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Biomedical subjects

M A Harris

Publications and source records attributed to M A Harris.

At least 73 records · Page 4Linked to original sources
PubMed1997

Neonates with congenital heart disease, Part IV: Total anomalous pulmonary venous return.

Significant radiographic findings of TAPVR with unobstructed blood flow include the following: 1. Increased pulmonary vascular markings with dilated pulmonary arteries 2. Cardiomegaly 3. A "snowman" configuration of the heart, seen after pulmonary vascular resistance falls and blood flow through the lungs increases In TAPVR with obstructed blood flow, findings include the following: 1. A hazy, reticular, ground-glass appearance of the lung fields 2. Normal to small cardiac size.

Female↗
PubMed1996

Prostaglandins in selected reproductive tissues in preterm and full-term gestations.

We investigated differences in maternal plasma and trophoblast prostaglandin metabolism associated with preterm births. Tissue prostaglandins (PGs) E2 and F2 alpha and the stable plasma PGF2 alpha metabolite, 13,14-dihydro-15-keto-PGF2 alpha, were measured in preterm (< 37 weeks) and term (< or = 37 weeks) births. Amnion PGE2 in preterm (106.1 +/- 15.7 ng/g wet weight tissue; x +/- SEM; n = 37) was lower than in term (176.6 +/- 22.7 ng/g wet weight; x +/- SEM; n = 34, P < 0.02). Placenta PGE2 was lower in preterm (34.7 +/- 19.7 ng/g wet weight; x +/- SEM) than in term (103.3 +/- 28.0 ng/g wet weight; x +/- SEM, P < 0.04). Preterm PGF2 alpha was consistently lower in the amnion (106.8 +/- 17.5 ng/g wet weight) and placenta (102.5 +/- 8.7 ng/g wet weight) than in term amnion (188.2 +/- 24.8 ng/g wet weight; P < 0.01) and placenta (128.9 +/- 7.8 ng/g wet weight; P < 0.03). Chorionic PGE2 and plasma PGF2 alpha metabolite followed this trend but did not reach significance. These findings suggest qualitative and quantitative differences in maternal and trophoblast eicosanoid metabolism between term and preterm parturition.

Adult↗
PubMed1996

Plasma ascorbic acid concentrations are related to cardiovascular risk factors in African-Americans.

This study was undertaken to examine relationships among blood pressure, blood lipids, and plasma concentrations of ascorbic acid and malondialdehyde (MDA) equivalents (indicative of lipid peroxidation) in adult African-Americans. Subjects (n = 172, mean age = 48.0 y) were recruited from among the memberships of several Seventh-Day Adventist Churches. Plasma ascorbic acid and MDA equivalents were inversely correlated (r = -0.44, P < 0.0001). There were significant inverse correlations between plasma ascorbic acid levels and both systolic (r = -0.39, P < 0.0001) and diastolic blood pressure (r = -0.25, P < 0.03), and between plasma ascorbic acid and serum total cholesterol (r = -0.25, P < 0.03), LDL-cholesterol (LDL-C) (r = -0.33, P < 0.004), and the ratio of LDL-cholesterol to HDL-cholesterol (LDL-C/HDL-C) (r = -0.32, P < 0.004). Serum HDL-cholesterol was positively related to plasma ascorbic acid (r = 0.22, P < 0.05). The correlations for MDA equivalents and the blood pressure and blood lipid variables were of similar magnitude to those of plasma ascorbic acid, but were in the opposite direction. Multiple regression analysis revealed ascorbic acid to be a significant independent contributor to the prediction of blood pressure and LDL-C concentration. These data suggest that plasma concentrations of ascorbic acid and MDA equivalents are related to several cardiovascular risk indicators in black Americans.

Adult↗
PubMed1996

Immortalized murine osteoblasts derived from BMP 2-T-antigen expressing transgenic mice.

