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Biomedical subjects

G Wright

Publications and source records attributed to G Wright.

At least 163 records · Page 9Linked to original sources
PubMed1990

Recognition of paternal pronuclei in human zygotes.

The possibility of pronuclear gender determination using morphological criteria only was investigated in 140 two-pronucleate and 39 tripronucleate zygotes. Zygotes were videotaped on different focal points and the positions of the polar bodies, pronuclear diameters, number and distribution of nucleoli, and presence of sperm tail remnants were indicated on diagrams. The three known criteria used for recognition of the paternal pronucleus in rodent zygotes were investigated. These criteria are (a) the presence of sperm tail remnants, (b) an increased pronuclear diameter, and (c) the farthest distance from the second polar body. Sperm tail remnants were observed in only 3/342 (1%) of the pronuclei. Pronuclear diameters and positions of the largest pronuclei did not reveal any trends. Pronuclei of tripronucleate zygotes were frequently smaller than those of two-pronucleate ones. The parental origin of human pronuclei cannot be determined morphologically using standard light optics. Microsurgical removal of paternal pronuclei from polyspermic zygotes should therefore be implemented with caution.

Cell Nucleus↗
PubMed1990

Structure-activity relationships of N2-substituted guanines as inhibitors of HSV1 and HSV2 thymidine kinases.

A series of N2-phenylguanines was synthesized and tested for inhibition of the thymidine kinases encoded by Herpes simplex viruses type 1 and type 2. Compounds with hydrophobic, electron-attracting groups in the meta position of the phenyl ring such as m-trifluoromethyl (m-CF3PG, IC50 = 0.1 microM) were the most potent inhibitors of both enzymes. Many derivatives were significantly more potent against the type 2 thymidine kinase, and can effectively discriminate between the two enzymes. Among other N2-substituted guanines, alkyl and benzyl derivatives were moderately potent inhibitors, and the type 2 enzyme was again more sensitive than the type 1 enzyme. None of the compounds inhibited the thymidine kinase isolated from the host HeLa cell line, suggesting that members of this class of compounds may be useful nonsubstrate, antiviral compounds for latent herpesvirus infections.

Chemical Phenomena↗
PubMed1990

Synthesis and cytotoxicity of deoxyadenosine analogues: isomer distribution in the sodium salt glycosylation of 2,6-disubstituted purines.

Several 2-substituted deoxyadenosine derivatives were synthesized and screened for cytotoxicity toward hematopoietic cells in culture. To prepare intermediates for these syntheses, the sodium salts of 2,6-dibromopurine and 2,6-bis(methylthio)purine were reacted with 1-chloro-3,5-di-p-toluyl-alpha-D-erythro-pentofuranose in acetonitrile. Similar reactions using 6-chloropurines have been reported to give only 9-beta and 7-beta nucleosides as major and minor products, respectively. 2,6-Dibromopurine, however, gave 9-beta and 9-alpha isomers as major and minor products, along with a lesser amount of the 7-beta isomer. 2,6-Bis(methylthio)purine, in contrast, produced 9-beta and 7-beta isomers as major and minor products. These results are discussed in terms of sugar anomerization and possible steric and kinetic effects of base substituents in the sodium salt glycosylation reaction. Reactions of the 9-beta nucleoside isomers with ammonia and alkylamines produced several 2-bromo, 2-methylthio, and 2-amino deoxyadenosines. All of the compounds showed weaker cytotoxic activity than 2-bromodeoxyadenosine against hematopoietic cells in culture, when [14C]leucine incorporation into cellular proteins was measured.

Animals↗
PubMed1990

Observations on the morphology of pronuclei and nucleoli in human zygotes and implications for cryopreservation.

The effects of cryopreservation on human zygotes at various stages between the appearance of pronuclei and their close association were investigated. Pronuclear zygotes (n = 233) from 101 patients were frozen using propanediol 21-35 h following egg collection. The incidence of implantation of thawed pronuclear zygotes frozen 29-35 h following oocyte collection was significantly higher than that of younger pronuclear zygotes (28 versus 10%, respectively). Zygote age did not affect cell survival following cryostorage. The diameter and association of pronuclei and the number and distribution of nucleoli were determined from video tape recordings of 140 fresh zygotes. Pronuclear migration continued after pronuclear enlargement. The number of nucleoli remained constant during pronuclear migration, but their random distribution within the pronucleus diminished. Strongly adhered pronuclei had significantly more aligned nucleoli on adjacent sides than pronuclei which were still visually separated by ooplasm. This equatorial distribution of nucleoli was noted in the majority of zygotes older than 26 h. The findings suggest that zygote cryopreservation should be initiated when pronuclear migration is completed. This moment can be determined accurately by studying pronuclear association and nucleolar alignment.

