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.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Insecticide poisoning in pregnancy. A case report.

A 25-year-old multigravida drank an organochlorine insecticide in an attempt to commit suicide at 16 weeks of pregnancy. This resulted in the death of twin fetuses and vaginal bleeding. The pregnancy was terminated using gemeprost, syntocinon and later surgical evacuation of the uterus. She developed respiratory arrest after the fetuses were aborted and also after surgical evacuation. On both occasions, she was intubated and mechanically ventilated. We believe that organochlorine insecticides may be fetocidal. In addition, surges in blood levels may occur during termination of pregnancy, delivery or evacuation of retained products of conception.     

Oral contraceptive marketing in Ibadan, Nigeria.

The demographic transition in Nigeria is gradually moving towards the second stage. There is clear evidence of a declining mortality but the fertility rate remains exceptionally high. A realistic approach towards reducing fertility rate is the use of oral contraceptive. This study assesses the distribution system of oral contraceptive in Ibadan, the second largest city in Nigeria. The findings revealed that the people are aware of modern oral contraceptives as they purchase them freely at chemist shops. But effective distribution is hampered by existing channels and high costs. A local source recommended is the proprietary medicine stores, often at convenient locations to the potential users of contraceptives. The current cost which is between $1.3 and $19.5 per couple-years of protection is exorbitant, consuming 0.5-7.8% of the gross annual income of the average individual. Therefore, the government should subsidize the prices of oral contraceptives, to facilitate freedom from the tyranny of excessive fertility.     

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.     

Ameloblastoma: analysis of 207 cases in a Nigerian teaching hospital.

OBJECTIVE: The aim of the study was to review all the cases of ameloblastoma seen at the Oral and Maxillofacial Surgery Clinic of the Lagos University Teaching Hospital, Nigeria, between 1980 and 2003. METHODS AND MATERIALS: In this retrospective study, case files and biopsy reports of new cases of ameloblastoma covering a 24-year period were retrieved and analyzed for sex, age on presentation, histologic type, and site distribution. RESULTS: A total of 207 cases of ameloblastoma were seen in the given period. One hundred and ninety-eight (95.7%) were benign, and 9 (4.3%) were malignant. A male-to-female ratio of 1.1:1 was found. The average ages on presentation for ameloblastoma and ameloblastic carcinoma were 31.67 and 46.44 years, respectively. The lesion was found to be more common in the premolar-molar region of the mandible. The most common histologic type was follicular ameloblastoma (25.1%). Nine (4.3%) cases of ameloblastic carcinoma were also reported. CONCLUSIONS: Ameloblastoma with a predilection for the posterior mandibular region is relatively common in our environment. Sex and site distributions are similar to previous reports in the literature.     

Health and economic consequences of septic induced abortion.

Over a period of 7 years, 230 cases of illegally induced abortions complicated by sepsis were treated at the University College Hospital, Ibadan, Nigeria. The number of terminations complicated by sepsis doubled from 25.4 (between 1981 and 1985) to 51.0 (between 1986 and 1987) cases per year. Peritonitis was the commonest associated complication while maternal mortality was 8.3%. The average cost of treatment was US$223.11, while the average monthly earnings was US$45.00. Legalization of abortion would have resulted in a saving of US$50,022.28. Provision of legal abortion would reduce the incidence of sepsis after termination while reproductive health education and information dissemination and provision of easily accessible family planning services would greatly reduce the number of unwanted pregnancies.     

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.      

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.