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Biomedical subjects

M Lane

Publications and source records attributed to M Lane.

At least 19 recordsLinked to original sources
PubMed1998

Comparison of statins in hypertriglyceridemia.

In 1996, the first 2 studies using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") therapy in hypertriglyceridemic subjects were published. In subjects with isolated triglyceride elevations who were treated with atorvastatin 5, 20, and 80 mg/day, large and dose-related reductions were noted. In subjects with combined hyperlipidemia treated with 10 mg simvastatin, triglyceride reduction similar to that reported for the 5 mg atorvastatin dose was seen. In response to these findings, we conducted comparative assessments to determine whether all statins are effective in lowering triglyceride levels and whether their effect on triglycerides is related to factors such as drug, dose, and baseline triglyceride levels. To standardize these assessments, we devised a ratio that related changes in triglyceride levels to the known predictable response of low-density lipoprotein (LDL) cholesterol to statins. This triglyceride/LDL cholesterol ratio was obtained by dividing the percent change from baseline in the triglyceride level by the percent change from baseline in the LDL cholesterol level. The triglyceride/LDL cholesterol ratio was initially applied to several published studies, and found to be approximately 1.0 and 0.5 in hypertriglyceridemic and nonhypertriglyceridemic populations, respectively. We then assessed the effect of various statins on triglycerides using a pooled laboratory database of 2,689 subjects who had participated in 7 separate studies with similar designs. All of the studies had a placebo run-in followed by a randomized, double-blind, active treatment phase of at least 4 weeks with a statin. Entry into these studies required a triglyceride level of <400 mg/dL. In subjects with baseline triglyceride >250 mg/dL, significant and dose-dependent reductions in triglyceride of 22-45% were seen with all statins. When baseline triglyceride was <150 mg/dL, no significant or dose-dependent effect on triglyceride was seen. The triglyceride/LDL cholesterol ratio was evaluated using a linear model that included baseline triglyceride level, drug, and dose. Only the baseline triglyceride level was significantly (p <0.001) related to this ratio. Moreover, the triglyceride/LDL cholesterol ratio was fairly constant across all statins and doses for patients with baseline triglyceride levels of <150 mg/dL, 150-250 mg/dL, and >250 mg/dL, at 0.0+/-0.3, 0.5+/-0.2, and 1.2+/-0.3, respectively. We conclude that all statins are effective in decreasing triglyceride levels, but only in hypertriglyceridemic patients. Due to the relatively constant triglyceride/LDL cholesterol ratio, our analysis indicates that the more effective the statin is in decreasing LDL cholesterol, the more effective it will also be in decreasing triglyceride levels in patients with hypertriglyceridemia.

Anticholesteremic Agents↗
PubMed1998

Intracellular divalent cation homeostasis and developmental competence in the hamster preimplantation embryo.

The intracellular magnesium and calcium ion concentrations of in vivo-developed 2-cell hamster embryos were measured using ratiometric fluorometry. Intracellular magnesium and calcium ion concentrations were found to be 0.369 +/- 0.011 mM and 129.3 +/- 7.5 nM respectively. Culture of 1-cell hamster embryos for 24 hr to the 2-cell stage in control medium containing 0.5 mM magnesium and 2.0 mM calcium resulted in approximately a threefold increase to 343.5 +/- 8.0 nM in intracellular calcium ion concentration, while magnesium ion levels were not altered (0.355 +/- 0.007 mM). Increasing medium magnesium concentrations to 2.0 mM significantly increased intracellular magnesium ion concentrations of cultured 2-cell embryos with a concomitant reduction in intracellular calcium ion concentrations. Furthermore, increasing the medium magnesium concentration to 2.0 mM significantly increased development of 1-cell embryos collected at either 3 or 9 hr post-egg activation to the morula/blastocyst and blastocyst stages. Resultant blastocysts had an increased total cell number and increased development of the inner cell mass. Most important, however, culture with 2.0 mM magnesium increased the fetal potential of cultured 1-cells twofold. Therefore, because highest rates of development were observed in a medium that resulted in reduced intracellular calcium ion concentrations, it appears that altered calcium homeostasis is associated with impaired developmental competence of 1-cell embryos in culture.

