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Biomedical subjects

M A Harris

Publications and source records attributed to M A Harris.

At least 91 records · Page 5Linked to original sources

Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells.

Human prostate cancer cells are known to produce several growth regulatory factors, including transforming growth factor beta (TGF beta) and heparin-binding fibroblast growth factors (FGFs), which may play as-yet-undefined roles in prostate gland morphogenesis, as well as in prostate cancer cell behavior. Recently, a family of proteins in the extended TGF beta family, the bone morphogenetic proteins (BMPs), has been identified which stimulates bone formation in vivo, and in which, the proteins are likely involved in a variety of morphogenetic processes during embryogenesis. These powerful morphogenetic factors are capable of redirecting muscle mesenchyme cells to differentiate along the lines of bone tissue. We examined a number of well-characterized rat and human prostate cancer cell lines for the expression of BMP 2, 3, 4, and 6 messenger RNA. Poly(A+)-RNA was isolated from normal human and rat ventral prostate, from the rat prostate adenocarcinoma PAIII tumor and cultured cells derived from it, and from human prostate cancer cell lines PC-3, LNCaP, and DU-145. BMP mRNA levels were measured using BMP 2, 3, 4 and Vgr-1 (BMP 6) cDNA probes. Both normal and neoplastic prostate tissue expressed these BMP mRNAs, although the level of expression varied from tumor to tumor. Normal human prostate expressed BMP 4 mRNA predominantly, as did the human prostate cancers PC-3 and DU-145. PC-3 also expressed BMP 2 mRNA and BMP 3 mRNA in large amounts. Normal rat ventral prostate expressed all these BMP mRNAs, but the rat prostate adenocarcinoma PAIII expressed predominantly BMP 3 mRNA. The reason that different BMPs are expressed in varying amounts by these normal and neoplastic cells is unknown. However, if these BMPs are expressed in biologically active form, they could be responsible for important effects on normal prostate growth and morphogenesis, on neoplastic prostate cell behavior, and could even contribute to the capacity of prostatic cancer cells to stimulate new bone formation at metastatic tumor sites in bone.

Adenocarcinoma↗

Age-related changes in oxygen saturation over the first year of life: a longitudinal study.

Stability of oxygen saturation depends on maturation and function of individual components of the respiratory system. The aim of this study was to record and analyse comprehensive oxygen saturation data in a longitudinal study over the first year of life. Detailed sleep studies were performed on 15 normal infants eight times in the first year of life. The accrued oxygen saturation data were analysed on a computerized oximetry data analysis system. Results show the mean sleep saturation levels trending upwards and stabilizing by 185 days. There was an inverse curvilinear relationship between mean age and median desaturation time and the median number of desaturations at < or = 95, < or = 92 and < or = 90% saturation. The mean cumulative desaturation time < or = 90% in the first 4 months was 11.08 min (range 2.5-36.57 min). This study demonstrates monotonic patterns of increasing saturation and decreasing number and time of desaturations < or = 95% and < or = 90% but a random pattern of desaturations < or = 85% occurs across the first 6 months of life. Cumulative desaturation times over the first 4 months of life were high and could be important to the development of maturity of the respiratory system. After 6 months, all indices of saturation and desaturation point to a stable and mature respiratory system.

Aging↗

Urinary excretion of chromium following ingestion of chromite-ore processing residues in humans: implications for biomonitoring.

Biomonitoring programs for urinary chromium (Cr) typically attempt to evaluate occupational exposure via the inhalation route. This study investigated whether Cr can be detected in the urine of people following the ingestion of soils that contain relatively high concentrations of chromium in chromite ore processing residue (COPR). To evaluate the reasonableness of using urinary monitoring to assess environmental exposure, six volunteers ingested 400 mg of soil/day (low-dose group), two others ingested 2.0 g of soil/day (high-dose group) for 3 consecutive days, and one person ingested a placebo on each of 3 days. The soil and COPR mixture contained concentrations of total chromium (Cr) and hexavalent chromium [Cr(VI)] of 103 +/- 20 and 9.3 +/- 3.8 mg/kg, respectively. Therefore, the low-dose group ingested 41 micrograms Cr/day [including 3.7 micrograms Cr(VI)] and the high-dose group ingested 206 micrograms Cr/day [including 18.6 micrograms Cr(VI)] on each of 3 consecutive days. All urine samples were collected and analyzed individually for total Cr on the day prior to dosing, during the 3 days of dosing, and up to the first void 48 h after the last dose. No significant increases in urinary Cr excretion were found when background excretion data were compared with data following each of the 3 days of dosing or in daily mean urine concentrations of the high- vs the low-dose groups. It appears that Cr present in a soil and COPR mixture at Cr doses up to 200 micrograms/day is not sufficiently bioavailable for biomonitoring of urine to be informative.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Influence of postexercise glucose ingestion upon serum potassium levels and ECG function.

