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D Jacobs

Publications and source records attributed to D Jacobs.

At least 19 recordsLinked to original sources
PubMed2001

Docking sites on substrate proteins direct extracellular signal-regulated kinase to phosphorylate specific residues.

Mitogen-activated protein (MAP) kinases such as extracellular signal-regulated kinase (ERK) are important signaling proteins that phosphorylate (S/T)P sites in many different protein substrates. ERK binding to substrate proteins is mediated by docking sites including the FXFP motif and the D-domain. We characterized the sequence of amino acids that can constitute the FXFP motif using peptide and protein substrates. Substitutions of the phenylalanines at positions 1 and 3 had significant effects, indicating that these phenylalanines provide substantial binding affinity, whereas substitutions of the residues at positions 2 and 4 had less effect. The FXFP and D-domain docking sites were analyzed in a variety of positions and arrangements in the proteins ELK-1 and KSR-1. Our results indicate that the FXFP and D-domain docking sites form a flexible, modular system that has two functions. First, the affinity of a substrate for ERK can be regulated by the number, type, position, and arrangement of docking sites. Second, in substrates with multiple potential phosphorylation sites, docking sites can direct phosphorylation of specific (S/T)P residues. In particular, the FQFP motif of ELK-1 is necessary and sufficient to direct phosphorylation of serine 383, whereas the D-domain directs phosphorylation of other (S/T)P sites in ELK-1.

Amino Acid Sequence↗
PubMed2001

Maternal waist-to-hip ratio does not predict child gender.

It has been suggested that a high pre-conceptual waist-to-hip ratio (WHR) is a good predictor of male offspring and, thus, in cultures that value male children, an androgenous body shape may be judged as most attractive. The predictive value of WHRs is based on studies measuring women who already have children and correlating their WHRs with the proportion of existing male offspring. However, carrying a male child may alter WHRs in a different way to carrying a female child, and a high WHR may be an effect rather than a cause of male offspring. In order to test the predictive power of a pre-conceptual WHR and offspring gender, we took WHR measures from 458 women who intended to become pregnant and then correlated this with the genders of their subsequent children. We found no significant correlation. It is therefore not clear why a high WHR is preferred in some cultures. We suggest that differences in attractiveness preferences between different ethic groups are actually based on weight scaled for height (the body mass index or BMI) rather than the WHR since although there will be a preferred optimal BMI for each ethnic group, which will balance environmental and health factors, this optimal BMI may differ between groups and environments.

Body Constitution↗
PubMed2001

An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.

BACKGROUND: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. OBJECTIVE: To evaluate the clinical correlates of LBs in patients with AD. DESIGN AND METHODS: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. Logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. RESULTS: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. CONCLUSIONS: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients.

Aged↗
PubMed2001

Evaluation of the HUD lead hazard control grant program: early overall findings.

This study evaluates the effectiveness of lead hazard control methods used in the Lead Hazard Control (LHC) grant program of U.S. Department of Housing and Urban Development. The LHC Program awards funds to local jurisdictions to address lead hazards in privately owned, low-income dwellings. Grantees in 14 cities, states, or counties collected environmental data in over 2600-treated dwellings making this the largest study of residential lead hazard control ever undertaken. Grantees employed a range of treatments, the most common being replacement of windows and repair of deteriorated lead-based paint. In this paper, dust lead loading levels and blood lead levels of children (6 months-6 years, if present) were observed at four periods of time (preintervention, immediate, and 6- and 12-months postintervention) in 1212 dwellings. Dust lead loading levels were also observed in a subset of these dwellings at 24- and 36-months postintervention. The geometric mean floor and window dust lead loadings declined at least 50 and 88% (P<0.0001), respectively, immediately postintervention. Three years later, floor dust lead loadings remained at or below the immediate postintervention levels. Window dust lead loadings had moderate increases, but remained substantially reduced from preintervention levels and below clearance standards. At 1 year after intervention, geometric mean age-adjusted blood lead levels had declined from 11.0 to 8.2 microg/dL, a 26% decline (P<0.0001). The LHC Program interventions produced blood lead declines similar to or greater than the percentage changes reported in earlier 1-year lead intervention studies.

Child↗
PubMed2001

A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery.

