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Biomedical subjects

B Lieberman

Publications and source records attributed to B Lieberman.

At least 19 recordsLinked to original sources

Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation.

BACKGROUND: Ovarian failure is a common sequel to chemo/radiotherapy in patients successfully treated for cancer. Harvesting, cryopreserving and subsequently re-implanting ovarian cortical grafts can be used to re-establish reproductive potential in women with cancer. The safety issue, however, is of great concern because residual disease in autografted ovarian tissues might cause recrudescence of disease. METHODS: A total of 30 non-obese diabetic severe combined immunodeficient (NOD/LtSz-SCID) mice were individually xenografted s.c. with frozen-thawed ovarian tissue from 18 patients with lymphoma [13 Hodgkin's lymphoma (HL) and 5 non-Hodgkin's lymphoma (NHL)]. The animals were autopsied at 16 weeks, or earlier if cachectic. The xenograft, liver, spleen, sternum, para-aortic lymph nodes and thymus were prepared for histology, immunohistochemistry and human DNA microsatellite analysis. RESULTS: None of the animals grafted with ovarian tissue from lymphoma patients developed disease. However, all 3 animals grafted with lymph node tissue from an NHL patient developed B-cell lymphomas that were confirmed as human in origin by DNA microsatellite analysis. CONCLUSION: Ovarian tissue harvested before high-dose chemotherapy for HL or NHL may not carry a risk of disease transmission by autotransplantation, although the possibility is difficult to exclude completely.

Adult↗

Functional reverse transcriptases encoded by A-type mouse LINE-1: defining the minimal domain by deletion analysis.

Long interspersed elements, or LINEs, are retrotransposons that move via an RNA intermediate. In mice, one polymorphic variant of L1 has amplified relatively recently, giving rise to the A-type subfamily in species belonging to the genus and subgenus Mus. Retrotransposition of LINE-1 (L1) requires the function of the L1-encoded reverse transcriptase that is produced from open reading frame 2 (ORF2). Here, we employ a convenient yeast genetic assay to determine the reverse transcriptase activity of the ORF2 obtained from three A-type L1 elements: one, a cDNA from the RNA in ribonucleoprotein particles; another with a purported inactivating mutation; and the third, a hypothetical ancestral construct. Because there are no examples of A-type elements that have transposed recently to inactivate a gene, this assay is the first step towards demonstrating the functional capability of mouse A-type LINE-1 elements. One of the three elements was believed to have been inactivated during evolution by the substitution of leucine for a highly conserved phenylalanine or tryptophan residue among known reverse transcriptases. This mutation did not inactivate the L1 reverse transcriptase in the yeast assay; thus, all three of the elements tested encoded reverse transcriptase activity. We further examined the minimal reverse transcriptase domain within ORF2 by creating a series of deletions. The results demonstrate that removal of the L1 endonuclease domain from the N-terminal region of ORF2 does not affect reverse transcriptase activity as determined by this assay, and that approximately half of the ORF2 coding sequence from mouse A-type L1 elements is required for functional reverse transcriptase.

Animals↗

An embryo too many?

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Cryopreservation↗

Symptomatic unilateral pleural effusion as a presentation of ovarian hyperstimulation syndrome.

Isolated acute unilateral pleural effusion has twice been reported as the only symptom of ovarian hyperstimulation syndrome (Kingsland et al, 1989; Jewelewicz and Vande Wiele, 1975). The pathogenesis of this disorder is not fully understood and the presence of an isolated pleural effusion lends support to the role of systemic factors rather than purely the transudation of fluid from grossly enlarged ovaries in the progression of this disease. This article describes a second case of an isolated pleural effusion following in-vitro fertilization and embryo transfer.

Adult↗

Oestradiol and immunoreactive inhibin-like secretory patterns following controlled ovarian hyperstimulation with urinary (Metrodin) or recombinant follicle stimulating hormone (Puregon).

