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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 199 records · Page 11Linked to original sources
PubMed1994

Integration of antimicrobial host defenses: role of the bactericidal/permeability-increasing protein.

Our understanding of the complex and integrated host-defense systems against microbial infection has progressed rapidly with the characterization of individual components. However, the various factors must be studied not only in isolation, but also in a closer approximation to the in vivo situation, where these factors interact. This is well illustrated in recent studies of the role of the bactericidal/permeability-increasing protein.

Animals↗
PubMed1994

An algorithm based on graph theory for the assembly of contigs in physical mapping of DNA.

An algorithm is described for mapping DNA contigs based on an interval graph (IG) representation. In general terms, the input to the algorithm is a set of binary overlapping relations among finite intervals spread along a real line, from which the algorithm generates sets of ordered overlapping fragments spanning that line. The implications of a more general case of the IG, called a probe interval graph (PIG), in which only a subset of cosmids are used as probes, are also discussed. In the specific case of cosmids hybridizing to regions of a YAC, the algorithm takes cross-hybridization information using the cosmids as probes, and orders them along the YAC; if gaps exist due to insufficient coverage of cosmid contigs along the length of the YAC, repetitive use of the algorithm generates sets of ordered overlapping fragments. Both the IG and the PIG can expose problems caused by false overlaps, such as hybridizations due to repetitive elements. The algorithm, has been coded in C; CPU time is essentially linear with respect to the number of cosmids analyzed. Results are presented for the application of a PIG to cosmid contig assembly along a human chromosome 13-specific YAC. An alignment of 67 cosmids spanning a YAC took 0.28 seconds of CPU time on a Convex 220 computer.

Algorithms↗
PubMed1994

Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society.

Different pigmentary characteristics as well as different parameters of sun exposure have previously been identified as risk factors for developing cutaneous melanoma. The aim of the present study was to identify significant risk factors, determine the related magnitude of their estimated relative risks, and define criteria for the detection of persons at risk. Five hundred thirteen melanoma patients and 498 controls matched for age and sex underwent a whole-body examination for the number and type of melanocytic lesions and were interviewed on ultraviolet exposure and other potential risk factors. The total number of common melanocytic nevi on all body sites represented the most important risk factor in multiple logistic regression analysis with a relative risk of 7.6 for subjects with more than 100 versus no more than 10 melanocytic nevi. Other significant independent risk factors were the number of atypical melanocytic nevi (relative risk, 6.1 for at least 5 melanocytic nevi versus none), the number of actinic lentigines (relative risk, 3.5 for many versus none), hair color, skin type, and reported melanocytic nevus growth. No single parameter of sun exposure was significantly related to melanoma risk in the multivariate analysis. Groups with an estimated relative risk between 1 and 121.0 were distinguished by considering common and atypical melanocytic nevi as well as actinic lentigines as the decisive criteria. In conclusion, even without any information on the case history, whole-body examination and diagnosis of pigmented lesions was found to be an effective strategy for identifying persons at risk of developing melanoma. Furthermore, clinical recognition of at least 5 atypical melanocytic nevi without histologic examination is a key for identifying subjects at high risk.

Adult↗
PubMed1994

Associated factors in the prevalence of more than 50 common melanocytic nevi, atypical melanocytic nevi, and actinic lentigines: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society.

Several case-control studies identified common and atypical melanocytic nevi as major risk indicators for the development of cutaneous melanoma. The present investigation was planned to detect factors associated with the prevalence of these melanoma risk markers. Whole-body examination findings and interview data of 513 melanoma patients and 498 age- and sex-matched control subjects were analyzed. Existence of more than 50 common melanocytic nevi and the presence of atypical melanocytic nevi were significantly related to age and gender, with significantly elevated relative risk for their prevalence before the age of 60 and in males. Additionally, sunburns before the age of 20 were significantly associated with both more than 50 common melanocytic nevi (relative risk = 1.7) and the presence of atypical melanocytic nevi (relative risk = 1.5). Actinic lentigines were found more frequently with increasing age, and the presence of actinic lentigines was significantly related to a tendency of freckling in adolescence (relative risk = 2.0) and to two or more sunburns after the age of 20 (relative risk = 1.6). In conclusion, sunburns before the age of 20 contribute to the development of multiple melanocytic nevi and atypical melanocytic nevi. In adulthood, this type of sun exposure is associated with the development of actinic lentigines. The relative risk of developing cutaneous melanoma increases in association with the development of these benign melanocytic lesions.

