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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 37 records · Page 2Linked to original sources
PubMed1993

Neu differentiation factor (heregulin) induces expression of intercellular adhesion molecule 1: implications for mammary tumors.

Neu differentiation factor (NDF, also called heregulin) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation of the Neu/HER-2 receptor and induces phenotypic differentiation of certain mammary cancer cell lines to growth-arrested and milk-producing cells. To determine which molecules participate in the concomitant morphological alterations, we analyzed the expression of several cytoskeletal and surface molecules and found that NDF elevated the expression of the intercellular adhesion molecule 1 (ICAM-1) in cultured AU-565 human adenocarcinoma cells. The levels of both the protein and the mRNA of ICAM-1 were elevated after 3-5 days of treatment with NDF. Elevated expression of ICAM-1 was induced also by gamma-interferon and by the tumor-promoting phorbol ester (PMA), albeit with different kinetics. Down-regulation of protein kinase C or its inhibition by calphostin C partially inhibited the effect of NDF, implying that the induction of ICAM-1 may be mediated by protein kinase C. NDF transcripts were detectable in 3 of 9 human mammary tumors, suggesting that the in vitro effect of the factor may be relevant to breast cancer. By selecting Neu-positive human mammary tumors (n = 39), we found a significant correlation (P < 0.001) between the expression of ICAM-1 and histological features of invasive ductal carcinoma with a prominent carcinoma in situ component. When cultured in vitro the cells of these tumors grew in clusters and formed domelike structures reminiscent of comedo-type carcinoma in situ. In addition, the majority of patients with tumors that coexpressed ICAM-1 and Neu had no lymph node involvement, unlike most Neu-positive but ICAM-1-negative tumors, which metastasized to the lymphatic system. Taken together, our observations suggest that the induction of ICAM-1 by NDF may affect the morphology, differentiation state, and metastasis of Neu-expressing mammary tumor cells.

Adenocarcinoma↗
PubMed1993

Age-dependent change in the hyaluronic acid content of the human chorioretinal complex.

OBJECTIVE: Hyaluronic acid (HA) has a key role in the structure and organization of the extracellular matrix. We sought to identify the distribution of HA in human eye tissue with regard to age using a biotinylated HA-binding protein. METHODS: Fetal and adult (from donors ranging from 28 to 94 years of age) eye tissues were fixed less than 24 hours post mortem and embedded in JB-4 medium (Polysciences, Warrington, Pa). Sections of 2-microns thickness were used. Control sections were pretreated either with Streptomyces hyaluronidase or HA-binding protein inactivated by HA. The binding of the protein to HA was detected with avidinbiotin alkaline phosphatase and developed by incubation with naphthol as-mx phosphate and Texas Red Salt (Pierce, Rockford, Ill). RESULTS: Specific staining for HA was observed in fetal eyes in the choroid, Bruch's membrane, sclera, retinal pigment epithelium, and developing retina from the vitreoretinal interface to the inner plexiform layer. Specific staining decreased with age in the choroid, retinal pigment epithelium, and Bruch's membrane. Hyaluronic acid-specific staining was undetectable in tissues from donors over 50 years of age. CONCLUSIONS: The localization of HA in the chorioretinal complex and its disappearance after the fifth decade of life may play a role in aging and age-related retinal disorders.

Adult↗
PubMed1993

Purification and characterization of human serum hyaluronidase.

Hyaluronidase from fresh human serum was purified to apparent homogeneity in a two-step procedure. Potent serum inhibitors of hyaluronidase activity were removed during the course of the purification. Isolation of the enzyme was expedited by the use of a newly devised ELISA-like assay. Enzyme activity was measured by following the rates of hydrolysis of hyaluronan (HA) adsorbed onto microtiter wells. Following enzymatic digestion, the remaining HA was measured using a cartilage-derived biotinylated HA-binding protein and an avidin-peroxidase reaction. Molecular sieve chromatography yielded a doublet of proteins with apparent molecular sizes of 42 and 50 kDa. The molecular size of the major band of protein obtained on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions was 59 kDa. Under reducing conditions, however, the size increased to 72 kDa. The pH optimum of the enzyme was 3.7. Sodium chloride concentrations greater than 100 mM were inhibitory. Activity of the serum enzyme was further characterized with a new HA-substrate gel procedure. The serum enzyme activity is different from the liver-derived activity. The tissue source of this circulating enzyme is unknown.

Chromatography↗
PubMed1993

Are patients with neoplasia at an increased risk for cardiac myxomas?

A case-control study was undertaken to assess whether a significant association exists between the presence of a neoplasm or malignancy and the presence of a cardiac myxoma. We identified 13 patients seen at our institution between 1935 and 1990 whose autopsies revealed a cardiac myxoma that was undetected during the patient's lifetime. For each patient four control subjects were selected among the autopsied patients who had never had a cardiac myxoma; these were matched for age at death, gender, and year of autopsy. The institutional medical records and autopsy reports revealed that 46% of the patients and 65% of their controls had a neoplasm diagnosed prior to or at autopsy. The estimated odds ratio was 0.34 (95% confidence interval, 0.05 to 1.84). There was insufficient evidence to conclude that an association exists between the presence of a neoplasm and the presence of a cardiac myxoma (P = .2722).

Adult↗
PubMed1993

A revised HindIII map and sequence analysis of a large 'left-hand' non-essential region of the rabbit poxvirus genome.

Sequence analysis of a 21.5 kb region of the left-hand non-essential region of rabbit poxvirus (RPV) was performed to analyze the structure and gene organization of this region. Initial mapping and cloning studies revealed that the early published HindIII maps are incorrect in that the location of the terminal HindIII B and C fragments, as previously published, are reversed. The sequence of this region was compared to similar regions of several strains of vaccinia virus. The results indicate that this region of RPV has a high degree of homology with a similar region of vaccinia. Analysis of the translated open reading frames (ORFs) has facilitated the detection of several previously unreported ORFs related to human complement proteins. In addition, two defective copies of a homologue of the 77 kDa cowpox virus (CPV) host range gene which allows CPV to grow on Chinese hamster ovary cells have been detected, suggesting a gene duplication has occurred. However, one copy of this gene is segmented into three separate ORFs. Analysis has also identified a large number of indirect repeat elements. A possible role of these repeats in the generation of deletions and gene duplications is suggested.

Amino Acid Sequence↗
PubMed1993

Hyaluronate metabolism undergoes an ontogenic transition during fetal development: implications for scar-free wound healing.

Wound healing in the fetus occurs by a different process from that in the adult. Instead of healing with scar formation, fetal cutaneous wounds heal by regeneration that results in complete restoration of normal skin architecture. The mechanisms responsible for this remarkable phenomenon involve factors in the fetal environment and properties intrinsic to fetal cells. Hyaluronic acid (HA) is a major component of the fetal extracellular matrix (ECM) and is believed to play an important role in this process. In this study, HA and HA-stimulating activity (HASA) in fetal and adult wound fluid were examined using sensitive, newly developed assays. In an ovine model, higher levels of HA and HASA were observed in fetal as compared with adult wound fluid. This difference was most prominent in wound fluid from fetal lambs at 75 and 100 days gestation (term = 145 days); these samples contained persistently elevated HA and HASA levels for up to 2 weeks after wounding (HA peak levels 145 micrograms/mL and 110 micrograms/mL, respectively). In contrast, wound fluid from 120-day-gestation fetuses had significantly lower levels (P < .001) that were transient and similar to that in the adult (HA peak levels 70 micrograms/mL and 10 micrograms/mL, respectively). These observations confirm an ontogenic transition in wound HA metabolism from a fetal to an adult-like phenotype. Levels of HASA as a function of time after wounding correlated with levels of HA, suggesting a role for HASA in controlling HA deposition during tissue repair. Two patterns of HASA and HA synthesis were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Efficient 12-mutation testing in the CFTR gene: a general model for complex mutation analysis.

The identification of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has led to the identification of more than 225 presumed disease-causing mutations at the locus. The diagnosis of cystic fibrosis or the carrier state by direct DNA analysis is hindered by this large number. A practical assay must be able to detect enough mutations to achieve clinically significant sensitivity. The use of allele-specific oligonucleotide probes is the most promising of the available methods. However, to date this has generally involved tedious probe-by-probe hybridizations, due to variations in the oligonucleotides' denaturation temperatures caused by differences in their G-C base-pair content. We have developed a rapid, cost-effective assay that simultaneously detects 12 CFTR mutations after multiplex polymerase-chain-reaction amplification of genomic DNA. The test may be readily extended to detect additional mutations at minimal increase in the cost per test or the turnaround time. We improve specificity and avoid the need for individual hybridizations by the use of tetramethylammonium chloride to virtually eliminate the effects of G-C differences. Coupled with non-invasive sample-collection methods, this is an immediately practical assay for cystic fibrosis. More generally, it will serve as a model for the development of diagnostic tests in other genetic disorders involving complex mutation analysis.

Cystic Fibrosis↗
PubMed1993

Profile of hyaluronidase activity distinguishes carbon dioxide laser from scalpel wound healing.

