Genetic diversity of the Dwarf honeybee (Apis florea Fabricius, 1787) populations based on microsatellite markers.

Apis florea is one of two species of small, wild honeybee. The present study was conducted to evaluate the genetic diversity of Apis florea honeybee from 48 nests (colonies) using microsatellite markers in the South of Iran. All honeybee samples were analyzed for six microsatellite loci (A88, A107, A7, B124, A113 and A35). The six loci had different numbers of alleles in the sampled colonies ranging from 7 (loci A107) to 3 (loci A7, A35). Gene diversity in Apis florea ranged from 0.491 to 0.595. This range probably reflects the spreading of nests in a large region with a varied climate. Phylogenetic tree showed two distinct clusters including a) Minab region samples and b) Bandar Abbas, Bandar Khamir and Qeshm Island regions. All of these regions are geographically rich, having varied vegetation and climate conditions. Our findings are an important contribution to the methods of studying distribution and conservation of Apis florea.

Allele specific-PCR and melting curve analysis showed relatively high frequency of ß-casein gene A1 allele in Iranian Holstein, Simmental and native cows.

There are two allelic forms of A1 and A2 of ß-casein gene in dairy cattle. Proteolytic digestion of bovine ß-casein A1 type produces bioactive peptide of ß-casomorphin-7 known as milk devil. ß-casomorphin-7 causes many diseases, including type 1 diabetes, cardiovascular disease syndrome, sudden death and madness. The aim of the present study was to determine the different allelic forms of ß-casein gene in Iranian Holstein, Simmental and native cattle in order to identify A1 and A2 variants. The blood samples were collected randomly and DNA was extracted using modified salting out method. An 854 bp fragment including part of exon 7 and part of intron 6 of ß-casein gene was amplified by allele specific polymerase chain reaction (AS-PCR). Also, the accuracy of AS-PCR genotyping has been confirmed by melting temperature curve analysis using Real-time PCR machinery. The comparison of observed allele and genotype frequency among the studied breeds was performed using the Fisher exact and Chi-squared test, respectively by SAS program. Obtained results showed the A1 allele frequencies of 50, 51.57, 54.5, 49.4 and 46.6% in Holstein, Simmental, Sistani, Taleshi and Mazandarani cattle populations, respectively. The chi-square test was shown that no any populations were in Hardy-Weinberg equilibrium for studied marker locus. Comparison and analysis of the test results for allelic frequency showed no any significant differences between breeds (P>0.05). The frequency of observed genotypes only differs significantly between Holstein and Taleshi breeds but no any statistically significant differences were found for other breeds (P>0.05). A relatively high frequency of ß-casein A1 allele was observed in Iranian native cattle. Therefore, determine the genotypes and preference alleles A2 in these native and commercial cattle is recommended.

Lack of association between the TNF-α-1031genotypes and generalized aggressive periodontitis disease.

Periodontal disease is one of the most prevalent inflammatory illnesses and is a main cause of tooth loss in human population. Tumor necrosis factor-α (TNF-α) gene is one of pro-inflammatory cytokines which has important role in pathogenesis of periodontal disease. The main purpose of this study is to determine genotype abundance of TNF-α-1031 gene in both groups of patients and controls, and also investigation of relation of single nucleotide polymorphism (SNP) these genotypes with periodontal disease risk. DNA was extracted from blood tissue of 31 patients and 54 controls. The TNF-α-1031 polymorphism was evaluated by polymerase chain reaction- confronting two-pair primer (PCR-CTPP) method. In the GAP group, the frequencies of TT, TC and CC genotypes were 35.48%, 61.29 and 3.23%, respectively. In controls the frequencies of TT, TC and CC genotypes were 22.22%, 72.22%, and 5.56%, respectively. Results of this study showed that there was no significant association between TNF-α (-1031 T/C promoter) gene polymorphisms and the risk of generalized aggressive periodontitis disease.

Induction of linalool as a pharmaceutical and medicinal metabolite via cell suspension culture of cumin (Cuminum cyminum L.).

