OBJECTIVE: 1,4-Dihydropyridine calcium antagonists such as nifedipine are potent vasodilators. It is now commonly agreed that the oxidation of 1,4-dihydropyridine into pyridine, which is one of the main metabolic pathways, is catalysed by the cytochrome P450 (CYP) 3A4 isoform. In the present study, the inhibitory effects of 13 kinds of 1,4-dihydropyridine calcium antagonists clinically used in Japan on human CYP-isoform-dependent reactions were investigated to predict the drug interactions using microsomes from human B-lymphoblast cells expressing CYP. RESULTS: The specific activities for human CYP isoforms included 7-ethoxyresorfin O-deethylation (CYP1A1), phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), 7-benzyloxyresorufin O-dealkylation (CYP2B6), S-warfarin 7-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylaion (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and testosterone 6beta-hydroxylation (CYP3A4). Benidipine and amlodipine competitively inhibited the CYP1A1 activity. Nifedipine, nisoldipine and aranidipine competitively inhibited the CYP1A2 activity. No 1,4-dihydropyridie calcium antagonists used in this study inhibited the CYP2A6 activity. Barnidipine and amlodipine inhibited the CYP2B6 activity. Nicardipine, benidipine, manidipine and barnidipine competitively inhibited the CYP2C9 and CYP2D6 activities. Inhibition extent of the CYP2E1 activity by nifedipine and aranidipine were weak. Nicardipine, benidipine and barnidipine inhibited the CYP2C19 and CYP3A4 activities. Among the human CYP isoforms investigated, the inhibitory effects of 1,4-dihydropyridine calcium antagonists were potent on human CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP2D6 as well as CYP3A4. Furthermore, the isoform selectivity of inhibition by 1,4-dihydropyridine calcium antagonists was clarified. CONCLUSIONS: In consideration of the Ki values obtained in the in vitro inhibition study and the concentration of 1,4-dihydropyridine calcium antagonists in human liver, the possibility of in vivo drug interactions of nicardipine and other drugs which are mainly metabolised by CYP2C9 and/or CYP3A4 was suggested. The inhibition of human CYP isoforms by 1,4-dihydropyridine calcium antagonists except nicardipine might be clinically insignificant.

B-Lymphocytes↗

PubMedDate not supplied

Sex determination of blood stains with a recombinant DNA probe: comparison with radioactive and non-radioactive labeling methods.

A recombinant DNA probe hybridizing specifically to human repeat DNA sequence (pHY10) of which about 3000 copies are present on the Y chromosome was used for sex determination of degraded DNA samples of blood stains. Human blood stains of male and female origin were readily differentiated with the pHY10 DNA probe. This radioactive technique enabled reliable and sensitive sex determination from blood or dried blood stains greater than 20 years old. Less than 1 microliter of blood or 1 piece of 0.5 cm length thread of blood stain from cotton fabric was sufficient for the test using dot blot hybridization. Compared with the radioactive labeling method, the photobiotin labeling method showed one thirtieth to one fiftieth lower sensitivity and presented some problems which are expected to be resolvable.

Blood Stains↗

PubMedDate not supplied

An unexcluded paternity case investigated with hypervariable DNA loci.

A paternity case involving a putative father, a child, and the mother was referred to our laboratory for testing. Parentage was not excluded with 23 kinds of standard blood group markers and HLA, but the putative father requested more-affirmative evidence of paternity. Seven kinds of DNA probes that recognize hypervariable loci were applied. On the basis of the allelic frequencies and their confidence intervals previously reported among unrelated Japanese individuals, as well as confirmed codominant segregation of the polymorphism, the exclusion probability and paternity index were calculated for this case. The cumulative paternity index from the seven DNA probes was 1.4 x 10(6), which was 316 times higher than that from the 23 standard blood group markers and HLA. Accordingly, DNA polymorphism is considered to be informative enough for paternity testing.

Blood Grouping and Crossmatching↗

PubMedDate not supplied

Squamous cell carcinoma of the tongue as a second malignancy in a patient previously treated for osteosarcoma.

A 15-year-old girl was diagnosed with osteosarcoma; limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 2 years. One year after completion of chemotherapy, the patient was readmitted for systemic recurrence. Amputation of the lower extremity and wedge resection of lung metastasis were performed followed by combination chemotherapy. Two years after cessation of chemotherapy, ulcer of the tongue was noted and cervical lymph nodes were detected by palpation. Biopsy of the lesion showed squamous cell carcinoma. The patient underwent a radical partial tongue resection and postoperative irradiation, followed by chemotherapy. Six years after treatment for the second malignancy, the patient remains well without evidence of disease. Squamous cell carcinoma of the tongue as a second malignancy after treatment of osteosarcoma is quite rare. Long-term follow-up, with particular attention to the head and neck, may be warranted in children treated for osteosarcoma.

Adolescent↗

PubMedDate not supplied

Serial high resolution CT findings in nonspecific interstitial pneumonia/fibrosis.

PURPOSE: The purpose of this work was to evaluate the radiographic and serial high resolution CT (HRCT) findings in patients with nonspecific interstitial pneumonia/ fibrosis (NSIP). METHOD: We identified 15 patients with biopsy-proven NSIP. Radiography and initial and follow-up CT findings were reviewed. RESULTS: Predominant radiographic findings were bilateral infiltrates distributing in the middle and lower lung zones and decreased lung volumes. At initial CT, predominant patterns were peribronchovascular interstitial thickening (n = 6), parenchymal bands (n = 8), intralobular interstitial thickening (n = 12), and traction bronchiectasis (n = 14). Mixed pattern of ground-glass opacity and consolidation (n = 11) were predominant findings of increased lung opacity. At follow-up CT in 14 cases, the abnormalities had disappeared completely in 3, improved in 9, persisted in 1, and worsened in 1. CONCLUSION: The pulmonary abnormalities observed in NSIP on HRCT can disappear or be diminished in most cases after corticosteroid therapy. Intralobular interstitial thickening and traction bronchiectasis, which have been considered to be indicators of irreversible fibrosis, also show favorable responses.

Adult↗