Cortical granule exocytosis is triggered by different thresholds of calcium during fertilisation in sea urchin eggs

In sea urchin eggs, fertilisation is followed by a calcium wave, cortical granule exocytosis and fertilisation envelope elevation. Both the calcium wave and cortical granule exocytosis sweep across the egg in a wave initiated at the point of sperm entry. Using differential interference contrast (DIC) microscopy combined with laser scanning confocal microscopy, populations of cortical granules undergoing calcium-induced exocytosis were observed in living urchin eggs. Calcium imaging using the indicator Calcium Green-dextran was combined with an image subtraction technique for visual isolation of individual exocytotic events. Relative fluorescence levels of the calcium indicator during the fertilisation wave were compared with cortical fusion events. In localised regions of the egg, there is a 6s delay between the detection of calcium release and fusion of cortical granules. The rate of calcium accumulation was altered experimentally to ask whether this delay was necessary to achieve a threshold concentration of calcium to trigger fusion, or was a time-dependent activation of the cortical granule fusion apparatus after the 'triggering' event. Calcium release rate was attenuated by blocking inositol 1,4,5-triphospate (InsP3)-gated channels with heparin. Heparin extended the time necessary to achieve a minimum concentration of calcium at the sites of cortical granule exocytosis. The data are consistent with the conclusion that much of the delay observed normally is necessary to reach threshold concentration of calcium. Cortical granules then fuse with the plasma membrane. Further, once the minimum threshold calcium concentration is reached, cortical granule fusion with the plasma membrane occurs in a pattern suggesting that cortical granules are non-uniform in their calcium sensitivity threshold.     

Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring

BACKGROUND: Recognizing the disparities in cancer morbidity and mortality that exist between African Americans and whites, an urban university and its neighborhood community undertook the development of an education program to transfer state-of-the-art cancer prevention, detection, and treatment information from an academic medical center to community residents, including school-age children. METHODS: An intergenerational, multilevel intervention was developed to: 1) assess the health beliefs of the community, 2) identify, develop, and train an intergenerational group of community residents who would serve as health educators, and 3) promote behavioral change among the target population. RESULTS: Ten community residents were trained as educators. Over the course of two years they conducted cancer education programs that reached 775 adults. During the same period, the school-based educational intervention reached 264 seventh-grade students. CONCLUSIONS: Implications for the design and implementation of community-based cancer education programs in this African American community are identified.     

Cardiac cavernous hemangioma mimicking pericardial cyst: atypical echocardiographic appearance of a rare cardiac tumor

Cavernous hemangioma is a rare tumor with infrequent cardiac involvement. Preoperative or antemortem diagnosis may be difficult. Several prior case reports have described echocardiographic findings of cavernous hemangioma. We report here a 50-year-old white female patient with this tumor. Transesophageal echocardiography detected a mass with an echocardiographic appearance not previously described for cavernous hemangioma. The tumor appeared as a large echolucent unilocular cystic mass, leading to an erroneous preoperative diagnosis of pericardial cyst. This previously unreported finding should be recognized by echocardiographers in the evaluation of cardiac masses.     

Sequence and functional relationships between androgen-binding protein/sex hormone-binding globulin and its homologs protein S, Gas6, laminin, and agrin

Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an extracellular binding protein that regulates the bioavailability of sex steroids. ABP/SHBG is closely related to the globular (G) domain of vitamin K-dependent protein S family of proteins and more distantly related to the G domains of several extracellular matrix proteins. ABP/SHBG appears to have evolved from the fusion of two ancestral G domains. Expanding evidence suggests that ABP/SHBG has other functions that are mediated through membrane binding, including signal transduction; however, the types of binding proteins (receptors) have not been identified. Sequence comparisons of ABP/SHBG with G domains of its homologs protein S, Gas6, laminin, and agrin have identified regions of ABP/SHBG that may bind receptors related to homolog receptors. These membrane receptors include beta-integrins, alpha-dystroglycan, and receptor tyrosine kinases. The G domains of laminin and related proteins have clearly evolved from a common ancestor to interact with specific receptors and binding proteins. It remains to be determined if ABP/SHBG followed this evolutionary pathway.     

Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine

Dihydropteroate synthase (H2Pte synthase) is the target of the sulfur-based antimalarial drugs, which are frequently used in synergistic combination with inhibitors of dihydrofolate reductase (H2folate reductase) to combat chloroquine-resistant malaria. We have isolated the H2Pte synthase coding sequence of the most pathogenic human parasite Plasmodium falciparum. It forms part of a longer coding sequence, located on chromosome 8, that also specifies 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (CH2OH-H2pterinPP kinase) at its 5' proximal end. This domain is unusually large, with two long insertions relative to other CH2OH-H2pterinPP kinase molecules. To investigate a possible genetic basis for clinical resistance to sulfa drugs, we sequenced the complete H2Pte synthase domains from eleven isolates of P. falciparum with diverse geographical origins and levels of sulfadoxine resistance. Overall, point mutations in five positions were observed, affecting four codons. Parasite lines exhibiting high-level resistance were found to carry either a double mutation, altering both Ser436 and Ala613, or a single mutation affecting Ala581. The mutations at positions 436 and 581 have the same location relative to each of two degenerate repeated amino acid motifs that are conserved across all other known H2Pte synthase molecules. The amino acid alteration at residue 613 is identically positioned relative to a different conserved motif. The fourth amino acid residue (437) affected by mutation, though adjacent to the apparently crucial residue 436, shows no obvious correlation with resistance. Although these mutations have no exact counterparts in any other organism, that at position 581 falls within a region of three amino acids where H2Pte synthase is modified in various ways in a number of sulfonamide-resistant pathogenic bacteria. Copy-number analysis indicated that there was no amplification of the H2Pte synthase domain in resistant parasite lines of P. falciparum, compared to sensitive lines.     

Breastfeeding after reduction mammaplasty

A retrospective study was performed of 30 women who had undergone breast reduction and subsequently wished to breastfeed. Breastfeeding capabilities were assessed by a trained lactation consultant. Findings indicate that in women who have a physiological type of operation then breastfeeding is usually possible (18 patients out of 19), although complementary feeds may be required. We strongly suggest that all functioning breast tissue that remains after reduction mammaplasty be left attached to the nipple in a physiological manner to allow subsequent breastfeeding.     

An outcomes assessment of 15 years of patient care experiences in predoctoral pediatric dentistry

OBJECTIVE: To observe the features of the changes of color pattern electroretinogram (CP-ERG) in early primary open-angle glaucoma (POAG). METHOD: The detection and analyses of CP-ERGs in 29 patients (48 eyes) with POAG, 10 patients (16 eyes) with ocular hypertension and 33 age-matched normal volunteers (48 eyes) were made. RESULTS: The changes of CP-ERG in early POAG included reduction of amplitudes of P1 and N2 waves, prolongation of the peak times of red/black N2 and blue/black P1 waves. Part of the patients with ocular hypertension had the amplitude of N2 wave reduced. Five factors including the amplitude of blue/black N2 wave, the amplitudes of red/black P1 and N2 waves, the peak time of red/black N2 wave and the white/black P1 to N2 wave amplitude ratio from CP-ERG which are significantly correlated to the diagnosis of early POAG were selected by the multiple factor stepwise discriminatory analysis, and the stepwise discriminatory function was set up. CONCLUSIONS: CP-ERG is a useful method in detecting the retinal functions in early POAG, and is helpful to its early diagnosis.     

Transient posterior knee pain with the meniscal arrow

A 31% incidence of focal posterior knee pain was noted in our initial experience with all-inside meniscal repair using the absorbable Meniscal Arrow system (Bioscience, Tampere, Finland). The pain was transient, resolved by 6 months in all cases, and was unrelated to the length of implant. A typical case is presented to assist surgeons in counseling patients who experience transient posterior knee pain after meniscal repair with this system.     

High-dose toremifene as a cisplatin modulator in metastatic non-small cell lung cancer: targeted plasma levels are achievable clinically

OBJECTIVE: To determine changes in the incidence of candidemia in a neonatal intensive care unit (NICU) during a 15-year period (1981 to 1995) and to compare the prevalence and case fatality rates of Candida albicans and Candida parapsilosis infections. METHODS: A retrospective study was conducted of candidemia occurring in infants in a NICU between January 1, 1981, and December 31, 1995. Cases were identified through computerized searching of a microbiology blood culture database. Candidemia was considered contributory to mortality if death occurred within 3 days of positive blood cultures or if there was autopsy evidence of disseminated candidiasis. RESULTS: One hundred eleven cases of candidemia occurred in 107 infants, representing 1% of all NICU patients during the study period. The rate of candidemia in the NICU increased from 2.5 cases per 1000 admissions in 1981 to 1985, to 4.6 per 1000 admissions in 1986 to 1990 and to 28.5 per 1000 in 1991 to 1995 (P = 0.001). C. albicans was the predominant cause of candidemia between 1981 and 1990. C. parapsilosis was the most prevalent species between 1991 and 1995, causing 53 of 89 cases (60%). The mortality from C. albicans, 13 of 50 cases (26%), was significantly higher than the mortality from C. parapsilosis, 2 of 54 (4%) (P = 0.002; relative risk, 7; 95% confidence interval, 1.7 to 30). CONCLUSIONS: The rate of candidemia in our neonatal intensive care unit increased >11-fold in the 15 years from 1981 to 1995; the prevalent Candida species shifted from C. albicans to C. parapsilosis; and candidemia associated with C. albicans has significantly higher mortality than with C. parapsilosis.