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Biomedical subjects

M Leonard

Publications and source records attributed to M Leonard.

At least 19 recordsLinked to original sources
PubMed1992

Preferential chromosome loss in human papilloma virus DNA-immortalized mammary epithelial cells.

Human papilloma virus (HPV) DNA-immortalized human mammary epithelial cells may provide a model system for studying the molecular basis of immortalization and its role in breast neoplasia. Cytogenetic analyses were performed on clones derived from HPV 16- and HPV 18-immortalized human mammary epithelial cells. The majority of the clones contained near-diploid karyotypes. The single most frequent whole-chromosome loss was that of chromosome 19. Regions that showed preference for deletion and/or translocation included 2pter, 11qter, and 15pter. Evidence of chromosome 19 loss was confirmed by polymerase chain reaction (PCR)-generated, chromosome 19-specific, dinucleotide microsatellite repeat polymorphism analysis.

Breast↗
PubMed1992

The kinetics of interactions of bilirubin with lipid bilayers and with serum albumin.

Rate constants for the hydration of bilirubin bound to unilamellar bilayers of dioleoylphosphatidylcholine and albumin were measured by stopped-flow methods. Rate constants for association of bilirubin with these vesicles and albumin were calculated from measured rate constants for dissociation and the equilibrium binding constants of bilirubin and lipids or albumin. Rate constants for hydration (dissociation) for bilirubin bound to dioleoylphosphatidylcholine and albumin were 71 s-1 and 1.8 s-1 respectively. Rate constants for association were 4.0 10(7) s-1 and 1.1 10(9) M-1 s-1, respectively. Both rates for interactions of bilirubin with bilayers were essentially independent of temperature in the range 0-40 degrees C, indicating that barriers to entry and exit of bilirubin from bilayers were entropic. Rates of transbilayer movement of bilirubin in dioleoylphosphatidylcholine were too fast to resolve by measuring rates of hydration of bilirubin. Rate constants for hydration of bilirubin bound to bilayers with less avidity for bilirubin as compared with dioleoylphosphatidylcholine also were too fast to measure with stopped-flow methods. In addition to providing details of the energetic basis for interactions between bilirubin and membranes, the data allow for calculating the maximal rates at which bilirubin could transfer spontaneously from sites on albumin in blood to the interior of cells. The data show, in this regard, that this rate is 10-50 fold faster than measured rates of uptake of bilirubin by intact liver.

Bilirubin↗
PubMed1991

Isolation of bovine Y-derived sequence: potential use in embryo sexing.

To obtain bovine Y-derived probes, we have constructed a bovine plasmid library enriched for Y-specific DNA sequences by the deletion enrichment method. The resulting clones were analyzed by hybridization to Southern blots of male and female genomic DNA. From 200 clones tested, two (BC1.2 and BC1.34) were entirely male specific, six gave a male-female differential hybridization pattern, and the remaining reacted similarly with male and female DNA. Interspecies somatic cell hybrid studies and chromosomal in situ hybridization confirmed that the BC1.2 sequence was derived from the Y chromosome. This 54-bp fragment is present at about 2000-2500 copies in the bovine male genome. No polymorphism was revealed with any of the restriction enzymes used, suggesting enzyme site conservation within blocks of repeats. Evolutionary study has shown that the BC1.2 sequence is conserved within Bos and Bison genera and remains male specific. The male specificity and repeated nature of the BC1.2 sequence have enabled us to use it as a molecular probe for sex determination on small numbers of cells by in situ hybridization.

Animals↗
PubMed1991

Horizontal rotation of the condyle after sagittal split osteotomy of the mandible.

Displacement of the proximal segment of the condyle such that the condyle is no longer in its correct position has been cited as a major factor in postsurgical skeletal relapse after mandibular, sagittal split osteotomy. This study examined the effects of sagittal split osteotomy on the horizontal rotation of the condyle in 16 dissected mandibles for which clamp, screw, and wire fixations were used to advance the mandible or set it back. The results showed that, after sagittal split osteotomy, horizontal rotation usually occurred, regardless of the position of the distal segment or the type of fixation used. Our finding that 82% of the condylar angles increased after surgery indicates that the lateral pole of the condyle had rotated anteriorly, while the medial pole had rotated posteriorly. There were no consistent differences in horizontal rotation between the condyles on the side where the proximal segment had been fixed first and those on the side where it had been fixed second; nor did the sizes of the original intercondylar angles affect the magnitudes of change in the postoperative intercondylar angles. The only statistically significant difference (p = 0.005) between the angles after fixation by the three different methods was between screw and wire osteosyntheses when the distal segments were in the forward position. The reason for this difference is unclear.

