Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots.

Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1-3) and have discrete boundaries defined by recombination hot spots. Using publicly available genetic markers, we have constructed a first-generation haplotype map of chromosome 19. As expected for this marker density, approximately one-third of the chromosome is encompassed within haplotype blocks. Evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered. In contrast, several long blocks are inconsistent with our evolutionary models, and different mechanisms could explain their origins.

Activation of the leukocyte NADPH oxidase in a cell-free system: phosphorylation vs. amphiphiles.

We examined the ability of C-terminal deletion mutants of p47PHOX, a cytosolic subunit of the leukocyte NADPH oxidase, to support the activity of the oxidase in two different cell-free systems, one using protein kinase C and the other an anionic amphiphile (SDS or arachidonic acid) as the oxidase-activating agent. Two deletion mutants were studied: p47PHOXdelta330 and p47PHOXdelta348, each named according to the first residue of the deleted polypeptide. Wild-type (WT) p47PHOX and both mutants were phosphorylated by protein kinase C, but the WT protein was the most heavily phosphorylated, containing 6.0 +/- 0.5 mol phosphate/mol protein. Of the two deletion mutants, only p47PHOXdelta348 could support oxidase activity, and then only in the amphiphile-activated system; neither of the mutants supported oxidase activity in the system activated by protein kinase C. Translocation correlated with activity: WT p47PHOX translocated to the membrane in response to both protein kinase C and amphiphile, but p47PHOXdelta348 translocated only in the amphiphile-activated system. Comparison of these findings with the results of earlier studies suggests that the phosphorylation of p47PHOX is an important component of oxidase activation. The findings provide no information, however, about whether amphiphiles participate in the activation process in intact cells. Consequently, a mechanism of in vivo oxidase activation involving both phosphorylation and the generation of an amphiphile remains a distinct possibility.

Isolation and biochemical properties of four forms of glycosylated porcine prolactin.

Four isoforms of glycosylated prolactin (G-pPRL) were isolated from porcine pituitary glands by affinity chromatography and concanavalin A-Sepharose, based upon differences in their affinity for the lectin. Structural analysis indicated differences in the carbohydrate units of the four G-pPRLs. N-glycanase treatment cleaved the oligosaccharide from the G-pPRLs, establishing N-linked glycosylation. The binding of G-pPRLs to receptors from lactating rabbit mammary glands was only 3-8% that of nonglycosylated pPRL (NG-pPRL). The immunological crossreactivity of the G-pPRLs varied from 36 to 65% that of NG-pPRL. When tested in the pigeon crop sac bioassay, G-pPRLs were only 11-40% as active as NG-pPRL. The metabolic clearance rate of one of the G-pPRLs was slower and another faster than that of NG-pPRL. We conclude that there are several forms of G-PRL of variable immuno- and bio-potencies in the porcine pituitary, and that the current radioimmunoassay for the hormone does not measure the actual bioactivity.

Unintended and unwanted pregnancy in Halifax: the rate and associated factors.

We present the results of a study designed to assess the incidence of unintended and unwanted pregnancies in Halifax, Nova Scotia, and to characterize the socioeconomic and demographic factors associated with women at high risk. Of 200 pregnancies, 32.5% were unintended and 16.5% unwanted. This, together with the rate of therapeutic abortions among Halifax area women, suggests that approximately 45% and 32% of conceptions leading to viable pregnancies are unintended and unwanted, respectively. Contrary to data collected in 1971, the majority of these women were single. Marital status and parity were significant determinants of both pregnancy intention and wantedness. According to these results, unintended and unwanted pregnancies continue to occur at high rates among certain groups of women living in the Halifax region, despite improvements in the efficacy and availability of contraceptives.