Osteoblast cell lines capable of undergoing bone formation in vitro would provide useful models for understanding gene expression during bone cell differentiation. To that end, transgenic mice were produced using a 2.9-kilobase bone morphogenetic protein 2 (BMP-2) promoter fragment, driving simian virus 40 T antigen as the transgene. The expression of simian virus 40 T antigen driven by the BMP-2 promoter immortalizes the cells. From the calvaria of the transgenic mouse, several osteoblastic cell lines were isolated and cloned. One clonal osteoblast cell line, called 2T3, has been characterized and shown to produce mineralized bone nodules. Recombinant human BMP-2 (rhBMP-2) accelerates the formation of these mineralized bone nodules. 2T3 cells express alkaline phosphatase, collagen type I, osteocalcin, and endogenous BMP-2 messenger RNA (mRNA) in a similar chronological order as normal freshly isolated fetal rat calvarial cells during early nodule formation and subsequent mineralization. The 2T3 cells also exhibit extensive growth and multilayering during differentiation, as demonstrated by growth curves and transmission electron microscopy. As with freshly isolated fetal rat calvarial cells, 1,25-dihydroxyvitamin D3 inhibited alkaline phosphatase activity and alkaline phosphatase mRNA expression, but stimulated osteocalcin mRNA expression, but stimulated osteocalcin mRNA expression. rhBMP-2 also accelerated the expression of alkaline phosphatase activity and mRNA, osteocalcin mRNA, and BMP-2 mRNA in 2T3 cells along with the formation of larger and more mineralized bone nodules. The 2T3 cell exhibits autoregulation at the mRNA and transcriptional levels. The 2T3 osteoblast cell line offers a system for examining autoregulation of the BMP-2 gene and downstream gene expression during osteoblast differentiation. 2T3 cells are reclonable and maintain their differentiation capabilities.

Animals↗
PubMed1996

Neonates with congenital heart disease, Part II: Congenital cardiac defects with increased pulmonary blood flow.

Generally, cardiac lesions with increased pulmonary blood flow demonstrate cardiomegaly, increased pulmonary vascular markings, and pulmonary congestion on the chest x-ray. These findings occur as a result of the following: 1. A left-to-right shunt or mixing lesion in which excess volume of blood flow causes dilation of cardiac chambers, resulting in the appearance of cardiomegaly, and in which increased pulmonary artery blood flow causes increased pulmonary vascular markings 2. Obstruction of blood flow that produces pulmonary venous hypertension and resultant pulmonary edema The next article in this series will address cardiac lesions with decreased pulmonary blood flow.

Aortic Coarctation↗
PubMed1995

The mouse bone morphogenetic protein-4 gene. Analysis of promoter utilization in fetal rat calvarial osteoblasts and regulation by COUP-TFI orphan receptor.

Bone morphogenetic protein-4 (BMP-4) is one of a member of related polypeptides that are important in bone formation and other developmental processes. We isolated the BMP-4 gene from a mouse genomic library and characterized the exon-intron structure and one of the candidate promoters. Two alternative 5'-noncoding exons, 1A and 1B, were identified by reverse transcription polymerase chain reaction assays. Quantitative competitive polymerase chain reaction using Exon 1A, Exon 1B, and Exon 3 primers indicate the 1A-containing transcript is the primary BMP-4 mRNA expressed in bone cell cultures. Primer extension analysis supports that 1A is the major promoter utilized in bone cell cultures as well as in 9.5-day mouse embryos. 1A promoter activity indicate selective DNA regions functional in bone cells. We found potential regulatory response regions in the 1A 5'-flanking region of the BMP-4 gene for the chicken ovalbumin upstream-transcription factor I (COUP-TFI). Specific binding to the COUP-TFI response regions in the BMP-4 1A promoter was demonstrated. By co-transfection of a COUP-TFI expression plasmid with the BMP-4 1A promoter in fetal rat calvarial osteoblasts, we demonstrated that COUP-TFI inhibits the BMP-4 promoter activity. This suggests that COUP-TFI could act as a silencer for BMP-4 transcription in vivo.

