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Biomedical subjects

D W Rowe

Publications and source records attributed to D W Rowe.

At least 73 records · Page 4Linked to original sources
PubMed1986

Relationship of somatomedin-C concentration to bone age in boys with constitutional delay of growth.

Serum somatomedin-C (Sm-C) levels increase sharply during puberty, leading to difficulty in the interpretation of Sm-C values obtained from children who exhibit a discrepancy between chronological age (CA) and pubertal development. To evaluate the utility of assessing Sm-C levels on the basis of bone age (BA), we measured serum Sm-C levels in 44 boys with constitutional delay of growth (CDG). Levels of Sm-C were compared with the normative data of the Nichols Institute Reference Laboratories (NIRL), Los Angeles, by age category, substituting BA for CA. We found the mean Sm-C level in boys with CDG to be lower than that for NIRL normal subjects in each age category for both CA and BA, but the regression curve for Sm-C levels based on BA more closely approximated the NIRL regression curve than did the curve based on CA. The rise in Sm-C levels observed in NIRL normal subjects between CA 13 to 14 years is delayed in boys with CDG until CA 15 to 17 years only when a correction for BA is not made. We conclude that in boys with CDG, Sm-C levels should be interpreted on the basis of BA rather than CA, especially during the peripubertal period. The observation of blunted Sm-C levels in all age categories, even when BA was used, suggests that short children with presumed CDG may be at high risk for a "nonclassic" form of growth hormone deficiency.

Adolescent↗
PubMed1985

Bleomycin selectively elevates mRNA levels for procollagen and fibronectin following acute lung injury.

We employed the technique of dot blot hydridization of radiolabeled cDNA probes to examine the role of specific mRNA content in the control of extracellular matrix turnover in the remodeling rat lung. Following bleomycin instillation, total RNA content gradually doubled during the first 5 days following the initial lung injury, then rose much more rapidly during the ensuing 9 days. Individual mRNAs for procollagens I and III and for fibronectin were selectively enriched 2- to 4-fold above total RNA during the first week after bleomycin instillation. No comparable increases were observed in specific RNAs from liver, indicating that the response observed in the lung was not generalized to other organs. Moreover, the increases in mRNA species for procollagen types I or III in the lung could not be related to the influx of inflammatory cells which migrate into the lungs during acute injury, as cells obtained by alveolar lavage contained no mRNAs for procollagens.

Animals↗
PubMed1985

Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta.

Type I osteogenesis imperfecta (OI) is characterized clinically by a moderate fracture frequency with minimal bone deformity and dominant inheritance. Previous studies of the collagenous proteins synthesized by dermal fibroblasts obtained from unrelated patients with this form of OI suggested that the biochemical basis of the disease was reduced production of type I collagen. This study was designed to determine if this biochemical finding segregated with the disease within an individual family. Dermal fibroblast strains were established from three generations of a family having the typical features of type I OI. Analysis of the collagenous proteins made in culture revealed an elevated alpha 1(III) to alpha 1(I) collagen type ratio and an elevated alpha 1(I) to alpha 2(I) collagen chain ratio. The procollagen that accumulated in the medium reflected these ratios to the same degree. Total collagen synthesis was significantly reduced in affected family members. Therefore, the most striking abnormality in affected members was a 50-75% reduction of type I collagen production. Furthermore, the ratio of the alpha 1(I)/alpha 2(I) collagen messenger RNA (mRNA), measured by dot hybridization, was one-half of the value of uninvolved family members and unrelated controls. Since the reduction in the production of type I collagen and the altered alpha 1(I)/alpha 2(I) mRNA ratio clearly segregated with affected individuals within this family, these biochemical measurements may be a useful genetic marker for type I OI.

Adult↗
PubMed1985

Radioimmunoassay for type I procollagen in growth hormone-deficient children before and during treatment with growth hormone.

Type I procollagen concentrations were measured by radioimmunoassay in sera from 14 growth hormone-deficient children before and during 12 months of treatment with human growth hormone. Basal procollagen levels were lower than those of control children and comparable to those of normal adults. With treatment, the mean procollagen level increased into the range of the control children and was significantly greater than the baseline level at 1, 2, 3, and 12 months (p less than 0.01; p less than 0.05). Although there was no significant statistical correlation between the growth velocity during treatment and the serum procollagen level, there was a suggestion that a high basal procollagen may be predictive of a less than optimal response to human growth hormone.

