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Biomedical subjects

J Kroll

Publications and source records attributed to J Kroll.

At least 19 recordsLinked to original sources

Model studies on reactions of plant phenols with whey proteins.

Whey proteins were modified by reaction with selected phenolic compounds (ferulic-, chlorogenic-, caffeic- and gallic acid) and related substances (quinic acid and p-quinone) as well as with extracts from coffee, tea, potato and pear at pH 9. The derivatives formed were characterized in terms of their physicochemical and digestion properties. The derivatization was accompanied by a reaction at the lysine and tryptophan side chains, whereby their content was decreased in comparison to that in the control whey proteins. Moreover, the solubility of the derivatives decreased over a broad pH range and the derivatization influenced the hydrophobe-hydrophile character of the whey proteins. The isoelectric points were shifted to lower pH values in the order of reactivity as follows: gallic acid > p-quinone > caffeic acid > chlorogenic acid. The other derivatives showed no or few changes compared to the control whey proteins. The formation of high molecular fractions was documented with SDS-PAGE. Especially the derivatives of chlorogenic-, caffeic-, gallic acid and p-quinone showed an increase in molecular weight of beta-lactoglobulin fraction from 18,300 to 20,000 Da. A dimer formation in molecular range 40,000 was also registered. MALDI-TOF-MS was applied to characterize the binding of the individual phenolic compounds or their oxidation products to the whey protein fractions, alpha-lactalbumin and beta-lactoglobulin. In vitro experiments showed that the digestion of the derivatized whey proteins with the enzymes of the gastrointestinal tract (trypsin, chymotrypsin, pepsin and pancreatin) was adversely effected. Similar results with regard to physicochemical characterization and digestion properties of the whey proteins treated with the applied extracts from plant beverages, fruit and vegetable were also documented. Coffee and tee were comparatively the most reactive extracts.

Electrophoresis, Polyacrylamide Gel↗

Interactions of glycinin with plant phenols--influence on chemical properties and proteolytic degradation of the proteins.

Soya glycinin was derivatized with different phenolic substances (caffeic-, chlorogenic-, gallic acid and quercetin). The protein derivatives formed have been characterized in terms of their properties where they showed changes in the content of free epsilon-amino groups, tryptophan and thiol groups. The derivatives have also been characterized in terms of their solubility at different pH-values to document the influence on the functional properties. Another objective of this paper was to demonstrate the influence on the digestibility of the proteins with one of the main enzymes of the gastro-intestinal tract (pancreatin) on the basis of in vitro experiments after derivatization with phenolic substances. The enzymatic digestion of the derivatized proteins was promoted.

Digestion↗

Cardiac rehabilitation for community-based patients with myocardial infarction: factors predicting discharge recommendation and participation.

Although there is substantial evidence that cardiac rehabilitation is beneficial for post myocardial infarction (MI) patients, such programs are currently under utilized. This study examined systematic criteria predicting physician referral to and patients' participation in cardiac rehabilitation programs. Patients discharged for MI were interviewed in-hospital and at 6-12 weeks post discharge to determine referral, participation, and completion. Stepwise logistic regression analyzed factors associated with rehabilitation. Factors associated with referral to rehab were catheterization (p < 0.001), bypass surgery (p < 0.01), cardiologist/cardiac surgeon appointment (p < 0.02), and age (p < 0.01). Participation was increased for those with bypass surgery (p < 0.001), and referral to cardiologist or cardiac surgeon (p < 0.001). Type of provider significantly influences referral to and participation in cardiac rehabilitation. This suggests that encouragement plays a strong role in attendance for rehabilitation. The same strong encouragement should be given to the broader range of MI patients who stand to benefit from cardiac rehabilitation.

Adult↗

Do race and gender influence the use of invasive procedures?

