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Biomedical subjects

C Rosen

Publications and source records attributed to C Rosen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of zinc and other nutritional factors on insulin-like growth factor I and insulin-like growth factor binding proteins in postmenopausal women.

Insulin-like growth factor I (IGF-I) is a critical factor in the regulation of various physiologic effects, including bone formation and protein metabolism. Nutrient intake is a main regulator of circulating IGF-I. The relation of zinc status and IGF-I in adulthood has not been studied adequately even though suboptimal intakes of zinc are reported widely in the elderly. This study examined the relation between calculated nutrient intakes from 119 postmenopausal women and concentrations of IGF-I and IGF binding proteins (IGFBPs). Dietary intake was evaluated by 4-d weighed diet records at baseline and 2 y. Mean intakes of 25 nutrients were calculated. Concentrations of IGF-I and IGFBPs were measured by radioimmunoassays at baseline and 2 y. Mean age (63 +/- 4 y), weight (66 +/- 9 kg), and nutrient intake were correlated with the mean IGF-I concentration at baseline (172 +/- 57 microg/L) and 2 y (142 +/- 43 microg/L). IGF-I concentrations were significantly correlated with mean protein and zinc intake at baseline (r = 0.313, P = 0.001; r = 0.298, P = 0.001, respectively) and 2 y (r = 0.256, P = 0.008; r = 0.331, P = 0.001, respectively). After age, weight, and other nutrient intakes were adjusted for in multiple regression at baseline and 2 y, zinc remained the major determinant of IGF-I concentrations. These results suggest that low zinc intake is associated with low IGF-I concentrations in healthy postmenopausal women and that the effects of zinc may be independent of protein intake.

Aged↗
PubMed1998

A proline-rich region in the Zeste protein essential for transvection and white repression by Zeste.

The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.

ATP-Binding Cassette Transporters↗
PubMed1998

The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin.

Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass with age, is an important age-related cause of frailty and loss of independence in the elderly. Because the decline in BCM with age parallels a decline in GH secretion from young adulthood to old age, loss of GH secretion has been considered an important contributory cause of sarcopenia in the elderly. To test this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD age, 66.9 +/- 7.8 yr), 24-h GH concentrations and secretory kinetics were correlated with BCM (measured by whole body counting of 40K) and percent body fat (measured by dual energy x-ray absorptiometry or neutron inelastic scattering). Serum leptin levels were determined as a measure of adipocyte mass. Contrary to prediction, GH secretion was lower in women with higher BCM (r = 0.50; P < 0.05), whereas their mean fat mass was higher (r = 0.51, P < 0.05). These data indicate that sarcopenia in postmenopausal women is not associated with reduced GH secretion and is inversely correlated with fat mass. Serum leptin levels were inversely associated with GH secretion (r = -0.67; P < 0.006). Although a causal relationship has not been demonstrated, these data suggest that leptin could modulate GH secretion through its action on the aging hypothalamic-pituitary axis, or that GH regulates leptin secretion.

Adipocytes↗
PubMed1997

Chip, a widely expressed chromosomal protein required for segmentation and activity of a remote wing margin enhancer in Drosophila.

The mechanisms allowing remote enhancers to regulate promoters several kilobase pairs away are unknown but are blocked by the Drosophila suppressor of Hairy-wing protein (Suhw) that binds to gypsy retrovirus insertions between enhancers and promoters. Suhw bound to a gypsy insertion in the cut gene also appears to act interchromosomally to antagonize enhancer-promoter interactions on the homologous chromosome when activity of the Chip gene is reduced. This implicates Chip in enhancer-promoter communication. We cloned Chip and find that it encodes a homolog of the recently discovered mouse Nli/Ldb1/Clim-2 and Xenopus Xldb1 proteins that bind nuclear LIM domain proteins. Chip protein interacts with the LIM domains in the Apterous homeodomain protein, and Chip interacts genetically with apterous, showing that these interactions are important for Apterous function in vivo. Importantly, Chip also appears to have broad functions beyond interactions with LIM domain proteins. Chip is present in all nuclei examined and at numerous sites along the salivary gland polytene chromosomes. Embryos without Chip activity lack segments and show abnormal gap and pair-rule gene expression, although no LIM domain proteins are known to regulate segmentation. We conclude that Chip is a ubiquitous chromosomal factor required for normal expression of diverse genes at many stages of development. We suggest that Chip cooperates with different LIM domain proteins and other factors to structurally support remote enhancer-promoter interactions.

