A systematic analysis of cell cycle regulators in yeast reveals that most factors act independently of cell size to control initiation of division.

Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms.

Ageing and long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience.

OBJECTIVES: The aim of this study was to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. METHODS: Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell count changes following the completion of 5 years of cART using linear mixed models. RESULTS: A total of 37 916 CD4 measurements were observed for 892 patients over a combined total of 9753 patient-years. Older patients (> 50 years old) at cART initiation had estimated mean (95% confidence interval) changes in CD4 counts by year-5 CD4 count strata (< 500, 500-750 and > 750 cells/µL) of 14 (7 to 21), 3 (-5 to 11) and -6 (-17 to 4) cells/µL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. CONCLUSIONS: Our results suggest that duration of cART and increasing age do not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients, indicating that the level of immune recovery achieved during the first 5 years of treatment is sustained through long-term cART.

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers.

The hagfish slime gland thread cell. I. A unique cellular system for the study of intermediate filaments and intermediate filament-microtubule interactions.

Thread cell differentiation in the slime gland of the Pacific hagfish Eptatretus stouti has been studied using light microscopy and scanning and transmission electron microscopy. Thread cell differentiation is remarkable in that the life history of the cell is largely dedicated to the production of a single, tapered, cylindrical, highly coiled, and precisely packaged cytoplasmic thread that may attain lengths of 60 cm and diameters approaching 1.5 micron. Each tapered thread, in turn, is comprised almost entirely of large numbers of intermediate filaments (IFs) bundled in parallel. During differentiation of the thread, the IFs become progressively more tightly packed. Various numbers of microtubules (MTs) are found among the bundled IFs during differentiation of the thread but disappear during the latter stages of thread differentiation. Observations of regularly spaced dots in longitudinal bisections of developing threads, diagonal striations in tangential sections of developing threads, and circumferentially oriented, filament-like structures observed at the periphery of developing threads cut in cross section have led us to postulate a helically oriented component(s) wrapped around the periphery of the developing thread. The enormous size of the fully differentiated thread cell, its apparent singular dedication to the production of IFs, the ease of isolating and purifying the threads and IF subunits (see accompanying paper), and the unique position of the hagfish in the phylogenetic scheme of vertebrate evolution all contribute to the attractiveness of the hagfish slime gland thread cell as a potential model system for studying IF subunit synthesis, IF formation from IF subunits, aggregation of IFs into IF bundles and the interaction(s) of IFs and MTs.

Hagfish slime gland thread cells. II. Isolation and characterization of intermediate filament components associated with the thread.

The slime glands of hagfish have two major cell types, gland thread cells (GTCs) and gland mucous cells (GMCs), both of which upon contact with water contribute to the formation of an abundant quantity of viscous mucus. In previous studies we reported a method for the isolation of GTCs and showed that each ellipsoidal thread cell normally contains a single tapered thread which is uniquely coiled into a space-saving conformation and occupies most of the cell volume. Subsequently, the developing thread was found to consist mainly of intermediate filaments (IFs) aligned in parallel not only to one another but also to a far fewer number of interspersed microtubules (see accompanying paper). In the present report, urea extracts of GTCs were purified and characterized to establish the properties of thread components. One major (alpha) and two minor (beta, gamma) components prepared by anion exchange chromatography were shown to have similar apparent molecular weights of 63,500 +/- 500 daltons but different isoelectric pH values (alpha, 7.56; beta, 5.67; gamma, 5.31). Although the amino acid content of alpha differed significantly from beta and gamma, each of the three was highest in Gly, relatively high in Glx, Ser, Thr, Asx, Ala, Val, and Leu, and relatively low in Cys/2 and Trp. The amino acid compositions of beta and gamma were very similar, and only beta showed evidence of carbohydrate. The threonine content of the alpha component was higher than has been reported for IFs of different origin, and the high content of hydroxyamino acids (18, 19 residues per 100) in alpha, beta, and gamma has been approached only by several IF polypeptides from human or bovine epidermal keratins. Mixtures of the purified components formed 9-11-nm filaments in vitro. The results indicate that the hagfish thread cell is a rich source of IFs, which have a structure that facilitates formation of macrofibrils within the cell.