Amino Acid Sequence↗
PubMed1995

Deer antler tissue contains two types of bone morphogenetic protein 4 mRNA transcripts.

Previously we isolated a bone morphogenetic protein 4 (BMP-4) cDNA from human prostate cancer cells and found that the 5' noncoding exon 1 of this BMP-4 cDNA was different from that of human bone cell BMP-4 cDNA. Recently we identified two alternate exon 1s, 1A and 1B, for BMP-4 gene by reverse transcription-polymerase chain reaction (RT-PCR) assays from fetal rat calvarial osteoblasts. In order to further examine alternate exon 1 usage in the BMP-4 gene, we screened deer antler tissue cDNA library. We isolated two types of cDNA clones encoding BMP-4 from this deer antler cDNA library. Sequencing of these clones have revealed a single open reading frame encoding a 408 amino acid protein. Comparison of 5' noncoding exon 1 portion of these cDNA sequences with those of human bone and prostate BMP-4 cDNA sequences and mouse BMP-4 genomic DNA sequence demonstrated that deer antler tissue expresses both exon 1A and 1B containing BMP-4 mRNA transcripts. This suggests that BMP-4 gene may contain alternate promoters or alternate splicing sites in deer antler tissue.

Amino Acid Sequence↗
PubMed1995

Sleep pattern and supplementary oxygen requirements in infants with chronic neonatal lung disease.

Seven infants with chronic neonatal lung disease and baseline oxygen saturation greater than 90% were studied with overnight polysomnography in their prescribed oxygen environment, and on a second night with 0.25 L/min additional oxygen. All had sleep fragmentation and decreased rapid-eye-movement (REM) sleep, which was reversed after the increased oxygen. Sleep duration (p < 0.003), percentage REM sleep (p < 0.001), and mean REM sleep period length (p < 0.001) were increased, and arousals in REM sleep decreased (p < 0.05), with improved oxygenation. We conclude that, in infants with chronic neonatal lung disease, arousal mechanisms minimise oxygen desaturation but induce sleep disruption.

Arousal↗
PubMed1995

Low-dose aspirin does not attenuate platelet aggregation or atherosclerosis in miniature swine but decreases production of aortic wall prostacyclin.

The objectives of this study were to determine if, and at what dose, aspirin could attenuate atherosclerosis in hypercholesterolemic Yucatan miniature swine, and to determine the influence of aspirin on aortic wall prostacyclin production and platelet aggregation. 30 Yucatan miniature swine (age 3 months) were fed either regular diet (RD), atherogenic diet (AD), or AD plus one of four aspirin dosages (2,4,8, or 16 mg/kg/d) for 6 months. The extent of atherosclerotic lesions in the abdominal aorta and coronary arteries was evaluated by sudanophilic staining and histological grading using Stary's classification, respectively. Aortic wall production of prostacyclin (PGI2) and platelet aggregation were assessed. Lesions were similar among the AD groups (45.3 +/- 4.3%) and significantly higher than RD (1.4 +/- 0.4%). PGI2 production was significantly lower (p < 0.05) in all aspirin-treated groups. Platelet aggregation was not affected by treatment. It is concluded that the range of aspirin dosages (2-16 mg/kg/d) does not attenuate the development of atherosclerosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells.