OBJECTIVE: To assess the influence of race and gender influence on the use of invasive procedures in patients with acute myocardial infarction (AMI) in community hospitals. DESIGN: Prospective, observational. SETTING: Five mid-Michigan community hospitals. PATIENTS: All patients (838) identified with AMI between January 1994 and April 1995 in 1 of these hospitals. MEASUREMENTS AND MAIN RESULTS: After adjusting for age, hospital of admission, insurance type, severity of AMI, and comorbidity, using white men as the reference group, the rate of being offered cardiac catheterization (CC) was 0.88 (95% confidence interval [95% CI], 0.60 to 1.29) for white women; 0.79 (95% CI, 0.41 to 1.50) for black men; and 1.14 (95% CI, 0.53 to 2.45)for black women. Among patients who underwent CC, after also adjusting for coronary artery anatomy, the rate of being offered angioplasty, using white men as the reference group, was 1.22 (95% CI, 0.75 to 1.98) for white women; 0.61 (5% CI, 0.29 to 1.28, P =.192) for black men; and 0.40 (95% CI, 0.14 to 1.13) for black women The adjusted rate of being offered bypass surgery was 0.47 (95% CI, 0.24 to 0.89) for white women; 0.36 (95% CI, 0.12 to 1.06) for black men; and 0.37 (95% CI, 0.11 to 1.28)for black women. CONCLUSIONS: Our study shows that white women are less likely than white men to be offered bypass surgery after AMI. Although black men and women with AMI are less likely than white men to be offered percutaneous transluminal coronary angioplasty or coronary artery bypass grafting in both unadjusted and adjusted analyses, these findings did not reach statistical significance. Our study is limited in power due to the small number of blacks in the sample.

Black or African American↗

Boundary violations: a culture-bound syndrome.

A backlash against the self-actualizing psychotherapy movements of the 1960s and 1970s in concert with recent concerns about professional sexual misconduct has led some forensic psychiatrists to redefine many routine components of therapy as boundary behaviors. This concern has been followed by the development of conservative guidelines for how therapists should conduct themselves at the newly-defined boundary crossings so as to avoid "violations." The slippery-slope argument that seemingly innocuous boundary crossings may lead inexorably to professional sexual misconduct has lent an urgency and legitimacy to the guideline enterprise, obscuring the perspective that the newly postulated boundaries do not represent the consensus of practitioners in the field. Otherwise highly controversial claims about what is ethical and proper behavior in psychotherapy gain a mantle of incontrovertibility when linked to predictions that ignoring published boundary guidelines will result in damage to patient and litigation against therapist. In this article, three widely advanced boundary guidelines are examined (therapist neutrality, therapist anonymity, and stable fee policy) for coherence and relevance to the richly diverse practice of psychotherapy.

Culture↗

The use of angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction in community hospitals. Michigan State University Inter-Institutional Collaborative Heart (MICH) Study Group.

BACKGROUND: Previous studies documenting underutilization of angiotensin-converting enzyme inhibitors (ACEIs) in acute myocardial infarction (AMI) have been limited to Medicare populations. HYPOTHESIS: This study examines ACEI prescription rates and predictors in a community sample of hospitalized patients with AMI. METHODS: The charts of 1163 community patients with AMI, prospectively identified at admission between January 1, 1994, and April 30, 1995, were reviewed. RESULTS: Only 64 of 158 (40%) patients considered ideal candidates for ACEI prescription were discharged with a prescription for an ACEI. In a multivariate logistic regression model, prior ACEI utilization [adjusted odds ration (OR) = 3.26; 95% confidence interval (CI) = 2.05-5.20], presence of congestive heart failure (OR = 2.33; CI = 1.50-3.61) and black race (OR = 2.20; CI = 1.34-3.64) were identified as positive predictors of ACEI prescription. Conversely, lack of left ventricular ejection fraction (LVEF) measurement (OR = 0.46; CI = 0.28-0.75), LVEF > 40 ( OR = 0.27; CI = 0.18-0.40), and acute renal failure (OR = 0.08; CI = 0.01-0.44) were negative predictors. Women were also less likely to be discharged with an ACEI prescription (OR = 0.71; CI = 0.48-1.05). Furthermore, women were significantly less likely to have LVEF measured prior to discharge than were males (77 vs. 85%, p = 0.001). CONCLUSION: This study underscores the need for improvement in the utilization of ACEI in eligible patients with AMI. It also identifies opportunities for improvement in prescription rates, especially in women.

