Androgen receptor in human skin

Cytosol androgen receptor was assayed in 18 human skin biopsies by an exchange technique with a labelled potent synthetic androgen, methyltrienolone (R 1881), under conditions which measured total (i.e. both free and occupied) binding sites. Androgen binding sites were only present in skin biopsies from patients with marked seborrhoea often accompanied by acne (8 cases) and no sites were detected in normal skin biopsies (7 cases). Three biopsies from seborrhoeic patients, however, did not contain androgen receptor. Although no direct quantitative correlation could be drawn between binding site concentration and sebum excretion, it would seem that the androgen receptor content nevertheless constitutes an important parameter in the study of the hormonal control of seborrhoea.     

Harmonization of Animal Clinical Pathology Testing in Toxicity and Safety Studies

Ten scientific organizations formed a joint international committeeto provide expert recommendations for clinical pathology testingof laboratory animal species used in regulated toxicity andsafety studies. For repeated-dose studies in rodent species,clinical pathology testing is necessary at study termination.Interim study testing may not be necessary in long-durationstudies provided that it has been done in short-duration studiesusing dose levels not substantially lower than those used inthe long-duration studies. For repeated-dose studies in nonrodentspecies, clinical pathology testing is recommended at studytermination and at least once at an earlier interval. For studiesof 2 to 6 weeks in duration in nonrodent species, testing isalso recommended within 7 days of initiation of dosing, unlessit compromises the health of the animals. If a study containsrecovery groups, clinical pathology testing at study terminationis recommended. The core hematology tests recommended are totalleukocyte (white blood cell) count, absolute differential leukocytecount, erythrocyte (red blood cell) count, evaluation of redblood cell morphology, platelet (thrombocyte) count, hemoglobinconcentration, hematocrit (or packed cell volume), mean corpuscularvolume, mean corpuscular hemoglobin, and mean corpuscular hemoglobinconcentration. In the absence of automated reticulocyte countingcapabilities, blood smears from each animal should be preparedfor reticulocyte counts. Bone marrow cytology slides shouldbe prepared from each animal at termination. Prothrombin timeand activated partial thromboplastin time (or appropriate alternatives)and platelet count are the minimum recommended laboratory testsof hemostasis. The core clinical chemistry tests recommendedare glucose, urea nitrogen, creatinine, total protein, albumin,calculated globulin, calcium, sodium, potassium, total cholesterol,and appropriate hepatocellular and hepatobiliary tests. Forhepatocellular evaluation, measurement of a minimum of two scientificallyappropriate blood tests is recommended, e.g., alanine aminotransferase,aspartate aminotransferase, sorbitol dehydrogenase, glutamatedehydrogenase, or total bile acids. For hepatobiliary evaluation,measurement of a minimum of two scientifically appropriate bloodtests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase,5'-nucleotidase, total bilirubin, or total bile acids. Urinalysisshould be conducted at least once during a study. For routineurinalysis, an overnight collection (approximately 16 hr) isrecommended. It is recommended that the core tests should includean assessment of urine appearance (color and turbidity), volume,specific gravity or osmolality, pH, and either the quantitativeor semiquantitative determination of total protein and glucose.For carcinogenicity studies, only blood smears should be madefrom unscheduled sacrifices (decedents) and at study terminationto aid in the identification and differentiation of hematopoieticneoplasia.     

IMMUNOHISTOCHEMICAL DETECTION OF p53 PROTEIN OVEREXPRESSION VERSUS GENE SEQUENCING IN URINARY BLADDER CARCINOMAS

PURPOSE: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.