Preferential involvement of chromosome 1q in a primary breast carcinoma

The cytogenetic findings by G- and C-banding in a primary breast carcinoma are reported. The tumor is characterized by a high modal number of chromosomes (79) and 14 markers of ten different origins. Chromosome #1 is more frequently involved in structural and numerical aberrations than is any other chromosome; nine copies of 1q were present in each cell examined. This observation supports the hypothesis that duplication of chromosome 1q may play an important role in the progression of malignant tumors.     

Effects of somatostatin on somatotroph adenomas of the human pituitary: An in vitro functional and morphological study

The effects of somatostatin or the somatostatin analog SMS 201–995 were studied on 4 densely granulated somatotroph adenomas and 4 sparsely granulated somatotroph adenomas in vitro. Release of growth hormone (GH) into culture media during incubation with somatostatin or SMS 201 -995 were measured by radioimmunoassay, and light-microscopical and ultrastructural morphometric parameters were compared with those of cultured control somatotroph adenoma cells of the same tumor. In all tumors except for 1 densely granulated somatotroph adenoma, somatostatin or SMS 201–995 decreased GH release into culture media in 24- and 2-hour incubations. After 48-hour incubation with somatostatin or SMS 201–995, there was no change in cell size or secretory granule diameter. One densely granulated adenoma showed decreased cytoplasmic volume density (CVD) of Golgi apparatus and secretory granules, and a sparsely granulated adenoma had reduced CVD of endoplasmic reticulum. All the tumors that responded with decreased GH release exhibited increased CVD of lysosomes after incubation with somatostatin or SMS 201–995. These results indicate that both densely and sparsely granulated somatotroph adenomas respond to somatostatin inhibition and, furthermore, that inhibition of hormone release is associated with accumulation of lysosomes, suggesting lysosomal degradation of stored hormone. Hospital 20 Nov. (ISSSTE) Coyoacan y Felix Cuevas, Colonia del Valle and (Dept Patologia) y Hospital de Especialidades (C.M.N., IMSS) Cuauhtemoc y Dr. Marquez, Mexico City (IF).     

The occurrence of Chlamydia trachomatis in the semen of men participating in an IVF programme

Chlamydia trachomatis is one of the most common causative agentsof sexually transmitted diseases. The authors studied the occurrenceof C.trachomatis in the semen of 184 asymptomatic men participatingin the IVF programme. Twenty-six (14.1%) of the 184 tested werepositive for C.trachomatis, these patients and their wives receivingdoxycycline capsules twice, 100 mg on the first day and 100mg/day for the following 13 days. This treatment was effectivein 88.5% of the cases and in the rest, treatment continued witherithromycin 250 mg four times/day for 2 weeks. The authorscompared the semen parameters (cell count, motility, morphology,bovine mucus penetration and hypo-osmotic swelling test) inthe infected and non-infected groups and observed no significantdifference between these two groups     

Clonal aberrations of chromosomes X, Y, 7 and 10 in normal kidney tissue of patients with renal cell tumors.

By means of G-banding techniques, chromosome aberrations were studied in short-term cultures of normal renal parenchymal cells from 45 patients with renal cell carcinoma. Clonal chromosomal aberrations were detected in 29 patients; loss of the Y chromosome as well as trisomy X, 5, 7, 9, 10, 12, and 18 was found. Chromosomes 7 and 10 were involved preferentially. Results of fluorescence in situ hybridization with chromosome 7- and 10-specific DNA probes on non-cultured normal kidney cells suggested that the aberrations developed in vivo.     

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.     

Gender, suicidality and bipolar mixed states in adolescents

BACKGROUND: The purpose of this study was to determine the relationship between mixed states and suicidality among adolescent outpatients presenting with a DSM-IV defined major depressive episode (MDE). METHODS: Two-hundred and forty-seven adolescents meeting the criteria for MDE were screened for the presence of concurrent, intra-MDE hypomania/mania (i.e., mixed states). All patients were asked whether they had current suicidal ideation or had recently attempted any self-destructive physical act associated with the thought of dying (i.e., a suicide attempt). The data were subjected to analysis using univariate logistic regression. RESULTS: One hundred of the 247 (40.5%) adolescents were bipolar type I or type II. Of these, 82% were in mixed states. Of the patients with suicidal ideation, 62.8% were girls, and of those with histories of a suicide attempt, 69.4% were girls. Girls had more than twice the risk of having suicidal ideation (OR=2.2, p=0.004) and nearly 3 times the risk of having histories of a suicide attempt than boys (OR=2.87, p<0.0001). Being in a mixed state per se did not predict either suicidal ideation or a suicide attempt among all of the 247 patients. However, mixed states apparently independently contributed to the risk of (non-fatal) suicidal behavior among girls only. Of the mixed states, girls had nearly 4 times the risk of having made a suicide attempt compared with those without mixed states (OR=3.9, p=0.003). Age, presence of psychotic features and family history of mood disorder had little or no bearing on suicidality. LIMITATIONS: Correlational chart review study, no data collection on Axis I and Axis II comorbidity and adverse life-events. CONCLUSIONS: This report of greater suicidality in adolescent girls in a mixed state parallels the well-known adult literature of high frequency of mixed states in women. The findings are of relevance to the controversy of antidepressants and suicidality in juvenile depressives in that they identify a vulnerable group. In line with earlier suggestions by the senior author [Akiskal, H.S., 1995. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J. Am. Acad. Child Adolesc. Psych. 34, 754-763], our data highlight the public health importance of the wider recognition of bipolar mixed states in juvenile patients masquerading as unipolar depression. Finally, it appears to us that it is the failure of our formal nosology on mixed states--rather than the antidepressants per se--which is the root problem in this controversy.     