Bone Screws↗
PubMed1991

Reduction in lactate accumulation correlates with differentiation-induced terminal cell division of leukemia cells.

Lactate accumulation in the medium and glucose utilization decreased during the induction of in vitro differentiation of mouse erythroleukemia (MEL) and human myeloid leukemia (HL-60) cells. The decrease in lactate accumulation occurred as early as 24 h after inducer treatment was initiated and occurred prior to the decrease in glucose utilization. The decrease in lactate accumulation was greater than that predicted by the decrease in glucose utilization, i.e., the ratio of glucose used glycolytically, as measured by lactate accumulation, to glucose used in other pathways ('glycolytic ratio') markedly decreased during differentiation in these cell lines. Differentiation correlated with the abrogation of the high levels of lactate accumulation first described by Warburg as characteristic of some transformed and neoplastic cells. Studies on both parental and differentiation-resistant variant MEL cell lines indicated that the changes in lactate accumulation were not dependent on the changes in glucose utilization and could be dissociated from them. Moreover, the changes in lactate accumulation only occurred in cells able to undergo differentiation-induced terminal cell division. This regulatable expression of lactate accumulation in MEL and HL-60 cells in vitro may make them useful model systems for the elucidation of the molecular mechanisms controlling lactate formation in malignant cells.

Acetamides↗
PubMed1991

Effect of sodium bicarbonate infusion on serum osmolality, electrolyte concentrations, and blood gas tensions in cats.

The effects of single IV injections of sodium bicarbonate (0.5 mEq/kg of body weight, 1 mEq/kg, 2 mEq/kg, and 4 mEq/kg) on serum osmolality, serum sodium, chloride, and potassium concentrations, and venous blood gas tensions in 6 healthy cats were monitored for 180 minutes. Serum osmolality increased and remained significantly (P less than 0.05) increased for 120 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium was increased significantly (P less than 0.05) for 30 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium decreased and remained significantly (P less than 0.05) decreased for 120 minutes in cats given 1 g of 20% mannitol/kg, and serum osmolality was significantly (P less than 0.05) decreased at 30 and 60 minutes. Serum chloride decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and was significantly decreased for 30 minutes in cats given 2 mEq and 4 mEq of sodium bicarbonate/kg. Serum chloride decreased and remained significantly (P less than 0.05) decreased for 30 minutes in cats given 1 g of 20% mannitol/kg. Serum sodium and serum osmolality did not change significantly (P less than 0.05) in cats given 4 ml of 0.9% sodium chloride/kg. Serum potassium decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and for 120 minutes in cats given 2 mEq/kg or 4 mEq/kg. There was a significantly (P less than 0.05) greater decrease in serum potassium that lasted for 30 minutes after given sodium bicarbonate at the dosage of 4 mEq/kg, compared with other dosages given.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Generalized anxiety disorder: some biochemical aspects.

Fifty-one patients who met DSM-III criteria for generalized anxiety disorder, and who were recruited to participate in a drug outcome study, filled out a variety of rating scales and had blood samples drawn for plasma norepinephrine, epinephrine, and free 3-methoxy-4-hydroxyphenylglycol (MHPG) after a 20-min rest period. This group was compared to 15 normal controls who also had their blood drawn after a 20-min rest period. While the two groups were initially found to have significantly different levels of plasma free MHPG through the use of t tests, this finding was not confirmed by subsequent discriminant analysis.

Adolescent↗
PubMed1990

[Diagnosis of the sex of bovine embryos using molecular biology].

Thanks to a bovine genomic library enriched with Y chromosome-specific sequences, a probe specific to this chromosome of genera Bos and Bison and repeated on about 2,000 copies in the male genome was isolated. To be compatible with embryo transfer and/or freezing, sex determination has to be done on a 10-20 cell embryo biopsy from a day-7 bovine blastocyst. The in situ hybridization with biotinylated BC 1.2 probe and immunocytochemical revelation permitted the visualization of the hybridization signal on the nucleus of each cell. Because of the numerous steps required, this technique was difficult to apply routinely. For that reason we worked out the polymerase chain reaction technique. From the BC 1.2 sequence, we determined several oligonucleotide primers and probes with the aim of amplifying the Y chromosome-specific sequences. This technique, which is easy to perform and to automate, enabled us to obtain a strong male-specific hybridization signal on genomic DNA and embryo cells.

Animal Husbandry↗
PubMed1989

The interactions of bilirubin with model and biological membranes.