Animals↗
PubMed1998

Culture and transfer of human blastocysts increases implantation rates and reduces the need for multiple embryo transfers.

OBJECTIVE: To determine whether the transfer of blastocysts on day 5, developed in sequential culture media, resulted in an increase in implantation rate compared with embryos transferred on day 3. DESIGN: Comparative study of embryo culture regimes. SETTING: Private practice assisted reproductive technology center. PATIENT(S): Twenty-three patients undergoing routine IVF cycles. INTERVENTION(S): Culture of embryos to day 3 in either standard culture conditions or a serum-free chemically defined medium. One hundred one embryos were subsequently cultured from day 3 to day 5 in a second serum-free medium specifically designed to support development of the blastocyst. MAIN OUTCOME MEASURE(S): Embryo cell number and quality on day 3. Blastocyst development on day 5. Implantation rate (determined by fetal heart) and ongoing pregnancy rate (PR). RESULT(S): Implantation rates for embryos transferred at the blastocyst stage of development were twice that observed for embryos transferred on day 3, around the eight-cell stage. Significantly more embryos were required for transfer on day 3, compared with day 5, to establish similar PRs. CONCLUSION(S): Viable human blastocysts can be obtained in sequential culture media in the absence of coculture and serum. Transfer of blastocysts in IVF will facilitate high PRs while limiting the number of embryos transferred and therefore minimizes the risk of multiple gestation.

Adult↗
PubMed1998

Amino acids and vitamins prevent culture-induced metabolic perturbations and associated loss of viability of mouse blastocysts.

Culture of in-vivo-developed mouse blastocysts in a simple culture medium based on a balanced salt solution supplemented with carbohydrates for 3 h significantly perturbed embryo metabolism. Maximal perturbation occurred after just 6 h of culture. Similarly, culture of rat blastocysts in a simple culture medium for 3 h also resulted in perturbed metabolism. Cultured mouse and rat blastocysts both had an abnormally elevated rate of glycolysis of approximately 100% after culture (P < 0.05). Rates of pyruvate oxidation by mouse blastocysts were also significantly reduced after culture in a simple medium for 6 h (P < 0.01). Furthermore, the developmental competence of mouse blastocysts after transfer was significantly reduced by just 6 h of culture in a simple medium (P < 0.05). Addition of Eagle's amino acids or vitamins to the culture medium reduced the perturbation of both the glycolytic activity and oxidative capacity of cultured mouse blastocysts and acted in synergy to further the inhibition. Importantly, culture with amino acids and vitamins prevented any loss of viability of mouse blastocysts after culture for 6 h. It can be concluded that the mouse blastocyst is sensitive to its environment and that culture-induced stress results in the loss of normal cellular function, as manifested in this case by an abnormal pattern of glucose utilization and loss of viability.

Amino Acids↗
PubMed1998

Culture of viable human blastocysts in defined sequential serum-free media.

In human in-vitro fertilization (IVF), embryos are routinely transferred to the uterus on either day 2 or day 3 of development, resulting in a 10-15% implantation rate. However, in other mammalian species, the transfer of cleavage stage embryos, which normally reside in the oviduct, to the uterus results in a significantly lower implantation rate compared with blastocysts. It is therefore proposed that, in order to increase implantation rates in human IVF, one has to move to extended culture and transfer at the blastocyst stage. The transfer of blastocysts will not only help synchronize the embryo with the female tract but will facilitate the identification of those embryos with little or no developmental potential. In order to culture viable blastocysts it is important to use more than one culture medium to cater for the changing requirements of the preimplantation embryo as it develops and differentiates. If sequential culture media are not used, one can obtain blastocysts but their resultant viability is low. The use of sequential serum-free media in human IVF has resulted in > 50% of embryos becoming blastocysts with an implantation rate of approximately 50%. Further advances in human embryo culture should come from the replacement of protein with the glycosaminoglycan hyaluronate, which is more suitable than albumin in supporting implantation in the mouse, and which will eliminate biological variation and possible contamination from blood products. With the routine culture of human blastocysts will come the introduction of non-invasive tests of embryo viability, capable of identifying those blastocysts most likely to develop from a given cohort. As the implantation rate of blastocysts is higher than that of the cleavage stage embryo, fewer embryos will be required for transfer in order to establish a successful pregnancy, thereby reducing the number of multiple gestations and increasing the overall efficiency of human IVF.

Animals↗
PubMed1998

Calcium homeostasis in early hamster preimplantation embryos.

The development in culture of 1-cell hamster embryos prior to the completion of fertilization is not well understood. In this study it was observed that culture for only 6 h of these early 1-cell embryos collected before pronuclei formation (3 h post-egg activation; PEA) significantly increased intracellular free calcium levels (194.3 +/- 3.1 nM) compared to levels in similarly aged 1-cell embryos collected from the oviduct at 9 h PEA, after pronuclei formation is complete (134.2 +/- 6.8 nM). Not only was the developmental competence of cultured 3-h PEA embryos with elevated intracellular free calcium levels compromised as compared with that of embryos collected from the oviduct at 9 h PEA; these embryos also had impaired cytoplasmic mitochondrial distribution (ratio of 0.62 +/- 0. 06 for cultured embryos compared to 0.44 +/- 0.04 for in vivo-developed embryos) and decreased lactate metabolism (2.93 +/- 0. 22 pmol/embryo per 3 h for cultured embryos compared to 5.37 +/- 0. 36 for in vivo-developed embryos). This impairment in mitochondrial distribution and function and reduced development in culture by 3-h PEA embryos appears related to the ability to regulate intracellular calcium homeostasis. Intracellular free calcium levels were reduced by culture with increased medium magnesium concentrations, calcium channel inhibitors nifedipine or verapamil, or an intracellular calcium chelator. All of these treatments also stimulated development of 3-h PEA embryos to the morula/blastocyst stages and prevented impairment in mitochondrial organization and function. Conversely, culture with low medium magnesium and high calcium concentrations that increased intracellular free calcium levels resulted in low development and reduced mitochondrial function. Therefore, it appears that removal of the early embryo from the oviduct results in an inability to regulate intracellular calcium levels. As increased magnesium concentrations, nifedipine, and verapamil inhibit L-gated calcium channels, it may be a loss of regulation of these channels that alters calcium homeostasis resulting in impaired developmental competence.

Animals↗
PubMed1997

Nonessential amino acids and glutamine decrease the time of the first three cleavage divisions and increase compaction of mouse zygotes in vitro.

PURPOSE: The objective of this study was to determine the effect of supplementing embryo culture media with amino acids on the duration of the first three cell cycles of mouse zygotes in vitro. METHODS: Zygotes were cultured in the presence of different groups of amino acids and cleavage assessed every 30 min. RESULTS: Culture of zygotes with Eagle's nonessential amino acids and glutamine significantly reduced the time of cleavage divisions to the eight-cell stage compared to culture without amino acids. Beneficial effects of amino acids were found to be cumulative over time. Nonessential amino acids and glutamine also increased the percentage of eight-cells that compacted after 57 hr of culture compared to embryos in medium devoid of amino acids. CONCLUSIONS: The present data suggest that media for the development of cleavage-stage embryos, such as in clinical IVF, should be supplemented with Eagle's nonessential amino acids and glutamine.

Amino Acids↗
PubMed1997

The distribution of estrogen receptor-beta mRNA in forebrain regions of the estrogen receptor-alpha knockout mouse.

Neurons in the hypothalamus of estrogen receptor alpha-knockout (ER alphaKO) mice have been shown to concentrate radiolabeled estrogen and estrogen treatment regulates the expression of progesterone receptor mRNA. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of ER beta mRNA in ER alphaKO mouse forebrain. The results of these studies revealed an extensive distribution of ER beta mRNA in the hypothalamic regions including medial preoptic area, suprachiasmatic nucleus, paraventricular nucleus, dorsomedial nucleus, medial tuberal nucleus, and the premammillary nuclei. Additional labeled perikarya were also detected in the glomerular layer of the olfactory bulb; tenia tecta; anterior septum; bed nucleus of the stria terminalis; medial, basolateral and cortical nuclei of the amygdala; cerebral and entorhinal cortex; the septohippocampal nucleus; Ammon's horn of the hippocampus and the dorsal raphe. The results of these in situ hybridization histochemical studies have provided novel information about the distribution of ER beta mRNA in the ER alphaKO mouse forebrain. In addition, these morphological data provides evidence that estrogen may exert its actions in the ER alphaKO mouse brain via ER beta and thereby maintain organizational and activational effects.

Animals↗
PubMed1997

Differential regulation of mouse embryo development and viability by amino acids.

The amino acid requirements of the preimplantation mouse embryo in culture changes as development proceeds from the zygote to the blastocyst stage. Eagle's non-essential amino acids and glutamine significantly increased cleavage rates during the first four cell cycles, while Eagle's essential amino acids without glutamine did not confer any benefit to embryo development before the eight-cell stage. After the eight-cell stage, non-essential amino acids and glutamine no longer stimulated cleavage rates but significantly increased blastocoel development and blastocyst hatching. In contrast, after the eight-cell stage essential amino acids increased cleavage rates as well as stimulating development of the inner cell mass of the resultant blastocysts. Fetal development after transfer of blastocysts was also significantly increased by culture with essential amino acids from the eight-cell stage. Consequently highest rates of development in vitro and viability after transfer were achieved when embryos were cultured with non-essential amino acids and glutamine to the eight-cell stage followed by development to the blastocyst stage in the presence of all 20 amino acids. Analysis of the parameters measured revealed a significant relationship between number of blastocyst cells and inner cell mass development with viability after transfer. Blastocyst formation and hatching could not be used to assess subsequent developmental potential.

Amino Acids↗
PubMed1996

Is body focus restricted to self-evaluation? Body focus in the evaluation of self and others.

OBJECTIVE: Clinicians have suggested that the core pathology of the eating disorders is an extreme body focus in self-evaluation. This study investigated whether women who focus on their own bodies place a similar focus on body shape when evaluating others and expect others to have a strong body focus in their self-evaluations. METHOD: Eighty-four undergraduate women completed the Eating Attitudes Test (EAT-26), which largely measures body focus in self-evaluation. Each was also shown a series of photographs of women and asked what aspects of the photos they first noticed and how the depicted women felt about themselves. Finally, each responded to scenarios in which they or a hypothetical woman overate or dieted. RESULTS: High EAT-26 scores were associated with an elevated number of "fat" or "thin" feelings attributed to women in the slides and a marginally greater number of body-related observations made about the slides. High EAT-26 scores were also associated with inferred negative feelings of others after overeating and positive feelings of others after dieting. In fact, the relationships between EAT-26 scores and feelings in response to hypothetical overeating and dieting situations were no stronger when applied to the self than when applied to others. However, when presented with a situation in which they overate, participants showed stronger relationships between their EAT-26 scores and their expected weight change and dieting behavior than they predicted would occur for others after an identical period of overeating. DISCUSSION: Extrapolating findings to a clinical population, women with eating disorders may focus on others' body shapes as well as their own. These women may also expect others to be as emotionally invested in their own body shapes as they are themselves, but may not expect others to be as prone to gain weight or to diet as strictly as they do. Treatment for this somewhat recalcitrant belief system is discussed, as are directions for future research.

Adolescent↗
PubMed1996

Environment of the preimplantation human embryo in vivo: metabolite analysis of oviduct and uterine fluids and metabolism of cumulus cells.

OBJECTIVE: To determine the levels of metabolites surrounding the human oocyte and embryo in vivo. DESIGN: Oviduct and uterine fluids were collected throughout the menstrual cycle. Cumulus cells were collected at oocyte retrieval and their production of metabolites was assessed. Samples were analyzed for pyruvate, lactate, and glucose by microfluorimetry. PATIENTS: Luminal fluids were collected from naturally cycling patients at the time of routine clinical investigation. Patient consent and hospital ethics approval were obtained for this study. RESULTS: Pyruvate in the oviduct did not vary with the day of cycle, the mean value was 0.24 mM. Lactate and glucose concentrations varied with the day of cycle; lactate increasing from 4.87 mM in the follicular phase to 10.50 mM at the time of ovulation, whereas glucose decreased from 3.11 mM in the follicular phase to 0.50 mM midcycle and subsequently increased to 2.32 mM in the luteal phase. The concentrations of pyruvate, lactate, and glucose in uterine fluid remained constant throughout the cycle (0.10, 5.87, and 3.15 mM, respectively). All metabolite concentrations in uterine fluid were significantly different from those in the oviduct midcycle. Cumulus cells readily consumed glucose in vitro, with lactate being the major metabolite produced. CONCLUSION: These data indicate that lactate and glucose concentrations in the oviduct change with day of cycle and that the human embryo is exposed to different metabolite concentrations as it passes along the tract. Furthermore, cumulus cells readily consume glucose, producing lactate. Therefore, the early human embryo is exposed to low glucose and high lactate levels in vivo.