Amino Acid Sequence↗
PubMed1997

Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing.

A high-throughput direct-differential cDNA sequencing approach was employed to identify genes differentially expressed in normal breast as compared with breast cancer. Approximately 6000 expressed sequence tags (ESTs) from cDNA libraries of normal breast and breast carcinoma were selected randomly and subjected to EST-sequencing analysis. The relative expression levels of more than 2000 unique EST groups were quantitatively compared in normal versus cancerous breast. Of many putative differentially expressed genes, a breast cancer-specific gene, BCSGC1, which was expressed in high abundance in a breast cancer cDNA library but scarcely in a normal breast cDNA library, was identified as a putative breast cancer marker. In situ hybridization analysis demonstrated stage-specific BCSG1 expression as follows: BCSG1 was undetectable in normal or benign breast lesions, showed partial expression in ductal carcinoma in situ, but was expressed at an extremely high level in advanced infiltrating breast cancer. The predicted amino acid sequence of BCSG1 gene has a significant sequence homology to the non-amyloid beta protein fragment of the Alzheimer's disease amyloid protein. BCSG1 overexpression may indicate breast cancer malignant progression from benign breast or in situ carcinoma to the highly infiltrating carcinoma.

Amino Acid Sequence↗
PubMed1997

Cloning and characterization of a novel human DNase.

The therapeutic significance of recombinant human DNase I in treating the patients with cystic fibrosis has risen our interests in identifying other human DNase I-like enzymes to study their biological significance. Here we described our work of cloning and characterization of a novel gene, which encodes a human protein homologous to human DNase I. A full length cDNA clone of this gene consists of 1290 bp, encoding a polypeptide of 306 amino acids. The deduced amino acid sequence of this novel human DNase (nhDNase) is 45% identical to that of human DNase I. Among sixteen human tissues examined by Northern Blot, high level expression of nhDNase was found in human liver and spleen. Recombinant protein of nhDNase was produced in a Baculovirus expression system and purified by chromatography and reverse-phase HPLC. Purified recombinant nhDNase migrated as a single band of about 33 kD molecular weight analyzed by SDS-PAGE. The DNase activity of nhDNase was demonstrated by assay of hydrolysis of S.S.DNA. Its activity was dependent upon the presence of divalent metal irons, calcium and magnesium. However, unlike bovine pancreas DNase I, nhDNase was not inhibited by G-actin of bovine muscle, which indicates the physiological significance of this enzyme in clinical implication.

Actins↗
PubMed1997

Significance of preformed anti-donor antibodies in liver transplantation.

The significance of a positive cross-match in liver transplantation remains controversial, as documented by a number of recent conflicting reports. In this study, we evaluated 195 consecutive orthotopic liver transplant recipients in whom the cross-match was either negative or positive for T or B cells. Special emphasis was placed on the outcome of patients with high levels of preformed IgG antibodies directed against donor T cells. IgG anti-donor antibodies were confirmed by flow cytometry in all cases. Of 10 patients with strong T-cell antibodies, there was one early death due to nonimmunological causes. Transplantation was successful in 9/10 patients followed for 3 months to 3 years. Graft survival, incidence of acute rejection, and number of liver biopsies in patients with a positive cross-match (strong T, weak T, or B cell) were not significantly different from those of patients with a negative cross-match. In the strong T cell antibody group, one patient had early graft dysfunction, with extensive hepatic necrosis and histological signs of antibody-induced damage. Two other patients also showed some evidence of possible antibody-mediated events, such as neutrophil infiltration and hepatocyte swelling. These lesions were reversible, and the patients had uneventful recoveries. Thus, in our experience, preformed antibodies did not preclude good graft survival.

Adolescent↗
PubMed1997

Hormone replacement therapy in postmenopausal women: urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density.