PURPOSE: Individual and institutional practices remain an independent predictor factor for allogeneic blood transfusion. Application of a standardized multidisciplinary transfusion strategy should reduce the use of allogeneic blood transfusion in major surgical patients. METHODS: This prospective non randomized observational study evaluated the effects of a standardized multidisciplinary transfusion strategy on allogeneic blood products exposure in patients undergoing non-emergent cardiac surgery. The developed strategy involved a standardized blood conservation program and a multidisciplinary allogeneic blood transfusion policy based mainly on clinical judgement, not only on a specific hemoglobin concentration. Data obtained in a first group including patients operated from September 1997 to August 1998 (Group pre: n=321), when the transfusion strategy was progressively developed, were compared to those obtained in a second group, including patients operated from September 1998 to August 1999 (Group post: n=315) when the transfusion strategy was applied uniformly. RESULTS: Patient populations and surgical procedures were similar. Patients in Group post underwent acute normovolemic hemodilution more frequently, had a higher core temperature at arrival in the intensive care unit and presented lower postoperative blood losses at day one. Three hundred forty units of packed red blood cells were transfused in 33% of the patients in Group pre whereas 161 units were transfused in 18% of the patients in Group post (P <0.001). Pre- and postoperative hemoglobin concentrations, mortality and morbidity were not different among groups. CONCLUSION: Development of a standardized multidisciplinary transfusion strategy markedly reduced the exposure of cardiac surgery patients to allogeneic blood.

Aged↗
PubMed2001

The role of whole grains in disease prevention.

Despite universal acceptance of the importance of whole grains in the diet, consumer knowledge of the benefits of whole grains and intake of these foods are low. This review summarizes the research supporting whole-grain consumption and gives practical suggestions about how to increase whole-grain intake. Whole-grain foods are valuable sources of nutrients that are lacking in the American diet, including dietary fiber, B vitamins, vitamin E, selenium, zinc, copper, and magnesium. Whole-grain foods also contain phytochemicals, such as phenolic compounds, that together with vitamins and minerals play important roles in disease prevention. The exact mechanisms linking whole grains to disease prevention are not known but may include gastrointestinal effects, antioxidant; protection, and intake of phytoestrogens. Dietary intake studies indicate that consumption of whole grains is far less than the recommended intake of 3 servings a day, with an average daily intake of 1 or fewer servings a day. A new whole-grains health claim, allowed in July 1999 by the Food and Drug Administration, and inclusion of a whole-grain recommendation in the 2000 revision of the US Dietary Guidelines for Americans, should help increase whole-grain consumption.

Blood Glucose↗
PubMed2001

The versatility of the nasolabial flap enhanced by the delay procedure.

BACKGROUND: The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall following Mohs surgery. However, both extirpation of a tumor in the region of the base of the flap or previous use of the flap often destroy the proximal axial blood supply to the flap, excluding its immediate utilization. We describe a different use of the nasolabial flap and a technique for preserving its capacity in the case of reutilization OBJECTIVE: To describe the versatility of the nasolabial flap and a delay procedure that enables its exploitation despite prior disruption of the proximal blood supply. METHODS: Three different uses of the same nasolabial flap are demonstrated in one patient. The surgical techniques are discussed in detail. RESULTS: The reconstructive results were excellent. There were no postoperative complications. CONCLUSION: The nasolabial flap is a versatile and effective option for the closure of nasal defects of the cheek and nasal sidewall. When the nasolabial flap has been used before, or its blood supply compromised, the delay procedure can reestablish its applicability.

Basal Cell Carcinoma↗
PubMed2001

Chemolysis of struvite stones by acidification of artificial urine--an in vitro study.