Cumin is an important medicinal plant in Iran. Plant cell suspension culture is a method for the production of medicinal and secondary metabolites. The linalool is a plant secondary metabolite that has been recognized as a neuroprotective agent. The purpose of this study was to evaluate the effects of salicylic acid elicitor on induction of linalool in cell suspension culture of cumin. For this purpose, the cumin seeds were prepared, to obtain sterile seedling, were disinfected with sodium hypochlorite and alcohol, and were cultured on MS basal medium. This research was conducted in two separate experiments including callus induction and suspension cultures. Leaf explants were prepared from sterile seedlings and used to produce callus on MS medium supplemented with 1 mg/l NAA and 0.5 mg/l BAP. In order to establish suspension culture, the appropriate calli were transferred to liquid medium. Then cell cultures were treated with elicitors. The effects of elicitor on the production of linalool secondary metabolite and cell viability were assessed by GC-Mass and tetrazolium test respectively. For this purpose, the salicylic acid (at concentrations of 0, 1, 2, 4 and 8 mg/l) was used. The experimental design was a completely randomized design with five treatments and three replications. The results of cell culture and GC-Mass analysis showed that salicylic acid had significant effects on the linalool production (<0.01). At all concentrations of salicylic acid, viability of the cells in suspension culture experiments was lower than control. Increasing the elicitor concentrations lead to reduction in cell survival. In conclusion it is possible to produce linalool as a secondary metabolite and pharmaceutical agent in cell culture of cumin. It is necessary to determine the best combination of medium and elicitor.

Bilayer insulator tunnel barriers for graphene-based vertical hot-electron transistors.

Vertical graphene-based device concepts that rely on quantum mechanical tunneling are intensely being discussed in the literature for applications in electronics and optoelectronics. In this work, the carrier transport mechanisms in semiconductor-insulator-graphene (SIG) capacitors are investigated with respect to their suitability as electron emitters in vertical graphene base transistors (GBTs). Several dielectric materials as tunnel barriers are compared, including dielectric double layers. Using bilayer dielectrics, we experimentally demonstrate significant improvements in the electron injection current by promoting Fowler-Nordheim tunneling (FNT) and step tunneling (ST) while suppressing defect mediated carrier transport. High injected tunneling current densities approaching 10(3) A cm(-2) (limited by series resistance), and excellent current-voltage nonlinearity and asymmetry are achieved using a 1 nm thick high quality dielectric, thulium silicate (TmSiO), as the first insulator layer, and titanium dioxide (TiO2) as a high electron affinity second layer insulator. We also confirm the feasibility and effectiveness of our approach in a full GBT structure which shows dramatic improvement in the collector on-state current density with respect to the previously reported GBTs. The device design and the fabrication scheme have been selected with future CMOS process compatibility in mind. This work proposes a bilayer tunnel barrier approach as a promising candidate to be used in high performance vertical graphene-based tunneling devices.

Hemospermia: long-term outcome in 165 patients.

Long-term course of hemospermia has not been addressed in the sexual medicine literature. We report our 15 years' experience. From 1997 to 2012, 165 patients presented with hemospermia. Mean age was 38 years. Mean follow-up was 83 months. Laboratory evaluation and testis and transabdominal ultrasonography was done in all. Since 2008, all sonographies were done by the first author. One patient had urinary tuberculosis, one had bladder tumor and three had benign lesions at verumontanum. One patient had bilateral partial ejaculatory duct obstruction by stones. All six patients had persistent, frequently recurring or high-volume hemospermia. All pathologies were found in young patients. In the remaining 159 patients (96%), empiric treatment was given with a fluoroquinolone (Ciprofloxacin) plus an nonsteroidal anti-inflammatory drug (Celecoxib). In our 15 years of follow-up, no patient later developed life-threatening disease. Diagnostic evaluation of hemospermia is not worthwhile in the absolute majority of cases. Advanced age makes no difference. Only high-risk patients need to be evaluated. The vast majority of cases may be safely and effectively treated with empiric therapy. Almost all patients do well in long term.

Electromechanical piezoresistive sensing in suspended graphene membranes.

Monolayer graphene exhibits exceptional electronic and mechanical properties, making it a very promising material for nanoelectromechanical devices. Here, we conclusively demonstrate the piezoresistive effect in graphene in a nanoelectromechanical membrane configuration that provides direct electrical readout of pressure to strain transduction. This makes it highly relevant for an important class of nanoelectromechanical system (NEMS) transducers. This demonstration is consistent with our simulations and previously reported gauge factors and simulation values. The membrane in our experiment acts as a strain gauge independent of crystallographic orientation and allows for aggressive size scalability. When compared with conventional pressure sensors, the sensors have orders of magnitude higher sensitivity per unit area.

Total elbow replacement with the Coonrad-Morrey prosthesis: our medium to long-term results.

