PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m²; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (O₂) at ventilatory anaerobic threshold (O₂AT) and at peak effort (peak O₂) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, O₂AT was 40.72 (5.92) ml/kg per min, and peak O₂ was 52.95 (8.13) ml/kg per min. Using bivariate Pearsons correlation, and in separate multivariate regression analyses, O₂AT and peak VO₂ showed a significant and reasonably good correlation with FMD (r=0.84, P<0.001 and r=0.77, P=0.001, respectively), independent of age, body mass index and serum total cholesterol (=0.77, P<0.001, R² of the overall model=0.79 and =0.70, P<0.005, R² of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries.     

Profiles of HIV voluntary counseling and testing of clients at a district hospital,Chiang Mai Province,northern Thailand,from 1995 to 1999

Voluntary HIV counseling and testing (VCT) is a central component of comprehensive HIV prevention strategies targeting individual risk reduction. VCT data are essential for planning and improving HIV/AIDS intervention strategies. The objective of this study is to describe demographic profiles, reasons for seeking HIV counseling and testing, rate of declining HIV testing after pretest counseling, rate of failure to return for HIV test results, and HIV prevalence and associations among 3570 clients who sought VCT at Sansai Hospital in northern Thailand from 1995 to 1999. Data were abstracted retrospectively from client-level data recorded by the hospital counselors on a standard form. HIV prevalence was 29% and remained high throughout the study period. Reasons for seeking VCT for men and women were markedly different and highly correlated with rates of declining the test, failure to return for test results, and HIV prevalence. Declining VCT and failing to return were high among uneducated clients (p <.001). Failure to return among men was associated with HIV prevalence (OR = 1.72, p =.003), particularly for those who had risk behaviors (OR = 5.92, p <.001) and those who wanted to know their HIV serostatus (OR = 4.44, p =.002). Overall, VCT acceptance and returning for test results were high. VCT services at the community level can reach high-risk individuals, especially male partners of women tested as part of routine prenatal care.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.      

Migraine headaches and panic attacks

Migraine headache and panic attacks are two common conditions which first occur at an early age and appear to have a number of underlying physiologic abnormalities in common. In a population-based telephone interview survey examining headache occurrence in approximately 10,000 subjects, 12-29 years old, we assessed the prevalence of panic disorder (and a less severe entity designated as panic syndrome) using an abbreviated version of the National Institute of Mental Health Diagnostic Interview Survey. Subjects with panic disorder or panic syndrome reported more frequent occurrence of headaches during the preceding week, as well as headaches of longer duration and substantially more headaches with migraine symptoms than individuals without a history of panic attack. Males with panic disorder were 7 times more likely than those without this condition to report the occurrence of a migraine headache in the previous week. In addition, 5.5% of males and 9.5% of females with panic disorder or panic syndrome reported 25% of the total migraine headaches described by all study subjects in the one-week recall period.     

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.      

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.