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Biomedical subjects

Masayuki Baba

Publications and source records attributed to Masayuki Baba.

44 records · Page 3Linked to original sources

Tandem repeat polymorphism of the CYP2E1 gene: an association study with esophageal cancer and lung cancer.

BACKGROUND: Cytochrome P-450 (CYP) enzymes have been shown to play important roles in chemical carcinogenesis. Reports have indicated that polymorphism in CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an important role in alcohol metabolism and participates in the metabolic activation of various carcinogens, such as N-nitrosodimethylamine. Recently, we found repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4 and A4/A4) of the CYP2E1 gene. In the present study, we investigated whether these polymorphisms are associated with lung cancer and esophageal cancer. METHODS: DNA was isolated from blood samples of 192 healthy control subjects, 85 patients with lung cancer, and 82 patients with esophageal cancer in Japanese males. DNA samples were amplified by polymerase chain reaction in the 5'-flanking region of the CYP2E1 gene and in exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were examined using fluorescence-based single strand conformational change polymorphism analysis. Written informed consent was obtained from all the subjects. RESULTS: In the CYP2E1 gene 5'-flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p = 0.02), but no difference was found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%; p< 0.0001; habitual alcohol drinkers). CONCLUSIONS: The distribution of genotypes and allele frequencies of the tandem repeats of the 5'-flanking region of the CYP2E1 gene was significantly different in patients with esophageal cancer.

5' Flanking Region↗

[Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson's disease].

A rapid and excessive increase in extracellular dopamine(DA) after L-DOPA administration is considered one of the major causes for L-DOPA-induced peak-dose dyskinesia. Therefore, inhibition of excessive rise in L-DOPA-derived DA is likely to be an ideal treatment for L-DOPA-induced dyskinesia. Based on our previous experimental studies that 8-OH-DPAT, a potent 5-HT1A agonist, attenuates an increase in L-DOPA-induced extracellular DA in the striatum of the rat model of Parkinson's disease, we hypothesized that L-DOPA-induced dyskinesia in patients with Parkinson's disease is alleviated by a 5-HT1A agonist. In the present study, we administered tandospirone citrate, a selective 5-HT1A agonist, to patients with Parkinson's disease suffering from L-DOPA-induced dyskinesia. Tandospirone(15-60 mg/day) was administered to 10 patients with L-DOPA-induced peak-dose dyskinesia. Twelve weeks after tandospirone treatment, duration of dyskinesia, subjective and objective severity of dyskinesia, and parkinsonian features were evaluated. Severity of dyskinesia was decreased in 5 patients; among these, 3 patients experienced slight worsening of parkinsonian features. Four patients showed no change in dyskinesia; among these, 2 patients showed worsening of parkinsonian features. One patient had slight worsening of dyskinesia without any change in parkinsonian features. The present study demonstrated that tandospirone is effective in alleviating L-DOPA-induced dyskinesia in 50% of the patients. However, at the same time 50% patients showed slight worsening of parkinsonian features. Both the anti-dyskinetic effect and the worsening of parkinsonian features are thought to be induced by tandospirone's potent 5-HT1A agonistic activity. Diverse effect of tandospirone may be caused by its partial agonist activity on 5-HT1A receptors, or may indicate that other causes for the expression of dyskinesia exist apart from excessive rise in brain DA levels. Administration of a 5-HT1A agonist is a choice for patients with dyskinesia if the care is taken so as not to induce worsening of parkinsonian features. Further studies such as double-blind trials are needed to confirm the usefulness of a 5-HT1A agonist for L-DOPA-induced dyskinesia.

Adult↗

Peripheral neuropathy and microangiopathy in rats with insulinoma: association with chronic hyperinsulinemia.