PURPOSE: To assess the ability of the urinary N-telopeptide of type I collagen (NTx) to monitor and predict therapeutic effects of hormone replacement therapy (HRT) in postmenopausal women. PATIENTS AND METHODS: To assess the relationship between baseline or change in NTx (predictive variable), and change in lumbar and hip bone mineral density (BMD; outcome variable), we conducted a 2-year randomized controlled study at academic university and private practice medical centers in 236 healthy women 1 to 3 years postmenopausal; 227 women completed the study. Women received estrogen plus progesterone plus calcium (treated group) or calcium alone (control group). RESULTS: In the treated group NTx significantly (P < 0.0001) decreased, and spine and hip BMD significantly (P < 0.00001 and P < 0.005, respectively) increased; in the control group NTx did not change but BMD decreased significantly (P < 0.01). Subjects in the highest quartiles for baseline NTx (67 to 188 units) or decreasing NTx (-66% to -87%) through 6 months demonstrated the greatest gain in BMD in response to HRT (P < 0.05 and P < 0.005). For every increase of 30 units in baseline NTx the odds of gain in BMD in response to HRT increased by a factor of 5.0 (95% confidence interval [CI] 1.9 to 13.3); for every 30% decrease in NTx through 6 months, the odds of gaining BMD in response to HRT increased by a factor of 2.6 (95% CI 1.6 to 4.4). In the control group an increase of 30 units in mean NTx across the study indicated a higher odds of losing BMD by a factor of 3.2 (95% CI 1.6 to 6.5). A high baseline NTx (> 67 units) indicated a 17.3 times higher risk of BMD loss if not treated with HRT. CONCLUSION: These data support the clinical utility of NTx to monitor the antiresorptive effect of HRT in recently postmenopausal women, and to predict changes in BMD in response to HRT.

Absorptiometry, Photon↗
PubMed1997

Electrical injury from subway third rails: serious injury associated with intermediate voltage contact.

BACKGROUND: Railway and subway-associated electrical trauma is rare and typically involves high voltage (> 20,000) arc injuries. Not all rail systems utilize such high voltage. We report 16 cases of electrical trauma due to 600 V direct contact with subway 'third' rails. METHODS: A case series of injured patients presenting to Shriners Burns Institute, Boston or Massachusetts General Hospital between 1970 and 1995 was retrospectively analyzed. RESULTS: A total of 16 cases was identified. Among seven subway workers, the mechanism of rail contact was unintentional by a tool, a hand or by falling; no deaths occurred. Among nine non-occupational victims, injuries involved suicide attempts, unintentional falls, or risk-taking behavior. This group suffered greater burn severity, operative procedures, and complications; three deaths occurred. CONCLUSIONS: This is the largest report series of direct electrical trauma from a subway third rail. The high morbidity and mortality from this 600 V contact suggests that the traditional classification of low voltage (< 1000 V) exposure can be subdivided to reflect the serious and lethal potential of intermediate range exposures compared to household range exposures (0-220 V).

Accidents↗
PubMed1997

Water budget during ultra-endurance exercise.

We examined water gains and water losses in a group of athletes after an ultra-endurance event. Thirteen male triathletes competed in a triathlon consisting of 21 km canoeing, 97 km cycling, and 42 km running. Water loss determinations included sweat rate (940 +/- 163 g.h-1), urine output (41 +/- 38 g.h-1), and respiratory water loss (88 +/- 10 g.h-1). Water gain measurements included water intake (737 +/- 137 g.h-1) and the water content of the food intake (10 +/- 7 g.h-1), and we estimated the water of metabolism for carbohydrate (49 +/- 5 g.h-1) and fat (41 +/- 5 g.h-1) and the water released after glycogen utilization (104 +/- 64 g.h-1). Total water gain averaged 940 +/- 160 g.h-1, while the total water loss averaged 1069 +/- 163 g.h-1. Body weight changed from 69.87 +/- 7.14 kg before the race to 66.65 +/- 6.75 kg after the race (-4.61 +/- 2.94%). The sum of the exogenous water gains and the endogenous water gains (940 g.h-1) replaced almost 90% of the total water loss (1069 g.h-1). The difference (1334 g) represented a loss of about 1.9% of the initial body mass (69.87 kg). The exogenous water gains alone (747 g.h-1) replaced about 70% of the total water loss, and the difference represented a loss of over 4% of the initial body mass. Because of the nature of the endogenous sources of water gain, the total amount of water gain almost replaces the total amount of water loss (difference approximately 12%) even in the presence of a reduction in body mass (> 4%).

