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Biomedical subjects

P J Klein

Publications and source records attributed to P J Klein.

At least 19 recordsLinked to original sources
PubMed2003

Effects of dietary butylated hydroxytoluene on aflatoxin B1-relevant metabolic enzymes in turkeys.

We have shown previously that the extreme sensitivity of turkeys to aflatoxin B(1) (AFB(1)) is due to a combination of efficient AFB(1) activation by cytochrome P450s (CYPs) 1A and deficient detoxification by glutathione S-transferases (GSTs). Phenolic antioxidants such as butylated hydroxytoluene (BHT) have been shown to be chemoprotective in some animal models due, in part, to modulation of AFB(1)-relevant phase I and/or phase II activities, and we wished to determine whether BHT has a similar effect in turkeys. Ten-day-old male turkeys were maintained on diets amended with 1000 or 4000 ppm of BHT for 10 days, then sampled. Hepatic microsomal CYP 1A activity as well as conversion of AFB(1) to the putative toxic metabolite, the exo-AFB(1)-8,9-epoxide (AFBO), were significantly lower compared with control. Conversely, dietary BHT significantly increased activities of several isoforms of hepatic cytosolic GST, as well quinone oxidoreductase (QOR). Western immunoblotting confirmed that dietary BHT increased expression of homologues to rodent GST isoforms Yc1, Yc2 and Ya. There was, however, no observable BHT-related increase in GST-mediated specific conjugation with microsomally-generated AFBO. In total, our data indicates that dietary BHT modulates a variety of AFB(1)-relevant phase I and phase II enzymes, while having no measurable effect towards specific AFB(1) detoxification by GST.

Aflatoxin B1↗
PubMed2001

Metabolism of aflatoxin B1 by normal human bronchial epithelial cells.

Aflatoxin B, (AFB1) is a potent hepatocarcinogen in animal models and a suspected carcinogen in humans. High concentrations of AFB, have been found in respirable grain dusts, and may therefore be a risk factor for human lung cancer in certain occupations. To study the potential for AFB, activation in human lung, cytochrome P-450 (CYP)-mediated activation and glutathione S-transferase (GST)-mediated detoxification of AFB1 were examined in cultured normal human bronchial epithelial (NHBE) cells. Cells were exposed to 0. 15 microM or 1.5 microM AFB, for 48 h and media was collected for metabolite analysis by high-performance liquid chromatography (HPLC). At 0. 15 microM, AFB1 was metabolized only to the detoxified metabolite aflatoxin Q1 (AFQ1). At 1.5 microM AFB1, both aflatoxin M1 (AFM1), and AFQ1 were produced. Cells pretreated with 50 degrees M 3-methylcholanthrene (3MC), a CYP 1A inducer, for 72 h prior to 0.15 microM AFB1, produced the activated AFB1 8,9-epoxide (AFBO). Similarly, microsomes prepared from 3MC-pretreated cells formed AFBO, but microsomes from noninduced cells did not. While AFB1-DNA adducts were not detected at low AFB1 concentrations in untreated NHBE, 3MC induction caused the production of AFB1-DNA adducts at 0.015 and 0.15 microM AFB1. Western immunoblots showed that the primary CYP isoforms responsible for AFB1 activation in the liver, 1A and 3A4, to be constitutively expressed in NHBE cells. Expression of CYP 1A was significantly increased in 3MC-pretreated cells, while CYP 3A4 expression increased slightly, but not to the extent of the 1A isoforms. The principal AFBO detoxifying enzyme, glutathione S-transferase (GST), was constitutively expressed in NHBE cells, and was increased approximately twofold by 3MC pretreatment. Cytosolic fractions from neither control nor 3MC-induced NHBE had measurable AFBO conjugating activity, indicating that these cells may lack AFB1-relevant GST activity. From these data, it appears that NHBE cells activate AFB1 inefficiently, but possess CYPs reportedly responsible for metabolism of AFB1. These data support earlier findings showing modest CYP-mediated AFB1 activation in human airways, but indicate that exposure to polycyclic aromatic hydrocarbons (PAHs), such as 3MC, which induce CYP(s) that specifically activate AFB1 may increase the harmful effects of AFB1 exposures in human airways.

Aflatoxin B1↗
PubMed2001

Breast implants and cancer: causation, delayed detection, and survival.

Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a meta-analysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer. The meta-analysis results obtained by combining the epidemiology studies support the overall conclusion that breast implants do not pose any additional risk for breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This analysis suggests that breast implants may confer a protective effect against breast cancer. Women with implants should be reassured by the consistency of scientific studies which have uniformly determined that, compared with women without implants, they are not at increased risk for cancer, are not diagnosed with later-stage breast malignancies, are not at increased risk for breast cancer recurrence, and do not have a decreased length of survival.

Animals↗
PubMed2000

Biochemical basis for the extreme sensitivity of turkeys to aflatoxin B(1).

Poultry are the most susceptible food animal species to the toxic effects of the mycotoxin aflatoxin B(1) (AFB(1)). Feed contaminated with even small amounts of AFB(1) results in significant adverse health effects in poultry. The purpose of this study was to explain the biochemical mechanism(s) for this extreme sensitivity. We measured microsomal activation of AFB(1) to the AFB(1)-8,9-epoxide (AFBO), the putative toxic intermediate, as well as cytosolic glutathione S-transferase (GST)-mediated detoxification of AFBO, in addition to other hepatic phase I and phase II enzyme activities, in 3-week-old male Oorlop strain turkeys. Liver microsomes prepared from these turkeys activated AFB(1) in vitro with an apparent K(m) of 109 microM and a V(max) of 1.25 nmol/mg/min. Preliminary evidence for the involvement of cytochromes P450 (CYP) 1A2 and, to a lesser extent, 3A4 for AFB(1) activation was assessed by the use of specific mammalian CYP inhibitors. The possible presence of avian orthologues of these CYPs was supported by activity toward ethoxyresorufin and nifedipine, as well as by Western immunoblotting using antibodies to human CYPs. Cytosol prepared from turkey livers exhibited GST-mediated conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB), but at a much lower rate than that observed in other species. Western immunoblotting indicated the presence of alpha and sigma class GSTs and another AFB(1)-detoxifying enzyme, AFB(1)-aldehyde reductase (AFAR). Turkey liver cytosol also had quinone oxidoreductase (QOR) activity. Importantly, cytosol exhibited no measurable GST-mediated detoxification of microsomally activated AFB(1), indicating that turkeys are deficient in the most crucial AFB(1)-detoxification pathway. In total, our data indicate that the extreme sensitivity of turkeys to AFB(1) may be attributed to a combination of efficient AFB(1) activation and deficient detoxification by phase II enzymes, such as GSTs.

Aflatoxin B1↗
PubMed1998

Developmental changes in the specificity of memory over the first year of life.

In two experiments with 260 infants between 2 and 12 months of age, we examined how differences between the conditions of encoding and retrieval affect retention. Initially, 9- and 12-month-olds were tested with a different cue (Experiment 1) or in a different context (Experiment 2) after delays spanning their respective forgetting functions. These data were then combined with corresponding data previously collected from 2-to 6-month-olds trained and tested in an equivalent task. The resulting analyses revealed that the specificity constraints on memory retrieval become progressively looser at the extremes of the forgetting function with age. With increasing age, retention was less affected by cue changes after shorter absolute delays and, except at 6 months, by context changes after longer absolute delays. This pattern dovetails with evidence of decreasing specificity in the retrieval cues required for deferred imitation during infants' 2nd year and reveals that the memory abilities of older children evolve gradually from early in infancy.

Age Factors↗
PubMed1997

Risk factors for work-related violent victimization.

This case-control study used the National Crime Victimization Survey database (a national sample of housing addresses) to examine sociodemographic risk factors for becoming a victim of work-related robbery and assault. Cases (N = 267) reported having been violently victimized in the previous 6 months. Controls (N = 1,783) were chosen from all nonvictims of violent crime at the end of the 6-month period. Risk factors varied by type of victimization, and differences were evident between men and women. Men less than 45 years of age had an increased risk for assault [odds ratio (OR) = 2.0-2.7], compared with those 55 years of age and older; and those with a family income of less than $40,000 had an increased risk for assault (OR = 1.7-1.9), compared with those having a family income of $50,000 or more. We found a decreased risk for those with a high school education (OR = 0.6), compared with those with some college education. For women, an increased risk was seen for ages 16-18 years (OR = 3.3) and 25-34 years (OR = 2.3), compared with those 55 years of age or older. Women who were divorced or separated (OR = 4.4) and never-married (OR = 2.1) were at higher risk than women who were married. We found a decreased risk for nonwhites (OR = 0.5), compared with whites.

Adolescent↗
PubMed1996

Test development and validation of a back education posttest.