INTRODUCTION: Semiconstrained total elbow replacement is now a well recognised and reliable surgical option for advanced elbow disease, mainly rheumatoid arthritis. METHODS: We report a retrospective analysis of 31 primary total elbow replacements in 28 patients with a mean follow-up duration of 55 months. The mean age of the patients was 65 years. The indications included 27 cases of rheumatoid arthritis, 3 fractures and 1 case of osteoarthritis. Twenty-one elbows in nineteen patients were assessed using the Mayo elbow performance score (MEPS) in a special follow-up clinic. In the other nine patients (ten elbows), the assessment was carried out with case notes and x-rays. RESULTS: The mean pre-operative MEPS in the 21 elbows recalled was 40. This improved to 89 post-operatively (range: 55-100). Sixteen of the twenty-one elbows were considered excellent, two good, two fair and one poor. The range of movement was recorded in eight of the other ten elbows and the mean was 98°. At the last follow-up visit, x-rays were normal in 23 elbows although the ulnar component was loose in 3, the humeral component loose in 2. There were also two cases of non-union of the medial epicondyle and one patient had mild heterotopic ossification. Complications included one infection, which needed irrigation and debridement with a satisfactory final result, and two cases of ulnar nerve palsy/neurapraxia. Two elbows were considered failures due to severe pain caused by prosthetic loosening. These were referred for revision surgery. CONCLUSIONS: Excellent pain relief and good function can be achieved in the medium and long term with the Coonrad-Morrey-semiconstrained total elbow replacement prosthesis in patients with severe destructive elbow arthropathy.

Efficacy of influenza vaccination in patients with cirrhosis and inactive carriers of hepatitis B virus infection.

BACKGROUND: Influenza can causes morbidity and mortality that are greatly enhanced in patients with underlying chronic diseases such as Cirrhotic patients. This study was performed to assess the immunogenicity of Influenza vaccination in patients with cirrhosis and inactive carriers of Hepatitis B virus infection. METHODS: In this clinical study 93 enrolled subjects divided into 3 groups: Cirrhotic (N=28), Inactive carriers of Hepatitis B (N=31) and subjects (N=34). All the participants were vaccinated by Influenza vaccine (Influvac®). Serum samples were taken before and 4 weeks after vaccination and the Humoral Immunogenicity was assessed by the Hemagglutination Inhibition (HI) test. RESULTS: Four weeks after vaccination, seroconversion rates of vaccine strains ranged between 71.4% and 100% in Group 1, 70.6% and 94.1% in Group 2, and 58.1% and 80.7% in Group 3. No significant differences were seen in the rates of Seroconversion and antibody Geometric Mean Titers (GMTs) against Influenza A (H1N1 and H3N2) vaccine components in the three groups (P>0.05).The rates of Seroconversion and antibody GMTs against Influenza B vaccine component were significantly higher in Cirrhotic and inactive carriers of Hepatitis B than healthy subjects (P<0.005). No significant (P>0.05) differences in the rates of Seroprotection were observed within the three groups. Antibody GMTs against all three strains of Influenza vaccine increased significantly (P<0.001) after vaccination in three groups. CONCLUSION: Influenza vaccination is effective in Cirrhotic patients and inactive carriers of Hepatitis B as well as healthy individuals. It means that vaccination should be considered in such patients in order to reduce the morbidity and mortality of Influenza.

Prevalence of Rotavirus, Adenovirus, and Astrovirus Infections among Patients with Acute Gastroenteritis in, Northern Iran.

BACKGROUND: The aim of the study was to determine the incidence of non-bacterial acute gastroenteritis associated with diarrheal diseases in Mazandaran Province, northern Iran. METHODS: A total of 400 symptomatic cases from patients with acute gastroenteritis from Mazandaran Province in Iran were screened using EIA method for the presence of rotavirus, adenovirus and astrovirus during 2005-2006. Chi-square tests were used for testing relationships between different variables. RESULTS: Rotavirus, adenovirus and astrovirus were detected in 62%, 2.3%, and 3% of samples, respectively. The maximum rate of rotaviruses was detected in the <1-year-old age group, while minimum rate was found in the 10 years and older age group. Astrovirus and adenovirus were detected predominantly in the 2-5-year-old age group of children, with a prevalence of 8.3% and 3.5% respectively. All studied viral gastroenteritis peaked in the winter, and minimum rate were found in summer. CONCLUSION: Our statistical analyzes indicated that viral gastroenteritis, especially Rota-viral, had the highest number of occurrences in colder seasons notably in winter and more frequently were observed among younger children.