Model for assessment of proficiency of human immunodeficiency virus type 1 sequencing-based genotypic antiretroviral assays

Use of sequencing-based genotyping as a diagnostic assay for human immunodeficiency virus (HIV) antiretroviral resistance is increasing. Periodic evaluation of the proficiency of laboratories performing this assay should be established. It is important to identify components of the assay that influence the generation of reliable sequencing data and that should and can be monitored. A model was developed to determine what parameters were reasonable and feasible for assessing the performance of genotyping assays. Ten laboratories using the genotyping platform, HIV-1 Genotyping System (HGS) v. 1 and software versions 1.1 or 2.0, participated in two rounds of testing. For each round, each group was sent a panel consisting of three clinical samples to sequence in real time. Six months later, seven laboratories using the TRUGENE HIV-1 Genotyping Kit participated in a separate round, working with both panels at the same time. Analysis of the data showed that one main indicator of genotyping proficiency was achievement of > or =98% sequence homology of a sample tested to a group consensus sequence for that sample. A second was concordant identification of codons at sites identified with resistance mutations in the sample, although scoring of these criteria is still undetermined from this study. These criteria are applicable to all sequence-based genotyping platforms and have been used as a baseline for assessing the performance of genotyping for the determination of antiretroviral resistance in our ongoing proficiency program.     

Studies of immunological function in mice with defective androgen action. Distinction between alterations in immune function due to hormonal insensitivity and alterations due to other genetic factors.

The presence of androgen receptors in thymocytes and the well-described effects of exogenous androgens on thymus size suggest a role for androgenic hormones in thymocyte growth and maturation. Testicular feminization (Tfm/Y) mice which bear a heritable defect in the androgen receptor protein were studied to investigate how androgens might influence immune phenotype and function. These mice were compared to two types of controls; their Tabby/Y normal male littermates and male mice of the C57 Bl/6 strain from which the Tabby and Tfm mice were derived. Thymuses and spleens from Tfm/Y mice were larger than both types of controls. Phenotypic differences in thymocyte and splenocyte subpopulations identified by the T-cell markers CD3, CD4 and CD8 suggested that T-cell maturation was altered in the androgen-resistant animal. However, both Ta/Y and Tfm/Y were found to be high producers of interleukin-4 (IL-4) by both spleen and thymus cells, while cells from the C57 mice produced predominantly IL-2. These findings suggest that some immunological features of the Tfm/Y mouse may be related to its defect in androgen action, but that high levels of IL-4 production are probably related to other genetic changes in the C57 background.     

Psychological functioning among mothers of children with insulin-dependent diabetes mellitus: a longitudinal study

Mothers of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) were assessed repeatedly over a period of 6 years in order to determine the psychological correlates of managing this chronic illness. Both maternal depression and overall emotional distress after the 1st year of the IDDM increased slightly with illness duration and were also influenced by other factors. Mothers' adjustment shortly after their children were diagnosed with IDDM was a strong predictor of their long-term emotional symptomatology. However, mothers' symptoms over time were not related to medical aspects of IDDM (i.e., the extent of the children's metabolic control, number of rehospitalizations, or their compliance with the medical regimen) and were also unrelated to the levels of depression or anxiety reported by their children. Mothers generally found it easier to cope with the IDDM the longer their children had the illness. However, the degree to which mothers perceived the IDDM to be bothersome or difficult to manage at any given point in time was associated with their overall levels of emotional distress.     

Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex

Numerous spironolactone bodies have been detected in the zona glomerulosa cells of the adrenal cortex of a 36-year-old spironolactone-treated woman whose non-tumorous right adrenal gland was removed surgically because of primary hyperaldosteronism. Electron microscopy revealed spherical laminated whorls which consisted of a central core composed of an amorphous electron-dense material surrounded by numerous smooth-walled concentric membranes. Continuous with and deriving from the endoplasmic reticulum, they were present in viable cells and were not associated with ultrastructural features indicating cellular injury. Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds. Thus, they can be regarded as neither specific to spironolactone treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex.