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Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 91 records · Page 5Linked to original sources
PubMed1997

Hyaluronidases in tissue invasion.

Hyaluronidases are broadly distributed enzymes with varying substrate specificities, a wide range of pH optima, and different catalytic mechanisms. They may be used by organisms to invade one another. Hyaluronidases have also been invoked as mechanisms for tumor invasion and metastatic spread. In this review, we will concentrate more on the different kinds of hyaluronidases involved in tissue invasion other than cancer metastasis, present some of the rapidly accumulating new data, and address the paradox that both hyaluronidase as well as its hyaluronan substrate are associated with invasion.

Animals↗
PubMed1996

Cardiac myxomas.

Explore the source record for details and available documents.

Heart Neoplasms↗
PubMed1996

Hyaluronan-binding properties of human serum hemopexin.

Hemopexin, the heme-binding serum glycoprotein, exhibits a complex electrophoretic pattern on two-dimensional immunoelectrophoresis on agarose gels into which hyaluronic acid is incorporated in the first and monospecific anti-hemopexin in the second dimension. This heterogeneity reflects a range of interactions of hemopexin isoforms with hyaluronic acid. Electrophoretic patterns of individual human sera greatly differ in their contents of hyaluronan-interacting hemopexin species. Hemopexin itself has no hyaluronidase activity.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1996

[Are emergency physicians' diagnoses accurate?].

METHODS AND AIM OF THE STUDY: The on-scene performance during all missions of the emergency physician-operated rescue helicopter and mobile intensive care unit based at a large-city hospital over a period of 1 year was retrospectively analysed; 2,254 hospital discharge reports were available (92% of the patients treated by the emergency physicians [n = 2,493]). The following parameters were investigated: reliability of the primary diagnosis established by the emergency physician (by comparison with the discharge diagnoses); initial on-scene therapeutic measures; means of transportation (with or without accompanying emergency physician); and level of care of the target hospital. RESULTS: The most common reasons for a mission were cardiopulmonary diseases (55%), neurological disorders (18%), and traumatic events (7%). The diagnoses, therapeutic measures, and mode of transportation were correct in 2,033 (90%) patients with a discharge report. Severe errors of assessment by the emergency physician were identified in 73 patients (3%): life-threatening conditions were not recognised and/or grossly incorrect therapeutic measures were taken and/or the chosen means of transportation was unsuitable. Relative errors in assessment occurred in 4% (n = 83): the most crucial diagnosis was not made, but the patient was escorted by the emergency physician (without therapeutic errors) to a suitable hospital. In 3% (n = 65) of the cases, the patient's condition was overestimated by the emergency physician as suggested by the obviously exaggerated on-scene therapy. Underestimations of the severity were most common in patients with cardiopulmonary diseases and increased in frequency and severity with increasing age and the presence of a concomitant neurologic deficit. Underestimations of a severe condition in younger patients were extremely rare; overestimations of the severity and consequent overtreatment were particularly common in traumatised patients independent of age. CONCLUSIONS: In the context of quality management measures, a careful evaluation of on-scene diagnoses, therapeutic measures, and decisions made by the emergency physician is a suitable procedure for identifying systematic errors. A high percentage of correct diagnoses and therapy at the emergency site can only be ensured by clinically experienced physicians who constantly deal with patients with acutely life-threatening conditions.

Adolescent↗
PubMed1996

Hyaluronan (hyaluronic acid) in human saliva.