The partitioning of bilirubin between albumin and model and biological membranes and the differential partitioning of bilirubin between membranes with different lipid and protein compositions were measured. Partition coefficients were independent of the concentration of bilirubin in membranes up to at least 7 mol of bilirubin/mol of phospholipid. The avidity of albumin for bilirubin was greater than that of membranes, but the avidity of the latter for bilirubin depended on the composition of the membrane. Bilirubin partitioned preferentially into model membranes comprised of microsomal lipids greater than dioleoylphosphatidylcholine = plasma membrane lipids much greater than egg phosphatidylcholine = dimyristoylphosphatidylcholine. Partitioning into membranes was increased if these contained proteins, but the effect of proteins could not be attributed to specific binding to sites on proteins, as reflected by the temperature independence of partition coefficients. Differential partitioning of bilirubin into different membranes of pure lipids also was independent of temperature. Differences in the bulk phase fluidity of membranes does not appear to account for the preferential partitioning of bilirubin into some membranes. It appears that bilirubin partitions into elements of free volume of differing sizes in membranes with variable lipid compositions and that the size of these elements can be increased by adding proteins to membranes.

Animals↗
PubMed1989

Arc welders' respiratory health evolution over five years.

The respiratory health of 138 arc welders and 106 control subjects in the same company was studied in 1981 and in 1986. Most of the subjects welded mild steel using the Metal Inert Gas (MIG) process. The controls were workers in the same company, not exposed to any known pulmonary risk. The welders and controls in the analysis had not changed their professional activity nor their smoking habits during these five years. The examinations consisted of a questionnaire on respiratory symptoms, a thoracic auscultation, a chest X-ray and lung function tests: flow-volume curve and steady state CO transfer test. The examinations in 1986 confirmed the risk of non specific radiological impairment (pulmonary reticulo-micronodulation) and of obstruction in the small bronchi, which had already been observed in 1981 in the arc welders in this company. These impairments did not seem to have evolved more than in the controls, but do however justify regular surveillance of the respiratory health of arc welders.

Adult↗
PubMed1989

Multifocal adenocarcinoma of the proximal small intestine in a patient with celiac sprue.

Adenocarcinoma of the small intestine is a known complication of celiac sprue. We report a 63-year-old man with a history of celiac disease who developed anemia, guaiac-positive stools, and jaundice. Five discrete adenocarcinomas of the proximal small intestine were identified over a 9 year period. Endoscopic retrograde cholangiopancreatographic (ERCP) and radiographic evaluation of the small bowel were helpful in diagnosing adenocarcinoma involving the ampulla of Vater and jejunum. This case demonstrates for the first time the multifocal, malignant potential of sprue. It also illustrates the importance of an aggressive, systematic work-up of patients whose course has changed despite dietary restriction.

Adenocarcinoma↗
PubMed1989

Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats.

The effects of sodium bicarbonate (0.5 mEq/kg of body weight, 1.0 mEq/kg, 2.0 mEq/kg, and 4.0 mEq/kg) on ionized and total calcium concentrations were determined in clinically normal cats. Also, serum pH, whole blood pH, and serum albumin, serum total protein, and serum phosphorus concentrations were measured. Intravenous administration of sodium bicarbonate to awake cats decreased serum ionized calcium and serum total calcium concentrations. All dosages of sodium bicarbonate were associated with significant decreases of serum ionized calcium concentration. This effect lasted for greater than 180 minutes when cats were given 2.0 mEq/kg or 4.0 mEq/kg. When cats were given 4 mEq of sodium bicarbonate/kg, serum ionized calcium concentration was significantly decreased, compared with that when cats were given lower doses, but only at 10 minutes after infusion. After sodium bicarbonate infusion, serum total calcium concentration, measured by ion-specific electrode and colorimetry, was lower than baseline values at most of the times evaluated. Decreases in serum ionized calcium and serum total calcium concentrations can be attributed only in part to an increase in serum or whole blood pH and to a decrease in serum protein concentration. Serum total calcium concentrations measured by ion-specific electrode and by colorimetry were positively correlated, but the variability was high. Only 44% of the variability in serum ionized calcium concentration could be predicted when serum total calcium, albumin, total protein, phosphorus, and bicarbonate concentrations and pH were considered.

Animals↗
PubMed1989

Activation mechanisms of the Xenopus beta globin gene.

