follow-up, 6 (9%) of the 67 patients in group B had a new early-stage, intestinal-type gastric cancer endoscopically diagnosed. The above results suggest that H. pylori eradication may improve neutrophil infiltration and intestinal metaplasia in the gastric mucosa and inhibit the development of new carcinomas. This finding should be confirmed in a randomized, controlled trial.

Adult↗

[Farmer's lung complicated by bilateral pneumothorax and mediastinal emphysema].

A 35-year-old woman was admitted to the hospital because of severe coughing and right-sided chest pain. She had worked on a farm for 13 years. For the preceding 2 years, she noticed a productive cough, a mild fever, and dyspnea after working in a barn for longer than 6 hours. Chest radiological examinations revealed low lung volumes, especially in the right upper lobe, and diffuse small granular shadows in both lung fields. Pathological examinations of lung specimens, which were obtained by transbronchial lung biopsy, showed alveolitis and granulomas in the interstitium. Micropolyspora faeni organisms were detected in hay from the barn. A M. faeni serum precipitation test revealed that her serum had antibodies against that organism. From these findings, we gave her a diagnosis of chronic farmer's lung. Prednisolone was given because her dyspnea and hypoxemia had increased. During the steroid treatment, bilateral pneumothorax and mediastinal emphysema developed. Bullae were removed surgically because she did not respond well to medical treatment. Although steroid administration may have caused these complications, bilateral pneumothorax and mediastinal emphysema are rare in patients with chronic farmer's lung.

Adult↗

[Congenital antithrombin III deficiency associated with pulmonary thromboembolism].

A 42-year-old man was admitted to the hospital because of sudden left-lateral chest pain and dyspnea. The chest roentgenogram on admission showed a string-like shadow and pleural effusion, and analysis of arterial blood gases revealed hypoxemia. Many bilateral segmental defects were seen on a radioisotope perfusion scan of the lungs, and the chest CT scan showed a low-density area in the trunk of the pulmonary artery. From these findings, pulmonary thromboembolism was diagnosed. The serum antithrombin III (ATIII) activity and the antigen value were low, and the patient's son's serum ATIII level was also low. Both the patient and his son were given the diagnosis of congenital ATIII deficiency. Gene analysis revealed two point mutations in exon 6 of the ATIII gene, so we classified this case as type IIc. The patient was treated with intravenous urokinase and heparin, and was then given warfarin. The arterial blood gas tensions improved, and the low-density area of the pulmonary artery on the CT scan disappeared, as did the pulmonary perfusion defect on the radioisotope scan. The clinical manifestations of members of 28 families with congenital ATIII deficiency reported in Japan were reviewed. Patients in whom many point mutations were detected in the ATIII gene were rare.

Adult↗

[Systematic ultrasound guided transrectal core prostate biopsy based on serum level of prostate-specific antigen].

Between August 1995 and June 1996, a total of eighty Japanese men underwent ultrasound guided systematic biopsy of the prostate. Sixty-six men were clinically suspected of having prostatic cancer by elevated serum PSA (Tandem-R kit) value or digital rectal examination (DRE). Overall, 63 of the 80 (78.8%) men had elevated serum PSA with normal DRE and 30 of the 80 men (37.5%) had prostatic cancer. In patients with PSA values of 0 to 4.0 ng/ml, 4.1 to 10.0 ng/ml and 10.1 ng/ml or more, the positive predictive value of PSA was 33.3%, 23.3% and 66.7%, respectively. In patients with PSA levels of 4.1-10.0 ng/ml, the positive predictive values of digital rectal examination, transrectal ultrasonography and PSA density were 30.0%, 28.0% and 31.8%, and the false-negative rates were 20.0%, 0% and 0%, respectively. Along with the findings of transrectal ultrasonography and PSA density, estimation of PSA value and abnormal findings of digital rectal examination may help minimize the number of biopsies in patients with PSA values of 4.1-10.0 ng/ml. Systematic biopsies were performed without major complications. The biopsy missed the cancer in 4.6%.

Aged↗

[A clinicopathological study on carcinoma of the renal pelvis and ureter].

We investigated the clinicopathological features of 62 patients with transitional cell carcinoma of the renal pelvis and ureter. Four patients had been treated for bladder cancer. Among 58 patients without precedent bladder cancer, 6 had coexistent bladder cancer and bladder cancer subsequently developed in 13. The 5-year cause-specific survival rate was 33% in cases with coexistent bladder cancer, 75% in those with subsequent bladder cancer and 62% in patients without association of bladder cancer. Distant metastases were found in 23 of 62 (37%) cases, the most frequent site being lymph nodes. The site of the primary tumor (renal pelvis and/or ureter) and the pathological findings such as grade, stage, type of infiltration, venous and lymphatic invasion, were significantly correlated to cause-specific survival. Multivariate analysis showed the most influential factors to be the type of infiltration and the site of the primary tumor. Therefore, patients with INF beta or gamma tumors both in the renal pelvis and ureter had a poor prognosis. However, association of bladder cancer was not related to survival.