Hyaluronan (hyaluronic acid) is a glycosaminoglycan that functions as a constituent of ground substance, a mediator of cell proliferation and would healing, and that plays a prominent part in tumorigenesis as well as in embryogenesis. Its presence and possible role in saliva has been subjected to little study. Unstimulated and stimulated pure parotid and mixed saliva was obtained from 10 volunteers. The protein content of the samples was assayed and the hyaluronan concentration was evaluated by means of an enzyme immunosorbent-like assay using a hyaluronan-binding peptide. Stimulated whole saliva had the highest protein content (mean 1.26 mg/ml) followed by unstimulated parotid saliva (1.15 mg/ml), stimulated parotid saliva (0.95 mg/ml) and unstimulated whole saliva (0.93 mg/ml). Absolute hyaluronan concentrations were highest in unstimulated whole saliva (mean 459.2 ng (nanograms)/ml), and lowest in stimulated parotid saliva (82.7 ng/ml). When hyaluronan concentrations are expressed as ng/mg of protein, the highest are in the unstimulated whole saliva (mean 477.5 ng/mg protein) followed by stimulated parotid saliva (229.7 ng/mg), unstimulated parotid saliva (179.6 ng/mg) and stimulated whole saliva (159.9 ng/mg). There are wide variations in the levels of hyaluronan in human saliva depending on the type of saliva and the conditions at the time of collection. Regulation of hyaluronan metabolism represents an intricate balance between production and degradation, and it is unclear whether elevated concentrations of hyaluronan in response to tissue proliferation, regeneration or repair. The hyaluronan may contribute to the healing properties of saliva, assisting in protecting the oral mucosa and adding to the lubricating properties of saliva.

Adult↗
PubMed1996

Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis.

Both hyaluronan and one of its receptors, CD44, can be demonstrated in the early human conceptus and in placental stroma. The variants of CD44 resulting from variable exon splicing are found in metastasizing human malignancies and are also involved in hyaluronan uptake and degradation. The resulting hyaluronan fragments are known to be highly angiogenic. We postulated that the self-limited process of trophoblast invasion of the uterine decidua results in part from the strategy of alternative splicing of CD44, similar to that used by invasive cancer cells in the course of metastatic spread and possibly angiogenesis. Monoclonal antibodies specific for CD44s and for an exon expressed during metastatic tumour progression, CD44v7, were used to examine this hypothesis. In this study we found human trophoblasts, for the first time, to express CD44. Intermediate trophoblasts of first and second trimester exhibited the standard form of CD44 while extravillous trophoblasts, which are responsible for the invading characteristics of the placenta, were positive for the alternatively spliced form, the CD44v7-8. Moreover, in the case of placenta accreta there was a prominent membrane staining of the trophoblasts that were embedded in the fibrin layer over the myometrium. The highly metastatic choriocarcinoma cells also expressed CD44v7-8. We propose, therefore, that the invading trophoblasts utilize the alternatively splicing machinery. These cells retain their invasive capabilities through the permissive ECM by carrying the CD44v7-8 isoform, which binds weakly to hyaluronan and thus prevents it from being degraded by intracellular hyaluronidase.

Alternative Splicing↗
PubMed1996

The application of health care surrogate laws to older populations: how good a match?

OBJECTIVE: The Health Care Surrogate Act (HCSA) in Illinois has been proposed as a model for state laws naming surrogate medical decision-makers for those without advance directives (ADs). Our objective was to determine if the HCSA identifies the same surrogate as older persons would choose for themselves. If not, is the discrepancy between legally identified surrogate and preferred surrogate troublesome to respondents? Because it is documented that black Americans have a variety of family structures, some of which may not be reflected in the HCSA list, we also wished to determine if discrepancies between surrogates named by the law and those desired by patients are associated with black or white race. DESIGN, SETTING AND PARTICIPANTS: A convenience sample of 144 patients aged 65 and older, without cognitive impairment, was interviewed at the geriatrics clinic of an academic medical center. MAIN OUTCOME MEASURES: Respondents without ADs who had a different stated choice for surrogate medical decision-maker than the surrogate defined by the Illinois HCSA, based on their existing family. RESULTS: Twenty-six percent of respondents without ADs chose a surrogate that differed from the surrogate defined by the HCSA. However, 67% of those with a different choice for surrogate than defined by law were not troubled by the discrepancy. The proportion of black subjects (25%) and white subjects (31%) who had surrogate discrepancies was not significantly different (P = .6). CONCLUSION: Because the Illinois HCSA named surrogates who would be agreeable to the majority of our respondents, it appears that it may be a useful model for state surrogacy laws.