Adolescent↗
PubMed1984

Two-dimensional echocardiography in double orifice mitral valve.

In a patient with endocarditis and significant aortic insufficiency, two-dimensional echocardiography revealed an abnormal mitral valve configuration with division of the valve into two separate orifices. At autopsy, a double orifice mitral valve with two sets of valve leaflets was observed. Appreciation of this echocardiographic abnormality is important because double orifice mitral valve is associated with other congenital anomalies and this echocardiographic configuration may be confused with other cardiac abnormalities.

Adult↗
PubMed1983

Left ventricular performance during exercise in patients with left bundle branch block: evaluation by gated radionuclide ventriculography.

To investigate changes in left ventricular (LV) function during exercise in patients with left bundle branch block (LBBB), 22 patients without a history or physical findings of previous myocardial infarction or LV dysfunction were studied by gated radionuclide ventriculography (GRNV) at rest and during bicycle exercise. Coronary arteriography demonstrated greater than 75% diameter narrowing of at least one coronary artery in nine patients. Of the remaining 13 patients, GRNV demonstrated wall motion abnormalities in seven patients either at rest or with exercise. During exercise, mean ejection fraction (EF) did not increase in patients without coronary artery disease (CAD). Patients with CAD had a 12-point fall in mean EF with exercise. We conclude that LV reserve, as demonstrated by ability to increase EF with exercise, is impaired in patients with LBBB even in the absence of CAD or other underlying cardiac disease and that standard GRNV criteria to exclude the presence of CAD (a greater than five-point increase in EF with exercise and normal wall motion) are not strictly applicable in screening patients with LBBB.

Adult↗
PubMed1983

Cellular zinc accumulation in anencephaly and spina bifida.

Cultured skin fibroblasts were established from three newborns with NTDs (2 with anencephaly, one with SB), a 12-year-old with SB and three controls. Cells were plated at confluent densities and incubated with 65ZnCl2 for 2, 6, and 24 hours, or at subconfluent densities for 1-7 days. Radioactivity and DNA were determined in whole cell sonicates. Zinc uptake by confluent NTD cells was similar to controls at 2 hours, but was lower at 24 hours (p less than 0.001). In subconfluent cultures in log-phase growth, NTD cells accumulated greater amounts of zinc per microgram DNA than a control at 2-4 days (p less than 0.001) but did not differ at 1 and 7 days. Decreased zinc uptake in static cultures, and increased zinc accumulation in growing cultures, suggest that one or more cellular defects of zinc bioavailability may contribute to the pathogenesis of NTDs in some patients.

Anencephaly↗
PubMed1983

Abnormal alpha 2-chain in type I collagen from a patient with a form of osteogenesis imperfecta.

Dermal fibroblasts in culture from a woman with a mild to moderate form of osteogenesis imperfecta synthesize two species of the pro alpha 2-chain of type I procollagen. One chain is normal. The abnormal chain has a slightly faster mobility than normal during electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Analysis of cyanogen bromide peptides of the pro alpha-chain, the alpha-chain, and of the mammalian collagenase cleavage products of the pro alpha- and alpha-chains indicates that the abnormality is confined to the alpha 2(I)CB4 fragment and is consistent with loss of a short triple-helical segment. Type I collagen production was decreased, perhaps because the molecules that contained the abnormal chain were unstable, with a resultant alteration in the ratio of type III to type I collagen secreted into culture medium. Collagen fibrils in bone and skin had a normal periodicity but their diameters were 50% of control; the bone matrix was undermineralized. The structural abnormality in the alpha 2(I)-chain in this patient may affect molecular stability, intermolecular interactions, and collagen-mineral relationships that act to decrease the collagen content of tissues and affect the mineralization of bone.

Cells, Cultured↗
PubMed1983

Collagen genes and brittle bones.