Adolescent↗
PubMed1994

Differential diagnosis of keratoacanthomas and squamous cell carcinomas: diagnostic value of DNA image cytometry and p53 expression.

DNA-cytometry and immunohistochemistry with the anti-p53 antibody DO-1 was performed in 24 keratoacanthomas (KA) and 21 squamous cell carcinomas (SCC) (13 well-differentiated, 8 moderately differentiated) to establish the possible value of these methods for the differential diagnosis of both epithelial tumors. Aneuploidy was detected in 1 (4%) KA and 12 (57%) SCC (p < 0.05). In the latter tumors, histologic grade was associated with an abnormal DNA-content. Six (46%) well and 6 (75%) moderately differentiated SCC were shown to be aneuploid. Over-expression of p53 protein was found in 16 (76%) SCC and 14 (66%) KA (p > 0.05; not significant). However, quantification of p53 expression by evaluating both the intensity of immunostaining and the number of cells with over-expression by means of an immunoreactivity score (IRS) showed significant differences (p < 0.05). There was no correlation of p53 over-expression and aneuploidy in the tumors examined. The analysis of ploidy and immunostaining with anti-p53 antibodies may give useful additional information regarding the differential diagnosis of SCC and KA, if only aneuploidy or a high IRS are considered.

Carcinoma, Squamous Cell↗
PubMed1994

Effect of lipopolysaccharide (LPS) chain length on interactions of bactericidal/permeability-increasing protein and its bioactive 23-kilodalton NH2-terminal fragment with isolated LPS and intact Proteus mirabilis and Escherichia coli.

The target-specific cytotoxicity for gram-negative bacteria and the endotoxin-neutralizing activity of the 55-kDa bactericidal/Permeability-increasing protein (BPI) and its bioactive 23-kDa NH2-terminal fragment depend on the strong attraction of BPI for the lipid A region of lipopolysaccharides (LPS). We have shown before that smooth gram-negative bacteria with long-chain LPS are more resistant to BPI (especially holo-BPI) than are rough strains. It has been suggested that the high BPI resistance of some gram-negative bacteria, such as Proteus mirabilis, might also reflect the structural diversity of lipid A. To explore this possibility, we compared the antibacterial activity and binding of natural and recombinant holo-BPI and a recombinant NH2-terminal fragment (rBPI-23) to an isogenic rough (Re-LPS chemotype) and a smooth (S-LPS chemotype) strain of P. mirabilis and to LPS isolated from the two strains. Holo-BPI and rBPI-23 were both potently active against the Re strain of P. mirabilis (90% lethal dose, 20 nM). In contrast, the smooth strain was > or = 100 times more resistant to holo-BPI but only 10 times more resistant to rBPI-23. rBPI-23 was also more potent against several Escherichia coli strains from clinical bacteremia isolates. Differences in the antibacterial potency of BPI toward the Re and S strains of P. mirabilis correlated with differences in the binding of holo-BPI and rBPI-23 to these bacteria. In contrast, the binding of biosynthetically (in vitro transcribed and translated) 35S-labeled holo-BPI and NH2-terminal fragment to isolated Re- and S-LPS from P. mirabilis in solution was similar. Moreover, in the Limulus amebocyte lysate assay, holo-BPI and rBPI-23 potently neutralized both forms of LPS with equal effectiveness. Together, these results strongly suggest that BPI recognizes Proteus lipid A and that the relative resistance of (smooth) P. mirabilis to holo-BPI is due to the inhibitory effect of long polysaccharide chains of tightly packed LPS in the envelope.

Antimicrobial Cationic Peptides↗
PubMed1994

Comparison of PCR and other diagnostic techniques for detection of Helicobacter pylori infection in dyspeptic patients.