Adult↗

[Regulation of the endothelial function and angiogenesis by vascular endothelial growth factor-A (VEGF-A].

VEGF-A (vascular endothelial growth factor-A) is an endothelial-specific growth factor that stimulates endothelial function and angiogenesis. VEGF-A plays an important role during development of the vascular system, wound healing, vascularization of tumors, and for angiogenesis in ischemic tissues including the heart. VEGF-A stimulates many actions of endothelial cells including proliferation, migration, and nitric oxide release via binding to and activation of the two primarily endothelial-specific receptor-tyrosine kinases KDR and Flt-1. KDR and Flt-1 stimulate multiple signal transduction pathways in endothelial cells. This review provides an overview of the role of VEGF-A in the regulation of endothelial function, angiogenesis, and arteriogenesis with regard to activation of signal transduction pathways and their functional consequences in the endothelium. Moreover, this article discusses recent developments exploring the therapeutic potential of VEGF-A for treatment of cardiovascular diseases.

Adult↗

The health and activities limitation index in patients with acute myocardial infarction.

Utility assessment is required to estimate quality-adjusted life years, but is often avoided due to the cumbersome nature of elicitation techniques. The Health Activities and Limitations Index (HALex) offers a method of utility assessment using existing values from the National Health Interview Survey (NHIS) and a utility algorithm to derive preferences. The authors assessed the construct validity of the HALex by comparing derived values with directly assessed HALex utilities in patients post acute myocardial infarction (AMI). OLS regression was used to model the relationship between utilities and patient demographics, comorbidities, and treatment. The mean and median utility for patients (n = 160) was.57 (SD = 22) and.55 respectively, and was not statistically different from the mean [.57 (SD =.30)] and median (.58) for similar NHIS respondents (n = 46). Patients with a comorbidity index of three or less had mean utilities.13 higher than the mean utility for patients with an index of four or more. No relationship was found between patients' age, race, and income and their utilities. The HALex scoring algorithm is a promising means to obtain utilities, and provides a methodology to easily estimate utilities for patients, but is not without limitations.

Activities of Daily Living↗

Physicochemical properties and susceptibility to proteolytic digestion of myoglobin-phenol derivatives.

This paper deals with the interactions of chlorogenic, caffeic, and quinic acids and p-quinone with myoglobin. The myoglobin derivatives formed have been characterized in terms of physicochemical properties and susceptibility to proteolysis. The results show that the free amino group and tryptophan contents of the myoglobin-phenol derivatives decrease with the increasing extent to which the protein becomes derivatized. Furthermore, the solubility of myoglobin-phenol derivatives decreases in the pH range 3.5-6.5 as compared to solubility of the native protein. The reaction also influences the hydrophilic-hydrophobic character of the protein. The isoelectric point of the derivatized myoglobin is shifted to a lower pH value, and formation of high molecular fractions is also documented. This paper also demonstrates the influence of the protein derivatization with plant phenols on susceptibility to digestion by trypsin, alpha-chymotrypsin, and pepsin, determined in vitro. The enzymatic digestion of the derivatized proteins is adversely affected.

Hydrolysis↗

Use of no-suicide contracts by psychiatrists in Minnesota.

