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Biomedical subjects

M Rosenberg

Publications and source records attributed to M Rosenberg.

At least 73 records · Page 4Linked to original sources
PubMed2000

Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization.

OBJECTIVE: To examine the expression pattern of human cartilage glycoprotein 39 (HC gp-39) mRNA in human cartilage and bone. DESIGN: In-situ hybridization analysis was used to examine the expression pattern of human cartilage glycoprotein 39 (HC gp-39) mRNA in adult human osteoarthritic articular cartilage from various stages of disease, as well as in human osteophytic tissue and in human fetal bone. RESULTS: In cartilage from patients with mild osteoarthritic cartilage degeneration, HC gp-39 was expressed at moderate to high levels only in chondrocytes of the superficial zone. In advanced OA cartilage, cloning chondrocytes of the superficial zone expressed high levels of HC gp-39 and chondrocytes of the mid- and deep zones were also positive. HC gp-39 was undetectable in the chondrocytes of normal articular cartilage. In osteophytic tissue, the expression of HC gp-39 mRNA was intense in flattened, end-stage osteoblasts and in primary osteocytes in both endochondral and intramembranous bone formation. Proliferating osteoblasts expressed low to moderate levels. Notably, mature osteocytes were negative for HC gp-39 expression. Chondrocytes in the secondary ossification center of developing fetal cartilage demonstrated high expression while growth plate and mineralized cartilage chondrocytes had lower expression. Osteoblasts at sites of endochondral and intramembranous bone formation were positive for expression of HC gp-39. CONCLUSIONS: The stage-specific expression of HC gp-39 in fetal development and adult remodelling bone and cartilage provides evidence for a specific functional or structural role for HC gp-39 in bone and cartilage tissue. HC gp-39 is expressed in diseased human osteoarthritic cartilage and osteophyte, but not in non-diseased tissue, and its distribution within the tissue changes as disease progresses. OA is characterized not only by cartilage degeneration, but by increased subchondral bone formation and osteophytosis. The results from this study indicate that the increased HC gp-39 expression in OA serum and synovial fluid may reflect not only cartilage degeneration but increased osteogenesis.

Adipokines↗
PubMed2000

Evolution of two-component signal transduction.

Two-component signal transduction (TCST) systems are the principal means for coordinating responses to environmental changes in bacteria as well as some plants, fungi, protozoa, and archaea. These systems typically consist of a receptor histidine kinase, which reacts to an extracellular signal by phosphorylating a cytoplasmic response regulator, causing a change in cellular behavior. Although several model systems, including sporulation and chemotaxis, have been extensively studied, the evolutionary relationships between specific TCST systems are not well understood, and the ancestry of the signal transduction components is unclear. Phylogenetic trees of TCST components from 14 complete and 6 partial genomes, containing 183 histidine kinases and 220 response regulators, were constructed using distance methods. The trees showed extensive congruence in the positions of 11 recognizable phylogenetic clusters. Eukaryotic sequences were found almost exclusively in one cluster, which also showed the greatest extent of domain variability in its component proteins, and archaeal sequences mainly formed species-specific clusters. Three clusters in different parts of the kinase tree contained proteins with serine-phosphorylating activity. All kinases were found to be monophyletic with respect to other members of their superfamily, such as type II topoisomerases and Hsp90. Structural analysis further revealed significant similarity to the ATP-binding domain of eukaryotic protein kinases. TCST systems are of bacterial origin and radiated into archaea and eukaryotes by lateral gene transfer. Their components show extensive coevolution, suggesting that recombination has not been a major factor in their differentiation. Although histidine kinase activity is prevalent, serine kinases have evolved multiple times independently within this family, accompanied by a loss of the cognate response regulator(s). The structural and functional similarity between TCST kinases and eukaryotic protein kinases raises the possibility of a distant evolutionary relationship.

Amino Acid Sequence↗
PubMed2000

Prophylaxis against Frey's syndrome in parotid surgery.