Inhibin (and its alpha-subunit) may be of particular value as a marker for follicular development in in-vitro fertilization (IVF) in comparison with the classic follicle stimulating hormone (FSH)-dependent marker oestradiol in patients following pituitary desensitization and treatment with recombinant FSH (rFSH). This preparation lacks luteinizing hormone (LH), which is essential for thecal cell androgen secretion and thus oestradiol production. Our study has assessed oestradiol and immunoreactive inhibin-like secretion following ovarian stimulation with rFSH or a purified urinary FSH preparation (Metrodin) (uFSH). A randomized, assessor-blind study was initiated using patients receiving a single treatment cycle of IVF (using fresh embryos) following pituitary desensitization with intranasal buserelin (500 microg daily) and the i.m. injection of either rFSH (n = 38) or uFSH (n = 17). Ovarian ultrasound examinations were performed and bloods (10 ml) collected prior to FSH treatment and every 1-2 days until ovulation induction with human chorionic gonadotrophin. LH and FSH concentrations were measured by an immunoradiometric assay, and inhibin-like immunoreactivity by a radioimmunoassay and an enzyme-linked immunosorbent assay, both with alpha-subunit specificity. Oestradiol concentration was measured with a coated tube radioimmunoassay. Following desensitization, basal LH, FSH and oestradiol concentrations were measured, as was that of immunoreactive inhibin. Following treatment with either rFSH or uFSH, LH concentrations remained low while FSH concentrations rose to a plateau of 5.6-6.7 IU/l in both groups. In contrast, the concentration of oestradiol was higher (P < 0.05) with rFSH than with uFSH in the last four days of treatment, a pattern that was repeated for inhibin-like immunoreactivity. The change in oestradiol and inhibin concentrations during treatment was approximately 2-fold higher with rFSH. The total number of follicles obtained with rFSH was similar to that with uFSH. However, the number of follicles with a diameter of >/= 15 mm was higher the rFSH group, and there was a concomitant increase in the number of oocytes recovered. Oestradiol concentration and inhibin-like immunoreactivity (determined by either method) were associated with total follicle number and number of follicles >/= 15 mm in diameter, as well as with each other (P < 0.001). When ovarian hormone output was normalized per follicle produced, oestradiol output was higher for rFSH than for uFSH P = 0.04). Inhibin output was clearly higher using rFSH than uFSH. There were seven pregnancies (one miscarriage) with rFSH and two with uFSH. Despite similar concentrations od FSH in patients, rFSH (Puregon) appears to be more potent in vitro in terms of follicular number, ovarian hormone secretion (both concentration and output/follicle) and oocyte recovery. In both groups, LH concentrations of approximately 1.3 IU/l were sufficient to support oestradiol secretion similar to that normally found in IVF programmes using human menopausal gonadotrophin preparations containing large amounts of LH. Despite known problems of specificity with the assays od inhibin, its measurement was of similar value to oestradiol as a marker of follicular development.

Adult↗

Minor congenital anomalies, major congenital malformations and development in children conceived from cryopreserved embryos.

A total of 91 children (68 singletons, 20 twins and three triplets) who were conceived from cryopreserved embryos between 27 December 1989 and 18 January 1994, and 83 normally conceived control children (81 singletons and two twins) of a similar age, sex and social class, were assessed for minor congenital anomalies and major congenital malformations. Their development was assessed using the Griffiths Scales of Mental Development. The incidence of minor congenital anomalies (31.9% in the cryopreserved embryo group and 21.7% in the controls) and major congenital malformations (3.3 and 2.4% respectively) in our two groups of children was statistically similar. The relative risk (odds ratio and 95% confidence interval) in the cryopreserved embryo group compared with the controls was 1.7 (0.8, 3.3) for minor congenital anomalies and 1.4 (0.2, 8.5) for major congenital malformations. The minor congenital anomalies were mostly naevi and haemangiomas. The major congenital malformations included Down's syndrome, Beckwith-Wiedemann syndrome and hypophosphataemic rickets in the cryopreserved embryo group and hydronephrosis and gastroschisis in the controls. The Griffiths assessment showed that children from the cryopreserved embryo group and the controls were functioning at a similar level. The mean Griffiths quotient and subquotient values were greater than the standard 100 in children with or without congenital abnormalities. These results in the cryopreserved embryo group are reassuring in that the minor congenital anomaly and major congenital malformation rates were similar to those in normally conceived children of a similar age, sex and social class and their development was not adversely affected by cryopreservation.

Case-Control Studies↗

Outcome in children from cryopreserved embryos.

A cohort of 91 children from cryopreserved embryos and 83 control children who were conceived normally had their development assessed using the Griffiths's scales of mental development. The controls (81 singletons and two twins) of a similar age, sex, and social class were selected from siblings, cousins, and peers of the cryopreserved embryo group (68 singleton, 20 twins, and three triplets). Children from cryopreserved embryos had a lower mean birth weight and mean gestational age and a higher proportion were born by caesarean section. One child from the cryopreserved embryo group had Down's syndrome, three had squints, and four had conductive hearing loss while in the control children, six had squints, and nine had conductive hearing loss. In both groups, including the child with Down's syndrome, the mean Griffiths's quotient was greater than the standard 100. In the children from cryopreserved embryos, the singleton and multiple birth subgroups had statistically similar assessment results. The mean (SD) Griffiths's quotient was 105.69 (13.55) in children from cryopreserved embryos and 108.18 (9.80) in controls at a chronological age of 25.08 (12.86) and 29.19 (14.65) months respectively. Overall, the development in children from cryopreserved embryos did not cause concern though formal testing had highlighted small differences compared with other children conceived normally and of a similar social class.