A Study on the Prevalence of Cryptosporidium in HIV Positive Patients.

BACKGROUND: AIDS is acquired by infection with HIV (human immuno-deficiency virus). It leaves the host susceptible to malignant and unusual infections especially opportunistic ones. Most of AIDS patients infected with opportunistic parasitic infections die because of chronic diarrhea and deaths due to Cryptosporidium diarrhea in AIDS patients are considerable in the recent two decades. The aim of this study is to find Cryptosporidium parasite in AIDS patients referring to the center of Diseases consultation in Kermanshah province and to determine the frequency of infection in those patients. METHODS: In this study stool and blood samples were collected from 75 AIDS patients referring regularly to the Center of Diseases Consultation in Kermanshah and the gathered information were filled in the questionnaires together with their personal information regarding their names, sex and etc. Stool samples were tested using direct and formalin ether methods and then the smears that were dyed using modified acid fast staining were examined. Peripheral blood samples were used to determine the CD4 counts. RESULTS: The results showed that the frequency of infection with Cryptosporidium in AIDS patients was 26.7% (20 cases). CONCLUSION: According to the study, as the number of CD4 decreased in the patients, the probability of infection with opportunistic parasites increased and increase in the number CD4 that is normally accompanied with strengthening the body immune system resulted in the decrease in the frequency of infection with Cryptosporidium.

Downregulation of topoisomerase IIbeta in myeloid leukemia cell lines leads to activation of apoptosis following all-trans retinoic acid-induced differentiation/growth arrest.

Among the topoisomerase (topo) II isozymes (alpha and beta), topo IIbeta has been suggested to regulate differentiation. In this study, we examined the role of topo IIbeta in all-trans retinoic acid (ATRA)-induced differentiation of myeloid leukemia cell lines. Inhibition of topo IIbeta activity or downregulation of protein expression enhanced ATRA-induced differentiation/growth arrest and apoptosis. ATRA-induced apoptosis in topo IIbeta-deficient cells involved activation of the caspase cascade and was rescued by ectopic expression of topo IIbeta. Gene expression profiling led to the identification of peroxiredoxin 2 (PRDX2) as a candidate gene that was downregulated in topo IIbeta-deficient cells. Reduced expression of PRDX2 validated at the mRNA and protein level, in topo IIbeta-deficient cells correlated with increased accumulation of reactive oxygen species (ROS) following ATRA-induced differentiation. Overexpression of PRDX2 in topo IIbeta-deficient cells led to reduced accumulation of ROS and partially reversed ATRA-induced apoptosis. These results support a role for topo IIbeta in survival of ATRA-differentiated myeloid leukemia cells. Reduced expression of topo IIbeta induces apoptosis in part by impairing the anti-oxidant capacity of the cell owing to downregulation of PRDX2. Thus, suppression of topo IIbeta and/or PRDX2 levels in myeloid leukemia cells provides a novel approach for improving ATRA-based differentiation therapy.

Evaluation of patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity during antituberculosis [correction of antituberclosis] treatment.

For evaluation the extent of antituberculosis drug-induced hepatotoxicity and also to determine the patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity induced by antituberculosis medications, a prospective study was conducted on 112 patients in a tertiary care university teaching hospital for three years. Causality, preventability, predictability and severity of hepatotoxicity were determined based on the available standard algorithms. Of 112 patients, 31 (27.7%) demonstrated hepatotoxicity. Two patients died from complications of liver-related illness. The mean duration of treatment before the onset of hepatotoxicity was 16.7+/-3.2 days. Malnutrition was present in 17 of 112 patients. Most of hepatotoxicity (25/31 or 80.6%) occurred within the first month of treatment. Reintroduction of antituberculosis drugs was possible in 29 of 31 patients. Univariate and multivariate analysis did not show significant relationships between the rate of hepatotoxicity with age, sex, nutrition and nationality. Our results showed that hepatotoxicity induced by antituberculosis drugs is a nonpreventable and unpredictable reaction. The causality of this reaction is classified as category A based on European grading of causality. This study noted that the frequency of hepatotoxicity induced by antituberculosis drugs in Iranian patients is higher than other studied populations.

Evaluation of carpal tunnel release using the Knifelight instrument.