The hagfish slime gland: a model system for studying the biology of mucus.

The hagfish slime gland may provide a model system for studying certain aspects of the biology of mucus. Mucus is obtained in nonhydrated form by electrically stimulating the anesthetized hagfish and the secretions are stirred into ammonium sulfate. Centrifugation and filtration are than used to isolate the two major secretory products, mucous vesicles and threads. Specific advantages of the model and potential applications for research are discussed.

Threads in the hagfish slime gland thread cells: organization, biochemical features, and length.

Scanning electron microscopy in conjunction with cell isolation procedures revealed details of the packing of threads in hagfish slime gland thread cells. Biochemical studies indicate that the thread is largely composed of a protein subunit with a molecular weight of 63,500. Mathematical calculations suggest that the thread may attain lengths of 60 centimeters or more.

Barriers to the delivery of the hepatitis B birth dose: a study of five Papua New Guinean hospitals in 2007.

Hepatitis B is highly endemic in Papua New Guinea (PNG). Vaccination at birth is a key mother-to-child transmission prevention strategy. Despite recommendations for newborns to be vaccinated within 24 hours of delivery, a 2005 survey showed 23% coverage among children born in health facilities. Our study examined hepatitis B birth-dose coverage and knowledge, practices and barriers to vaccine delivery in five major PNG hospitals. Data on births and vaccines administered were sourced from the National Department of Health (NDoH) and directly from the five hospitals. A maternity unit audit and staff survey were undertaken. Across the five hospitals, the hospital-level data of hepatitis B birth-dose coverage was 79% (range: 40-96%) compared to 19% from national data (range: 0-106%). Despite hospitals having adequate vaccine supply, access to appropriately stored vaccine in maternity units was compromised with only one unit having a vaccine-specific temperature-monitored refrigerator. In interviews of 25 staff, incorrect reasons given for delaying vaccination were prematurity (60%), low birthweight (48%) and difficult birth (36%). This study found encouraging birth-dose coverage rates in five major hospitals but 20% of babies still missed receiving the recommended vaccine. The NDoH Immunization Unit will use the results of this study to inform strategies to improve hepatitis B birth-dose coverage in hospitals.

Delayed involution of the mammary epithelium in BALB/c-p53null mice.

In mammals, weaning of neonates and subsequent milk stasis initiates removal of the secretory epithelium of the mammary gland by apoptosis. The p53 tumor suppressor gene is induced rapidly following weaning of neonates, but its role in the process of involution has not been defined. Therefore, experiments were performed to identify the cell types in which the p53 gene is expressed during involution and determine the consequences of its absence in BALB/c-p53null mice. Both p53 mRNA and protein were detected in the mammary epithelium within 48 h following weaning and resulted in an eightfold increase in levels of p21WAF1 mRNA. Induction of p21WAF1 mRNA was absent in BALB/c-p53null mice, and therefore, was shown to be p53-dependent. The BALB/c-p53null mice exhibited delayed involution of the mammary epithelium, as measured by 60% greater epithelial area compared to BALB/c-p53(wt) mice through 5 days post-weaning. The delay was transient with no differences being apparent at 7 days post-weaning. Expression of the stromal protease stromelysin-1 was unaffected by the absence of p53 suggesting that stromal responses were intact. These data demonstrate that p53 participates in the first stage of involution initiated by the epithelium itself, but does not affect the second phase during which stromal proteases are induced.

ATP gated potassium channels in acute myocardial hibernation and reperfusion.