Cell Nucleolus↗
PubMed1990

The effect of condom use on cervical intraepithelial neoplasia grade I (CIN I).

A prospective, controlled study of condom use in patients with histologically-proven CIN I was undertaken. Forty-six patients were studied, 22 by random allocation and 24 by nonrandom allocation to either condom use or non-condom use for 6 months. At the end of this time, patients were reassessed cytologically, colposcopically and histologically. There was no significant difference between the groups with respect to outcome. Six patients' lesions (13%) progressed in this period, 5 (11%) to CIN III. Condom usage is not an effective treatment for CIN I.

Adult↗
PubMed1990

Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia.

A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.

Acetylcarnitine↗
PubMed1990

Regulation and role of phospholipases in host-bacteria interaction.

Deacylating phospholipases play essential roles in numerous biological events, requiring tight control of hydrolytic activity. Most cells, unless stimulated or perturbed, exhibit little phospholipid turnover. Activation of phospholipases A (PLA) is usually triggered by membrane perturbing conditions or agents. Some activators indiscriminately activate any PLA, others are highly specific. Our studies concern an activator that is a potent bactericidal protein with membrane-perturbing properties, isolated from polymorphonuclear leukocytes (PMN), that is only cytotoxic for gram-negative bacteria and primarily responsible for the fate of several gram-negative bacterial species, ingested and killed by the PMN. It is this protein that activates the hydrolysis of the phospholipids of the killed bacteria (E. coli) by three PLA: 1) an E. coli PLA, the pldA gene product; 2) a PLA2 of PMN; 3) a soluble PLA2 in the extracellular fluid of an inflammatory exudate. However, this activator protein does not trigger the action of many other PLA2, all members of a highly conserved class of PLA. Our structural studies (including genetic engineering) of both responsive and non-responsive PLA2 have revealed that the amino acid composition and sequence of the NH2-terminal alpha-helix of the PLA2 molecule are major determinants of the ability of the PMN protein to activate a given PLA2. Our results provide another demonstration that these important enzymes have diverged during evolution to perform different biological functions.

Animals↗
PubMed1990

Effects of bilateral adrenalectomy on the induction of learned helplessness behavior.

In the learned helplessness model of depression, naive Sprague-Dawley rats are exposed to a 40-minute uncontrollable shock training and are subsequently tested in a shock escape paradigm. "Helpless rats" exhibit 11 to 15 failures in a 15-trial test while "nonhelpless" rats and naive controls score 0 to 5 failures in the same test. We report on the effect of bilateral adrenalectomy on the induction of learned helplessness. Most of the adrenalectomized rats (70%) became helpless whereas sham controls responded to the training and testing similarly to naive nonoperated rats (20% to 30% helpless). This increase in behavioral deficits after adrenalectomy was reversed by administration of corticosterone, the naturally occurring glucocorticoid in rat. We conclude that secretion from the adrenal cortex is necessary for the incorporation of a learned response after stress and that a dysregulation of the hypothalamic-pituitary-adrenal axis seems to be involved in helpless behavior.

Adrenalectomy↗
PubMed1989

Videocinematography of fresh and cryopreserved embryos: a retrospective analysis of embryonic morphology and implantation.

Eleven morphologic criteria were studied from videotapes of 323 fresh and 103 thawed embryos. The proportion of thawed embryos (30/39; 77%) with more than one abnormality was (P = 0.03) higher than that of fresh embryos (5/13; 38%), despite similar implantation rates (18% and 15%, respectively). The best predictor of thawed embryo implantation was cell-cell adherence: when scored "positive," 11 of 17 women (65%) became pregnant, whereas none became pregnant (0/15; P = 0.0002) when blastomeres did not adhere. The total number of abnormalities for thawed embryos was an important prognostic. An increased percentage variation of zona pellucida thickness was the most important prognostic for fresh embryos. When the "best" embryo had a zona pellucida that varied more than 25%, 24 of 60 (40%) resulted in pregnancy; pregnancies were not induced (0/21) when the "best" embryo had less than 10% variation (P = 0.0003).

Blastomeres↗
PubMed1989

Coculture of human zygotes on fetal bovine uterine fibroblasts: embryonic morphology and implantation.

Zygotes from in vitro fertilization patients (n = 116) were randomly allocated to culture in either conventional plastic petri dishes or coculture on a monolayer of fetal bovine uterine fibroblasts. Embryos (n = 288) remained 26 to 32 hours in these culture systems. Video tape recording for later morphological analysis (11 parameters) was performed on 117 conventionally cultured and 104 cocultured embryos, shortly before replacement, by an independent observer, unaware of the culture conditions for each embryo. A significantly greater number of cocultured embryos (52%) had "good" morphology (zero or only one abnormal characteristic) as compared with conventionally cultured embryos (30%). The most outstanding morphological characteristic of cocultured embryos was the expanded appearance of their blastomeres. The incidence of implantation per embryo increased from 13% to 19% when the coculture rather than conventional culture system was used, and the incidence of ongoing pregnancy per patient after coculture doubled to 35%.