Adult↗

[A randomized study on intravesical pirarubicin (THP) chemoprophylaxis of recurrence after transurethral resection of superficial bladder cancer].

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of tetrahydropyranyladriamycin (THP) following complete transurethral resection (TUR) of superficial bladder cancer. A total of 80 patients were randomized into "THP" or "control" group. In the THP group, 20 mg of THP dissolved in 40 ml saline (or 5% dextrose) was administered intravesically once a week for 10 weeks, starting from about 7 days after TUR. In the control group, 40 ml saline was given with the same schedule. The patients were followed up by cystoscopy and urinary cytology every 3 months. The number of evaluable patients was 36 for the THP group and 37 for the control group. The non-recurrence rates in the THP group and control group were 79.4% versus 63.2% at 1 year and 69.8% versus 47.4% at 3 to 5 years, respectively. These figures were not statistically significant. However, THP instillation significantly reduced tumor recurrence rates for multiple tumors, and also tended to decrease recurrence rates for primary and pT1 tumors. Adverse effects were observed in 53.6% of the patients in the THP group, but they were tolerable. Our results suggest that intravesical THP instillation would not be effective for all patients with superficial bladder cancer. Further study is warranted in a selected group of patients.

Administration, Intravesical↗

The role of interleukin-5 (IL-5) in allergic airway hyperresponsiveness in mice.

In order to investigate the role of IL-5 in allergic airway inflammation and hyperresponsiveness, the effects of rat anti-IL-5 monoclonal antibody (NC-17), recombinant soluble murine IL-5 receptor, and some immunosuppressors were studied in mice model. Three inhalations of an antigen by actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (mononuclear cells and eosinophils) and the amount of IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) increased significantly. NC-17 and soluble IL-5 receptor inhibited the antigen-induced increase of eosinophils with little effect on bronchial hyperreactivity. Cyclosporin A, FK-506, and cyclophosphamide clearly inhibited the antigen-induced increase of IL-5 and eosinophils in BALF. Airway hyperreactivity is inhibited by cyclosporine A and FK-506 but not by cyclophosphamide. Furthermore, to investigate the role of mast cells in the onset of allergic airway hyperreactivity, we have examined the effect of repeated antigen provocation in WBB6F1-W/Wv mice (W/Wv), mast-cell-deficient mice. Whereas significant elevation of IL-5 level and the number of eosinophils on BALF was observed, airway reactivity to acetylcholine was not changed at all. These results indicate that IL-5 may play an important role for the antigen-induced eosinophilia in BALF but not in airway hyperresponsiveness in mice.

Acetylcholine↗

Conformation and dynamics of [3-13C]Ala- labeled bacteriorhodopsin and bacterioopsin, induced by interaction with retinal and its analogs, as studied by 13C nuclear magnetic resonance.

13C nuclear magnetic resonance (NMR) spectra of [3-13C]Ala-labeled bacteriorhodopsin (bR), bacterioopsin (bO), and regenerated bR with retinal or bO complex with retinal analogs were recorded in order to gain insights into how the conformation and dynamics of apoprotein (bO) vary with or without retinal or its analogs. First, we assigned the 13C NMR peak resonating at 16.3 ppm to Ala 53 of both bR and bO, which appears to contact the side chain of Lys 216 at the site of the Schiff base in the former, utilizing the 13C NMR peaks of A53V and A53G proteins in comparison with those of wild-type bR and bO. Characteristic spectral differences between the apoprotein and bR were observed upon removal of the retinal: the changes of the peak intensities at 16.4, 15.9, and 16.9 ppm are notable. We found that the loops (17.4 ppm) and transmembrane alpha II helical region (15.9 ppm) acquired motional freedom with a correlation time of 10(-5)s when the retinal was removed, as detected by proton spin-lattice relaxation times in the rotating frame. A 13C NMR spectrum very similar to that of native bR was recorded when bR was regenerated by addition of retinal to bO. On the other hand, the addition of the retinal analogs retinol or beta-ionone, which are bound in the retinal binding site but are incapable of forming a Schiff base to the apoprotein, caused distinct spectral changes different from those of bR, as manifested from the displacements of 13C chemical shifts. These spectral changes must be ascribed to significant conformational changes of apoprotein at various locations in the protein, including the site of Ala 53 induced by modified interaction between the apoprotein and chromophore.

Alanine↗

Cortical glucose metabolism in psychiatric wandering patients with vascular dementia.

The cerebral metabolic rate for glucose (CMRglc) in 18 patients with vascular dementia (VD) and 15 age-matched normal subjects was measured with positron emission tomography (PET) and the 18F-fluorodeoxyglucose technique. Nine of the 18 VD patients manifested abnormal wandering behavior with some psychiatric symptoms: they showed relatively spared CMRglc, which was higher than that of nonwandering patients, especially in the bilateral frontal lobes, left parietal lobe, left temporo-parieto-occipital region, left occipital lobe, and cerebellum. The results suggest that psychiatric wandering behavior of patients with VD could be correlated with partial sparing of CMRglc in the regions listed above.