We have examined expression of bone morphogenetic protein 3 (BMP-3) mRNA in normal rat osteoblasts in culture as they undergo differentiation to form bone-like structures, and have found that expression of BMP-3 mRNA in primary fetal rat calvarial (FRC) cells is discontinuous and shows at least four different-sized transcripts. BMP-3 mRNA expression has a distinct temporal pattern during bone cell differentiation of FRC osteoblasts. Previously, we showed that BMP-3 mRNA is expressed in normal and neoplastic rat and human prostate tissues, and in human osteosarcoma cells, as multiple transcripts. To compare the nature of these transcripts in different tissues, three cDNA clones encoding BMP-3 have been isolated by reverse transcription-polymerase chain reaction (RT-PCR) and cDNA library screening from human prostate cancer PC-3 cells, rat prostate adenocarcinoma PA III cells, and primary FRC cells. Analysis of these clones has revealed that the nucleotide sequence of BMP-3 found in human prostate cells is identical to that found in human bone cells. The rat BMP-3 sequences from bone and prostate cells are also identical but show a high degree of variation in the pro- or precursor region compared with human BMP-3. The biological significance of these differences in these two species is unknown.

Adenocarcinoma↗
PubMed1995

Interaction of acute changes in exercise energy expenditure and energy intake on resting metabolic rate.

The effects on resting metabolic rate (RMR) of energy intake and exercise energy expenditure were examined in eight trained men under four conditions: 1) high energy flux (HF), 90 min of exercise at 75% VO2max on 3 d while in energy balance; 2) low energy flux (LF), no exercise for 3 d while in energy balance; 3) negative energy balance (NEB), exercise on 3 d while consuming low-flux meals; and 4) positive energy balance (PEB), no exercise for 2 d while consuming high-flux meals. Eight untrained men were studied in LF. There were effects of exercise energy expenditure and energy intake on RMR, and an exercise x diet interaction (P < 0.05). RMR was greater in trained than in untrained subjects only when trained subjects were in HF. These data indicate that RMR is influenced by exercise, energy intake, and their interaction and suggest that higher RMR in trained vs untrained individuals results from acute effects of HF rather than from a chronic adaptation to exercise training.

Adolescent↗
PubMed1995

Effects of nasal continuous positive airway pressure on apnoea index and sleep in infants.

OBJECTIVE: We examined the effectiveness of nasal continuous positive airway pressure (CPAP) for treatment of sleep apnoea in infants. METHODOLOGY: We studied five infants who all had significant central and mixed apnoea and severe sleep fragmentation. Polysomnographic recordings were performed on 2 consecutive nights in these infants. One night was used as a control study and during the second night nasal CPAP was applied throughout the night. RESULTS: Nasal CPAP significantly reduced apnoea in each infant, with the apnoea index (apnoeas/h) decreasing from 65.6 +/- 14.6 during the control study to 10.5 +/- 14.6 during CPAP in non-rapid eye movement (non-REM) sleep, and from 106 +/- 13.9 during the control study to 26.6 +/- 13.9 during CPAP in REM sleep. Nasal CPAP also improved the sleep fragmentation markedly; REM sleep increased from 14.2 +/- 1.2% of sleep during the control study to 27.1 +/- 1.2% of sleep during CPAP. CONCLUSIONS: We conclude that nasal CPAP is an effective treatment for infantile apnoea. Sleep apnoea in these infants is associated with profound sleep fragmentation, which is reversed by nasal CPAP.

Female↗
PubMed1994

Hepatocyte nuclear factor-3 (HNF-3) binds to the insulin response sequence in the IGF binding protein-1 (IGFBP-1) promoter and enhances promoter function.

IGF binding protein-1 is an important short-term modulator of IGF bioavailability. Hepatic transcription of IGFBP-1 is increased by glucocorticoids and suppressed by insulin. We previously identified adjacent glucocorticoid and insulin response sequences approximately 90 bp 5' to the RNA cap site in the IGFBP-1 promoter. This insulin response sequence contains a sequence highly related (10/12 bases) to a consensus HNF-3 binding sequence. Gel shift and supershift studies confirm that this sequence binds HNF-3 alpha, beta and gamma. Co-expression of HNF-3 beta enhances IGFBP-1 promoter activity in NIH-3T3 cells. Mutation of this HNF-3 binding sequence disrupts this effect as well as the ability of glucocorticoids to stimulate and of insulin to inhibit IGFBP-1 promoter activity in H4IIE and HepG2 hepatoma cells. HNF-3 binding at this site may play an important role in the multihormonal regulation of hepatic IGFBP-1 gene expression.