Advance Directives↗
PubMed1996

Human vitreous hyaluronidase: isolation and characterization.

PURPOSE: Hyaluronic acid (HA) is the predominant glycosaminoglycan (GAG) of the human vitreous. Interaction of this HA with vitreous collagen is important for maintaining gel structure. The mechanism of HA homeostasis in the vitreous is incompletely understood. The aim of this study was to determine whether hyaluronidase, an endoglycosidase that degrades HA, was present in human vitreous. METHODS: Vitreous samples were collected from post-mortem eye bank specimens and from non-hemorrhagic, non-inflamed biopsy specimens. Vitreous hyaluronidase was purified by a series of column chromatographic steps, and its activity was measured by an ELISA-like assay and by substrate gel electrophoresis through and HA-impregnated gel. The purified hyaluronidase was also analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by Western blotting. RESULTS: Hyaluronidase activity was detected in vitreous samples from both post-mortem and biopsy specimens. The enzyme was most active at acid pH, but demonstrated significant activity at neutral pH. The partially purified enzyme migrated as a 59 kDa protein on SDS-PAGE, and a single band on Western blots. CONCLUSIONS: Hyaluronidase is present in the human vitreous. Thus, hyaluronidase may be involved in HA catabolism in the vitreous and may play a role in determining its gel structure.

Blotting, Western↗
PubMed1996

Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind vehicle-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and tolerability of 2 widely used topical alpha-hydroxy acids at low concentrations, 8% glycolic acid and 8% lactic (L-isoform) acid creams, in the treatment of photodamaged skin. DESIGN: A single-center, 22-week, double-blind, vehicle-controlled, randomized clinical trial assessed the overall severity of photodamage on the faces and forearms of volunteers, based on 7 individual clinical components of cutaneous photodamage. SETTING: The study was performed in an outpatient clinical research unit at the Massachusetts General Hospital, Boston. PATIENTS: Seventy-four women, aged 40 to 70 years, with moderately severe photodamaged facial skin were enrolled in the study. One subject withdrew from the study early because of skin irritation, and 6 subjects withdrew from the study for personal reasons. INTERVENTIONS: Glycolic acid, L-lactic acid, or vehicle creams were applied twice daily to the face and outer aspect of the forearms. MAIN OUTCOME MEASURES: Improvement in alpha-hydroxy acid-treated photodamaged skin as determined by patient self-assessments and physician evaluations of efficacy and irritancy. RESULTS: The percentage of patients using either 8% glycolic acid or 8% L-lactic acid creams on the face achieving at least 1 grade of improvement (using a scale from 0 through 9) in overall severity of photodamage was significantly greater than with the vehicle cream (76% glycolic acid, 71% lactic acid, and 40% vehicle; P < .05). On the forearms, after 22 weeks, treatment with glycolic acid cream was superior to the vehicle in improving the overall severity of photodamage and sallowness (P < .05). L-Lactic acid cream was significantly superior to the vehicle in reducing the overall severity of photodamage (P < .05), mottled hyperpigmentation (P < .05), sallowness (P < .05), and roughness on the forearms (P < .05) at week 22. CONCLUSIONS: Topical 8% glycolic acid and 8% L-lactic acid creams are modestly useful in ameliorating some of the signs of chronic cutaneous photodamage. These agents are well tolerated and available without prescription.

Administration, Topical↗
PubMed1996

Beneficial effect of granulocyte-colony stimulating factor in scleromyxoedema associated with severe idiopathic neutropenia.

The treatment of scleromyxoedema is notoriously difficult. We present a patient with long-standing diffuse scleromyxoedema associated with functional impairment who developed chronic idiopathic neutropenia complicated by recurrent life-threatening infections. Treatment with recombinant granulocyte--colony stimulating factor led to normalization of the neutrophil count, prevented further systemic infections, and unexpectedly was associated with a striking clinical improvement of her skin disorder and decrease in mucin deposition in the dermis.