In 1990 the authors reported their preliminary study of the prevention of Frey's syndrome in 55 patients utilizing a superficial musculoaponeurotic system (SMAS) flap in parotid gland surgery. During the past 10 years, numerous studies have supported their original thesis that interposition of living tissue between the resected gland bed and the skin could prevent the development of this complication. The authors have expanded their own patient population and now consider this a definitive study on the prevention of Frey's syndrome. A total of 160 patients are presented with a follow-up period of 5 to 22 years. All patients underwent subtotal or total parotidectomy performed by one of the authors. A history was acquired and testing for Frey's syndrome (Minor's starch iodine test) was performed. As a result of this approach, and in spite of the intensive search for it, no cases of Frey's syndrome were encountered. The hoped-for secondary benefit of preventing the postparotidectomy retromandibular depression was somewhat less satisfactory, although most patients remain satisfied with their appearance. The debilitating symptoms in Frey's syndrome, which is reported to have an incidence of 5% to 50% in the typical parotidectomy patient, can be avoided with thoughtful preoperative planning. The authors favor an aesthetic incision followed by the development of an SMAS flap. The parotidectomy is then performed using the surgeon's preferred technique. The SMAS flap is then placed into the bed of the resected parotid gland. This institutes a protective tissue barrier guarding against the aberrant anastomotic communication between the postganglionic secretomotor fibers intended for the parotid gland, and the now adjacent sweat glands. Their patient population is large enough to provide significant evidence that Frey's syndrome can be prevented, compared with a meta-analysis of parotid patients in multiple other studies in the literature. Assuming the patient's history and pathology does not preclude its use, the SMAS flap should be considered the standard of care for preventing Frey's syndrome in the postparotidectomy patient. If the SMAS flap is not available, a temporoparietal fascial flap has proved to be a good alternative.

Female↗
PubMed2000

Results of a gender-climate and work-environment survey at a midwestern academic health center.

UNLABELLED: AND CLIMATE determine how faculty's perceptions of medical school gender climate differ by gender, track, rank, and departmental affiliation. METHOD: In 1997, a 115-item questionnaire was sent to all University of Wisconsin Medical School faculty to assess their perceptions of mentoring, networking, professional environment, obstacles to a successful academic career, and reasons for considering leaving academic medicine. Using Fisher's exact two-tailed test, the authors assessed gender differences both overall and by track, rank, and departmental cluster. RESULTS: Of the 836 faculty on tenure, clinician-educator, and clinical tracks, 507 (61%) responded. Although equal proportions of men and women had mentors, 24% of the women (compared with 6% of men; p < .001) felt that informal networking excluded faculty based on gender. Women's and men's perceptions differed significantly (p < .001) on 12 of 16 professional environment items (p < .05 on two of these items) and on five of six items regarding obstacles to academic success. While similar percentages of women and men indicated having seriously considered leaving academic medicine, their reasons differed: women cited work-family conflicts (51%), while men cited uncompetitive salaries (59%). These gender differences generally persisted across tracks, ranks, and departmental clusters. The greatest gender differences occurred among clinician-educators, associate professors, and primary care faculty. CONCLUSIONS: Women faculty perceived that gender climate created specific, serious obstacles to their professional development. Many of those obstacles (e.g., inconvenient meeting times and lack of child care) are remediable. These data suggest that medical schools can improve the climate and retain and promote women by more inclusive networking, attention to meeting times and child care, and improved professional interactions between men and women faculty.

Career Mobility↗
PubMed2000

Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci.

The mevalonate pathway and the glyceraldehyde 3-phosphate (GAP)-pyruvate pathway are alternative routes for the biosynthesis of the central isoprenoid precursor, isopentenyl diphosphate. Genomic analysis revealed that the staphylococci, streptococci, and enterococci possess genes predicted to encode all of the enzymes of the mevalonate pathway and not the GAP-pyruvate pathway, unlike Bacillus subtilis and most gram-negative bacteria studied, which possess only components of the latter pathway. Phylogenetic and comparative genome analyses suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which are highly divergent from those of mammals, were horizontally transferred from a primitive eukaryotic cell. Enterococci uniquely encode a bifunctional protein predicted to possess both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acetyl-CoA acetyltransferase activities. Genetic disruption experiments have shown that five genes encoding proteins involved in this pathway (HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase) are essential for the in vitro growth of Streptococcus pneumoniae under standard conditions. Allelic replacement of the HMG-CoA synthase gene rendered the organism auxotrophic for mevalonate and severely attenuated in a murine respiratory tract infection model. The mevalonate pathway thus represents a potential antibacterial target in the low-G+C gram-positive cocci.

Acetyl-CoA C-Acetyltransferase↗
PubMed2000

The rel gene is essential for in vitro growth of Staphylococcus aureus.

The stringent response in Staphylococcus aureus is mediated by the nucleotide guanosine pentaphosphate, whose synthesis is catalyzed by the product of the rel gene. We report here that the rel gene is essential for the in vitro growth of S. aureus, distinguishing it from all other bacteria tested for this requirement.

Genes, Bacterial↗
PubMed2000

Essentiality, expression, and characterization of the class II 3-hydroxy-3-methylglutaryl coenzyme A reductase of Staphylococcus aureus.