Aged↗

Behavior of the cell cycle-associated proteins in an unusual G0-arrestable cancer cell line.

An adenocarcinoma cell line which has the ability to arrest in G0 phase under exhausted culture conditions was established. Using the cell line, we investigated the expression of cell cycle-associated proteins including cdc2, cdk2, cyclin A, cyclin Dl, and Rb during entry into or withdrawal from the cell cycle. MAP kinase expression was also investigated as one of the most downstream proteins of the signal transduction of growth factors. The cells in the quiescent state did not express cdc2. In contrast, cdk2 was expressed weakly, and cyclin A and cyclin D1 were strongly expressed in the quiescent cells. The expression of cdk2 and cyclin D1 in the quiescent cells was reduced after stimulation by renewal of the medium and then increased, accompanied by Rb phosphorylation and cdc2 expression around the G1/S transition. Cdc2 and the hyperphosphorylated form of Rb disappeared as the cells became quiescent. MAP kinase expression was unchanged throughout all the phases analyzed. The results indicate that down-regulation of neither cdk2, cyclin A, cyclin D1, nor MAP kinase is necessary to arrest cells in G0, but that only Rb dephosphorylation and down-regulation of cdc2 are accompanied by an arrest of cell proliferation in G0 in the cell line.

Adenocarcinoma↗

Determination of the 8-methyl ether of xanthurenic acid in human serum by high-performance liquid chromatography with fluorescence detection.

We developed a simple and sensitive assay for the 8-methyl ether of xanthurenic acid in serum by high-performance liquid chromatography with fluorescence detection (excitation at 340 nm, emission at 450 nm). The compound under study in serum samples was extracted with Sep-Pak C18 cartridge and the extract was applied to an octadecylsilane-bonded column (Nucleosil 5C18, 150 x 4 mm I.D.). The mobile phase used was a mixture of 0.05 M sodium acetate buffer (pH 6.0), containing 5 mM sodium 1-octanesulfonate and 0.1 mM Na2EDTA, and acetonitrile (93:7, v/v). The 8-methyl ether of xanthurenic acid from serum samples was sufficiently separated to be clearly distinguishable. The quantification limit was 2 x 10(-14) mol, which was sensitive enough to detect 8-methyl ether of xanthurenic acid in serum from normal subjects. The method was applied to samples from patients with deficiency in tryptophan metabolism, xanthurenic acid/3-hydroxy kynurenineuria and showed a striking elevation in serum 8-methyl ether of xanthurenic acid.

Amino Acid Metabolism, Inborn Errors↗

Time-dependent inactivation of aromatase by 6-alkylandrosta-1,4-diene-3,17-diones. Effects of length and configuration of 6-alkyl group.

Series of 6alpha- and 6beta-alkylandrosta-1,4-diene-3,17-diones (3 and 4) were synthesized and evaluated as time-dependent inactivators of aromatase in human placental microsomes to gain insights to the structure-activity relationship of varying the 6-n-alkyl substituents (C-1--C-7) to the time-dependent inactivation activity. All of the inhibitors synthesized were powerful to good competitive inhibitors of aromatase, with apparent Ki's ranging from 4.7 to 54 nM. The 6beta-ethyl (4b) and 6beta-n-pentyl (4e) compounds were the most potent among them (Ki = 4.7 and 5.0 nM for 4b and 4e, respectively). In a series of the 6alpha-alkyl steroids, the inhibitors 3a-d having C-1--C-4 at the 6-position as well as the 6 alpha-n-heptyl (3g) compounds did not. In contrast, in the 6beta-alkyl steroid series, only the methyl analog 4a inactivated aromatase in a time-dependent manner, and the other alkyl steroids having more than two carbons at C-6beta did not. The inactivations were prevented by the substrate androstenedione, and no significant effects of L-cysteine on the inactivation were observed in each case. These results along with molecular modeling with the PM3 method indicate that both length and stereochemistry of a straight alkyl substituent at the C-6 position of androsta-1.4-diene-3,17-dione (3h) play an important role in the cause of a time-dependent inactivation of aromatase. No significant correlation between affinity for the enzyme and the inactivation ability in the 6-alkylandrosta-1,4-diene-3,17-diones is observed.

Alkylation↗

Formation of the enzyme complex in mitochondria is required for function of trifunctional beta-oxidation protein.

The first Japanese patient with mitochondrial trifunctional protein deficiency has been identified. The patient's alpha and beta-subunits were synthesized, transported into the mitochondria, and converted to the mature size, but rapidly disappeared. The newly synthesized mature alpha and beta-subunits in the control cells were incorporated into the enzyme complex, alpha4beta4, whereas those in the patient's cells were present as monomers. We propose that formation of the enzyme complex is required for stabilization of trifunctional protein.

Autoradiography↗