OBJECTIVE: The aim of the study was to look for strategies that improve the clinical outcome of struvite stones. An in vitro experimental set up with artificial stones made of struvite (BON(N)-STONES) was chosen to perform standardized and reproducible analyses on various artificial urines with pH-values that may be reached by acidification with oral methionine treatment. MATERIALS AND METHODS: Artificial ball-shaped stones made of struvite (BON(N)-STONES) with a diameter of 0.8 cm were used. The investigations on chemolysis were performed using a dissolution device which simulates the physiological conditions in the upper urinary tract with computer-assisted on line measurement of data. For chemolysis of struvite BON(N)-STONES artificial urines according to Griffith at four different pH-values (pH 5.75, pH 6.0, pH 6.25, pH 6.5) were used. Furthermore natural and struvite BON(N)-STONES were treated with Suby G-solution (pH = 4.0). RESULTS: Comparing natural and artificial struvite stones after treatment with Suby G there was no significant difference regarding their dissolution rate. The dissolution rate of struvite stones in artificial urine rose with a decreasing pH-value. The diminution of the pH-value from 6.5 to 5.75 lead to an increase of the dissolution rate of more than 35%. This increase in the dissolution rate decreased with falling pH-value. CONCLUSIONS: The acidification of urine accelerated the dissolution rate of struvite stones in vitro. Considering in vivo conditions the intake of 1,500-3,000 mg L-methionine may lead to a sufficient acidification for a good dissolution of struvite stones.

Humans↗
PubMed2001

Grain processing and nutrition.

Whole grains provide a wide range of nutrients and phytochemicals that optimize health. Epidemiologic studies support the protectiveness of whole grain consumption for cardiovascular disease and cancer. Dietary guidance endorses increased whole grains in our diet. A crucial question remaining is the effect of processing of whole grains on their content of nutrients and phytochemicals. Although processing is often considered to be a negative attribute in nutrition, and some forms of processing reduce nutritional value, many factors support the importance of processing of grains to enhance grain consumption. First, whole grains as harvested are generally not consumed directly by humans but require some processing prior to consumption. While refining, that is, removal of the bran and the germ, reduces the nutrient content of grain, milling of grains otherwise concentrates desirable grain components and removes poorly digested compounds and contaminants. Cooking of grains generally increases digestibility of nutrients and phytochemicals. Studies in both animal models and humans support the notion that processed grains are often nutritionally superior to unprocessed grains, probably because of enhanced nutrient bioavailability in processed grains. Processing of grains also provides shelf-stable products that are convenient and good tasting for consumers.

Animals↗
PubMed2001

Induction of hepatitis C virus E1 envelope protein-specific immune response can be enhanced by mutation of N-glycosylation sites.

Deglycosylation of viral glycoproteins has been shown to influence the number of available epitopes and to modulate immune recognition of antigens. We investigated the role played by N-glycans in the immunogenicity of hepatitis C virus (HCV) E1 envelope glycoprotein, a naturally poor immunogen. Eight plasmids were engineered, encoding E1 protein mutants in which the four N-linked glycosylation sites of the protein were mutated separately or in combination. In vitro expression studies showed an influence of N-linked glycosylation on expression efficiency, instability, and/or secretion of the mutated proteins. Immunogenicity of the E1 mutants was studied in BALB/c mice following intramuscular and intraepidermal injection of the plasmids. Whereas some mutations had no or only minor effects on the antibody titers induced, mutation of the fourth glycosylation site (N4) significantly enhanced the anti-E1 humoral response in terms of both seroconversion rates and antibody titers. Moreover, antibody induced by the N4 mutant was able to recognize HCV-like particles with higher titers than those induced by the wild-type construct. Epitope mapping indicated that the E1 mutant antigens induced antibody directed at two major domains: one, located at amino acids (aa) 313 to 332, which is known to be reactive with sera from HCV patients, and a second one, located in the N-terminal domain of E1 (aa 192 to 226). Analysis of the induced immune cellular response confirmed the induction of gamma interferon-producing cells by all mutants, albeit to different levels. These results show that N-linked glycosylation can limit the antibody response to the HCV E1 protein and reveal a potential vaccine candidate with enhanced immunogenicity.

Amino Acid Sequence↗
PubMed2001

Narcissism, eroticism, and envy in the supervisory relationship.

Supervision takes place in a framework of time, place, and duration agreed upon by teacher and student. But beyond the formal arrangements of supervision lie a host of behaviors that express conscious and unconscious fears and wishes that are aroused in student and teacher by their meetings. This paper focuses on supervisors' motivations for teaching, and the ways in which their narcissistic vulnerabilities and their feelings for their students may influence the frame of supervision and its outcome.

Aggression↗
PubMed2000

Relationship between persistence of abdominal symptoms and successful outcome after cholecystectomy.