Thirteen trained runners were studied to determine whether postexercise glucose ingestion contributes to electrocardiogram (ECG) alterations by enhancing decreases in serum potassium (K+) concentrations. For the two randomly ordered trials, subjects ingested a 100 g (25% w/v glucose polymer) drink, either alone or with the addition of 3 g of potassium chloride (KCl), within 15 min following a 90-min run. ECG parameters, serum K+, and glucose concentrations were measured preexercise (Time 0), 2-3 min post-exercise (Time 1), and 25 (Time 2) and 60 (Time 3) min postexercise. The data suggest that postexercise glucose ingestion may cause ECG changes that are not directly related to the return of K+ to muscle, and that these changes, although characteristic of hypokalemia, may be related to serum glucose excursions rather than to absolute levels of serum K+. The addition of KCl may have prevented these changes by delaying gastric emptying of glucose.

Adult↗

Expression of the BMP 2 gene during bone cell differentiation.

Bone morphogenetic protein 2 (BMP 2) and transforming growth factor beta (TGF beta) are actively involved in bone formation and remodeling. TGF beta, a powerful stimulant in the early stage of bone cell growth and matrix formation, inhibits differentiation and in vitro mineralized nodule formation in primary fetal rat calvarial osteoblast system. TGF beta also negatively regulates BMP 2 expression at the transcriptional level. BMP 2 gene expression is controlled by a battery of transcriptional factors, some known and some yet to be identified. Immortalized osteoblast cell lines generated from a transgenic mouse carrying BMP 2 promoter-driven SV40 large T antigen transgene are described as powerful tools for studying regulation of BMP 2 gene expression and bone cell differentiation at the molecular level.

Animals↗

Use of nasal mask CPAP instead of tracheostomy for palliative care in two children.

Nasal continuous positive airways pressure (nCPAP) is recommended in children for the treatment of obstructive sleep apnoea which persists following adenotonsillectomy. Nasal CPAP was successfully used in the palliative care of two severely disabled children with upper airway obstruction as an alternative to tracheostomy. Nasal CPAP resulted in the correction of obstructive apnoea in sleep, with the added benefit of sleep consolidation and fewer nocturnal arousals requiring parental attendance. There was also an unexpected benefit of reduced airway problems in the awake state in these children. Nasal CPAP is an effective form of treating upper airway obstruction for palliative care in association with other major disabilities.

Airway Obstruction↗

Cloning and sequence of bone morphogenetic protein 4 cDNA from fetal rat calvarial cell.

A cDNA clone encoding bone morphogenetic protein 4 (BMP 4) has been isolated from a primary fetal rat calvarial cell cDNA library. Sequencing of this clone has revealed a single open reading frame encoding a 408 amino acid protein. Comparison of 5' noncoding exon 1 portion of this cDNA with that of human bone and prostate BMP4 cDNA shows that BMP4 gene expression may possess tissue specificity.

Amino Acid Sequence↗

Abnormalities of von Willebrand factor multimers in drug-associated thrombotic microangiopathies.

Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA-plasma samples by sodium dodecyl sulfate-1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL)vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin-C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug-associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder.

Adolescent↗

Acidic fibroblast growth factor gene 5' non-coding exon and flanking region from hamster DDT1 cells: identification of the promoter region and transcriptional regulation by testosterone and aFGF protein.

Selected clones of Syrian hamster DDT1-MF2 cells are responsive to testosterone for growth. Heparin binding growth factor 1 (HBGF-1) or acidic fibroblast growth factor (aFGF) can replace testosterone (T) in the stimulation of growth in these cells. This phenomena is correlated with testosterone's ability to elevate aFGF mRNA two- to threefold in DDT1 cells. To better understand the possible mechanisms of regulation of aFGF mRNA by steroids and other growth factors, we isolated the aFGF 5' non-coding exon and its flanking region from a EMBL3 DDT1 genomic library, using a 5' non-coding exon 69 bp DDT1 aFGF cDNA probe. Clones spanning 30 kb of genomic DNA were isolated. After restriction mapping and DNA sequence analysis, the clones were shown to contain all of the 5' non-coding exon included in the cDNA and approximately 10 kb of 5' flanking region. RNase protection and primer extension assays confirmed that the 5' non-coding exon is included in the DDT1 aFGF mRNA and that a major transcription start site is approximately 136 bp upstream of the 5' non-coding splice junction of this exon. The 5' flanking region DNA was inserted into pBLCAT3 reporter gene and transfected into DDT1 cells. Chloramphenicol acetyltransferase (CAT) assays demonstrated that there are promoter elements in the -1645/-392 and -392/+131 regions of the aFGF gene in the context of DDT1 cells. NIH 3T3 cells, on the other hand, show no CAT activity with these aFGF-CAT plasmids. CAT assays also demonstrated that addition of testosterone (T) or aFGF to DDT1 cells increased CAT activity threefold. This activity was mapped to -1645 to -4 bp region of this DDT1 aFGF gene promoter.