PIP: In Canada during June-July 1992, 200 postpartum mothers at the Grace Maternity Hospital in Nova Scotia completed a questionnaire so researchers could examine unplanned and unwanted pregnancies in metropolitan Halifax. Most of the pregnancies (67.5%) were planned. Women with unintended pregnancies were younger than those with intended pregnancies (p 0.005). Married women were significantly more likely to have an intended pregnancy than single women (odds ratio [OR] = 15.53; p 0.001). The more children a woman had, the more likely that a pregnancy was unintended (p 0.05). Women with unplanned pregnancies tended to have never used contraception (25% vs. 14%; p 0.05) or have used withdrawal as their principal method of family planning (25% vs. 5%; p 0.001). Women with planned pregnancies were much more likely to have used oral contraceptives as their principal method of family planning (64% vs. 24%; p 0.001). Most women with unintended pregnancies (86.5%) did not use effective birth control around the time of conception. The leading reasons for unintended pregnancy were carelessness (37%) and unintended intercourse (25%). Contraceptive failure was responsible for 13.5% of unintended pregnancies. Most unintended pregnancies (51%) were also unwanted, resulting in 16.5% of all 200 pregnancies being unwanted. Single women were much more likely to have an unwanted pregnancy than married women (OR = 17) or women living with a partner (OR = 5.8) (p 0.01). The more children a woman had, the more likely that a pregnancy was unwanted (p 0.01). Renters were more likely to have an unwanted pregnancy than did owners (OR = 6.5; p 0.05). Program planners and administrators planned to use these results to determine resource allocations to high risk populations. The results suggest the need for improved birth control counseling and to learn more about the decision women not planning or wanting to conceive to discontinue contraception. Widespread acceptance of emergency contraception would reduce unwanted pregnancies.

Effects of low humidity on small premature infants in servocontrol incubators. II. Increased severity of apnea.

Apneic spells were recorded in 8 of 19 premature infants nursed in high and low humidity alternately in servocontrol incubators. A significantly greater proportion of severe apnea occurred in low than in high humidity. It is postulated that this frequency and severity was due to the increased (as well as widely fluctuating) ambient temperature during low humidity.

Contribution of twin pregnancy to perinatal mortality and fetal growth retardation; reversal of growth retardation after birth.

A survey of factors associated with perinatal mortality in 511 twins and fetal growth retardation and its reversal in 262 twins is presented. The incidence of stillbirth was almost 50% higher in twins than in singletons and the neonatal mortality was six times as high. Eighty percent of the neonatal deaths occurred in infants born prior to or at 30 weeks of gestation; 93% of the deaths were in infants weighing less than 1500 g and 75% occurred within 48 hours of birth. Fetal malnutrition was the main cause of stillbirth, and respiratory distress syndrome and asphyxia neonatorum were the main causes of neonatal death. One quarter of the twins had fetal growth retardation, a prevalence 10 times that in singletons. In almost all, the growth retardation was reversed by high-energy feedings. Although twins represented only 1% of all pregnancies and 2% of live births, they composed 12% of infants with early neonatal death and 17% of growth-retarded infants. A program is suggested for reduction of twin mortality and morbidity.

Apnea in premature infants: recording by arterial catheter.

Respirations and apnea were recorded through an arterial catheter and observed simultaneously in 13 premature infants. Based on simultaneous clinical observation and characteristic recordings of preapneic and apneic periods, three distinct mechanisms of evolution of apneic spells were noted. Studies to elucidate pathophysiologic changes during apnea should recognize varied mechanisms of their origin.

The unwanted pregnancy.

A questionnaire was submitted to the mothers of 200 consecutively delivered infants; 15% of mothers were unmarried. The results showed a high prevalence of unwanted pregnancy, most accounted for by well educated, married women having their first or second baby, and despite access to contraceptive agents. Most of the married women and over 50% of the unmarried who had not wanted to become pregnant wanted the baby after its birth.

The role of interleukin 4 in specific antibody responses by human B cells.

This study was designed to investigate the requirement for interleukin 4 (IL-4) in specific antibody responses by human lymphocytes. Addition of IL-4 to antigen (influenza virus)-stimulated cultures of tonsillar mononuclear cells was found to suppress specific antibody production significantly at doses as low as 10 units/ml. Specific immunoglobulin (IgG), IgA, and IgM antibodies were all equally inhibited by IL-4. Inhibition of the antibody response with IL-4 was completely abrogated by an IL-4 blocking antibody showing that the effect was specific for IL-4. It was also found that anti-IL-4 did not inhibit specific antibody production, showing that IL-4 was not required for responses to antigen. In contrast, significant inhibition was obtained with anti-Tac, indicating an important role for IL-2. In the absence of T helper cells antibody responses to influenza virus were completely restored with T cell replacing factor [TRF; IL-2 or low-molecular-weight B cell growth factor (BCGFlow)], but not with IL-4. In fact, IL-4 significantly suppressed the antibody response obtained when either IL-2 or BCGFlow was used as a TRF. Addition of IL-4 at different times after in vitro stimulation with antigen and IL-2 showed that the inhibitory activity of IL-4 was maximal during the first 3 days of culture and was lost by day 4. IL-4 therefore seems to inhibit an early activation event (possibly dependent on IL-2 or BCGFlow), or B cell proliferation essential for specific responses to antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Survey of a neonatal population for the prevalence of cytomegalovirus.