OBJECTIVE: The no-suicide contract is widely recommended as an important intervention in the care of suicidal patients; however, there are no data demonstrating its effectiveness or its acceptance in the professional community. This study examines the use of no-suicide contracts by psychiatrists in Minnesota. METHOD: A postcard questionnaire was mailed to 514 psychiatrists in Minnesota inquiring about their practices and experiences with no-suicide contracts. RESULTS: There were 267 responses, yielding a response rate of 52%. No-suicide contracts were used by 152 (57%) of the respondents. Within this group, 62 (41%) of the psychiatrists had patients who committed suicide or made serious attempts after entering into a no-suicide contract. CONCLUSIONS: Among the respondents to the questionnaire, slightly more than half used no-suicide contracts, indicating that such contracts are not universally accepted as standard practice among these psychiatrists. More data are needed to determine the effectiveness of no-suicide contracts in preventing suicide.

Female↗

Predictors of participation in health care at menopause.

Patient participation in health care is widely advocated but little is known about the factors influencing patients' active participation. To learn whether attitudes and beliefs helped predict patient participation, 252 midlife women completed measures of self-efficacy, perceived barriers to participation, attitudes, subjective norms, and intentions following a decision to support intervention on menopause. Two months following the intervention, 63 women who had visited a health care provider returned questionnaires by mail regarding self-reported participation in the health care encounter and satisfaction with the decision about estrogen replacement therapy. The results were that self-efficacy (beta = .19; p < .05) significantly predicted intention to participate in the next health care encounter. Both patient intentions (beta = .40;p < .05) and perceived barriers (beta = -.27; p < .05) were significant predictors of self-reported participation. Active participation (beta = .42;p < .05) and attitude (beta =.25;p < .05) were associated with increased satisfaction with decision. Participation resulted in increased self-efficacy (beta = .30;p < .05). The conclusions were that midlife women who express more confidence in their ability to participate in their health care have greater intentions to participate. Women who experience fewer barriers to participation and have more intention to participate are more likely to report actively participating in a health care encounter, and self-reported participation and more positive attitudes toward participation are associated with greater satisfaction with decisions.

Adult↗

A novel function of VEGF receptor-2 (KDR): rapid release of nitric oxide in response to VEGF-A stimulation in endothelial cells.

VEGF-A induces angiogenesis and regulates endothelial function via production and release of nitric oxide (NO), which is produced by endothelial nitric oxide synthase (eNOS). While the upregulation of eNOS expression has been shown to be mediated via VEGF receptor KDR, there is controversy about which of the VEGF receptors triggers the release of nitric oxide in endothelial cells. In order to determine the levels of NO produced in response to VEGF-A stimulation in different endothelial cells, a reporter assay measuring the formation of cGMP as the direct product of NO-induced activation of guanylate cyclase was performed. Using two independent experimental strategies, we were able to prove that VEGF receptor KDR, but not VEGF receptor Flt-1, can induce NO release in endothelial cells. First, we made use of porcine aortic endothelial cells (PAE) expressing either KDR or Flt-1. While KDR-expressing PAE/KDR cells responded to VEGF-A stimulation with a significant elevation of intracellular cGMP already after 2 min, Flt-1-expressing PAE/Flt-1 cells did not show any signal in this RIA-based cGMP assay. In a second experimental strategy freshly isolated human umbilical vein endothelial cells (HUVEC) were stimulated either with the KDR-specific ligand VEGF-E or with the Flt-1-specific ligand PIGF-2. VEGF-E induces cGMP elevation in this setting, while PIGF-2 was unable to do so, clearly demonstrating that KDR is responsible for NO release in endothelial cells. In our assays cGMP formation is fully dependent on NO generation since the NOS inhibitor L-NAME can block this VEGF-A-induced action. These data show that the VEGF receptor KDR is responsible for NO release in endothelial cells, highlighting a new function of KDR and further supporting the importance of KDR in the regulation of the vasculature.

Animals↗

A dual inhibitor of platelet-derived growth factor beta-receptor and Src kinase activity potently interferes with motogenic and mitogenic responses to PDGF in vascular smooth muscle cells. A novel candidate for prevention of vascular remodeling.