Sequence comparisons have implied the presence of genes encoding enzymes of the mevalonate pathway for isopentenyl diphosphate biosynthesis in the gram-positive pathogen Staphylococcus aureus. In this study we showed through genetic disruption experiments that mvaA, which encodes a putative class II 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is essential for in vitro growth of S. aureus. Supplementation of media with mevalonate permitted isolation of an auxotrophic mvaA null mutant that was attenuated for virulence in a murine hematogenous pyelonephritis infection model. The mvaA gene was cloned from S. aureus DNA and expressed with an N-terminal His tag in Escherichia coli. The encoded protein was affinity purified to apparent homogeneity and was shown to be a class II HMG-CoA reductase, the first class II eubacterial biosynthetic enzyme isolated. Unlike most other HMG-CoA reductases, the S. aureus enzyme exhibits dual coenzyme specificity for NADP(H) and NAD(H), but NADP(H) was the preferred coenzyme. Kinetic parameters were determined for all substrates for all four catalyzed reactions using either NADP(H) or NAD(H). In all instances optimal activity using NAD(H) occurred at a pH one to two units more acidic than that using NADP(H). pH profiles suggested that His378 and Lys263, the apparent cognates of the active-site histidine and lysine of Pseudomonas mevalonii HMG-CoA reductase, function in catalysis and that the general catalytic mechanism is valid for the S. aureus enzyme. Fluvastatin inhibited competitively with HMG-CoA, with a K(i) of 320 microM, over 10(4) higher than that for a class I HMG-CoA reductase. Bacterial class II HMG-CoA reductases thus are potential targets for antibacterial agents directed against multidrug-resistant gram-positive cocci.

Amino Acid Sequence↗
PubMed2000

Self-perception of breath odor: role of body image and psychopathologic traits.

Oral malodor is a common complaint in Western society and is an important reason why adults seek dental counsel. In the present study, an attempt was made to evaluate the contribution of psychopathologic traits and of body-image char acteristics on participants' self-perception of breath odor. 60 participants without any specific complaint concerning breath odor (55% men: M age 35.5 yr., SD= 10) were evaluated. Variables included self-evaluation of participants' own breath odor (gener ally and current), an organoleptic evaluation of an impartial judge of odor, measurement of the volatile sulfide level in the oral cavity, and questionnaires referring to psychopathologic symptoms and body-image characteristics. Stepwise regression analysis showed that in addition to impartial measurements, self-perception of breath odor among noncomplaining subjects can be predicted by their feelings and attitudes toward the body and by their hostility.

Adult↗
PubMed2000

Two methods of inducing low plasma progesterone concentrations have different effects on dominant follicles in cows.

The effects of two methods of inducing low progesterone concentrations on the shape of the plasma progesterone curve and on follicular characteristics in lactating cows were studied. A low ascending progesterone curve was elicited by three PGF2alpha injections on d 3 to 4 of the estrous cycle; a low constant curve by induction of corpus luteum regression on d 6 and insertion of two progesterone-containing intravaginal devices from d 6 to 15 of the cycle. Plasma progesterone concentration was highest in the untreated control group, intermediate in low ascending group, and lowest in the low constant group. On d 15, both control and low ascending groups had one large healthy and one large atretic follicle, suggesting a turnover of follicular waves; in the low constant group, the presence of only one very large healthy follicle indicated follicular persistence. Estradiol concentration in the follicular fluid and its production by granulosa cells were highest in the low constant, intermediate in the low ascending, and lowest in the control group. Androstenedione concentration in the follicular fluid and its production by theca cells were higher in the low constant than in the low ascending and control groups. The results indicate that the low ascending progesterone curve affected follicular development and steroidogenesis differently from the low constant curve. We suggest that the low ascending curve mimics the effects of naturally occurring low plasma progesterone concentrations better, and it might, therefore, be used as a model for studying the effects of low plasma progesterone on fertility.

Androstenedione↗
PubMed2000

Factors affecting the production of (-)-mitorubrinic acid by Penicillium funiculosum.

The optimum conditions for the production of (-)-mitorubrinic acid by mutant strain of Penicillium funiculosum CCM F-8080 were examined in shaken flask cultures. The highest production of this metabolite was achieved in a medium with glucose as the sole carbon source and (NH4)2HPO4 as the nitrogen source. The most suitable concentrations of the given sources for production of (-)-mitorubrinic acid are 80 g/l glucose and 2 g/l (NH4)2HPO4 (maximal production, 814.9 mg/l). We also observed the influence of concentration of L-phenylalanine and inorganic phosphate in culture medium on the production of (-)-mitorubrinic acid. The biological activity of mitorubrinic acid as trypsin inhibitor was determined (IC50 41.05 mumol/l).