OBJECTIVE: ATP gated potassium (KATP) channels and adenosine are of crucial importance in coronary blood flow regulation and activation of KATP channels and adenosine receptor stimulation protect against infarction and development of stunning. The aim of this study was to test the hypothesis that opening of KATP channels and adenosine receptor stimulation are involved in perfusion-contraction matching, in acute hibernation, and in recovery after reperfusion. METHODS: 30 isolated piglet hearts (2-10 d old) and 20 isolated rabbit hearts were studied. The isolated piglet hearts were perfused with modified Krebs Henseleit (KH) solution enriched by washed human red blood cells; the isolated rabbit hearts were perfused with modified KH buffer. The effects of the KATP channel opener aprikalim (1 microM), the KATP channel antagonist glibenclamide (30 microM), and the adenosine receptor antagonist 8-(p-sulphophenyl)theophylline (SPT, 300 microM) on 2 h of low flow (10%) ischaemia and 1 h reperfusion were compared with saline in the piglet hearts. The effects of aprikalim (1 microM), glibenclamide (30 microM), and saline during 90 min of low flow (10%) ischaemia followed by 1 h reperfusion were also examined in the isolated rabbit hearts. RESULTS: At constant coronary flow aprikalim reduced perfusion pressure from 53(SEM 5) to 25(1) mm Hg (p < 0.001) in piglet hearts and from 55(5) to 39(5) mm Hg (p < 0.05) in rabbit hearts. Glibenclamide increased perfusion pressure from 47(5) to 61(6) mm Hg (p < 0.01) in piglet hearts and from 45(4) to 81(5) mm Hg (p < 0.001) in rabbit hearts. SPT increased perfusion pressure from 55(6) to 67(6) mm Hg (p < 0.05) in piglet hearts. Left ventricular systolic pressure remained unchanged in both models. During stepwise reductions in coronary flow a parallel stepwise reduction in left ventricular systolic pressure was observed in all groups. At 2 h of low flow ischaemia systolic pressure was 39(4)%, 37(5)%, 41(4)%, and 37(3)% of control for hearts treated with saline aprikalim, glibenclamide, and SPT, respectively. During the low flow period systolic pressure and MVO2 stabilised. An almost identical pattern occurred in rabbit hearts. After 30 min of recovery of piglet hearts left ventricular systolic pressure increased to 78(5)% (saline), 74(5)% (aprikalim), 84(5)% (glibenclamide), and 77(4)% (SPT) of control. The recovery as percentage of control in rabbit hearts was 63(11) (saline), 69(8) (aprikalim) and 56(13) (glibenclamide). CONCLUSION: Coronary vascular tone is highly responsive to KATP channel modulation and adenosine receptor blockade. KATP channels do not modulate either perfusion-contraction matching or acute hibernation and functional recovery during reperfusion in the red blood cell perfused piglet heart or the crystalloid perfused rabbit hearts. Moreover, adenosine receptor antagonism does not affect these phenomena in piglet hearts.

Pathophysiological correlates of thallium-201 myocardial uptake in experimental infarction.

The pathophysiological correlates of thallium-201 (201TI) myocardial uptake were studied in a 24-hour-old closed-chest canine infarct model. Reduction in regional 201Tl uptake correlated well with the magnitude of tissue creatine phosphokinase depletion and microsphere estimates of transmural blood flow. In low flow endocardial regions 201Tl occasionally under-estimated the magnitude of flow reduction. Even slight reductions of 201Tl uptake (less than 0.86 of normal) were associated with histopathological and histochemical evidence of necrosis.

The physiological role of relaxin in the pregnant rat. IV. The influence of relaxin on cervical collagen and glycosaminoglycans.