3T3 Cells↗
PubMed1994

Structure and sequence of mouse bone morphogenetic protein-2 gene (BMP-2): comparison of the structures and promoter regions of BMP-2 and BMP-4 genes.

Screening of a mouse spleen genomic DNA library with mouse BMP-4 and BMP-2 cDNA probes led to the isolation of mouse BMP-2 gene. This gene contains approximately 11 kb transcription unit and 3 exons. The deduced protein has 394 amino acids. The C-terminal amino acid mature coding region is identical to that of the human BMP-2. Comparison of mouse BMP-2 and BMP-4 gene shows little similarity in exon/intron structure, although the mature coding peptide regions of both genes share over 90% identity at the amino acid level.

Amino Acid Sequence↗
PubMed1994

Expression of bone morphogenetic protein messenger RNA in prolonged cultures of fetal rat calvarial cells.

In addition to structural proteins of bone, such as type I collagen, bone cells synthesize a number of growth regulatory peptides that are also stored in the bone matrix, presumably as a consequence of local production by osteoblasts. Among the bone growth regulatory peptides found in the bone matrix are the recently described bone morphogenetic proteins (BMPs). These factors were purified from bone matrix by their capacity to stimulate ectopic bone formation, but it is not known whether they are produced by normal bone cells and influence normal bone formation. To determine whether they are expressed by normal osteoblasts during differentiation, we used the technique of prolonged primary culture of fetal rat calvarial osteoblasts. These cultures have been shown to be an informative model for studying expression of bone-related genes by cultured osteoblasts, since specific genes are expressed as the cells undergo proliferation and differentiation. We found that the bone morphogenetic proteins 1, 2, 4, and 6 are expressed by cultures of fetal rat calvarial osteoblasts before they form mineralized bone nodules and as they express alkaline phosphatase, osteocalcin, and osteopontin. This model can be used for study of regulation of expression of bone morphogenetic proteins by osteoblasts.

Alkaline Phosphatase↗
PubMed1994

Effects of transforming growth factor beta on bone nodule formation and expression of bone morphogenetic protein 2, osteocalcin, osteopontin, alkaline phosphatase, and type I collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts.

Transforming growth factor beta (TGF-beta) is one of the most abundant of the known growth regulatory factors stored within the bone matrix. When bone is resorbed, TGF-beta is released in an active form and is a powerful bone growth stimulant. When injected into the subcutaneous tissue over the calvarial surface of rodents, it rapidly causes proliferation of the periosteal layer and accumulation of new woven bone. In this report, we describe the effects of TGF-beta 1 on first subcultures of fetal rat osteoblasts obtained from calvarial bones and cultured from confluence with ascorbic acid and beta-glycerophosphate. Under these conditions, nodules with characteristics of normal bone appear by day 8. Similar to experiments described by Antosz et al., TGF-beta added to confluent cultures inhibited the formation of bone nodules. Both the number and total area of the nodules were quantitated and shown to be completely inhibited by 2 ng/ml of TGF-beta 1. TGF-beta also impaired the expression of genes associated with bone formation, including type I collagen, alkaline phosphatase, osteopontin, and osteocalcin. TGF-beta also inhibited the expression of mRNA for the bone morphogenetic protein 2 (BMP-2). These results, showing suppression of markers representative of osteoblast differentiation, suggest that the effects of TGF-beta to stimulate bone formation in vivo are not likely a result of effects on differentiated mineralizing osteoblasts but, as suggested by previous studies, more likely are caused by effects on osteoblast precursors. These results also suggest that endogenous BMP-2 expression in fetal rat calvaria cells is important for bone cell differentiation.

Alkaline Phosphatase↗