Hyaluronic acid plays a key role in the process of wound repair. Deposition of this glycosaminoglycan polymer is in turn controlled by levels of the enzyme hyaluronidase. Hyaluronidase activity was examined in a rat incisional skin wound model comparing laser and scalpel wounds. A polyacrylamide gel electrophoresis (PAGE) hyaluronic acid substrate assay was used to detect differences in the rates of appearance, and level, of hyaluronidase activity in wound homogenates. The hyaluronidase activity in laser wounds appeared earlier, had a bimodal distribution, and increased to a higher level than that in scalpel wounds. The origin of hyaluronidase is not clear, but control of its appearance and modulation of its activity may be a more complex process than previously assumed.

Animals↗
PubMed1993

Circadian variation of sudden cardiac death reflects age-related variability in ventricular fibrillation.

BACKGROUND: Previous studies report a morning peak in the occurrence of out-of-hospital sudden cardiac death but lack detailed information on underlying arrhythmias. We used the documentation system of the semiautomated defibrillators used by emergency medical technicians to investigate the circadian pattern of defined arrhythmias and the influence of demographic patient characteristics on this pattern. METHODS AND RESULTS: From December 1988 to December 1990, 703 consecutive patients (63% men; age, 67 +/- 17 years) with sudden cardiac death were registered in the Klinikum Steglitz area of the Berlin emergency care system. Determination of time of day of the event was based on the arrival time of the rescue squad. A marked circadian variation (P < .0001) in the occurrence of sudden cardiac death was observed with a primary morning peak (6 AM to noon) and a secondary afternoon peak (3 to 7 PM). The subgroup of 294 patients with ventricular fibrillation as initially documented arrhythmia showed a similar circadian variation (P < .0001). In significant contrast (P < .01), patients with asystole (n = 260) or pulseless bradyarrhythmias (n = 149) were more evenly distributed during the daytime with a primary night trough. Multivariate logistic regression analysis revealed that the circadian pattern of ventricular fibrillation was similar in both gender groups but tended to differ with regard to age: patients older than 65 years demonstrated a monophasic distribution, whereas patients aged 65 years or less had a biphasic distribution with peaks in the morning and in the afternoon. CONCLUSIONS: The circadian pattern of sudden cardiac death reflects primarily a circadian variation in onset of ventricular fibrillation. The different circadian patterns of ventricular fibrillation, pulseless bradyarrhythmias, and asystole suggest different pathophysiological mechanisms of causation of death. The age dependence of the pattern of ventricular fibrillation may indicate different underlying external or endogenous triggers.

Adolescent↗
PubMed1992

Efficiency of a physician-operated mobile intensive care unit for prehospital thrombolysis in acute myocardial infarction.

The efficiency of an emergency medical system for routinely performed prehospital thrombolysis is evaluated for 1 of the 7 physician-staffed mobile intensive care units (MICU) in former West Berlin. During 19 consecutive months the MICU had 4,920 missions, and 1,226 patients had chest pain of presumed cardiac origin. The diagnosis at hospital discharge was acute myocardial infarction (AMI) in 406 patients and "interrupted" infarction in 11 patients (total 417). Correct on-scene electrocardiographic diagnosis of acute injury was made in 268 patients (64%) and was false-positive in 4 patients (1%). In 8%, present ST elevations were not recognized. In 27%, the electrocardiogram on scene was nondiagnostic (16% with no ST elevation, 11% with bundle branch block). Of all 417 patients with later hospital evidence of AMI, 317 (76%) were seen by the MICU physician within 4 hours, and 173 (41%) within the first hour from symptom onset. Two hundred three patients seen within 4 hours had diagnostic ST elevation on the scene, of whom 124 (61%) received prehospital thrombolysis (74 patients [36%] within the first hour). There was no prehospital death; hospital mortality was 6.3%. Because greater than 50% of all patients in the community, hospitalized because of AMI, made use of the MICU and 3/4 of them had called within 4 hours from symptom onset, a large proportion of all patients with AMI were candidates for the actually received prehospital thrombolysis.

Ambulances↗
PubMed1992

Blood eosinophilia in Hodgkin's disease. A follow-up of 25 cases in Venezuela.

Twenty-five patients with Hodgkin's disease and high eosinophil counts were observed for an average of 90 months. Fluctuations in the levels of eosinophils were important in the course of observation. No relation with stages, histologic type, or evolution was noticed. Steroid-containing regimens and severe premortem conditions seemed to lower the counts. Relapse-free survival was shorter in our 25 patients than in a control group of 50 patients with Hodgkin's disease and no eosinophilia who had approximately the same stage, histologic type, and treatment of disease. However, the overall survival was somewhat better for the eosinophilic patients with stages IIIB and IV (0.1 greater than P greater than 0.05).