Changes in the collagen and glycosaminoglycan components of cervical connective tissue were studied in nonpregnant, intact pregnant, and ovariectomized hormone-treated pregnant rats. Collagen concentration and solubility and the concentration of the glycosaminoglycans dermatan sulfate (DS), heparan sulfate, and hyaluronic acid (HA) in cervices taken from day 9 (D9) pregnant rats were similar to those in cervices from nonpregnant rats. In cervical tissue from late pregnant intact control rats on D18 and D22, the collagen concentration decreased, collagen solubility increased, and there was no significant change in total glycosaminoglycan concentration. In cervices from ovariectomized pregnant rats treated with progesterone and estrogen, collagen and glycosaminoglycan parameters resembled those of D9 and nonpregnant cervices on both D18 and D22. However, treatment of ovariectomized pregnant rats with progesterone, estrogen, and porcine relaxin (R) restored cervical collagen concentrations to those of intact controls on both D18 and D22. On D18 of pregnancy, cervical collagen solubility was partially increased by R treatment, and by D22, it was similar to that of intact D22 pregnant controls. R treatment also resulted in a significantly increased cervical concentration of HA. It is concluded that the decrease in collagen concentration, increase in collagen solubility, and increase in HA concentration resulting from R action may contribute in part to the increased extensibility of the cervix that occurs during late pregnancy in the rat.

The physiological role of relaxin in the pregnant rat. I. The influence of relaxin on parturition.

Length of gestation, duration of labor and delivery, and fetal survival were determined in control intact pregnant rats (group C). Pregnant rats were bilaterally ovariectomized on day 9 and given progesterone (P) implants and, in addition, one of the following injection regimens; estrogen (E; group OPE), E and porcine relaxin (R; group OPER), or porcine R (group OPR). Hormone treatments were given in doses designed to produce serum levels of these hormones similar to those observed in intact pregnant rats. The P implants were removed during the evening of day 21 to mimic the decline in serum P levels that normally occurs as a result of luteolysis. Animals in groups OPE and OPR exhibited significantly prolonged gestation, prolonged duration of labor and delivery, and reduced fetal survival compared with controls. Group OPER animals exhibited slightly but not significantly shorter length of gestation, similar duration of labor and delivery, and similar rate of fetal survival compared to control values. Group OPER animals showed normal maternal behavior and were able to suckle their young.

The physiological role of relaxin in the pregnant rat. II. The influence of relaxin on uterine contractile activity.

In control intact rats (group C), the frequency of intrauterine pressure cycles (IUPC) declines steadily during pregnancy from 80-130 cycles/3 h on day 10 (D10) to 20-30 cycles/3 h on D20. The decline in frequency is due to increasingly prolonged periods of myometrial quiescence, which increase from 30-90 min/3 h on D10 to 120-150 min/3 h by D20. During the 24 h preceding labor, the frequency of IUPC remains at less than 15 cycles/h until 3 h prepartum, when there is an abrupt increase to 30 cycles/h. Ovariectomized pregnant animals treated with progesterone (P) and estrogen (E; group OPE) exhibit significantly greater frequency of IUPC and significantly lower incidence of myometrial quiescence than intact pregnant rats from D12 and for the remainder of pregnancy. Ovariectomized pregnant rats that received P, E, and porcine relaxin (R: group OPER) or P and porcine R only (group OPR) exhibited declining frequency of IUPC similar to that observed in group C animals. Group OPER rats exhibited prolonged periods of myometrial quiescence of similar duration to those observed in control intact rats. In group OPR animals, however, the periods of myometrial quiescence were considerably diminished during late pregnancy. Group OPER animals exhibited a pattern of myometrial activity during labor and postpartum similar to that of control animals. The results suggest an important role for R in the control of myometrial activity during the second half of pregnancy and parturition in the rat.

The physiological role of relaxin in the pregnant rat. III. The influence of relaxin on cervical extensibility.