BACKGROUND: Patients frequently have persistent abdominal symptoms after undergoing cholecystectomy. The relationship between abdominal symptoms and biliary dysfunction is often unclear. OBJECTIVES: To describe the persistence rate of abdominal symptoms in a large cohort of patients after elective cholecystectomy, to identify predictors of symptom persistence and operative success, to understand which symptoms improve after cholecystectomy, and to describe the important determinants of an unsuccessful operation. METHODS: Secondary analysis of a prospective, multisite cohort study of 2481 patients undergoing elective cholecystectomy. RESULTS: The mean +/- SD number of abdominal symptoms per patient decreased from 3.1 +/- 2.0 to 1.1 +/- 1.3; 27% of patients who identified a symptom as most bothersome before surgery still had the symptom 6 months after surgery. Symptom persistence rates ranged from 5.6% (vomiting) to 40.2% (gas/flatulence). A balance score that quantified the abdominal symptom mix between dyspeptic and biliary symptoms shifted after surgery to the dyspeptic category. Predictors of persistence of a most bothersome symptom were dyspeptic symptom category, worse operative risk and self-rated health status, symptom duration longer than 6 months, and no previous episodes of acute cholecystitis. The major correlate of not achieving a very successful outcome (15.2% of patients) was the presence of postoperative abdominal pain. Other predictors included worse self-rated health status and physical functioning, symptom duration longer than 6 months before surgery, and no previous episodes of acute cholecystitis. CONCLUSIONS: Symptoms categorized as dyspeptic were more likely to persist than were biliary symptoms, although all symptoms showed a decrease in prevalence after cholecystectomy. More attention to the rationale for gallbladder removal and clarification of patient expectations for symptom relief might be necessary to improve outcomes after elective cholecystectomy.

Adolescent↗
PubMed2000

Improving cystine stone therapy: an in vitro study of dissolution.

OBJECTIVES: To perform an in vitro study analyzing the possibilities in therapeutic strategies for an effective treatment of cystine stones. METHODS: Artificial stones made of cystine [Bon(n)-Stones] with a ball-shaped size of 0.9 cm in diameter were used. Chemolysis of artificial cystine stones with different solvents (artificial urine, physiologic sodium chloride solution, acetylcysteine, tris-(hydroxymethylene)-aminomethane [THAM], and combinations of these) was investigated. An experimental arrangement with computer-assisted online measurement of data simulating the physiologic conditions in the upper urinary tract at varying pH values was used. RESULTS: All solutions showed a statistical improvement in the solubility of cystine stones compared with artificial urine and physiologic sodium chloride solution. The combination of THAM (pH 10) and 2% acetylcysteine was most effective (1 3.91 +/- 1.73 mg/hr) and demonstrated a 41 -fold higher ability to dissolve cystine calculi compared with artificial urine. CONCLUSIONS: Our data indicate that local chemolysis with special solutions is an effective treatment modality in cystine stone therapy.

Acetylcysteine↗
PubMed2000

Partner violence, social support, and distress among inner-city African American women.

This study examined the role of social support in the partner violence-psychological distress relation in a sample of African American women seeking medical care at a large, urban hospital (n = 138). Results from bivariate correlational analyses revealed that partner violence was related to lower perceived social support and greater psychological distress, and lower social support was related to more distress. Furthermore, findings based on path analysis indicated that low levels of social support helped account for battered women's increased distress. Findings point to the need for service providers to screen for partner violence in nontraditional sites, such as hospital emergency rooms, and to address the role of social support resources in preventive interventions with African American battered women.

Adult↗
PubMed2000

Grain processing and nutrition.

Whole grains provide a wide range of nutrients and phytochemicals that optimize health. Epidemiologic studies support the protectiveness of whole grain consumption for cardiovascular disease and cancer. Dietary guidance endorses increased whole grains in our diet. A crucial question remaining is the effect of processing of whole grains on their content of nutrients and phytochemicals. Although processing is often considered to be a negative attribute in nutrition, and some forms of processing reduce nutritional value, many factors support the importance of processing of grains to enhance grain consumption. First, whole grains as harvested are generally not consumed directly by humans but require some processing prior to consumption. While refining, that is, removal of the bran and the germ, reduces the nutrient content of grain, milling of grains otherwise concentrates desirable grain components and removes poorly digested compounds and contaminants. Cooking of grains generally increases digestibility of nutrients and phytochemicals. Studies in both animal models and humans support the notion that processed grains are often nutritionally superior to unprocessed grains, probably because of enhanced nutrient bioavailability in processed grains. Processing of grains also provides shelf-stable products that are convenient and good tasting for consumers.