The heritable diseases of connective tissue are caused by known or putative defects in the synthesis of collagens, proteoglycans, glycoproteins, or attachment proteins of the extracellular matrix. Abnormal synthesis of type I collagen has been reported in several clinical variants of osteogenesis imperfecta. Because clinical classification of these variants is limited by genetic heterogenity and variable expression, biochemical criteria should be used for precise definition of the variants. Newly recognized molecular defects in osteogenesis imperfecta include the diminished formation of type I collagen and alpha-1[I] messenger RNA; abnormal synthesis or faulty assembly of alpha-2[I]; deletion or insertion of base pairs in the gene for alpha-1[I] or alpha-2[I] and failure to secrete type I procollagen; and substitution of cysteine for glycine in the triple helix. These molecular defects are characteristic of several variants. However, the molecular lesion in most cases of severe osteogenesis imperfecta has not been identified; synthesis of type I collagen and alpha-1: alpha-2 chain ratios appears to be normal. Production of an alpha-1 trimer may represent one such lesion in severe disease.

Bone Diseases, Developmental↗
PubMed1983

Osteogenesis imperfecta and Paget's disease of bone. Biochemical and morphologic studies.

Osteogenesis imperfecta (OI) and Paget's disease of bone occurred in a patient whose brother has Paget's disease. Several other relatives have the dominant variety of OI. The familial occurrence of the two diseases is presumably due to chance and, to our knowledge, has not been previously reported. Examination of iliac crest bone biopsy specimens showed mild changes of both diseases in the proband. Electron microscopy of the bone collagen demonstrated type I collagen fibers, which are reduced in number, decreased in diameter, and stellate rather than smooth in outline. Three populations of collagen fibers were observed in the bone. The synthesis of type I collagen by dermal fibroblasts was diminished in the proband and affected relatives, but it was normal in the unaffected relatives. Since collagen fibers with a stellate outline have not been observed in OI bone, an intriguing question is the effect to the putative Paget agent (? viral) on collagen synthesis in OI.

Adult↗
PubMed1982

Regulation of collagen synthesis in fetal rat calvaria by 1,25-dihydroxyvitamin D3.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited type I collagen synthesis in the central bone but not the periosteum of fetal rat calvaria maintained in organ culture. The central bone synthesized primarily type I collagen, whereas the periosteum synthesized both types I and III collagen. Enhanced degradation of newly synthesized collagen seemed an unlikely mechanism for the observed decrease in collagen synthesis since 1,25-(OH)2D3 reduced both the labeling of intracellular procollagen and total [3H]hydroxyproline formation in fetal rat calvaria. As measured by cell-free translation of RNA extracted from calvaria, 1,25-(OH)2D3 decreased the level of functional procollagen mRNA and collagen synthesis to the same extent. Both collagen synthesis and procollagen mRNA levels were decreased as early as 3 h after exposure to 1,25-(OH)2D3 and were 50% of the control level by 24 hr. Upon removal of 1,25-(OH)2D3 from the cultures, collagen synthesis and procollagen mRNA remained depressed for 24 h but returned to control levels by 48 h. A reduction in collagen synthesis and procollagen mRNA was also observed in calvaria excised from 6-day-old rat pups given a single subcutaneous injection of 1,25-(OH)2D3 (1.6 ng/g body weight). We conclude that 1,25-(OH)2D3 inhibits the synthesis of type I collagen in the differentiated osteoblast by reducing the level of functional procollagen mRNA.

Animals↗
PubMed1982

Hearing and middle ear function in osteogenesis imperfecta.

Fifty-five patients with osteogenesis imperfecta (OI) were studied to determine the extent to which the peripheral auditory mechanisms share in the connective tissue lesion. Ninety-two unaffected relatives and 43 control subjects were also studied. Subjects were divided into age groups younger than and older than 30 years. Hearing loss, most frequently sensorineural, occurred in 49% (younger than 30 years) and 94% (older than 30 years) of patients with OI. A sensorineural pattern of hearing loss, here considered characteristic of OI, was observed in 47% of OI subjects irrespective of age, in 42% of relatives, and 5% of controls. Middle ear analysis by tympanometry and acoustic reflex analysis indicates that, although some patients with OI have a still middle ear system similar to that seen in otosclerosis, the majority display absent acoustic reflexes and increased compliance of the middle ear with notched tympanograms suggestive of anomalous ossicular articulation. Similar findings in otherwise uninvolved relatives suggest a genetic basis for these defects.

Acoustic Impedance Tests↗
PubMed1982

Initial diastolic indentation of the mitral valve in aortic insufficiency.