Comparative protein binding studies have been performed on the Xenopus beta globin gene promoter. Erythroblast nuclear extracts 'footprint' over the erythroid-specific consensus sequence, AGGATAAG, which is located immediately upstream of the CCAAT footprint. Nonerythroid cell extracts do not give rise to an AGGATAAG footprint but rather to an extended CCAAT footprint reminiscent of the CCAAT displacement protein (CDP). Erythroblast extracts also protect a sequence similar to the chicken stage selector element (SSE) immediately downstream of the CCAAT box footprint. In contrast to these discrete footprints observed using erythroblast extracts, Xenopus erythrocyte nuclear extracts give rise to more extensive promoter protection. We have previously reported that this promoter is active in transfected HeLa cells when linked to the SV40 enhancer and that transcriptional activation is accompanied by the formation in the chromatin of a nuclease hypersensitive site (HS) in this region. As a first step towards defining the roles of the various promoter-binding proteins in transcriptional activation and HS formation, we transfected deletion mutants of the promoter into HeLa cells. Deletion of the sequences upstream of -116 had no effect on transcription or HS formation. Indeed the upstream boundary of the HS remained unchanged (at around-170) even though plasmid sequences had replaced Xenopus sequences. If the HS boundary reflects resumption of nucleosomal structure, then sequences downstream of -116 must be able to position a nucleosome from at least 50 bp away. beta globin gene activation in a number of transfected cell lines is absolutely dependent on DNA replication. The replication requirement is not a consequence of template copy number or methylation, nor is it dependent on the direction in which the replication fork passes through the gene. We conclude that replication facilitates active transcription complex formation by disrupting a stable association of the template with negative factors, which could include histones. About 200 bp upstream of the Xenopus beta globin gene promoter is a tract of alternating A and T residues which adopts cruciform geometry at low levels of supercoiling. Because of this sensitivity to torsional stress, we have probed the structure of the (AT)n sequence in microinjected Xenopus oocytes, where the Xenopus beta globin gene is transcribed very efficiently. We find that S1 nuclease cleaves specifically in the middle of the (AT)n tract, suggesting that the gene is under torsional stress.

Animals↗
PubMed1989

Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks.

Fifty-five patients completed a 5-week double-blind study comparing alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. There was no concomitant behavioral treatment. Patient and therapist rating scales included Sheehan's Panic and Anxiety Attack Scales, the Marks-Sheehan Phobia Scale, the Hamilton Anxiety Scale, the Hamilton Depression Scale, and the Side Effects Checklist. The results generally support the efficacy of alprazolam, but not propranolol, in the treatment of panic disorder and agoraphobia with panic attacks. The significance of the results are discussed, as well as a number of the unique aspects of our procedures and patient population.

Adolescent↗
PubMed1988

Hemoglobin solutions coupled with polyethylene glycol 1900: preparation, purification, quality control and pharmacological trials by hemorrhagic shock.

The usefulness of hemoglobin solutions as oxygen transporters is limited by their high affinity for oxygen and rapid elimination from the circulation. Various chemical modifications of hemoglobin aimed at overcoming these two handicaps have been suggested. We have developed a conjugate of pyridoxylated human hemoglobin with monomethoxypolyoxyethtylene 1900, whose preparation and properties are described. We present comparative results on short-term or definitive survival of Wistar rats which, during hemorrhagic shock due to the loss of 60 or 80% of their blood mass, were given a solution of native or modified hemoglobin, in some cases purified by ion-exchange chromatography to remove non-heme proteins, lipids, and some endotoxins. The more complex the treatment used to improve the properties and the purity of the hemoglobin solutions, the longer the animals survived. The loss of hemoglobin in the urine was greatly reduced after conjugation: after 20 h, less than 6% of the total infused.

Animals↗
PubMed1986

The effects of vagotomy on compensatory ovarian hypertrophy and follicular activation after unilateral ovariectomy.

Following unilateral ovariectomy in the rat, the remaining ovary undergoes rapid compensatory changes including an increase in the number of antral follicles (follicular activation) and an increase in ovarian weight (compensatory ovarian hypertrophy). The ovary is innervated by the vagus nerve (Burden et al., 1983). In the present study, the effects of right and left cervical vagotomy and abdominal vagotomy on follicular activation and compensatory ovarian hypertrophy in the remaining right or left ovary were compared 15 days after unilateral ovariectomy. Neither right nor left cervical vagotomy affected compensatory ovarian hypertrophy of the right or left ovaries but abdominal vagotomy depressed compensatory ovarian hypertrophy in both the right and left ovaries. Left cervical vagotomy did not inhibit follicular activation, but right cervical vagotomy prevented follicular activation in the right but not left ovary. Also, abdominal vagotomy inhibited follicular activation in the right but not the left ovary. In animals with both ovaries which were subjected to the left or right cervical vagotomy or abdominal vagotomy follicular counts in both right and left ovaries were similar. Collectively, these data indicate that the vagus nerve participates in follicular activation after unilateral ovariectomy. The data also indicate that the right ovary is more dependent on vagal influences for follicular activation than the left ovary.

Animals↗