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R Stern

Publications and source records attributed to R Stern.

At least 109 records · Page 6Linked to original sources
PubMed1994

Molecular cloning of a mammalian hyaluronidase reveals identity with hemopexin, a serum heme-binding protein.

Hyaluronan is the most abundant glycosaminoglycan of the extracellular matrix and is a critical substrate for cellular attachment and locomotion. Little is known about the class of enzymes, termed hyaluronidases, that are responsible for hyaluronan catabolism in mammals. We have determined a partial amino acid sequence from a purified preparation of porcine liver hyaluronidase and have used this information as the basis for cloning complementary DNA that encodes the corresponding protein. When expressed in a recombinant baculovirus system, the protein exhibited hyaluronidase activity in a substrate-gel assay. The deduced sequence of this mammalian hyaluronidase is that of a 459-amino-acid polypeptide bearing four potential N-glycosylation sites as well as a copy of a proposed hyaluronan binding motif. Remarkably, amino acid sequence comparisons and immunologic cross-reactivities strongly suggest that the cloned protein is identical to hemopexin, an abundant, heme-binding serum protein. Although hemopexin has not previously been reported to possess any enzymatic activity, it includes a conserved domain found in collagenases, stromelysins, and other enzymes that metabolize the extracellular matrix. We conclude that hemopexin is the predominant hyaluronidase expressed in mammalian liver.

Amino Acid Sequence↗
PubMed1994

Circadian variation of cardiopulmonary disease onset in the general population: an emergency care system perspective from Berlin.

STUDY HYPOTHESIS: The objective of the present study was to determine the circadian pattern of onset of acute pulmonary emergencies in the general population and to analyze the influence of age and sex on these patterns. METHODS: Analysis of all 47,082 emergency calls during the years 1987 and 1988 of the Berlin emergency medical system. Analysis of circadian variation in incidence of subgroups with the leading symptom of respiratory distress, chest pain, or sudden unconsciousness. All cases of nontraumatic sudden death were analyzed. All missions were evaluated with regard to sex and age dependence. RESULTS: There is a circadian variation in acute cardiopulmonary emergencies with the highest incidence between 6 AM and noon. This applies to subpopulations of chest pain (9,068), respiratory distress (13,732), sudden unconsciousness (7,829), resuscitation attempts (4,787), and persons found dead without resuscitation attempts (4,780). Cases of chest pain, respiratory distress, and resuscitations show a second evening peak. Patients 65 years old or less have the highest rates in the afternoon, whereas those aged over 65 show a single morning peak (P < .0001). These relations are independent of sex and presenting complaint. CONCLUSION: Unselected populations show circadian variations in the incidence of cardiopulmonary emergencies. Age-related differences suggest different pathophysiological age-dependent mechanisms, eg, hormonal factors or lifestyle-dependent trigger mechanisms. Emergency medical systems should adjust the availability of emergency services to the distinct circadian differences of life-threatening cardiovascular and pulmonary diseases.

Adult↗
PubMed1994

Age-dependent changes of hyaluronan in human skin.

Hyaluronan is a major component of the extracellular matrix of skin. The large volume of water of hydration associated with hyaluronan may be a mechanism for maintaining the normal hydration of skin. As such, decreasing levels of hyaluronan deposition might underlie the changes associated with the aging process. To test this hypothesis, hyaluronan levels were determined in extracts of skin obtained at autopsy from individuals of different ages. However, no significant differences in hyaluronan concentrations were found. The distribution of hyaluronan polymer sizes in various extracts did not change as a function of age as measured by size exclusion chromatography. However, major differences in hyaluronan extractability did occur as a function of age. Sequential extraction was performed utilizing 1) 0.1% Triton X-100, 2) 4 M guanidine-HCl, and 3) papain digestion, to release species of hyaluronan progressively more tightly associated with tissue. With advancing age, hyaluronan polymers became progressively more tissue associated. The proportion of hyaluronan released after papain digestion increased from 7% of the total in fetal to 23% of the total in senescent skin. Finally, histolocalization of hyaluronan was examined in full-thickness sections of human skin of different ages. Major differences in compartmentalization were found. We conclude that neither the concentration nor polymer size of hyaluronan changes as a function of age. However, enhanced association with tissue occurs, presumably through hyaluronan-binding proteins and alterations in the histolocalization of hyaluronan. Such observations may underlie some of the changes in human skin that occur with aging.

Adult↗
PubMed1994

[Stress factors in acute myocardial infarct: the role of physical exertion and unusual life events].

OBJECTIVE: It is controversial whether the onset of myocardial infarction is a "random" event or whether there are triggering factors of the disease. Previous reports on possible triggers were based on case studies or inadequately controlled studies. The TRIMM study (Triggers and Mechanisms of Myocardial Infarction) was designed to determine the influence of physical activity and other external factors on the acute risk of myocardial infarction. METHODS: At Klinikum Steglitz, Berlin, all consecutive patients with myocardial infarction were included. In the Augsburg area, all patients with myocardial infarction in a prospectively defined cohort (n = 330,000) were registered by monitoring 26 hospitals. Information on the circumstances and possible triggers of the disease was obtained by standardized interviews. The control group was matched for age, sex, precinct, and time of a control event. The statistical analysis included a case-control comparison of patients with control subjects and a case-crossover comparison comparing the average exposure to a possible trigger with the time of the last exposure prior to the onset of disease. RESULTS: From January 1989 to December 1991, 1194 patients (74% men, 61 +/- 9 years) were enrolled 13 +/- 6 days after myocardial infarction. During the initial three hours after awakening, the occurrence of myocardial infarction was almost threefold compared to other times of day. A multivariate analysis yielded a twofold risk of myocardial infarction during physical exertion, statistically independently of time of day. 7.1% of patients had engaged in exertional physical activity at onset of the event, as opposed to 3.9% of control subjects. The case-crossover analysis demonstrated a relative risk of 2.1 (1.6-3.1) of exertional physical activity within 1 hour prior to myocardial infarction. Patients whose average frequency of physical exertion was < 4 versus > or = to 4 times per week had relative risks of 6.9 versus 1.3 (p < 0.01). Unusual life events within 24 hours and 24 hours to 4 weeks prior to the event occurred with similar frequencies and control subjects. CONCLUSIONS: Physical exertion appears to increase the acute risk of myocardial infarction in patients with coronary heart disease, particularly in untrained individuals. Unusual life events, however, are of less importance for the acute risk of disease. These findings are important for further investigation of triggering mechanisms of myocardial infarction and for improving preventive strategies.

Adult↗
PubMed1993

Second sight.

Explore the source record for details and available documents.

Problem Solving↗
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↗