An abnormal diastolic indentation of the mitral valve has been noted on short-axis two-dimensional echocardiograms in patients with aortic insufficiency. In order to assess the clinical usefulness of this finding, we reviewed the echocardiograms of 18 patients with this lesion who had undergone cineaortography. Results were compared with those of a control group of 100 patients. Initial diastolic indentation of the anterior mitral leaflet occurred in 8 of 12 patients with 3+ to 4+ aortic insufficiency. None of the patients with lesser regurgitation and no patients from the control group demonstrated this pattern. The presence of this abnormality appears to be a specific indicator of critical aortic insufficiency.

Adolescent↗
PubMed1982

The noninvasive diagnosis of coronary artery disease in patients with left bundle-branch block.

The prognosis in patients with left bundle-branch block (LBBB) is related primarily to the presence or absence of underlying cardiac disease. Because coronary artery disease (CAD) is the most common underlying disease found in these patients, it would be desirable, in the presence of LBBB, to have a noninvasive method of differentiating between patients with and without CAD. We reviewed our experience in patients with LBBB who had undergone coronary arteriography with regard to electrocardiographic (ECG) stress testing, exercise radionuclide ventriculography (RNV), and exercise thallium scintigraphy; we also reviewed their clinical histories. A clinical history of typical angina pectoris was specific for CAD, a false-positive history being present in only one of 12 patients without CAD. The frequency of a positive ECG ST response to exercise was equal in patients with and without CAD. False-positive ejection fraction and wall-motion responses to exercise were frequent by RNV. A modification of the usual RNV criteria for positivity improved specificity but resulted in poor sensitivity for CAD. False-positive thallium study results also were. frequent in these patients. The perfusion defects usually involved the ventricular septum; the inferior and posterior walls were involved only in patients with CAD. We conclude that the usual noninvasive diagnostic tests for CAD are of limited value in patients with LBBB.

Journal Article↗
PubMed1981

Marfan syndrome: abnormal alpha 2 chain in type I collagen.

Cells in culture from a woman with a variety of the Marfan syndrome produce two species of the alpha 2 chains of type I collagen. One alpha 2 chain appears normal; the abnormal chain has a higher apparent molecular weight than normal and migrates more slowly during electrophoresis in sodium dodecyl sulfate/polyacrylamide gels. A similar change in electrophoretic behavior is seen in the prepro alpha 2 chain and the pN alpha 2 chain (which contains the amino-terminal extension). Asymmetric cleavage of the pepsin-treated procollagens with a fibroblast collagenase locates the abnormal segment amino terminal to the cleavage site, and analysis of cyanogen bromide peptides of collagenase cleavage peptides and of whole collagens indicates that the abnormal segment is in either the alpha 2CB3 peptide or the short segment of alpha 2CB5 amino terminal to the collagenase site of the altered alpha 2 chain. The higher apparent molecular weight is consistent with the insertion of a small peptide fragment of approximately 20 amino acids. This alteration in chain size has marked effects on crosslinking because collagen from the patient's skin was 5-10 times more extractable in nondenaturing solvents than that from control skins. Although the abnormal chain was not found in several other individuals with the Marfan syndrome, these findings suggest that the phenotype may be the expression of a variety of primary structure alterations in the chains of type I collagen that interfere with normal crosslink formation.

Adult↗
PubMed1981

Collagen and collagen-derived fragments are chemotactic for tumor cells.

Organs that are rich in collagen such as liver, lungs, and bone are frequently sites of tumor cell metastasis. In this study, we have found that cultured tumor cells of human and rat origin migrated unidirectionally in response to collagen in vitro. Synthetic di- and tri-peptides that contained amino acid sequences found frequently in the collagen helix caused similar effects. These results are consistent with the hypothesis that collagen or collagen fragments released during connective tissue remodeling may be important in tumor cell metastasis.

Animals↗
PubMed1980

Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Parathyroid hormone decreased the incorporation of [3H]proline into collagenase-digestible protein in cultured 21-day fetal rat calvaria but had little effect on the labeling of noncollagen protein. After 24 hr of culture, there was a 50% reduction in collaghen synthesis and a 40% decrease in the level of functional procollagen mRNA as measured in a reticulocyte lystate translation assay. The effect of parathyroid hormone on both parameters was detectable after 6 hr of treatment. In these cultures, there was also a substantial degradation or release of newly synthesized collagen from the calvaria, but parathyroid hormone had little effect on the release of collagen into the medium. These results suggest that parathyroid hormone inhibits collagen synthesis primarily by decreasing the steady-state level of procollagen mRNA.

Animals↗