Body Fluids↗
PubMed1996

Nutrient uptake and culture of Sminthopsis macroura (stripe-faced dunnart) embryos.

Glucose and pyruvate uptake by individual embryos were measured in a marsupial species (stripe-faced dunnart) and a eutherian species (mouse). At each stage of development, nutrient uptake by the dunnart embryo was around an order of magnitude greater than that of the mouse embryo. The pattern of glucose uptake by the dunnart embryo was not like that for any eutherian embryo, all of which have a low glucose uptake before the blastocyst stage. Rather, in the dunnart embryo there was a significant increase in glucose uptake after the third cleavage division, increasing from 13.6 pmol embryo h-1 at the 4-cell stage to 34.9 pmol embryo h-1 by the 8-cell stage. This increase in glucose uptake before blastocyst formation may be attributed to an increased energy demand associated with the movement of cells within the dunnart embryo. Using a new culture system, it was possible to culture 66% of dunnart embryos at the 2-4-cell stage and 80% of those at the 8-16-cell stage to the unilaminar blastocyst stage. Embryos cultured from the 2-cell to the 4-cell stage were retarded by around 12 h when they reached the blastocyst stage. Developmental retardation was also reflected in the pattern of nutrient uptake, which lagged behind that of embryos developed in vivo. The present study has shown that it is possible to culture the early marsupial embryo to the blastocyst stage in a serum-free culture system, while concomitantly quantifying embryonic nutrient requirements. Such an approach is essential for species where there is a paucity of material for study.

Animals↗
PubMed1996

Alleviation of the '2-cell block' and development to the blastocyst of CF1 mouse embryos: role of amino acids, EDTA and physical parameters.

The role of amino acids, ethylenediaminetetraacetic acid (EDTA), transferrin, oxygen, glucose, glutamine, taurine and ammonium in CF1 mouse zygote development in culture was examined. Non-essential amino acids and glutamine were shown to alleviate the 2-cell block in culture, and acted in synergy with EDTA to facilitate development to the blastocyst stage. In the presence of amino acids and EDTA, transferrin conferred no beneficial effect. Development of zygotes was significantly impaired if amino acids were removed from the collection medium, even when they were subsequently cultured in the presence of amino acids. Zygote development to the blastocyst stage was significantly improved when modular incubator chambers were used compared to using a conventional incubator, and when an oxygen concentration of 7% was used as opposed to 20%. Addition of taurine to medium containing non-essential amino acids had no effect on embryo development, whereas the removal of glutamine and/or glucose from the culture medium significantly reduced blastocyst cell number. Removal of glucose from the culture medium also resulted in a significant decrease in implantations. Ammonium, generated from the breakdown of amino acids, significantly reduced blastocyst development. EDTA was found to confer its beneficial effects during the first 48 h of culture, and indeed was inhibitory during the second 48 h, resulting in loss of subsequent viability. In summary, the data demonstrate that development of CF1 zygotes to the blastocyst stage is readily achievable. In the presence of non-essential amino acids and glutamine the removal of glucose is detrimental to CF1 mouse embryo development in culture and reduces subsequent viability. Optimal development and maintenance of viability requires more than one culture medium to support the preimplantation period.

Amino Acids↗
PubMed1996

Selection of viable mouse blastocysts prior to transfer using a metabolic criterion.