Chronic Disease↗
PubMed1995

Urinary hyaluronic acid is a Wilms' tumor marker.

Wilms' tumor is a renal neoplasm that is histologically similar to fetal kidney tissue. Both Wilms' tumor and the fetal kidney have high levels of the glycosaminoglycan hyaluronic acid (HA) in the extracellular matrix. Preliminary studies suggest that urinary HA levels are elevated in Wilms' tumor patients. To test the utility of urinary HA as a Wilms' tumor marker, the authors compared HA levels in urine specimens from 105 Wilms' tumor patients with those of 17 age-matched controls. Preoperative urine samples (n = 92), early postoperative samples, obtained from 1 to 3 weeks after surgery (n = 63), and late postoperative samples, obtained from 1 to 6 months after surgery (n = 58) were collected from patients at 30 institutions between 1989 and 1993. The HA levels were determined in triplicate by a competitive enzyme-linked immunosorbent binding assay. Seventy-four percent of the preoperative urine specimens contained elevated HA levels compared with the controls. The preoperative HA levels were significantly higher than the early postoperative (P < .01), late postoperative (P < .01), and control levels (P < .01). There was significant correlation between preoperative HA levels and clinical tumor staging. The mean preoperative HA level for patients with histological evidence of nephroblastomatosis was higher than that for patients without nephroblastomatosis. In the late postoperative period, patients with relapse or persistent disease had higher levels of urinary HA than did the disease-free patients (P < .05). In Wilms' tumor patients, urinary HA levels are elevated preoperatively and decline progressively after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1995

Assessment of the central dopaminergic index of plasma HVA in schizophrenia.

Under fasting conditions, the dopamine (DA) metabolite homovanillic acid (HVA) in plasma originates mainly from central DA neurons or from central and peripheral noradrenergic (NA) neurons. The latter source contributes, in addition to HVA, the norepinephrine metabolites, for example, 3-methoxy-4-hydroxyphenylglycol (MHPG). It has been shown in primates that the association between HVA and MHPG in plasma or urine under varying rates of NA metabolism can be used to obtain an estimate of the central DA neuronal contribution of HVA to plasma or urine. This estimate is called the central dopaminergic index (CDI). Two studies presented here examine the applicability of this model in schizophrenia patients. The results were consistent with the proposed model and suggested that only about 30 percent of the total plasma HVA concentrations in our patients were derived from central DA neurons. A convenient modification of this model is proposed for future studies. Since the CDI of plasma HVA is not likely to be confounded by NA activity, this tool may prove useful in disentangling the roles played by the DA and NA systems in schizophrenia.

Brain↗
PubMed1995

Migration of bovine aortic smooth muscle cells after wounding injury. The role of hyaluronan and RHAMM.

The migration of smooth muscle cells is a critical event in the pathogenesis of vascular diseases. We have investigated the role of hyaluronan (HA) and the hyaluronan receptor RHAMM in the migration of adult bovine aortic smooth muscle cells (BASMC). Cultured BASMC migrated from the leading edge of a single scratch wound with increased velocity between 1 and 24 h. Polyclonal anti-RHAMM antisera that block HA binding with this receptor abolished smooth muscle cell migration following injury. HA stimulated the random locomotion of BASMC and its association with the cell monolayer increased following wounding injury. Immunoblot analysis of wounded monolayers demonstrated a novel RHAMM protein isoform that appeared within one hour after injury. At the time of increased cell motility after wounding, FACS analysis demonstrated an increase in the membrane localization in approximately 25% of the cell population. Confocal microscopy of injured monolayers confirmed that membrane expression of this receptor was limited to cells at the wound edge. Collectively, these data demonstrate that RHAMM is necessary for the migration of smooth muscle cells and that expression and distribution of this receptor is tightly regulated following wounding of BASMC monolayers.

Animals↗