Cervices from day 18 (D18) intact pregnant rats show significantly greater extensibility and ability to accommodate to extension than cervices from D9 pregnant rats. On D22, cervices from intact pregnant rats show even greater extensibility and accommodation to stretch. Cervices from ovariectomized pregnant rats treated with estrogen (E) and progesterone (P; group OPE) show markedly reduced extensibility and ability to accommodate to stretch compared with intact pregnant cervical tissue (group C) on both D18 and D22. Extensibility of group OPE cervices resembles that of cervices from D9 intact pregnant rats. Cervices from ovariectomized pregnant rats treated with E, porcine relaxin (R), and P (group OPER) or porcine R and P (group OPR) exhibit similar extensibility and ability to accommodate to stretch as cervices from intact pregnant rats on both D18 and D22. The importance of R for cervical softening during pregnancy and its interaction with E near term and during parturition are discussed.

Influence of light-dark cycle on antepartum serum relaxin and progesterone immunoactivity levels and on birth in the rat.

Relaxin and progesterone are produced by the corpora lutea in the pregnant rat. Relaxin immunoactivity levels are elevated in peripheral sera during the last 12 days of pregnancy. In rats maintained under a conventional photoperiod of 14 h of light (0600-2000 h) and 10 h of darkness (2000-0600 h), there is an antepartum elevation in serum relaxin to maximal levels coincident with the rapid decline in serum progesterone to basal levels during the light phase of the photoperiod 1 day before birth. Therefore, we postulated that this maximal elevation in serum relaxin levels may be temporally associated with functional luteolysis and linked to the photoperiod. In the present study the photoperiod was advanced near midpregnancy in order to examine further the relationship of the antepartum elevation in serum relaxin levels with both functional luteolysis and the photoperiod. Three groups of rats were maintained under a conventional photoperiod of 14 h of light (0500-1900 h) and 10 h of darkness until days 7 and 8 of pregnancy when the photoperiod was advanced 8 h in group 2 (G2) and advanced 18 h in G3 relative to the conventional photoperiod that was maintained in G1. Serum relaxin and progesterone levels were determined in blood samples obtained at 4-h intervals from 2000 h on day 19 of pregnancy until birth. The times of occurrence of birth, maximal relaxin levels, and decline of progesterone to basal levels in G2 and G3 were generaly advanced 50-60% of the advancement of the photoperiod. There was a close temporal association between the attainment of maximal relaxin levels and basal progesterone levels; they both occurred during the light phase of the photoperiod, approximately 24 h before birth in all three groups. We conclude that the antepartum elevation of serum relaxin to maximal levels may be associated with functional luteolysis and that its time of occurrence is influenced by the photoperiod. This study also provides evidence that the antepartum elevation of relaxin levels consists of two phases which occur at a 24-h interval. It is proposed that these two phases in the elevation of relaxin levels may be indicative of an increasingly effective endogenous circadian luteolytic process whose time of occurrence is influenced by the light-dark schedule.

Dynamic changes of multiple forms of serum immunoactive relaxin during pregnancy in the rat.

Relaxin isolated from the ovaries of pregnant rats has a mol wt of 6,500. This study determined the size(s) of the relaxin-immunoactive component(s) in the serum of rats during pregnancy. Peripheral sera from rats on days 15, 17, 19, and 21 of pregnancy were filtered through Sephacryl S-200 columns at 37 C and 4 C. Relaxin immunoactivity eluted in three components designated C1, C2, and C3, which had mol wts of approximately 60,000, 13,000 and 6,500, respectively. The distribution of relaxin immunoactivity among C1, C2, and C3 changed with the day of pregnancy. On day 15 of pregnancy essentially all relaxin immunoactivity was associated with C1. By day 17 approximately 20% of the relaxin immunoactivity was in C2 plus C3, and by day 21 the percentage in each of these two components increased to about 25%. C1 appears to possess relaxin bioactivity since the frequency of intrauterine pressure cycles in nonpregnant rats declined during cross-circulation with day 15 pregnant rats. C1 may not be attributable to the binding of 6,500 mol wt relaxin to a binding protein(s) since relaxin immunoactivity remained associated with a component(s) having a mol wt greater than 28,000 after incubation and gel filtration of day 15 serum in the presence of 2.0 M potassium thiocyanate at 37 C. Moreover, the levels of C1 as well as those of C2 and C3 were markedly increased in the peripheral serum of day-21 rats within 15 min of LH administration. C3 may be the 6,500-mol wt form of relaxin and C2 may be an intermediate in the processing of the 20,000-mol wt rat relaxin precursor to the 6,500-mol wt form of relaxin. The physiological significance, if any, of the multiplicity of relaxin-immunoactive components is unknown.