Adult↗
PubMed1996

Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4.

The tissue inhibitors of metalloproteinases (TIMPs) constitute a family of proteins, of which three members have so far been described. Using the expressed sequence tag sequencing approach, we have identified a novel TIMP-related cDNA fragment and subsequently cloned a fourth human TIMP (TIMP-4) from a human heart cDNA library. The open reading frame encodes a 224-amino acid precursor including a 29-residue secretion signal. The predicted structure of the new protein shares 37% sequence identity with TIMP-1 and 51% identity with TIMP-2 and -3. The protein has a predicted isoelectric point of 7.34. The open reading frame-directed expression of TIMP-4 protein in MDA-MB-435 human breast cancer cells showed metalloproteinase inhibitory activity on reverse zymography. By Northern analysis, only the adult heart showed abundant TIMP-4 transcripts with a 1. 4-kilobase predominant transcript band; very low levels of the transcripts were detected in the kidney, placenta, colon, and testes, and no transcripts were detected in the liver, brain, lung, thymus, and spleen. This unique expression pattern suggests that TIMP-4 may function in a tissue-specific fashion in extracellular matrix homeostasis.

Amino Acid Sequence↗
PubMed1996

Human posterior cricoarytenoid muscle compartments. Anatomy and mechanics.

OBJECTIVE: To document the presence and functional significance of distinct anatomical compartments in the human posterior cricoarytenoid muscle (PCA). DESIGN: Anatomic study of human cadaver larynges. SUBJECTS: Seventeen fresh larynges, harvested at autopsy from 8 men and 9 women, with no history of laryngeal disease or surgery. INTERVENTIONS: Twenty-three PCA muscles from 12 human cadaver larynges were dissected. Computed tomographic scanning and rigid body mechanical analysis were used to compute 3-dimensional motion with simulated individual contraction of PCA compartments in 5 fresh larynges. RESULTS: Discrete medial and lateral bellies with different orientations of muscle fibers were found in every muscle. The 2 bellies insert on opposing aspects of the muscular process of the arytenoid. Very little linear translation was effected by either muscle. The axes of rotation attributable to the 2 bellies differed significantly, with the medial belly effecting rotation about a more vertical axis. The axis of rotation for the lateral muscle belly was nearer the anterior posterior axis than that of the medial belly. CONCLUSIONS: These data indicate that PCA muscle contraction results in arytenoid rotation about a variable oblique axis without significant lateral gliding. There are 2 bellies within the human PCA muscle with differing mechanical actions on the cricoarytenoid joint.

Aged↗
PubMed1996

The role of postoperative irradiation in the management of sphenoid wing meningiomas. A preliminary report.

PURPOSE: To determine whether postoperative radiation therapy decreases recurrence rates in subtotally excised and recurrent sphenoid wing meningiomas. METHODS: Patients with primary subtotally excised and recurrent sphenoid wing meningiomas who underwent surgery between 1981 and 1994 (n = 105) were prospectively followed for recurrence. Postoperative radiation was not recommended in patients who had complete excision; therefore, their recurrence rates were not evaluated in this study. Patients with malignant meningiomas also were excluded from analysis. Recurrence was defined as evidence of tumor growth on neuroimaging with or without clinical symptoms. RESULTS: Follow-up information was available for 86 patients; 69 had primary subtotally excised tumors and 17 had recurrent tumors. Follow-up information was unavailable in the remaining 19 patients. Tumor location and histopathology, type of surgery performed, and patient sex and age were similar in the irradiated and nonirradiated subgroups. Postoperative irradiation was delivered to 31 patients with primary tumors and 11 with recurrent tumors; none of these 42 patients had recurrence during a mean observation period of 4.2 and 3.5 years, respectively. The nonirradiated group consisted of 38 patients with primary tumors and 6 with recurrent tumors; 16 of 18 patients who had primary meningiomas had a recurrence and 5 of 6 who had recurrent tumors had another relapse (mean interval between resection and recurrence, 4.4 years and 14 months, respectively). CONCLUSIONS: Postoperative radiation appeared to delay recurrence in subtotally excised and recurrent sphenoid wing meningiomas during the time frame of this study.