We have performed a prospective randomized controlled trial to compare the results of open carpal tunnel release with those of carpal tunnel release using a Knifelight (Stryker, Kalamazoo, MI). This is a new knife with its own battery-powered light source which enables the operation to be performed through a small incision in the palm of the hand. There were 43 patients in the open operation group and 39 in the Knifelight group. We found no difference in discomfort reported during surgery, in the operative time, in the grip strength measured at 2 and 6 weeks post-operatively or in the proportion of patients cured of their pre-operative symptoms. Patients in the Knifelight group had a statistically significant improvement in the time to return to work and in scar tenderness at 6 weeks post-operatively.

Characterization of the microflora of the human axilla.

It is widely accepted that axillary malodour is attributable to the microbial biotransformation of odourless, natural secretions into volatile odorous products. Consequently, there is a need to understand the microbial ecology of the axilla in order that deodorant products, which control microbial action in this region, can be developed in the appropriate manner. A detailed characterization of the axillary microflora of a group of human volunteers has been performed. The axillary microflora is composed of four principal groups of bacteria (staphylococci, aerobic coryneforms, micrococci and propionibacteria), and the yeast genus Malassezia. Results indicated that the axillary microflora was dominated by either staphylococcal or aerobic coryneform species. Comparisons between axillary bacterial numbers and levels of axillary odour demonstrated the greatest association between odour levels and the presence of aerobic coryneforms in the under-arm. As the taxonomy of cutaneous aerobic coryneforms is poorly understood, a further study was conducted to characterize selected axillary aerobic coryneform isolates. Using the molecular technique of 16S rDNA sequencing, selected genomic sequences of a number of axillary aerobic coryneform isolates were obtained. Comparisons with sequence databases indicated the likely presence of a range of Corynebacterium species on axillary skin, although the majority of isolates were most similar to either Corynebacterium G-2 CDC G5840 or C. mucifaciens DMMZ 2278. Although for a panel of individuals differences in the carriage of Corynebacterium species were noted, similar species were carried by a number of panellists. All isolates examined in this limited evaluation failed to demonstrate the capability to metabolize long-chain fatty acids (LCFAs) to shorter chain, more volatile products. The application of this modern molecular phylogenetic technique has increased understanding of the diversity of aerobic coryneform carriage in the axilla, and on human skin. The application of this technique in other studies to assess the ethnic differences in cutaneous bacterial ecology, or the effects on the microflora of specific product use, will assist in the future development of novel deodorant systems.

Absence of CCND1 gene amplification in breast tumours of BRCA1 mutation carriers.

BACKGROUND/AIMS: It was recently reported that significantly fewer breast tumours of BRCA1 mutation carriers overexpressed cyclin D1 and HER2 protein than tumours of age matched breast cancer cases unselected for family history. This study aimed to examine the genetic basis of this reduction by determining the frequency of tumours within this cohort showing DNA amplification of these genes. METHODS: Paraffin wax embedded sections of breast tumours from BRCA1 mutation carriers and age, grade, histological type, and tumour size matched non-familial controls that had previously been stained for cyclin D1 and HER2 protein overexpression were analysed for CCND1 and HER2 gene amplification using fluorescence in situ hybridisation. RESULTS: CCND1 amplification was detected in none of the 30 tumours of the BRCA1 mutation carriers and in 19 of 74 tumours of the matched controls. Of those samples previously determined to overexpress the HER2 protein, HER2 amplification was detected in one of three tumours from BRCA1 mutation carriers and in 13 of 17 tumours of the age matched non-familial cases. CONCLUSION: None of the tumours of BRCA1 mutation carriers showed CCND1 amplification and only one tumour showed HER2 amplification. In contrast, a large proportion of cyclin D1 and HER2 overexpression in tumours of non-familial breast cancer cases could be accounted for by amplification of these genes. These data suggest that breast tumorigenesis in BRCA1 mutation carriers occurs by a molecular mechanism distinct from that of age matched non-familial cases.

Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at diagnosis.