A sensitive and specific PCR-based assay to detect the Helicobacter pylori 16S rRNA gene present in formalin-fixed paraffin-embedded gastric biopsy specimens has been developed. A total of 95 patients with dyspepsia were evaluated for the presence of chronic active gastritis and an infection with H. pylori through the use of diagnostic assays based on biopsy specimens and serology. The "gold standard" for the presence of the bacteria was direct detection in histological sections of biopsy specimens by Giemsa stain. The results obtained with the PCR assay performed on the biopsy specimens (94% sensitivity and 100% specificity) were equivalent to the detection of H. pylori immunoglobulin G antibodies by the commercially available second-generation Cobas Core anti-H. pylori immunoglobulin G enzyme immunoassay (94% sensitivity and 98% specificity) for the diagnosis of H. pylori infection. Urease testing and bacterial culture of the biopsy specimens were inferior (88 and 70% sensitivity and 96% and 98% specificity, respectively). A Western blot (immunoblot) analysis had slightly greater sensitivity (96%), although specificity was reduced to 93%. This research prototype PCR assay was shown to be highly reliable for the detection of infection with H. pylori and the presence of chronic active gastritis in the population studied.

Adult↗
PubMed1994

Carcinoma of the prostate gland: MR imaging with pelvic phased-array coils versus integrated endorectal--pelvic phased-array coils.

PURPOSE: To compare the performance of pelvic phased-array (PPA) coils and integrated endorectal PPA coils in evaluation of local extent of prostate cancer. MATERIALS AND METHODS: Seventy-one men underwent magnetic resonance (MR) imaging within 3 weeks of radical prostatectomy. MR findings of tumor, extracapsular extension, seminal vesicle invasion, nodal involvement, and stage were compared with step-sectioned (3-4-mm intervals) whole-mounted pathologic specimens. Prospective consensus versus single-reader interpretation (kappa statistics) and PPA versus integrated endorectal PPA coils (McNemar test) were compared, and a rating scale of 1-6 was developed for analysis of receiver operating characteristics. Statistical significance was calculated at delta = .05. RESULTS: Comparison between consensus and single-reader image interpretation showed positive but poor agreement (kappa = .38) and no statistical significance. Staging accuracy was better (difference approached significance) for integrated endorectal PPA coils (77%) than for PPA coils (68%). CONCLUSION: The integrated endorectal PPA coil is better for evaluation of local prostatic cancer than is the PPA coil.

Humans↗
PubMed1994

Endocrine interactions: adrenal steroids and precursors.

Adult male rats (n = 48) were castrated and treated daily for 4 wk with adrenal steroids in the presence or absence of adjuvant testosterone. Dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (2 mg/kg body wt) were administered as cyclodextrin complexes to mimic the pharmacodynamics of the endogenous products. Although they are the substrates for testosterone synthesis in target tissues, supplements of adrenal steroids alone were unable to maintain integrity of sociosexual responses and androgen target tissues after castration. More surprising, groups administered adrenal precursor plus testosterone showed substantial suppression of the typical restoration of reproductive systems in castrates receiving androgen therapy. The adrenal steroids, however, were not functionally identical. Each steroid interacted with testosterone to leave its own distinctive "footprint" on androgen-sensitive systems. The conclusion is that the endogenous adrenal products are not simply passive precursors of testosterone. Adrenal steroids may serve as endocrine regulators of androgen bioavailability and bioactivity.

Adrenal Glands↗
PubMed1994

Bacterial lipopolysaccharide primes human neutrophils for enhanced release of arachidonic acid and causes phosphorylation of an 85-kD cytosolic phospholipase A2.

