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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 37 records · Page 2Linked to original sources
PubMed2001

In vitro test for the effectiveness of antioxidants as inhibitors of thiyl radical-induced reactions with unsaturated fatty acids.

Attacks of thiyl radicals on the double bonds of unsaturated fatty acids lead to stereomutation (cis-, trans-isomerization without double-bond migration) and addition reactions (thioether formation). On the basis of these findings, an in vitro test system has been developed which allows the study of the effectiveness of specific antioxidants in preventing thiyl radical-induced attacks on unsaturated fatty acids. The test involves thermal treatment of a mixture of oleic (cis-9-octadecenoic) acid and 1-tetradecanethiol with the antioxidant, followed by measurement of the extent of formation of the products of stereomutation and addition (i.e., elaidic (trans-9-octadecenoic) acid and isomeric 9(10)-S-tetradecylstearic acids, respectively) by gas chromatography of their methyl esters as a function of antioxidant concentration. Antioxidants such as octyl gallate, ascorbic acid 6-O-palmitate, ubiquinone 50 (coenzyme Q(10)), rac-alpha-tocopherol, and 2,6-di-tert-butyl-4-methylphenol (BHT) were tested for their ability to protect the >C=C< double bond of oleic acid against attacks of thiyl radicals generated from 1-tetradecanethiol by heating. The results show that octyl gallate, ascorbic acid 6-O-palmitate and, to some extent, ubiquinone 50 (coenzyme Q(10)) were highly effective in preventing reactions of free thiyl radicals with oleic acid, whereas rac-alpha-tocopherol and BHT were moderately effective.

Antioxidants↗
PubMed2001

High-yield preparation of wax esters via lipase-catalyzed esterification using fatty acids and alcohols from crambe and camelina oils.

Fatty acids obtained from seed oils of crambe (Crambe abyssinica) and camelina (Camelina sativa) via alkaline saponification or steam splitting were esterified using lipases as biocatalysts with oleyl alcohol and the alcohols derived from crambe and camelina oils via hydrogenolysis of their methyl esters. Long-chain wax esters were thus obtained in high yields when Novozym 435 (immobilized lipase B from Candida antarctica) and papaya (Carica papaya) latex lipase were used as biocatalysts and vacuum was applied to remove the water formed. The highest conversions to wax esters were obtained with Novozym 435 (> or =95%) after 4-6 h of reaction, whereas with papaya latex lipase such a high degree of conversion was attained after 24 h. Products obtained from stoichiometric amounts of substrates were almost exclusively (>95%) composed of wax esters having compositions approaching that of jojoba (Simmondsia chinensis) oil, especially when crambe fatty acids in combination with camelina alcohols or camelina fatty acids in combination with crambe alcohols were used as substrates.

Brassicaceae↗
PubMed2001

Evaluation of putative molecular biomarkers in abdominal and retroperitoneal leiomyosarcomas.

AIMS: Leiomyosarcomas (LMS) are diverse tumours with different biological behaviour. To evaluate the biological nature of intraabdominal and retroperitoneal leiomyosarcomas we retrospectively examined the immunoreactivity of p53, bcl-2 and proliferative activity expressed as Ki-67-labelling index in 43 tumours. METHODS: Immunohistochemical staining was performed using a peroxidase-streptavidin method on paraffin-embedded sections using specific anti- p53, anti- bcl-2 and anti Ki-67 monoclonal antibodies. RESULTS: Of 43 tumours, seven were located in the stomach, 11 in the small or large bowel, 12 in the uterus, 11 in the retroperitoneum and two cases in the urinary bladder. Five-year disease-free survival was 46.5%. Twenty-three patients (53.4%) died of the disease. Positive immunoreactivity for p53 and bcl-2 was found in 18 (41.9%) and 26 patients (60.5%), respectively. Positive Ki-67 staining was observed in eight patients (18.6%). Proliferative indices were higher in LMS with high mitotic activity (P=0.004) and high grade (P=0.009). All Ki-67 positive LMS were intermediate or high-grade tumours. Ki-67-labelling index showed inverse relationship to bcl-2 expression. A trend towards higher survival and expression of bcl-2, p53 or Ki-67 was found. CONCLUSIONS: Our results demonstrate that p53 and bcl-2 are expressed in a substantial number of intraabdominal and retroperitoneal leiomyosarcomas. In our study, the expression of these biomarkers did not predict patient outcome. Higher Ki-67 labelling indices were found in more biologically aggressive leiomyosarcomas.

Abdominal Neoplasms↗
PubMed2001

Neuropsychological effects of prefrontal slow rTMS in normal volunteers: a double-blind sham-controlled study.

Recent reports have suggested that repetitive transcranial magnetic stimulation (rTMS) is effective in major depression. Unlike ECT, rTMS does not involve a seizure and is associated with minimal side-effects, including cognitive difficulties. However, the effect of rTMS on cognitive functioning has not been systematically evaluated. This study was designed to examine the neuropsychological effects of slow rTMS in normal volunteers. Forty-six normal volunteers were randomly assigned to receive one session of right (N = 16) or left prefrontal (N = 15), or sham (N = 15) rTMS at 1 HZ. Patients were assessed before and after stimulation by a computerized neurospychological battery. All three groups showed significant improvement over time in processing speed (reaction time) and efficiency (correct responses per unit of time). However, no time by group interaction was found for any of the neuropsychological tests. These findings suggest that a single session of slow rTMS does not interfere with neurospychological functioning in normal volunteers, supporting clinical reports of no adverse cognitive effects.

