Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.      

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post- retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.      

Differential expression of cdk inhibitors p16, p21cip1, p27kip1, and cyclin E in cervical cytological smears prepared by the ThinPrep method

Our objective was to correlate p16, p21cip1, p27kip1, and cyclin E protein expression with the degree of dysplasia on ThinPrep Papanicolaou (Pap) smears using a modified immunoperoxidase staining. Smears read as normal, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or high-grade SIL (HSIL) were identified and tested for high-risk human papillomavirus (HR-HPV). Additional smears were processed for immunoperoxidase for p16, p21cip1, p27kip1, and cyclin E. Thirty-four smears were satisfactory for study. The p16 was positive in all nine HSIL, in four of nine LSIL, and in one of seven ASC-US. The p27kip1 was positive in all nine HSIL, in eight of nine LSIL, and in one of seven ASC-US. The p21cip1 was positive in all nine HSIL, in one of nine LSIL, and in one of seven ASC-US. Cyclin E was positive in seven of nine HSIL and in one of nine LSIL and in none of the ASC-US smears. Normal smears were negative for all the antigens. There was poor correlation of protein expression and HR-HPV infection. We concluded that p16, p21cip1, p27kip1, and cyclin E can be demonstrated on Pap smears and they are expressed differentially in dysplastic cells, with highest expression in HSIL. The p21cip1 and cyclin E showed the greatest correlation with HSIL.     

Detection of the CD56+/CD45- immunophenotype by flow cytometry in neuroendocrine malignancies

AIMS: Antibodies against CD56 are primarily used in flow cytometric studies to detect natural killer cells. However, they may be useful in the identification of neuroendocrine malignancies, especially if the cells do not express CD45, indicating a non-leucocyte origin. METHODS: A retrospective review was conducted on all solid tissue flow cytometric studies performed between January 1997 and September 2001, to identify all cases with a CD56+/CD45- immunophenotype. RESULTS: Twelve neuroendocrine malignancies (five metastatic small cell carcinomas, three Merkel cell carcinomas, two metastatic undifferentiated neuroendocrine carcinomas, one metastatic pancreatic neuroendocrine carcinoma, and one neuroblastoma) were identified. CONCLUSIONS: CD56+/CD45- neuroendocrine malignancies are only rarely detected in the flow cytometric analysis of solid tissue samples. However, the recognition of this immunophenotype is important to avoid their misclassification as natural killer cell malignancies. Furthermore, flow cytometry assists in the rapid identification of such cases, so that appropriate immunohistochemical studies can be performed to facilitate their correct diagnosis.     

Body fat, caloric intake, and plasma leptin levels in women with anorexia nervosa.

OBJECTIVE: To measure serum leptin concentrations in women with anorexia nervosa (AN) and to identify independent predictors of leptin levels, thereby allowing hormone levels to be modeled using regression analysis. METHODS: A cross-sectional study of 15 AN inpatients and 16 healthy control subjects. Age, height, weight, percent body fat, total caloric intake, fat intake, and fasting plasma leptin levels were recorded. Stepwise forward regression analysis was carried out to identify predictors of leptin levels. RESULTS: Circulating leptin concentrations in AN were 3.5+/-0.5 versus 7.6+/-1.2 ng/ml in control subjects. Percent body fat correlated best with leptin levels in anorexic and control subjects (r =.63; p =.0002), with caloric intake showing only a moderate correlation (r = .47; p = .008). Only percent body fat was a significant predictor of plasma leptin levels in our regression model. DISCUSSION: Leptin levels are proportionately lower in AN as compared to healthy controls. It appears that physiological regulation of plasma levels with respect to percent body fat is maintained in individuals with little body fat.     

The effects of oxytocin on intracranial pressure

The commonly used vasodilators sodium nitroprusside and nitroglycerine increase the intracranial pressure (ICP). Oxytocin is also a vasodilator although its primary effect is contraction of uterine smooth muscle. We therefore studied the effect of oxytocin on the ICP of cats. Twelve cats were assigned to two equal groups. One group had normal ICP and in the other the ICP was artificially increased by inflating a balloon placed in the extradural space. All of the cats initially received an oxytocin infusion for 15 min. After a period of stabilization, an additional dose of oxytocin was injected as a bolus. Oxytocin administered as an infusion did not change the ICP significantly in any of the cats. Oxytocin administered as a bolus increased the ICP from 27 +/- 4 to 31 +/- 2 mm Hg in the cats with artificially increased ICP. There were no significant changes in the mean blood pressure or heart rate in either group.