PP1 has previously been described as an inhibitor of the Src-family kinases p56(Lck) and FynT. We have therefore decided to use PP1 to determine the functional role of Src in platelet-derived growth factor (PDGF)-induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs). A synthetic protocol for PP1/AGL1872 has been developed, and the inhibitory activity of PP1/AGL1872 against Src was examined. PP1/AGL1872 potently inhibited recombinant p60(c-src) in vitro and Src-dependent tyrosine phosphorylation in p60(c-srcF572)-transformed NIH3T3 cells. PP1/AGL1872 also potently inhibited PDGF-stimulated migration of HCASMCs, as determined in the modified Boyden chamber, as well as PDGF-stimulated proliferation of HCASMCs. Surprisingly, in addition to inhibition of Src kinase, PP1/AGL1872 was found to inhibit PDGF receptor kinase in cell-free assays and in various types of intact cells, including HCASMCs. PP1/AGL1872 did not inhibit phosphorylation of the vascular endothelial growth factor receptor KDR (VEGF receptor-2; kinase-insert domain containing receptor) in cell-free assays as well as in intact human coronary artery endothelial cells. In line with the insensitivity of KDR, PP1/AGL1872 had only a weak effect on vascular endothelial growth factor-stimulated migration of human coronary artery endothelial cells. On treatment of cells expressing different receptor tyrosine kinases, the activities of the epidermal growth factor receptor, fibroblast growth factor receptor-1, and insulin-like growth factor-1 receptor were resistant to PP1/AGL1872, whereas PDGF alpha-receptor was susceptible, albeit to a lesser extent than PDGF beta-receptor. These data suggest that the previously described tyrosine kinase inhibitor PP1/AGL1872 is not selective for the Src family of tyrosine kinases. It is also a potent inhibitor of the PDGF beta-receptor kinase but is not a ubiquitous tyrosine kinase inhibitor. PP1/AGL1872 inhibits migration and proliferation of HCASMCs probably by interference with 2 distinct tyrosine phosphorylation events, creating a novel and potent inhibitory principle with possible relevance for the treatment of pathological HCASMC activity, such as vascular remodeling and restenosis.

3T3 Cells↗

Patient decision support intervention: increased consistency with decision analytic models.

BACKGROUND: Patient Decision Support (PDS) tools assist patients in using medical evidence to make choices consistent that are with their values and in using evidence about consequences of medical alternatives. OBJECTIVE: To evaluate a PDS intervention for perimenopausal hormone replacement therapy. We assessed the impact of the PDS on (1) consistency between the decision to take estrogen replacement therapy (ERT) or progesterone/estrogen replacement therapy (PERT) and the expected utility of treatment and (2) likelihood to take ERT and PERT pre- and postintervention. DESIGN: Content of the PDS was standardized. Randomized trial of three intensities of intervention: (1) brochure; (2) lecture/discussion; and (3) active decision support. SUBJECTS: Participants were perimenopausal community volunteers between the ages of 40 and 65 (n = 248). MEASURES: (1) Consistent with values (correlation between expected utility (EU) and likelihood of taking hormones); and (2) Likelihood to take hormone replacement therapy. RESULTS: (1) The brochure group was less consistent with the decision analytic model than the lecture/discussion and active decision support groups. (2) Influence on decisions: PDS tools increased the number of women certain about whether or not to take hormones. There were no differences among experimental groups. Of 99 women uncertain about ERT pre-PDS, 65% changed. Twenty-one (32%) decided against ERT and 44 (68%) decided for ERT. (3) More intensive interventions produced modest gains in a normative direction. CONCLUSIONS: PDSs using any of 3 formats reduce uncertainty and assist women to make informed decisions. Increased consistency with decision analytic models appears to be driven by better estimates of likelihood of outcomes.

Adult↗

VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR).