The success rate of human in-vitro fertilization (IVF) remains low, with only approximately 10% of embryos transferred resulting in a term pregnancy. A major contributor to this embryonic loss is poor embryo development in vitro. Such poor development can be attributed to both chromosomal and anatomic anomalies in oocytes after ovarian stimulation and to suboptimal embryo culture conditions. The low success rate of IVF is compounded by an inability to select those embryos most likely to implant after transfer (viable). Currently morphology is used almost exclusively as the sole criterion to decide which embryos are replaced. This procedure is not only subjective but has a poor correlation with subsequent developmental competence. Therefore, the development of techniques to quantify embryo viability prior to transfer will significantly increase pregnancy rates. We report here that the non-invasive assessment of glycolytic activity (percentage of glucose converted to lactate) in individual mouse blastocysts prior to transfer can be used successfully to identify viable embryos. Blastocysts with a low glycolytic activity, close to that of in-vivo developed blastocysts, had a significantly higher viability than those with abnormally elevated levels of glycolysis. Using glycolytic activity as a marker of viability resulted in a four fold increase in the pregnancy rate compared with embryos selected at random for transfer. We propose that the success of clinical IVF can be increased significantly by employing quantitative tests for viability.

Animals↗
PubMed1995

Removal of embryo-toxic ammonium from the culture medium by in situ enzymatic conversion to glutamate.

An enzymatic method for removing embryo-toxic ammonium from culture medium has been developed. Ammonium, produced by both embryo metabolism and spontaneous breakdown of amino acids at 37 degrees C, is transaminated by glutamate dehydrogenase to nontoxic glutamate. Initially, the individual components of the transamination reaction were titrated against mouse embryo development in vitro to determine embryo-safe levels. ADP, an allosteric activator of glutamate dehydrogenase, was found to inhibit embryo development and was therefore omitted from the final formulation (alpha-ketoglutarate, 0.44 mM; glutamate dehydrogenase, 0.375 U; NADH, 0.12 mM). It was found that 0.30 mM ammonium could be removed from the culture medium in situ in 3 h. In situ removal of ammonium significantly increases both blastocyst cell number, implantation, fetal development, and fetal weight after transfer. Removal of ammonium by the conventional method of renewing the culture medium also increased blastocyst cell number but did not affect postimplantation development. In conclusion, it is possible to alleviate the toxic effects of ammonium in vitro on pre- and postimplantation mouse embryo development by its transamination in situ, thereby facilitating the continual exposure to embryo-derived factor(s) which stimulates both pre- and postimplantation development.

Animals↗
PubMed1995

Breast cancer screening: racial/ethnic differences in behaviors and beliefs.

Racial/ethnic differences in breast cancer screening behaviors and beliefs were examined in 259 asymptomatic women, 50 years old or older, who participated in a no-cost worksite breast cancer screening program. Hispanics were more likely than African Americans to report having had mammography in the past year. Caucasians and Hispanics were more likely than African Americans to report having had a clinical breast examination in the past year. African Americans to report having had a clinical breast examination in the past year. African Americans and Hispanics were more likely to practice monthly breast self-examination than were Caucasians. African Americans were more likely to report cancer-related fears and worries as barriers to mammography, whereas Caucasians were more likely to report being too busy, inconvenience, and procrastination as barriers. African Americans also were more likely to evaluate their physicians and other health professionals positively than were Caucasians. These results suggest a need to make a special effort to address cancer-related fears as barriers to screening among African Americans, and time-related barriers to screening among Caucasians.

Black or African American↗
PubMed1995

The Gross Motor Performance Measure: validity and responsiveness of a measure of quality of movement.

BACKGROUND AND PURPOSE: This article presents the results of a study to validate a measure of gross motor performance for its capacity to detect changes in the quality of movement in children with cerebral palsy aged 0 to 12 years. SUBJECTS AND METHODS: On two occasions, 4 to 6 months apart, physical therapists from three children's treatment centers assessed 106 children with cerebral palsy, 18 children who had sustained an acute head injury, and 29 nondisabled children. Validity was demonstrated by comparing changes on the measure across diagnoses, severity, and age groups. RESULTS: Several a priori hypotheses were supported; however, relationships with parent and therapist ratings were not clearly demonstrated. CONCLUSION AND DISCUSSION: The measure was found to be differentially responsive to changes in "stable" and "responsive" groups.

Analysis of Variance↗