Assessment of physiotherapeutic treatment efficacy is dependent on valid outcome assessment. This study examined the validity of an existing back education knowledge posttest through a series of validation tests, generated a revised test. Methods included test-item analysis, content and construct validity, expert panel review, and a series of field trials. Purposive samples and subgroups, with varying levels of knowledge of back care concepts, participated in the study. Results of the study found the existing test possessed content validity. The final version of the alternate posttest was able to detect statistically significant differences among subgroups with varying knowledge levels by one-way analysis of variance (F = 116, p < .000). This research is an initial evaluation of a new instrument, and future research is required to fully validate this instrument.

Adolescent↗
PubMed1995

Accuracy of three-dimensional linear and angular estimates obtained with the Ariel Performance Analysis System.

Computer-assisted video motion analysis is a method of evaluating human kinematics that offers promise both for research and for clinical application. This study determined the upper limits of accuracy and consistency of linear and angular measures obtained using the Ariel Performance Analysis System. Reference standards included a meter stick and a universal 360 degrees goniometer. Average mean error observed for reconstruction of absolute point estimates was found to be less than 3.5 mm. Mean error estimate for three-dimensional (3D) reconstruction of a linear standard was found to be 1.4 mm (SD 0.30). Average mean angular error observed for 3D reconstruction of goniometer settings 10 degrees to 170 degrees was found to be 0.26 degrees (mean SD 0.21). System users are cautioned that some increased error associated with software derivation of joint angles exists as angles approach 180 degrees, use of wide-angle lens accessories introduces a systematic field-dependent bias; and planar rotation introduces some (< 2 degrees) random error.

Biomechanical Phenomena↗
PubMed1995

A meta-analysis of breast implants and connective tissue disease.

Case reports have raised questions about an increased risk of connective tissue diseases (CTDs) among women with breast implants. From the reviews of more than 2,600 manuscripts, abstracts, and dissertations, this meta-analysis included 13 epidemiology studies that provided a relative risk (RR) estimate for the possible association between breast implants and CTDs. The meta-analysis summary RR was 0.76 for CTD in general (95% confidence interval [CI]: 0.55, 1.04; homogeneity p-value = 0.073) and was 0.98 for scleroderma (95% CI: 0.57, 1.64; homogeneity p = 0.006). Irrespective of which studies were aggregated in this meta-analysis, there was no significant increased risk for scleroderma, rheumatoid arthritis, or CTD in general. Conclusions from this study are consistent with the most recent review by the British Medical Devices Agency that found no scientific evidence to date of an increased risk of CTD associated with silicone gel breast implants.

Arthritis, Rheumatoid↗
PubMed1988

Immunological reaction of guinea-pigs following intranasal Mycoplasma pneumoniae infection and immunization with the 168 kDa adherence protein.

Humoral responses to Mycoplasma pneumoniae proteins, especially the 168 kDa protein, were demonstrated by Western blotting in sera and bronchial washings of all groups of infected or immunized guinea-pigs. However, infection was not prevented by these local and systemic antibodies. Hilar lymphocytes of infected and immunized guinea-pigs were stimulated in vitro by sonicated M. pneumoniae antigen and by the 168 kDa protein. Stimulation was significantly lower in animals which had been infected twice or had been preimmunized and challenged by infection. Histologically the most severe lesions were seen in the twice-infected group followed by the preimmunized group which was subsequently infected.

Animals↗
PubMed1988

Exogenous enzymatic modulation of lectin binding sites in human tissue. Development of hemolysis in hemolytic-uremic syndrome (HUS) considering alteration of the glycocalyx in the erythrocyte membrane.

FITC-labelled lectins (DBA, PNA, RCAI, UEAI) with different carbohydrate specificity were used to look for possible alterations of the glycocalyx of erythrocyte membrane in patients with hemolytic uraemic syndrome (HUS; n = 34) in comparison with controls (n = 66). These investigations revealed that patients with the blood group A, B and O possess a significantly higher amount of sialic acid covered binding sites for PNA (p less than 0.05) on the membrane of red blood cells than controls, as measured by quantitative fluorescence microscopy. This significant difference was additionally found for sialic acid substituted RCAI binding sites on B erythrocytes (p less than 0.05). Without pretreatment of red blood cells with neuraminidase a significant difference between HUS patients and controls was observed for PNA on A, for RCAI on O and for UEAI on A erythrocytes. The measured values are influenced by contamination of red blood cells with serum glycoproteins as could be assessed by the lower values on washed erythrocytes. As a whole the results indicate that the composition of the glycocalyx in red blood cells of HUS patients seems to be altered and that the pathogenesis of this syndrome is additionally influenced by serum factors. With the exception of UEAI that possesses a significant higher amount of binding sites on washed erythrocytes of blood group O the other lectins used are not suitable for the demonstration of blood group specificity.