Adolescent↗
PubMed1992

Glucose and glucose analogs modulate collagen metabolism.

Patients with diabetes often develop complications involving collagen-containing connective tissues. Previous in vitro studies have demonstrated that glucose inhibits collagen fibril formation and subsequent cross-linking. Collagen with diminished cross-linking is more susceptible to collagenolytic degradation. This may underlie the decreased collagen levels. To test this hypothesis, D-glucose and its two analogs, L-glucose and 2-deoxy-D-glucose, were used in chick calvaria organ cultures to examine parameters of collagen metabolism. L-Glucose is not used by the cell and functions as an extracellular glucose-like molecule, while 2-deoxy-D-glucose inhibits normal D-glucose uptake by blockading the glucose transport mechanism. Each of these three sugars had the ability to inhibit collagen fibril formation. D-Glucose stimulated collagen synthesis; L-glucose had no effect; and deoxyglucose inhibited collagen synthesis. D-Glucose was able to reverse the inhibitory effect of deoxyglucose. D-Glucose did not change levels of degradation of newly synthesized collagen while both L-glucose and deoxyglucose stimulated collagen degradation. When glucose transport was inhibited by deoxyglucose, collagen degradation was further enhanced. We suggest that decreased collagen levels in the connective tissues of diabetics may result from a combination of inhibition of collagen fibril formation and subsequent cross-linking, as well as increased collagen degradation.

Animals↗
PubMed1992

Laryngeal involvement in systemic lupus erythematosus.

Laryngeal involvement in systemic lupus erythematosus (SLE) can range from mild ulcerations, vocal cord paralysis, and edema to necrotizing vasculitis with airway obstruction. In this report, four cases showing the range of severity of this disease manifestation are presented, accompanied by a comprehensive review of the literature. The clinical course of 97 patients with laryngeal involvement with SLE are reviewed, of whom 28% had laryngeal edema and 11% had vocal cord paralysis. In the majority of cases, symptoms such as hoarseness, dyspnea, and vocal cord paralysis resolved with corticosteroid therapy. Other, less common causes of this entity included subglottic stenosis, rheumatoid nodules, inflammatory mass lesions, necrotizing vasculitis, and epiglottitis. The clinical presentation of laryngeal involvement in patients with SLE follows a highly variable course, ranging from an asymptomatic state to severe, life-threatening upper airway compromise. With its unpredictable course and multiple causations, this complication remains a diagnostic and therapeutic challenge to physicians involved in the care of patients with SLE.

Adult↗
PubMed1992

Fetal cleft lip repair in rabbits: histology and role of hyaluronic acid.

This study examines the histologic and biochemical features of wound healing in a cleft lip model in the mid-third-trimester fetal rabbit. At days 1, 2, and 4 after the procedure, control, unrepaired, and repaired fetal heads were obtained, sectioned, and stained for histologic examination. The localization of hyaluronic acid in the wound was documented using a cartilage-derived hyaluronic acid-binding protein. In both repaired and unrepaired wounds, the fetal cleft healed without inflammatory cell infiltration or scar formation. Six months after birth, the repaired cleft showed complete regeneration of muscle across the wound and the collagen fibers were of normal density and orientation. Decreased hyaluronic acid deposition was observed in unrepaired clefts as compared with adjacent tissue; no such difference was detected in repaired clefts. Our findings support the hypothesis that a cleft lip repaired in utero heals without the scarring that accompanies postnatal repair. This may explain the lack of maxillary growth restriction after in utero cleft lip repair.

Animals↗
PubMed1992

A substrate-gel assay for hyaluronidase activity.

Hyaluronic acid (HA) is a key structural element of the extracellular matrix. Turnover rates of HA are determined in part by hyaluronidases, that are themselves modulated by hyaluronidase inhibitors. A substrate polyacrylamide gel electrophoresis procedure is described here that separates enzyme from inhibitors. The HA is embedded in the gel, and following electrophoretic separation, enzymatic digestion of the HA is allowed to occur. The gel is stained with Alcian blue and can be secondarily stained with Coomassie blue. Enzymatic activities appear as cleared bands on a light blue background, while major proteins appear as dark blue bands. The procedure can be performed in the presence or absence of sodium dodecylsulfate, though levels of hyaluronidase activity decrease when the detergent is used. Hyaluronidases active in the neutral or acid pH range can be detected. This technique will facilitate characterization of hyaluronidases and inhibitors from a wide variety of sources.

Alcian Blue↗