Benzoates↗
PubMed1999

Preparation and properties of glutaraldehyde cross-linked whey protein-based microcapsules containing theophylline.

Whey protein-based microcapsules containing a model drug, theophylline, were prepared in organic phase, using glutaraldehyde-saturated toluene. In all cases, spherical microcapsules, ranging from <400 to 1000 microm in diameter, were obtained. Results indicated that core crystals were embedded throughout the wall matrix. In all cases, retention efficiency of theophylline was higher than 74% and was not affected by cross-linking conditions. Results of theophylline release in simulated intestinal and gastric fluids at 37 degrees C indicated that the diffusion-governed core release was significantly affected by size of microcapsules, cross-linking conditions, and by type of dissolution medium. In all cases, core release in simulated intestinal fluid was faster than in simulated gastric fluid.

Capsules↗
PubMed1999

Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: induction of humoral tolerance in seroconverted patients after repeat administration.

Alglucerase, a macrophage-targeted enzyme replacement therapy for Gaucher disease, has been successfully used for several years to improve clinical symptoms and reverse disease progression. As part of an immunosurveillance program, 1,122 Gaucher patients were monitored for antibody response to glucocerebrosidase, the active component of alglucerase. Seroconversion was detected in 142 patients (12.8%) by enzyme-linked immunosorbent assay (ELISA) and confirmed by radioimmunoprecipitation. The majority (75%) of the seroconverted population had no detectable levels of circulating inhibitory antibody as assessed by in vitro inhibition of enzymatic activity of the therapeutic molecule. Of the remaining patients with putative inhibitory antibodies, the majority had only low levels of serum inhibitory activity, which was transient. A very small number of patients were identified as developing true neutralizing antibodies, as defined by the development of antibodies that impacted clinical efficacy. Many of the patient antibody responses were also diminished with time. Eighty-two of the 142 seroconverted patients have stopped producing antibody to the molecule and appear tolerized. The mean time for humoral tolerization was 28 months from initiation of therapy. Of 64 seroconverted patients followed for at least 30 months of therapy, the tolerization rate was 93%. These results show that although 12.8% of the patients on therapy developed antibodies to the molecule, 90% of these patients became tolerized over time.

Antibodies↗
PubMed1999

Unusual cell ultrastructure in ventral epidermis of the African reed frog Hyperolius viridiflavus, (Anura; Hyperoliidae).

The stratum corneum of the epidermis of Hyperolius viridiflavus contains several replacement layers. The outer layer is covered by mucopolysaccharide secretion. H. viridiflavus in their dry phase do not moult the sloughed off layers; these remain attached to the stratum corneum. Long and slender pillar-like cells situated under the stratum corneum extend through the stratum granulosum, stratum germinativum, and the basement membrane into the dermis. These cells abound in tonofilaments. Flask-shaped cells rich in mitochondria, reaching under the stratum corneum, extend into the stratum granulosum. They show delicate, membranous infoldings in their neck-like apical part. Granule-cells, arranged in 2 or 3 layers are situated in the stratum granulosum between the stratum corneum and germinativum. The germinative cells are large and separated from each other by wide intercellular spaces. ATPase activity was localized cytochemically in the baso-lateral cell membranes bordering with the intercellular spaces under the stratum corneum.

Adenosine Triphosphatases↗
PubMed1999

Causes and consequences of oral contraceptive noncompliance.

Compliance difficulties are more common among oral contraceptive users than is generally appreciated. Inconsistent use and method discontinuation are estimated to account for approximately 20% of the annual 3.5 million annual unintended pregnancies in the United States. In the past research focused on adolescents, for whom predictors of poor oral contraceptive compliance include multiple sex partners, low evaluation of personal health, low degree of concern about pregnancy, and previous abortion. More recent research confirms that compliance problems are common among all age groups, with 47% of women missing >/=1 pill per cycle and almost a quarter (22%) missing >/=2 pills per cycle. Good compliance has been linked to patient satisfaction with the clinician, the absence of certain side effects, establishing a regular daily routine to take oral contraceptives, and reading information distributed with oral contraceptive packaging. Clinicians are the focal point for improving oral contraceptive compliance. They should focus counseling on the transience of most side effects, instructions on dealing with a missed pill, provision of a backup method, and establishment of a daily pill-taking routine. Easy-to-understand literature should be given to patients to take home.

Adolescent↗