Vascular Endothelial Growth Factor-A (VEGF-A) is an endothelial-specific growth factor that induces angiogenesis, i.e., sprouting of capillaries from preexisting vessels in vivo. Endothelial nitric oxide synthase (eNOS) is an essential molecule in mediating VEGF-A-induced angiogenesis and endothelial function via production of nitric oxide (NO). Moreover, the protein level of eNOS is upregulated in response to VEGF-A. While VEGF-A-induced NO release in human trophoblast cells appears to be initiated via VEGF receptor-1, it is not clear which of the VEGF-receptors is mediating the signal for induction of eNOS protein expression. In addition, it is unclear whether other NOS isoforms are upregulated in response to VEGF-A stimulation. To address these questions, we stimulated human umbilical vein endothelial cells (HUVEC) with VEGF-A for 24 hours and evaluated expression of eNOS and iNOS protein. VEGF-A induces expression of both members of the NOS family. Using porcine aortic endothelial cells overexpressing either VEGF receptor-2 (PAE/KDR cells) or VEGF receptor-1 (PAE/Flt-1 cells), we have studied the regulation of iNOS and eNOS expression in response to VEGF-A stimulation. The activation of VEGF receptor-2 leads to an upregulation of both eNOS and iNOS protein, while stimulation of VEGF receptor-1 did not generate such a signal. Therefore, only VEGF receptor-2 mediates stimulation of eNOS and iNOS expression. We conclude that the two VEGF receptors have different and distinct functions regarding NO formation and NO release during VEGF-A-induced angiogenesis.

Animals↗

[Heart transplantation in infancy: experiences at the Giessen Pediatric Heart Center].

From June 1988 to December 1996 heart transplantations were performed in 36 newborns and infants below one year of age. Diagnosis were hypoplastic left heart syndrome (n = 26), endocardial fibroelastosis (n = 4), cardiomyopathy (n = 3), and other complex congenital heart defects (n = 3). Mean waiting time for transplantation was 52 days, the mean donor-recipient bodyweight ratio was 1.8. Seven patients (19%) died after transplantation mainly within the first month after transplantation. The cumulative probability of survival is 79% in all patients. The influence of increasing experience is indicated when patients transplanted from 1988-1993 (n = 15) are compared with transplants from 1994-1996 (n = 21). The overall survival in the first group was 50%, whereas patients transplanted from 1994 showed a probability of survival of 92%. The 1-year survival rate in the later group was 100%. In 20 patients a total of 31 rejection episodes were observed. 2 infants died due to rejection. 71% of all rejections occurred during the first month after transplantation. Renal function was slightly impaired one year after transplantation in all patients without tendency for deterioration in the sequel. The somatic development is normal in nearly all infants and the quality of life is excellent. All infants live at home without any restrictions. Two patients, however, suffer from a neurologic deficit. Until now there is no evidence of coronary vascular disease or malignancy. Heart transplantation is in our opinion a reconsiderable alternative in the treatment of complex cardiac disease and cardiomyopathy in infants.

Cause of Death↗

Reactions of a glucosinolate breakdown product (benzyl isothiocyanate) with myoglobin.

The interaction of various amounts of benzyl isothiocyanate (benzyl-ITC) with myoglobin is known to lead to the formation of derivatives. These have been characterised by the determination of solubility, free amino group, tryptophan content and chromatographic as well as electrophoretic behaviour. In the range between 2.5 and 125 mg benzyl-ITC/g protein, all properties of the reaction products correlate with the concentration of benzyl-ITC. However, at 250 mg benzyl-ITC/g myoglobin, a rather unexpected low degree of derivatization, as well as atypical chromatographic and electrophoretic behaviour, is observed. The proposed explanation was that conformational changes in the presence of a high concentration of hydrophobic benzyl-ITC made fewer amino groups accessible to the reagent. To test this hypothesis we have run the reaction under denaturing conditions. The results showed that the reaction of myoglobin with high concentrations of benzyl-ITC in the presence of 8 M urea led to a higher degree of derivatization than in the presence of water only. In addition, the Mr distribution of the reaction products was determined by MALDI-TOF-mass spectrometry and the overall degree of derivatization calculated from the spectra.

Hydrogen-Ion Concentration↗