A neonatal population of 542 was tested for cytomegaloviruria. 293 were normally grown and full term, 172 normally grown but premature, and 77 were undergrown. Two normally grown term infants and one premature were excreting the virus (o.55%). Only one, a normally grown term infant, had signs of classical cytomegalic inclusion disease. None of the undergrown infants was infected.

Influence of maternal oxygen administration on the term fetus before labor.

Thirty-two healthy pregnant women at term who were to undergo cesarean section following epidural anesthesia were randomly assigned to receive preoperatively, by face mask, room air or oxygen for more than 10 minutes. Patients were kept at a left lateral tilt position of 15 degrees and were unaware which gas was administered. Oxygenation significantly increased (p less than 0.05) maternal PO2 to 283 mm Hg (SD 67). The cord vein PO2 of the group receiving oxygen was 34 mm Hg (SD 6), significantly higher (p less than 0.01) than the value of 26 mm Hg (SD 7) in the group receiving room air. The cord artery PO2 of the oxygen group was also significantly higher (p less than 0.05) at 20 mm Hg (SD 6) versus 15 mm Hg (SD 6). No other cord gas values were significantly different. There was no significant difference in the cord vein-artery PO2 differential. There was no significant difference in the infants' hematocrits determined at 4 hours of age in the two groups. All infants were in excellent condition (1-minute Apgar score greater than or equal to 8).

Isolation of a complex of respiratory burst oxidase components from resting neutrophil cytosol.

The respiratory burst oxidase of neutrophils is a multicomponent enzyme, dormant in resting cells, that catalyzes the reduction of oxygen to O2- at the expense of NADPH. In the resting neutrophil, some of the components of the oxidase, including proteins p47phox and p67phox, are in the cytosol, while the rest are in a fraction that usually copurifies with plasma membrane. Recent evidence has suggested that at least some of the cytosolic oxidase components exist as a complex. We have now purified such a complex from the cytoplasm of resting neutrophils using an affinity column prepared with an antibody that recognizes the C-terminal decapeptide of p47phox. Immunoblotting showed that the complex contained both p47phox and p67phox. When supplemented with recombinant p67phox, the complex displayed considerable activity in a cell-free oxidase-activating system, and even without added p67phox, the complex could more than double O2- production in an oxidase-activating system supplemented with suboptimal amounts of cytosol. Isolation of the complex was blocked by preincubating the affinity column with CFSTKRKLASAV, the peptide against which the antibody was raised. On gel filtration, the complex migrated with a molecular weight of 240-300K, similar to that observed with whole neutrophil cytosol. The p47phox/p67phox ratio in the gel-filtered complex was approximately 1 to 1. These results indicate that in resting neutrophil cytosol, p47phox and p67phox exist as a complex.

Prevention of group-B beta-haemolytic streptococcal septicaemia in low-birth-weight neonates by penicillin administered within two hours of birth.

Between January, 1969, and May, 1974, 11 of 1208 low-birth-weight infants had early onset group-B streptococcal septicaemia. All 11 infants were of less than 35 weeks gestational age and 9 presented with the clinical and radiological signs of idiopathic respiratory distress syndrome. 10 died. Antibotics were given to 3 infants only, but not before the age of 12 h. From June, 1974, infants less than 35 weeks gestational age, and from January, 1977, infants less than 2500 g, received systemic penicillin by 2 h of age after throat, ear, umbilical, rectal, and blood cultures. Penicillin was continued for 10 days if group-B streptococci were isolated but was stopped at 48 h of age if all cultures were negative. Between June, 1974, and November, 1977, there was 1 case of septicaemia and no death from group-B streptococal infection in the 983 low-birth-weight infants born during this period. These data suggest that systemic penicillin from birth prevents low-birth-weight infants from dying of group-B streptococcal infection.