Animals↗
PubMed2000

Chemolysis of artificial cystine stones (BON(N)-STONES) in vitro using a new dissolution device: first results.

BACKGROUND AND PURPOSE: The treatment of cystine stones is a clinical problem. This in vitro study was performed to establish an experimental system that enables standardized and reproducible investigations on chemolysis of cystine stones to look for an improvement of dissolution strategies. MATERIALS AND METHODS: Artificial spherical stones made of cystine (BON(N)-STONES) with a diameter of 0.9 cm were used. A new dissolution device was developed simulating the physiological conditions in the upper urinary tract with computer-assisted online measurement of data. For chemolysis of artificial cystine stones, different solvents (artificial urine, physiologic sodium chloride solution, 2 % acetylcysteine, 8.4 % sodium bicarbonate solution, THAM, and combinations) were used. RESULTS: Chemolysis is an effective tool in the management of cystine stone disease. Statistical analysis showed significant differences (p < or = 0.05) for all solutions compared with artificial urine alone. A combination of THAM at pH 10 with acetylcysteine (2%) showed a 48-fold stronger ability to dissolve cystine calculi than did artificial urine. CONCLUSION: By performing standardized in vitro investigations, new basics to improve the dissolution of cystine stones have been developed. It is recommended to use artificial stones made of cystine and a dissolution device simulating physiological conditions for investigations on chemolysis in the future.

Acetylcysteine↗
PubMed2000

A new type of artificial urinary calculi: in vitro study by spiral CT.

RATIONALE AND OBJECTIVES: Artificial urinary calculi similar to natural stones have long been sought in urologic research. In an experimental study, the authors assessed the CT characteristics of a new type of artificially produced urinary calculus [BON(N)-STONE]. METHODS: Six different types of urinary calculi (uric acid, struvite, cystine, calcium oxalate, brushite, and apatite) were produced by a coating technique in which several layers of a suspension of pure substance were applied around a core and dried. A total of 60 stones (10 per group) were studied by spiral CT at two energy levels (100 and 120 kV, 250 mA) with 1-mm slice thickness. RESULTS: All calculi showed a small hyperdense core surrounded by a homogeneous matrix and a slightly hyperdense outer rim. From the least to the most dense, the stone types were uric acid, struvite, cystine, calcium oxalate, brushite, and apatite. Absolute CT values at 100 and 120 kV could differentiate between all groups of stones at a significance level of P < 0.001 or better. Attenuation values were in a comparable range to reported values for natural stones, with the exception of uric acid and struvite, which were notably lower. CONCLUSION: These artificially produced urinary calculi showed properties similar to those of natural stones. Thus, this seems to be a promising stone model for further investigations.

Humans↗
PubMed2000

DNA vaccination with genes encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2 induces partially protective immunity against lethal challenge in mice.

C57BL/6, C3H, and BALB/c mice were vaccinated with plasmids encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2, previously described as strong inducers of immunity. Seroconversion for the relevant antigen was obtained in the majority of the animals. T. gondii lysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-gamma) in spleen cell cultures from vaccinated BALB/c and C3H mice but not in those from control mice. Although not proliferating, stimulated splenocytes from DNA-vaccinated C57BL/6 mice also produced IFN-gamma. No interleukin-4 was detected in the supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio of specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-vaccinated C3H mice, suggesting that a Th1-type response had been induced. For BALB/c mice, the isotype ratio of the antibody response to DNA vaccination was less polarized. The protective potential of DNA vaccination was demonstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cysts of two different T. gondii strains: survival rates increased from 10% in controls to at least 70% after vaccination in one case and from 50% to at least 90% in the other. In vaccinated C3H mice challenged with a nonlethal T. gondii dose, the number of brain cysts was significantly lower than in controls. DNA vaccination did not protect BALB/c or C57BL/6 mice. Our results demonstrate for the first time in an animal model a partially protective effect of DNA vaccination against T. gondii.

Animals↗