Blood Group Antigens↗
PubMed1988

Endogenous as well as exogenous hormonal modulation of lectin binding sites in normal and neoplastic tissue of rat mammary gland.

Free and sialic acid conjugated binding sites for the lectin from Arachis hypogaea (peanut agglutinin, PNA) have been histochemically demonstrated in normal rat mammary tissue and in N-nitrosomethylurea (NMU) induced mammary tumors of rats. The lectin binding sites were predominantly associated with secretory activities of the normal and neoplastic breast tissue (secretory PNA binding sites). In normal breast tissue and in NMU induced mammary tumors the expression of secretory PNA binding sites was reduced after ovariectomy and by the antiestrogen tamoxifen. Estrogen stimulated the formation of free and sialic acid conjugated PNA binding sites in the presence of prolactin. In rat mammary tumors the estrogen induced formation of PNA binding sites was accompanied by an increase of the progesterone receptor concentration in the tumors. Comparative lectinhistochemical, morphological, and biochemical studies on NMU induced rat mammary tumors revealed that the expression of secretory PNA binding sites was associated with a good histologic differentiation and the presence of steroidhormone receptors. Endocrine therapeutic studies showed that tumors responding to therapy possessed higher amounts of secretory PNA binding sites than unresponsive tumors. Therefore secretory PNA binding sites represent a useful histochemical marker for hormone dependence in NMU induced mammary tumors.

Animals↗
PubMed1988

Detection and characterization of glycoconjugates in normal and malignant tissues by lectins.

Labelled lectins were used for the histochemical distinction of glycolipids with various terminal hexoses in different storage diseases as well as for the demonstration of differences in the composition of cell surface and intercellular glycoproteins in tissues at various stages of differentiation, in malignancy and in functional subsets of cells. Thereby the detection of some glycoproteins (i.e. in primary sensory neurones, in parietal cells or in polymorphonuclear leukocytes), which were invisible by formerly used methods, was also possible. In malignant tissues lectin binding was either altered or the intracellular localization of the lectin binding sites was changed. These differences did not represent tumour specific markers, rather they were found to reflect glycoprotein structures characteristic for an activated functional state or for an earlier grade of differentiation. Some of such glycoproteins were isolated by lectin affinity chromatography and their structures were further analysed by means of biochemical methods. In malignancy a reduced molecular weight and changes in the monosaccharide composition of surface or intracellular glycoproteins were found to be the main differences. Antibodies produced against the lectin affinity isolated glycoproteins allowed the demonstration of structural relationship of glycoproteins with identical or diverse lectin binding pattern. They proved to be also useful for diagnostic purposes, especially for the differential diagnosis of anaplastic tumours.

Animals↗
PubMed1988

Light microscopic quantitative investigation on the effects of prostaglandin E2 (PGE2) on the lectin binding pattern in rat gastric mucosa injured by ethanol or sodium taurocholate.

We have used quantitative lectin histochemistry to study the cellular binding of peanut agglutinin (PNA) and soybean agglutinin (SBA) at the rat gastric corpus mucosa that has been injured experimentally by either ethanol or sodium-taurocholate and was protected by pretreatment of a cytoprotective dosage of the natural prostaglandin E2 (PGE2). The investigation was carried out in order to get access to possible differences in the amounts of intracellular secretory glycoproteins, associated with the prostaglandin-administration. The stomachs of rats injured by either ethanol or taurocholate revealed significantly reduced intramucosal amounts of glycoproteins with specific affinity for PNA and SBA, whereas in the stomachs of rats equally injured by the necrotizing agents, but pretreated by prostaglandin E2, the amounts of these glycoproteins remained close to the data observed in the control animals. These results give raise to two possible explanations: a) the decrease in the amounts of intramucosal glycoproteins might be due to a shedding of epithelial cells, the extent of which would then be less high in the prostaglandin treated stomachs. b) A second concept would imply influences on the glycoprotein metabolism, suggesting opposite traffics to be induced by the necrotizing agents than by the protective ones. Taken at their face value, our findings make it very likely that i) although prostaglandin-cytoprotectian did occur, this was not associated with a complete prevention from superficial cell loss at the rat gastric corpus mucosa and ii) the cytoprotective effect of prostaglandins might be mediated by influences on the intracellular glycoprotein metabolism, a process which could favour the defensive anti-ulcerogenic factors of the gastric mucosa.

Animals↗