BACKGROUND: Hypoglycemia can precipitate or worsen peripheral neuropathy in patients with insulinoma or in diabetic patients on an intensive insulin regimen. It still remains unclear as to whether hyperinsulinemia itself is involved in neuropathic changes in these patients. We, therefore, explored the possible isolated effects of chronic hyperinsulinemia on neuropathic changes in insulinoma-bearing rats (I-rats). METHODS: I-rats were generated by a combined treatment with nicotinamide and streptozotocin. At 15 months after the treatment, they showed a wide range of the plasma insulin (PI) level with or without a decrease in the blood glucose (BG) level and were divided into three groups on the basis of the presence of hypoglycemia (BG < 2.5 mmol/L) or hyperinsulinemia (PI > 100 mU/L): the first exhibited only hypoglycemia, the second exhibited only hyperinsulinemia, and the third exhibited neither. Peripheral nerve function and structure as well as microvasculature were evaluated among these groups in addition to age-matched untreated control rats (C-rats). RESULTS: The first group of hypoglycemic I-rats showed a decrease (p < 0.05) in the axon/myelin ratio and an increase (p < 0.0001) in fibers undergoing axonal degeneration compared to C-rats, while the other two groups did not. On the other hand, the second group of hyperinsulinemic I-rats showed a decrease (p < 0.05) in the myelinated axonal size and an increase (all p < 0.05) in the F-wave latency and the densities of myelinated fibers and endoneurial microvessels exhibiting endothelial hyperplasia, vascular wall thickening, or pericytes debris compared to the third group of isoglycemic I-rats without hyperinsulinemia. CONCLUSION: These results suggest that hypoglycemia is associated with increased myelinated axonal damage, while hyperinsulinemia is associated with increased densities of small myelinated axons and endoneurial microvessels with microangiopathic changes in I-rats. We, therefore, propose that the observed findings may be relevant to the complicated features of neuropathy in diabetic patients with chronic hyperinsulinemia.

Animals↗

A new thin-type bronchoscope improves diagnostic accuracy of peripheral pulmonary carcinoma.

We investigated the XBF-4B40 (4B40) thin bronchoscope, which has a 4.0-mm outer diameter and a 2.0-mm biopsy channel, and studied its impact on the diagnosis of lung carcinoma. We analyzed 30 peripheral lung carcinoma cases by performing bronchoscopic examination using the 4B40 and the type 200 videoscope and recorded the most distal bronchus level reached. In addition, transbronchial aspiration biopsy, forceps biopsy, or brushing was performed, and the diagnosis accuracy between the two instruments was determined. The mean of the most distal bronchus reached by the 4B40 and the type 200 videoscope was the 4.5th and the 3rd, respectively. The 4B40 reached significantly further into the distal bronchus than the type 200 videoscope (p<0.0001). Accuracy for lesions detected in the right segment 1 or left segment 1+2 using the 4B40 and the type 200 videoscope was significantly different (p<0.0001) at 90.0 and 0%, respectively. The new type of bronchoscope, XBF-4B40, is useful for peripheral pulmonary lesion diagnosis with diagnosis accuracy improvements in the right segment 1 or the left segment 1+2.

Adenocarcinoma↗

Acute cholecystitis and duodenitis associated with Churg-Strauss syndrome.

We describe a patient with acute cholecystitis and duodenitis associated with Churg-Strauss syndrome. A 36-year-old male, who had been healthy, had abdominal pain following high fever. He had marked hypereosinophilia of 17,000/mm3. Radiographs of the chest disclosed a transient infiltrated lesion in the left lower lung. Ultrasonographic and gastroendoscopic examinations revealed acute cholecystitis and duodenitis, respectively. Endoscopic retrograde cholangiopancreatography demonstrated a filling defect suspecting aberrant ascariasis in the common bile duct. The patient suddenly developed distally dominant mononeuritis multiplex, especially in the upper limbs. Muscle biopsy revealed vasculitis of intramuscular arteries with infiltration of eosinophils. These findings fulfilled the diagnostic criteria of Churg-Strauss syndrome. Corticosteroid dramatically resolved the abdominal symptoms. Cholecystectomy and removal of the foreign body were performed. Histological examinations revealed that necrosis of the gallbladder was caused by occlusion due to thrombosed arteries and that the foreign body in the common bile duct was an aggregate of necrotic epithelium of the bile duct wall surrounded by inflammatory cells. Although abdominal complaints rarely appeared as an initial symptom in the patients with Churg-Strauss syndrome, this syndrome should be taken into consideration for an accurate diagnosis when the patients with abdominal pain of unknown origin had eosinophilia, asthma, or allergic rhinitis.

Acute Disease↗