Production of leukotriene B4 (LTB4) by human neutrophils (PMN) in response to different stimuli is increased after pretreatment with lipopolysaccharides (LPS). We have analyzed the steps in arachidonic acid (AA) metabolism affected by LPS by examining release of AA and its metabolites from [3H]AA prelabeled PMN. Pretreatment of PMN for 60 min with up to 1 microgram/ml of LPS alone had no effect, but release of [3H]AA was stimulated up to fivefold during subsequent stimulation with a second agent. In the absence of LPS-binding protein (LBP), priming was maximal after pretreatment of PMN with 10 ng of LPS/ml for 60 min; in the presence of LBP maximal priming occurred within 45 min at 0.1 ng of LPS/ml and within 15 min at 100 ng of LPS/ml. Treatment of PMN with 10 ng of LPS/ml also increased uptake of opsonized zymosan by up to 60%. Phospholipids are the source of released [3H]AA. No release was observed from [14C]oleic acid (OA)-labeled PMN suggesting that phospholipolysis may be specific for [3H]AA-labeled phospholipid pools. Cytosol from PMN primed with LPS contains two to three times the phospholipase A2 (PLA2) activity of control PMN, against 1-palmitoyl-[2-14C]arachidonoyl-phosphatidylcholine. This activity is Ca2+ dependent and dithiothreitol resistant. LPS priming is accompanied by reduced migration during SDS-PAGE of an 85-kD protein, identified as a cytosolic PLA2. The extent and kinetics of this effect of LPS on cPLA2 parallel the priming of [3H]AA release, both depending on LPS concentration either with or without LBP. These findings suggest that priming by LPS of AA metabolism by PMN includes phosphorylation of an AA-phospholipid-selective cytosolic PLA2 that is dissociated from activation until a second stimulus is applied.

Acute-Phase Proteins↗
PubMed1994

Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli.

Affinity purification of crude acid extracts of rabbit polymorphonuclear leukocytes using Escherichia coli (J5) as adsorbent yields the bactericidal/permeability-increasing protein (BPI), two 15-kD species (p15s), and the two most potent (cationic) defensin species (neutrophil peptides [NP] -1 and -2). Tested in buffered isotonic medium, the relative antibacterial potency of these proteins against E. coli J5 is BPI (IC50 0.2 nM) > p15A (10 nM) > NP -1 (400 nM). Sublethal doses of p15A or NP-1 can synergize with BPI to decrease the dose required to inhibit the growth of E. coli by up to 50-fold. BPI and p15A display similar features of antibacterial action distinct from defensin NP-1, but NP-1 acts synergistically only with BPI and not with p15A. All aspects of the combined action of BPI and NP-1 resemble those observed with higher concentrations of BPI alone, implying that NP-1 enhances BPI potency. Neither NP-1 nor p15A alter the amount of BPI binding to E. coli but BPI enhances binding of p15A to E. coli, raising the possibility that synergy between these two proteins may occur at least partially at the level of binding. The potent synergistic actions of these proteins can also be demonstrated against serum-resistant clinical isolates of encapsulated E. coli tested in whole blood and plasma ex vivo, suggesting that such combined action may contribute to host defense in vivo.

Animals↗
PubMed1994

Dynamic regulation of pituitary follistatin messenger ribonucleic acids during the rat estrous cycle.

FSH synthesis and secretion are regulated by a complex interplay of hypothalamic, gonadal, and pituitary factors. Recent evidence suggests that inhibin, activin, and follistatin, although originally identified as gonadal peptides, are also expressed in the pituitary, where they may be secreted and play an autocrine/paracrine role in the control of FSH beta gene expression. Attempts to study pituitary regulation of the genes encoding these proteins have been hampered by low levels of mRNA expression. Consequently, we developed quantitative reverse transcription-polymerase chain reaction assays for follistatin (FS) and the three subunits (alpha, beta A, and beta B) that comprise activin and inhibin. Expression of activin type II receptor (actRII) mRNA was also analyzed. Reasoning that mRNA levels of these FSH-regulating pituitary peptides might be modulated at times of increased FSH gene expression, two in vivo models were chosen for further investigation. 1) Two weeks after ovariectomy, rat pituitary FS mRNA levels increased substantially (4.09-fold vs. intact) with a modest increase in beta B-inhibin mRNA levels (1.88-fold vs. intact). No changes in alpha-inhibin, beta A-inhibin, or actRII mRNA levels were observed. 2) During the estrous cycle, pituitary FS gene expression varied strikingly, with a peak at 1800 h on proestrus (13.69-fold vs. 0900 h on proestrus), followed by a rapid decline at 2400 h on proestrus (2.10-fold vs. 0900 h on proestrus). A more detailed analysis of expression during proestrus revealed that peak FS mRNA levels preceded peak FSH beta gene expression by 6 h. Levels of the inhibin subunit and actRII transcripts varied minimally across the estrous cycle. We conclude that during the estrous cycle in rats, pituitary FS mRNA levels are regulated dynamically, whereas levels of inhibin/activin subunits and the activin receptor, actRII, very minimally. The observation that FS mRNA levels peak before maximal expression of FSH beta mRNA raises the possibility that FS facilitates, rather than inhibits, FSH biosynthesis in vivo.