Animals↗
PubMed1989

Familial XX chromosomal maleness does not arise from a Y chromosomal translocation.

To determine the mechanism for the coexistence of XX chromosomal maleness and true hermaphroditism in the same family, we performed cytogenetic and molecular genetic analyses, using DNA probes from the short arm of the Y chromosome. These studies excluded the following possible mechanisms: (1) an inherited, mitotically unstable Y chromosome that results in chromosomal mosaicism, (2) an inherited Y-to-X or Y-autosomal translocation, (3) recurrent Y-to-X translocation, and (4) incomplete inactivation of the X chromosomal homolog for the testicular determining factor. We conclude that the disorder of sexual differentiation observed in this family can be best explained by a dominant autosomal gene with variable expressivity.

Blotting, Southern↗
PubMed1989

Partial zona dissection of human oocytes when failure of zona pellucida penetration is anticipated.

Partial zona dissection (PZD) of human oocytes facilitates sperm penetration through mechanically made holes in the zona pellucida. Only 1 of 69 eggs was damaged when sucrose was used to shrink the ooplasm during micromanipulation. The fertilization rate of micromanipulated oocytes in 18 couples with male factor infertility was 68% (34/50), which compared favourably with insemination of non-micromanipulated controls (21/45, 47%). PZD was advantageous in oligozoospermic patients, but not in cases of asthenozoospermia, combined semen problems or immunological infertility. Three twin and two singleton pregnancies resulted following replacement of 23 micromanipulated and eight control embryos in 14 patients. No differences in embryo morphology and development rates were found between the micromanipulated and control groups. The incidence of polyspermy in couples with abnormal semen analyses was relatively low (less than 20%) possibly due to partial activation of the oocytes following exposure to sucrose. Polyspermy was high (57%) in normozoospermic patients with either immunological infertility (n = 3) or failure of fertilization in previous cycles (n = 4). In the three immunological patients, nine of 11 hyaluronidase and sucrose-exposed control embryos fertilized and six implanted, possibly indicating that cumulus and corona cells are contributing factors inhibiting fertilization in such cases.

Embryo Transfer↗
PubMed1989

In-vitro development and implantation of human embryos following culture on fetal bovine uterine fibroblast cells.

Human zygotes resulting from IVF were placed in two different culture systems to evaluate in-vitro development and to establish pregnancies in patients following embryo replacement. Treatment A (control) consisted of culturing zygotes in a modified Earle's Balanced Salt solution while treatment B consisted of culturing zygotes on a monolayer of fetal bovine uterine fibroblasts in this same culture medium. At the time of embryo replacement, embryos within treatments A and B had 3.7 and 4.3 blastomeres present, respectively. After 24 h in culture, the cellular fragmentation rate for treatment A embryos was 0.85 which was greater (P less than 0.05) than the fragmentation rate of 0.40 for embryos within treatment B. The incidence of implantation for patients whose embryos were given treatment A was 17.0% which was lower (P less than 0.05) than 35% for those given treatment B. Implantation rates increased with time in culture (43%) for treatment B embryos. Culture by treatment B of three-pronucleate zygotes resulted in 7/9 and 4/9 reaching the blastocyst and expanded blastocyst stages, respectively, whereas only 1/26 three-pronucleate zygotes cultured using treatment A reached either of these stages.

Blastocyst↗
PubMed1989

Structure and dynamics of staphylococcal nuclease mutants as studied by fluorescence quenching techniques.

Fluorescence techniques have been used to investigate the effect of mutations on the structure and dynamics of staphylococcal nuclease. An estimate of the accessibility to acrylamide of the enzyme's single tryptophan residue (Trp140) was obtained from the Stern-Volmer constant for fluorescence quenching. This was indicative of a partially buried tryptophan in the wild-type nuclease. Five single-site mutant nucleases (H124L, V66L, G88V, G79S and F76V) and one double mutant (V66L + G88V), with widely differing stabilities to denaturants, gave Stern-Volmer constants which were very similar to that of their parent enzyme. Studies of the temperature- and viscosity-dependence of quenching suggest that access by acrylamide to Trp140 is limited by diffusion rather than by protein structural fluctuations. Lifetime-resolved fluorescence anisotropy studies using steady-state instrumentation suggest that there is very little segmental motion of the Trp140; most of the anisotropy therefore decays due to protein rotation in the solution. Rotational correlation times for several nuclease mutants have been determined and these are very similar to that of the native nuclease. Thus it appears that these substitutions in the primary amino acid sequence, which have significant effects on the stability of the folded proteins, do not cause a significant change in the protein structure or dynamics around Trp140.

Escherichia coli↗