3T3 Cells↗

Application of pattern recognition techniques to evaluate polychlorinated dibenzo-p-dioxin and dibenzofuran distributions in surficial sediments from the lower Passaic River and Newark Bay.

Isomer-specific determinations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were performed in 19 surficial sediment samples collected from the lower Passaic River and Newark Bay, New Jersey. Total PCDD and PCDF concentrations ranged from 415 to 23,300 ng/kg (dry wt) and 37 to 8400 ng/kg, respectively. OCDD and OCDF were the predominant congeners in all samples, followed by the hepta-, hexa-, tetra-, and penta-chlorinated compounds. Forty-seven percent (9/19) of the sediment samples contained no detectable levels of 2, 3, 7, 8-TCDD. The concentrations of 2, 3, 7, 8-TCDD and 2, 3, 7, 8-TCDF ranged from nondetect to 510 ng/kg (geometric mean of 5 ng/kg) and from 2.8 to 480 ng/kg (geometric mean of 13 ng/kg), respectively. The composition of PCDD/Fs in sediments was evaluated using chemometric pattern recognition techniques. Principal components analysis and complete linkage:farthest neighbor cluster analysis revealed the presence of at least five distinctive fingerprint patterns in surficial sediments collected from different locations in the Newark Bay estuary. Differences among PCDD/F patterns were attributable to the relative presence or absence of 1, 2, 3, 4, 6, 7, 8-HpCDF and the hepta-, hexa-, and octa-chlorinated congeners. To determine whether the presence of PCDD/Fs in sediments could be associated with a single source, residues in sediments were compared to those found in three soil samples and one sump sediment sample from a former 2, 4, 5-T manufacturing plant. Significant compositional differences were observed between the two data sets. Fingerprint patterns in sediments were dominated by the higher PCDD/F chlorinated congeners and contained significantly lower levels of the tetra-chlorinated congeners, particularly 2, 3, 7, 8-TCDD, than soils from the former 2, 4, 5-T plant. These differences, as well as those observed among surficial sediments from different locations, indicate that there are clearly several different sources of 2, 3, 7, 8-TCDD and other PCDD/Fs to the estuary.

Benzofurans↗

Comparing the results of a Monte Carlo analysis with EPA's reasonable maximum exposed individual (RMEI): a case study of a former wood treatment site.

In the United States, there are about 250 former sites that treated wood with preservatives that are now in need of some degree of remediation. The soil at many of these sites is contaminated with creosote, polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). This paper compares the results of the current USEPA point estimate (deterministic) approach for predicting the health risks associated with exposure to PCDDs/PCDFs in soil with the results of a probabilistic approach which uses a Monte Carlo analysis. At many of these wood treatment sites the hazard posed by the PAHs, and especially pentachlorophenol, can be much greater than that due to PCDD and PCDFs; however, because at this site the health risk associated with PAHs was deemed negligible by ATSDR, only PCDDs/PCDFs were evaluated. Octachlorodibenzo-p-dioxin (OCDD) and octachlorodibenzofuran (OCDF) congeners were evaluated independently from the other congeners due to their prevalence in the environment and the availability of congener-specific data. The results of the reevaluation of the rodent bioassay data for 2,3,7,8-TCDD were considered in the probability distribution for the cancer potency factor. The authors' analyses indicate that when assessing exposure to soil via inhalation, ingestion, and dermal contact, the current regulatory approach used to estimate the reasonable maximally exposed individual (RMEI) (USEPA, Risk Assessment Guidance for Superfund, Vol. 1, Part A, 1989) can predict risks which are 10- to 100-fold greater than the 95th percentile risk predicted by a Monte Carlo analysis.

Abnormalities, Drug-Induced↗

Peripheral nerve entrapment, occupation-related syndromes and sports injuries, and bursitis.

A growing interest in nonarticular rheumatic conditions has been shown recently by the large number of articles published on the subject. In this review, three nerve entrapment syndromes and problems of four tendons of the ankle region are covered. Suprascapular neuropathy is underrecognized and, in many cases, may be treated conservatively. Entrapment of the radial and ulnar nerves may be caused by a variety of conditions, some of which are unusual. Tenosynovitis and rupture of the tendons of the ankle region, including the posterior tibial, anterior tibial, peroneus longus, and Achilles tendons, are reviewed.

Adult↗

Synthesis and structure-activity relationships of some 6 beta-acrylamido penicillins.