Activin Receptors↗
PubMed1994

Sternal wound infection: our experience with 200 cases.

More than 200 patients with sternal wound infections have been treated in the Plastic Surgery Department of our Medical Center over the years 1984-1993. Most of these were referrals from other hospitals. In recent years, the cases have become more severe, partially due to the fact that cardiac surgeons tend to operate older and sicker patients more readily than they previously did. 80% of these were post coronary bypass surgery, and the others heart and heart-lung transplants, repair of congenital heart anomalies, valve replacements etc. Several of the cases were cardiac surgery re-do's. Risk factors for developing this complication, such as diabetes, obesity, technical errors of sternal incision, prolonged intubation, the use of aortic balloon, etc. will be discussed. Many of our earlier patients had chronic fistulae following conservative therapy with old treatment modalities. In recent years, patients are usually referred at the acute stage. Most patients undergo removal of sternum and ribs. Previously, reconstruction included mainly transfer of the rectus ahdominis muscle, whereas lately the pectoralis muscles is utilized. Omentum was used in only one case. The importance of pre-operative imaging procedures has been thoroughly studied in our series. Especially important is the definition of the extent of the infection, and localization of foreign bodies causing chronic infections, such as suture material, epicardial electrodes etc. A change in infectants has also been noticed. In the first half of the study period, Pseudomonas aeruginosa comprised at least 40%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Our experience with diagnosis, evaluation and treatment of poststernotomy sternal wound infections].

During 1984-1992 162 patients with post-sternotomy sternal wound infections were treated. Between 0.4-5% of these undergoing sternotomy suffer from this complication which carries a mortality of about 50% when treated by conventional, nonsurgical methods. 80% of our patients had undergone aortocoronary bypass surgery and 11% valve replacement. Major risk factors identified for postoperative infection were prolonged mechanical ventilation, prolonged extracorporeal bypass, smoking, diabetes, obesity and chronic lung disease. Of 152 patients who underwent surgery, 35 had recurrent infections, especially during the first years of the study. 10 were managed by conservative methods. Reconstruction of the chest wall was performed in 125, using pectoralis major flaps (74 cases), rectus abdominis muscle flaps (53), myocutaneous flaps (5) and omental flap (1). Our series demonstrates the importance of a comprehensive, multi-disciplinary approach in evaluating and stabilizing these often critically ill patients. Computed tomography together with sinography have proven to be of major importance in diagnosing the location and extent of sternal wound infections. Strict adherence to antibiotic protocols, radical debridement of infected bone and soft tissues and subsequent reconstruction with muscle flaps has enabled us to reduce recurrent infection and improve morbidity and mortality rates.

Anti-Bacterial Agents↗
PubMed1994

The bactericidal/permeability increasing protein of neutrophils is a potent antibacterial and anti-endotoxin agent in vitro and in vivo.

The Bactericidal/Permeability Increasing protein (BPI) is a major constituent of the azurophilic granules of human and rabbit polymorphonuclear leukocytes (PMN). The cDNA of the highly conserved protein has been isolated from man, rabbit and cow. The ca. 50 kDa BPI and a ca. 25 kDa bioactive N-terminal fragment are cytotoxic only for Gram-negative bacteria (GNB). This target-cell specificity reflects the strong attraction of the highly cationic protein for the negatively charged lipopolysaccharides (LPS) in the bacterial envelope. Native and recombinant (r) holo-BPI and the N-terminal fragment (rBPI-23) bind with high affinity (apparent Kd 1-10 nM) to all forms of isolated LPS so far examined, and inhibit the numerous biological effects of LPS in vitro (including in whole blood ex vivo) as well as in animals. Under the same conditions the antibacterial activities of holo-BPI and rBPI-23 against GNB with rough chemotype LPS are the same, but against serum-resistant and smooth chemotype GNB rBPI-23 is up to 30-fold more potent than holo-BPI. Holo-BPI and rBPI-23 protect mice, rats and rabbits against lethal cytotoxic effects of LPS and in some cases against lethal inoculations with live GNB.

Animals↗