Molecular cloning of a cDNA for rat diabetes-inducible cytochrome P450RLM6: hormonal regulation and similarity to the cytochrome P4502E1 gene.

1. A polyclonal, monospecific antibody to a constitutive, diabetes-inducible and insulin-reversible cytochrome P-450 isozyme (RLM6) was used to screen a male rat liver cDNA library in lambda gt 11. Six clones harbouring the RLM6 cDNA insert were isolated initially from the expression library and three of these were further plaque-purified and sub-cloned. A 1.1 Kb cDNA insert, representing approximately 65% of the expected full length cDNA was characterized by restriction endonuclease mapping and sequenced by the dideoxy chain-termination method. Comparison of the nucleotide sequence of RLM6 cDNA to that of ethanol-inducible P4502E1 rat cDNA showed the two cDNAs to be identical, the RLM6 cDNA corresponding to nucleotides 310-1402 of the P4502E1 sequence. 2. RLM6 cDNA probe was used in Northern blot and RNA dot blot hybridization analysis to demonstrate that both streptozotocin-induced diabetes and fasting significantly elevated the steady-state level of RLM6 mRNA in male rat liver. Increased RLM6 mRNA level in the diabetic rat resulted in increased RLM6 apoprotein synthesis when polysomal RNA was used in a cell-free, protein-synthesizing system, indicating that the elevated RLM6 level observed in diabetic rats was correlated directly with the increased RLM6 mRNA concentration. 3. Daily insulin treatment of diabetic rats reversed the diabetes-dependent increase in RLM6 mRNA in a time-dependent manner, returning to control values after approximately 2 weeks of continuous insulin treatment. This insulin-dependent decrease of the RLM6 mRNA level was paralleled by a similar time-dependent decrease in serum acetone concentration. 4. Treatment of the male diabetic rat with testosterone also resulted in a decrease in both RLM6 mRNA and in vitro translated apoprotein. 5. Modulation of RLM6 mRNA level in the diabetic rat by insulin and testosterone, and the nucleotide sequence similarity with that of P4502E1 confirms that diabetes-inducible P450RLM6 and ethanol-inducible P4502E1 are coded for by the same gene.     

Hair dye use and risk of leukemia and lymphoma.

Data from a population-based case-control study of incident leukemia and non-Hodgkin's lymphoma among adult men in Iowa and Minnesota were used to evaluate risk associated with hair dye use. The relative risk for ever using hair dyes was 1.8 (95% confidence interval [CI] = 1.1-2.7) among leukemia patients, and 2.0 (CI = 1.3-3.0) among cases with non-Hodgkin's lymphoma. There was a suggestion of increased risk with extent of hair dye use. Given the widespread use of hair coloring products, these observations deserve more detailed evaluation in populations where the exposure is relatively common.     

Evaluation of maternal plasma creatine kinase activity as a marker of abnormal early pregnancy

We have tested the value of maternal plasma creatine kinase activity for diagnosing ectopic pregnancies obtained after in-vitro fertilization and embryo transfer. Plasma creatine kinase was assayed in 57 patients: 20 normal, 23 miscarriages and 14 ectopic pregnancies, for a total of 240 samples. All values were in the lower part of the normal range except only one in a miscarrying patient. A statistically significant difference was observed for a cut-off value of 45 IU/l between normal and ectopic pregnancies. However, for this cut-off point, the measurement of plasma creatine kinase activity had a sensitivity of 0.50 and a specificity of 0.76 for the diagnosis of ectopic pregnancy. The positive predictive value was 0.69. Creatine kinase activity measurements are thus of no practical value in this particular population, in which an early and specific marker of ectopic implantation would be of paramount interest. The association of human chorionic gonadotrophin (HCG) determinations and ultrasound scanning of the pelvis still remain the best paraclinical support for an early diagnosis of ectopic implantation.      

Norethindrone inhibition of testosterone secretion by an ovarian Sertoli-Leydig cell tumor

A woman with severe hyperandrogenemia and virilization was found to have a fall in serum testosterone (T) concentration while taking an oral contraceptive containing norethindrone (500 vs. 164 ng/dL). Subsequent surgical exploration revealed an ovarian Sertoli-Leydig cell tumor. In vitro, the tumor secreted T (mean, 1.88 ng/mg X 4 h). hCG did not stimulate T secretion. In addition, norethindrone inhibited T secretion (0.33 ng/mg X 4 h). We conclude that norethindrone directly suppressed T production by the Sertoli-Leydig cell tumor.     

The applicability and utility of the MMPI-based offender classification system in a correctional mental health unit

This study investigated the applicability and utility of Megargee and Bohn's MMPI-based offender classification system in correctional mental health units (MHUs). Previous studies found that 11 MHU samples (n = 1723) had substantially more offenders classified in the more pathological MMPI types than did 21 samples (n = 5881) drawn from general male populations in US prisons. In this study of 63 severely disturbed felons, 43% belonged to the most pathological type (‘group How’). Comparing MHU patients with general offenders from the same IvfIvIPI types on staff ratings and case history variables, we found that the MHU patients were significantly poorer in adjustment. Within the MHU sample, there was no difference in case history variables or adjustment ratings between those in the most and least severe MMPI types. These findings differed from those of studies using less severely disturbed, more heterogeneous, MHU populations. It was concluded that, in settings in which the entire population is flagrantly disturbed, the MMPI-based system is more useful in screening potential admissions than it is in making meaningful distinctions among those already admitted.