Syntheses are described for penicillins (4b approximately 4i, 5a and 5b) which possess a 6 beta-(2-heteroaryl-3-substituted)-propenamido side-chain of fixed geometry. In vitro results for these compounds against a range of Gram-positive and Gram-negative bacteria showed in most cases good stability against both penicillinase and TEM-1 beta-lactamase; analogues (4b approximately 4i) bearing a 2-(2-aminothiazol-4-yl) unit showed the best intrinsic activity, the cyclohexyl compound (4b) being the most promising. The 1-acetoxyethyl ester (6) of 4b was also prepared; in experimental animal studies the in vivo properties of this compound compared favourably with cefuroxime axetil and are reported together with selected in vivo data for the other compounds.

Animals↗

Potential sources of 1,2,8,9-tetrachlorodibenzo-P-dioxin in the aquatic environment.

A recent study reported elevated levels of 1,2,8,9-tetrachlorodibenzo-p-dioxin (1,2,8,9-TCDD) in crustaceans and finfish collected from Newark Bay, New Jersey (Rappe et al., 1989). The authors suggested that the presence of this compound in biota was due to operations at a former 2,4,5-trichlorophenoxy acetic acid (2,4,5-T) manufacturing facility located on the lower Passaic River. Since 1,2,8,9-TCDD had been identified in two soil samples claimed to be associated with the site, it was concluded that the former manufacturing plant was the source of this compound. A review of the scientific literature was conducted to evaluate whether this isomer is associated with the formulation of 2,4,5-T and to determine whether 1,2,8,9-TCDD is commonly found in the aquatic environment. Measurements and chromatographic data from known sources of polychlorinated dibenzo-p-dioxins indicate that incinerator fly ash, soot from wood-burning chimneys, and the combustion of polychlorinated biphenyls and some chlorophenoxy herbicides are sources of 1,2,8,9-TCDD. This isomer has never been found in samples of 2,4,5-T. We conclude, therefore, that the presence of 1,2,8,9-TCDD in Newark Bay biota is not associated with 2,4,5-T manufacturers but, rather, the result of various commercial, residential, municipal, and industrial combustion processes.

Animals↗

Contributions of sibling relations to the adaptation of youths with insulin-dependent diabetes mellitus.

Associations among sibling relations and the psychosocial and illness-specific adaptation of youths (N = 66) with insulin-dependent diabetes mellitus (IDDM) were examined. The findings suggest that sibling relations, especially sibling conflict, contribute an independent source of variance above and beyond that contributed by demographic characteristics, sibling constellation variables, and important dimensions of family relations in predicting the youths' adaptation. High family-life stress and high sibling status/power contributed unique variance in predicting internalizing behaviors, and male gender and sibling conflict contributed independently to externalizing problems. Sibling conflict also contributed unique variance to the youth's general self-esteem, along with social class and family cohesion, and to their adjustment to IDDM. Data suggest that parent-child dyads and sibling dyads represent interrelated and independent subsystems within the family, and that both subsystems may influence the psychosocial functioning of youths with IDDM.

Adaptation, Psychological↗

Single daily dose ceftriaxone therapy in epiglottitis.

Ceftriaxone as a single daily intravenous dose for 5 days was used to treat seven patients with proven Haemophilus influenzae epiglottitis. All children responded favourably. The serum levels achieved exceeded the MIC by up to 1500 times at the trough level during and for up to 24 h after the completion of the treatment. Side effects were mild and transient and did not disrupt the continuity of the treatment. Ceftriaxone potentially offers a number of clinical and economic advantages in the management of epiglottitis.

Ceftriaxone↗

The effect of sugar cereal with and without a mixed meal on glycemic response in children with diabetes.

The effect of sucrose consumption on glycemic control in children with insulin-dependent diabetes mellitus is unclear. Eight young subjects, 7-16 years of age, with a duration of diabetes of 2-8 years participated in this study. All subjects consumed four different breakfasts--oatmeal (OM) alone, oatmeal-sucrose (OMS), oatmeal-protein (OMP), and oatmeal with protein and sucrose (OMPS)--on four different days. Addition of sucrose resulted in a slightly greater area under the tolerance curve in 50% of the subjects; however, in 38% of subjects, the area decreased. The peak glucose level was lowest for OM, but there was no statistical difference in the peak levels of the four test meals. The most significant effect on glucose response was a delay in the peak time when protein was added to the meals. Peak times for OM and OMS (mean of 38 min) when fed alone were significantly (p less than 0.05, ANOVA) shorter when compared to the peak time for OMP and OMPS (mean of 54 min). The average recovery time for OMP was longest. Other indices (tolerance index and change of rise in blood glucose) measured were not significantly different among the test meals. This study demonstrates that adding limited sucrose to OM cereal has little effect on the blood glucose response in children with diabetes. Addition of protein and fat clearly delays the glycemic response.

Adolescent↗