Birth Weight↗

Psychosocial adjustment and the role of functional status for children with asthma.

This study examined the psychosocial adjustment of children with asthma compared to children with diabetes, with cancer, and healthy children and the role of functional status in psychosocial adjustment. The total sample included 100 children, aged 8-16 years, (mean = 11.5 years), consisting of 48 boys and 52 girls. Children with asthma scored significantly higher on measures of affective adjustment (depression and internalizing behavior), significantly lower on self-esteem, and evidenced significantly greater functional impairment. Children with cancer missed significantly more school days. After controlling for functional status, no significant differences remained in affective adjustment but absences remained significantly higher for the children with cancer.

Adaptation, Psychological↗

Molecular and electronic structures of two (anticonvulsant) diphenylhydantoin derivatives.

1-Benzyl-5,5-diphenyl-2,4-dioxo-3-imidazolidineacetic acid (AC), M(r) = 400.434, triclinic, P1, a = 8.7640 (3), b = 11.112 (1), c = 11.323 (2) A, alpha = 102.10 (2), beta = 95.44 (5), gamma = 109.12 (1)., V = 1002.65 (30) A3, Z = 2, Dx = 1.33 g cm-3, F(000) = 420, mu(Mo K alpha) = 0.852 cm-1, T = 293 K, R = 0.066 for 5551 unique observed reflections. The compound crystallizes from ethanol at room temperature in the form of colourless prism. 3-(2,4-Dichlorobenzyl)-5,5-diphenyl-2,4-dioxo-1-imidazolidineacetic++ + acid (AD), M(r) = 469.323, monoclinic, P2(1), a = 8.0399 (7), b = 9.7237 (6), c = 26.9768 (12) A, beta = 94.281 (4)., V = 2102.92 (96) A3, Z = 4, Dx = 1.48 g cm-3, F(000) = 968, mu(Mo K alpha) = 3.417 cm-1, T = 293 K, R = 0.066 for 5677 unique observed reflections. The compound crystallizes from ethanol at room temperature in the form of colourless prisms. Two approaches are employed in trying to understand the known differences in pharmacological activity: an analysis of the molecular geometries, and electronic structure calculations. A detailed analysis is made of the molecular geometries both from the X-ray diffraction results, and following energy minimization with molecular mechanics. The ab initio calculations employ the energy-minimized conformations. Several electronic properties are intercompared for AC, AD and their common parent molecule diphenylhydantoin (DPH). The analyses of geometry and electronic structure indicate dissimilarities between active and inactive compounds which may be linked to differences in the activity.

Anticonvulsants↗

Oxytocin induction of labour: hyponatraemia and neonatal jaundice.

To determine the effects of fluid restriction in induced labour with oxytocin in 5% dextrose solution, maternal venous blood and fetal cord venous blood were examined in 164 mothers in induced labour and 29 mothers with a spontaneous onset of labour. After satisfactory uterine activity was induced either the oxytocin infusion was managed according to routine delivery unit practice (n = 36), or infusion rates were halved (n = 45), or quartered (n = 43), or discontinued (n = 40). Despite fluid restriction during labour the mean sodium concentration in maternal blood or cord blood had fallen to a similar extent in all four induced groups at delivery. Potassium, urea, creatinine, total protein, and albumin in maternal blood or cord blood were affected differently by induced labour as compared with sodium. The fall in sodium concentration in maternal blood was a more consistent reflection of the total volume of fluid received, mean infusion rates and cord blood sodium after infusion rates were quartered or discontinued. The incidence of hyponatraemia was 5% in mothers and 8% in infants. A comparison of hyponatraemic and normonatraemic cord blood showed no significant differences in serum bilirubin levels or red cell counts, but more hyponatraemic infants developed neonatal jaundice. It is suggested that in induced labour fluid restriction alone does not prevent hyponatraemia and neonatal jaundice.

Adolescent↗

The relationship of breast feeding to third-day bilirubin levels.

The purpose of this study was to determine the relationship of feeding method to serum bilirubin levels on the third day of life. Two hundred eighty-one apparently healthy full-term neonates had third-day bilirubin levels drawn between 58 and 82 hours of age. Mean serum bilirubin levels were 5.6 mg/dL for formula-fed, 6.9 mg/dL for mixed-fed, and 7.5 mg/dL for breast-fed infants. The difference was statistically significant (P less than .01) between the formula-fed and breast-fed groups. Breast-fed infants lost more weight by the third day than formula-fed infants (mean weight loss 180 g for breast-fed infants, 100 g for formula-fed infants). A third-day bilirubin levels among the feeding groups were then compared using an analysis of covariance with weight loss as the covariate. By this method, type of feeding was still a significant predictor of third-day bilirubin levels (P = .04) as was weight loss (P = .03).

Adult↗