Adolescent↗
PubMed1996

Structure and expression of wild-type and suppressible alleles of the Drosophila purple gene.

Viable mutant alleles of purple (pr), such as prbw, exhibit mutant eye colors. This reflects low 6-pyruvoyl tetrahydropterin (PTP) synthase activity required for pigment synthesis. PTP synthase is also required for synthesis of the enzyme cofactor biopterin; presumably this is why some pr alleles are lethal. The prbw eye color phenotype is suppressed by suppressor of sable [su(s)] mutations. The pr gene was cloned to explore the mechanism of this suppression. pr produces two PTP synthase mRNAs: one constitutively from a distal promoter and one in late pupae and young adult heads from a proximal promoter. The latter presumably supports eye pigment synthesis. The prbw allele has a 412 retrotransposon in an intron spliced from both mRNAs. However, the head-specific mRNA is reduced > 10-fold in prbw and is restored by a su(s) mutation, while the constitutive transcript is barely affected. The Su(s) protein probably alters processing of RNA containing 412. Because the intron containing 412 is the first in the head-specific mRNA and the second in the constitutive mRNA, binding of splicing machinery to nascent transcripts before the 412 insertion is transcribed may preclude the effects of Su(s) protein.

Alcohol Oxidoreductases↗
PubMed1996

Genes regulating the remote wing margin enhancer in the Drosophila cut locus.

The mechanisms that allow enhancers to activate promoters from thousands of base pairs away are disrupted by the suppressor of Hairy-wing protein (SUHW) of Drosophila. SUHW binds a DNA sequence in the gypsy retrotransposon and prevents enhancers promoter-distal to a gypsy insertion in a gene from activating without affecting promoter-proximal enhancers. Several observations indicate that SUHW does not affect enhancer-binding activators. Instead, SUHW may interfere with factors that structurally facilitate interactions between an enhancer and promoter. To identify putative enhancer facilitators, a screen for mutations that reduce activity of the remote wing margin enhancer in the cut gene was performed. Mutations in scalloped, mastermind, and a previously unknown gene, Chip, were isolated. A TEA DNA-binding domain in the Scalloped protein binds the wing margin enhancer. Interactions between scalloped, mastermind and Chip mutations indicate that mastermind and Chip act synergistically with scalloped to regulate the wing margin enhancer. Chip is essential and also affects expression of a gypsy insertion in Ultrabithorax. Relative to mutations in scalloped or mastermind, a Chip mutation hypersensitizes the wing margin enhancer in cut to gypsy insertions. Therefore, Chip might encode a target of SUHW enhancer-blocking activity.

Animals↗
PubMed1996

The DNA-binding and enhancer-blocking domains of the Drosophila suppressor of Hairy-wing protein.

Mutations in the suppressor of Hairy-wing [su(Hw)] gene of Drosophila melanogaster can cause female sterility and suppress mutations that are insertions of the gypsy retrotransposon. Gypsy binds the protein (SUHW) encoded by su(Hw), and SUHW prevents enhancers promoter-distal to gypsy from activating gene transcription. SUHW contains 12 zinc fingers flanked by acidic N- and C-terminal domains. We examined the roles of each of the 12 zinc fingers in binding gypsy DNA and classified them into four groups: essential (fingers 6 through 10); beneficial but nonessential (fingers 1, 2, 3, and 11); unimportant (fingers 5 and 12); and inhibitory (finger 4). Because finger 10 is not required for female fertility but is essential for binding gypsy, these results imply that the SUHW-binding sites required for oogenesis differ in sequence from the gypsy-binding sites. We also examined the functions of the N- and C-terminal domains of SUHW by determining the ability of various deletion mutants to support female fertility and to alter expression of gypsy insertion alleles of the yellow, cut, forked, and Ultrabithorax genes. No individual segment of the N- and C-terminal domains of SUHW is absolutely required to alter expression of gypsy insertion alleles. However, the most important domain lies between residues 737 and 880 in the C-terminal domain. This region also contains the residues required for female fertility, and the fertility domain may be congruent with the enhancer-blocking domain. These results imply that SUHW blocks different enhancers and supports oogenesis by the same or closely related molecular mechanisms.

Amino Acid Sequence↗