Influence of litter size on antepartum serum relaxin and progesterone immunoactivity levels and on birth in the rat.

In the rat, the antepartum elevation of serum relaxin levels consists of two phases separated by a 24-h interval. The second phase, which occurs between 36 and 24 h before birth, is temporally closely associated with functional luteolysis. Relaxin levels then decline throughout the last approximately 24 h of pregnancy. We have postulated that the two phases in the antepartum elevation of serum relaxin levels may be indicative of an increasingly effective endogenous circadian luteolytic process. There is limited evidence that both luteolysis and birth are delayed in rats with small litters. The present study investigated in detail the relationship between litter size and the timing of both functional luteolysis and birth in rats. The number of conceptuses (C) in Sprague-Dawley-derived rats was surgically adjusted on day 8 of pregnancy (day 8) so that rats bore one, two, three, five, or a full complement (FC) of eight or more C. Rats were maintained under a photoperiod regimen of 14 h of light and 10 h of darkness (lights on from 2100-1100 h) beginning on day 8 and observed for birth at 10-min intervals from 2100 h on day 22. Serum levels of both relaxin and progesterone were determined in blood samples obtained at 4-h intervals from 2400 h on day 19 until birth. Ninety-five percent of the rats that had five or more C gave birth during the light phase on day 23, which was designated the normal birth interval. However, only 20% of the rats with three C or less, gave birth during the normal birth interval, and 47% gave birth about 24 h later during the light phase on day 24, which was designated the late birth interval. The 24-h delay in birth of rats with small litters which delivered during the late birth interval appears to be attributable to a delay in functional luteolysis; the antepartum decline in serum relaxin and progesterone levels occurred about 24 h later in these rats than in rats that delivered during the normal birth interval. It is concluded that the C may be associated with the luteolytic process and thereby influence the time of birth in rats. Additionally, the results of this study are consistent with our hypothesis that there is an endogenous circadian luteolytic process in rats during the antepartum period.

Factor V Leiden and thermolabile methylenetetrahydrofolate reductase gene variants in an East Anglian preeclampsia cohort.

Preeclampsia is a heritable condition that develops as a result of widespread vascular endothelial dysfunction. The thrombotic tendency in this condition has suggested a number of candidate genes, and there have been recent reports of positive association with the Leiden variant of factor V and the thermolabile variant of methylenetetrahydrofolate reductase. We attempted to reproduce these results in a large cohort of well-characterized women with preeclampsia, recruited prospectively within the East Anglian region of the United Kingdom. Women in the preeclampsia cohort (n=283) were genotyped for both the Leiden variant (G1691A) of factor V and the thermolabile variant (C677T) of methylenetetrahydrofolate reductase. Genotype and allele frequencies were compared with those of 2 control groups, one consisting of women recruited prospectively (n=100) from the same maternity hospital as the subjects and another consisting of normotensive women (n=100) from East Anglia. No significant differences were detected. Specifically, the carrier rate for the Leiden variant was 5.3% in the preeclampsia group and 5. 5% in the combined control group. T677 homozygotes for methylenetetrahydrofolate reductase were 11% and 11.5% in the 2 groups, respectively. We conclude that there is no evidence of association of preeclampsia with either of these 2 polymorphisms in our study population.

Neurologic complications of the tryptophan-associated eosinophilia-myalgia syndrome.

A case of tryptophan-associated eosinophilia, central nervous system complications, and multiple white matter lesions by magnetic resonance imaging is presented. Eosinophilia regardless of its cause should be included within the differential of patients exhibiting periventricular white matter lesions.