PURPOSE: Breast tumors of BRCA1 mutation carriers and those of early onset breast cancer cases share similar histological features, being generally high-grade, highly proliferative, aneuploid tumors that are predominantly estrogen- and progesterone-receptor negative. Because histological features of tumors of premenopausal women differ from those of tumors of older women, we sought to determine whether the immunophenotype of breast tumors of BRCA1 mutation carriers was influenced by age at diagnosis. EXPERIMENTAL DESIGN: We examined 31 breast tumors from BRCA1 mutation carriers and compared them with 81 tumors of age-matched (plus or minus 5 years) breast cancer patients unselected for family history. Tumors were further matched for histology, grade, and size. Paraffin-embedded tumor tissues were examined for protein expression of estrogen receptor (ER), PR, Ki-67, cyclin D1, TP53, HER2, beta-catenin, and cyclin E using immunohistochemical approaches. RESULTS: ER (P = 0.01), PR (P = 0.06), and cyclin D1 (P = 0.002) were less frequently expressed and Ki-67 (P = 0.01) and beta-catenin (P = 0.04) were more frequently expressed in tumors of BRCA1 mutation carriers than controls. After age stratification, we found a significant difference in the frequency of tumors of BRCA1 mutation carriers diagnosed before 50 years of age compared with age-matched controls that stained positive for ER (P = 0.01), PR (P = 0.03), Ki-67 (P = 0.008), cyclin D1 (P < 0.001), HER2 (P = 0.04), and beta-catenin (P = 0.05). However, no significant differences were observed in tumors of BRCA1 mutation carriers diagnosed at age 50 or older compared with age-matched controls. CONCLUSIONS: These data suggest that age at diagnosis, possibly related to menopausal status, may be an important factor in the expression of specific proteins in breast tumors of BRCA1 mutation carriers.

Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects.

Arylamines such as 2-naphthylamine and 4-aminobiphenyl are suspected human bladder procarcinogens that require bioactivation to DNA-reactive species to exert their carcinogenic potential. The goals of the present study were (i) to assay for the presence of the arylamine acetyltransferases NAT1 and NAT2, and of the cytochrome P450 isoform CYP1A2, in human bladder epithelium; and (ii) to determine whether the activities of these arylamine biotransforming enzymes differ between bladder cancer patients and control subjects. We measured in-vitro enzyme activities in biopsies of normal, undiseased bladder epithelium obtained from 103 bladder cancer patients. NAT1 activity was detectable in all samples, with mean levels higher than those found in human liver. Kinetic evidence also suggested low levels of NAT2 expression in this tissue, but there was no detectable CYP1A2 by either enzymatic or immunochemical measurements. We also compared several probe drug indices of in-vivo NAT1, NAT2 and CYP1A2 activity between 53 bladder cancer patients and 96 cancer-free control subjects who were carefully matched for age, gender and smoking status. NAT1 and NAT2 genotypes were also determined. No significant differences were found between bladder cancer patients and control subjects for a number of individual phenotypic or genotypic predictors of enzyme function. Our results suggest that although expression of particular arylamine biotransforming enzymes within the bladder tissue could play a significant role in locally bioactivating arylamine procarcinogens in theory, interindividual variations in CYP1A2, NAT1 and NAT2 activities do not significantly differ between bladder cancer patients and control subjects when potential arylamine exposures are controlled for

Frequency of BRCA1 and BRCA2 mutations in a clinic-based series of breast and ovarian cancer families.

Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast and ovarian cancer cases. In this study, we sought to determine the frequency of BRCA1- and BRCA2-mutation carrier families in a hospital-based cancer family registry. The frequency of families with germline truncating mutations in BRCA1 and BRCA2 was 17.3% (18/104) and 1.9% (2/104), respectively. Two novel truncating mutations, BRCA1 1848delGA and BRCA2 5694insT, were identified. We also sought to determine the carrier frequency of other affected family members for which the mutation lineage could be established within these families. Not including the probands, 72% (18/25) of the affected family members within the BRCA1 mutation-associated families were carriers, and all four affected members of the BRCA2 families were carriers. These data imply that risk evaluation based on cancer family history alone may result in inaccurate estimates, and where possible, mutation testing should be considered in other affected family members to verify carrier status.

Behavioral effects of alpha-MSH and MCH after central administration in the female rat.

The behavioral effects of alpha-MSH, MCH, and alpha-MSH + MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) (bilateral, 100 ng in 0.5 microliter). Infusion of alpha-MSH into the VMN increased aggressive behavior; in the MPOA it reduced exploration and increased anxiety. In both areas it stimulated sexual behavior. MCH also stimulated sexual behavior in the MPOA and VMN and had an anxiogenic effect in the MPOA. The effect of alpha-MSH on aggression and exploration was antagonized by MCH. When given together, the two peptides were mutually antagonistic on anxiety. This study indicates that MCH has central nervous system effects and may be a partial alpha-MSH agonist.