Adult↗
PubMed2001

Bupivacaine wound instillation via an electronic patient-controlled analgesia device and a double-catheter system does not decrease postoperative pain or opioid requirements after major abdominal surgery.

UNLABELLED: To assess the analgesic efficacy of patient-controlled bupivacaine wound instillation, 50 patients undergoing major intraabdominal surgery were enrolled into this prospective, placebo-controlled, double-blinded study. In all cases, a standard general anesthetic was administered. On completion of surgery, two multihole 20-gauge epidural catheters were tunneled through the proximal and distal apices of the surgical wound and placed above the fascia such that the tips were at the margin of the first and second thirds of the surgical wound, respectively. Postoperatively, a patient-controlled analgesia (PCA) device was connected to the instillation system. Either bupivacaine 0.25% (Bupivacaine Group) or an equal volume of sterile water (Control Group) was administered. The PCA device was programmed to deliver 9.0 mL with a 60-min lockout interval and no basal infusion. During the first six postoperative hours, a coinvestigator administered "rescue" morphine (2 mg IV). Thereafter, meperidine 1 mg/kg IM was administered on patient request for additional analgesia. Instillation attempts and actual number of injections were similar between the groups. The mean number of pump infusions and the mean "rescue" opioid requirements during the 24-h study period were similar between the groups. The total "rescue" morphine administered during the first six postoperative hours was 16 +/- 17 mg vs 18 +/- 14 mg for the Bupivacaine and Control Groups, respectively. The total meperidine administered during this period was 1.6 +/- 1.4 mg/kg and 2 +/- 1.2 mg/kg for the Bupivacaine and Control Groups, respectively. Preoperatively, hourly for the first six postoperative hours, and on removal of the instillation catheter, patient-generated visual analog scales for pain were similar at rest, on coughing, and after leg raise. In conclusion, bupivacaine wound instillation via an electronic PCA device and a double-catheter system does not decrease postoperative opioid requirements after surgery performed through a midline incision. IMPLICATIONS: After major abdominal surgery performed through a 20-cm incision, repeated 0.25% bupivacaine wound instillation via an electronic patient-controlled analgesia device and a double-catheter system does not decrease postoperative pain or opioid requirements.

Abdomen↗
PubMed2000

SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines.

The gene defect responsible for the X-linked lymphoproliferative disease (XLP) is associated with an impaired control of Epstein-Barr virus (EBV) infection. The gene has been recently identified and the encoded protein (designated SH2D1A, DSHP or SAP) was characterized. It is a 128 amino acid (aa) protein, containing a single Src homology 2 (SH2) domain. It interacts with signaling lymphocytic activation molecule (SLAM) expressed on the surface of activated T and B cells. We show that activated T, but not activated B, cells express the SH2D1A protein. NK cells express the protein as well. Tumor lines originating from B, T or NK cells exhibited similar SH2D1A protein expression as the corresponding normal cells, with some notable exceptions. EBV-carrying, tumor phenotype representative (type I), but not EBV-carrying lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt lymphoma (BL) lines expressed SH2D1A. The phenotypic switch from type I to type III in the EBV-carrying BL line Mutu was associated with a down-regulation of SH2D1A and up-regulation of SLAM. In contrast to normal ex vivo and long-term activated NK cells, 2 of 3 NK leukemia lines expressed SLAM. All 3 lines expressed SH2D1A, like their normal counterparts.

Amino Acid Sequence↗
PubMed2000

Paroxetine binding in aggressive schizophrenic patients.

Decreased central serotonergic activity has been associated with aggressive behavior in humans and animals. Whether or not this phenomenon is related to current aggression or to aggressive tendency is debatable. [3H]paroxetine binding in blood platelets represents the activity of serotonin peripheral binding sites. We investigated a possible association between [3H]paroxetine binding in blood platelets and current aggression or homicidal history in schizophrenic patients. Blood platelets of 11 aggressive schizophrenic patients were assayed for [3H]paroxetine binding in blood platelets and compared to findings in 15 non-aggressive schizophrenic patients, 15 presently non-aggressive schizophrenic patients with homicidal history, and 15 healthy volunteers. Clinical evaluation was performed using the Positive and Negative Syndrome Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scale. B(max) of [3H]paroxetine binding in blood platelets of currently aggressive schizophrenic patients was significantly higher than that in platelets of non-aggressive schizophrenic patients, presently non-aggressive patients with homicidal history and healthy volunteers. No difference was found between the last three study groups. No significant correlation was found between scores of all rating scales and the investigated biochemical parameters. An association was found between current aggression among schizophrenic patients and high B(max) values of [3H]paroxetine binding in blood platelets. This association is probably related to present state of aggression rather than to tendency towards aggression.

Adult↗
PubMed2000

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer.

BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.

Adult↗
PubMed2000

Simultaneous derivatization of acyl and S-alkyl moieties of acyl thioesters by using trimethylsulfonium hydroxide for gas chromatographic analysis.

The reaction of long-chain acyl thioesters, viz. lauric acid dodecyl thioester, 1,8-di-S-palmitoyl octanedithiol, and tristearoyl alpha-monothioglycerol, with trimethylsulfonium hydroxide in the presence of methanol leads to simultaneous derivatization of acyl moieties and S-alkyl moieties of acyl thioesters to the corresponding fatty acid methyl esters and methyl alkylsulfides, respectively. These derivatized products were analyzed by gas chromatographic technique.

Chromatography, Gas↗
PubMed2000

Antioxidants eliminate stereomutation and thioether formation during lipase-catalyzed thioesterification and transthioesterification for the preparation of uniform cis- and trans-unsaturated thioesters.

The lipase-catalyzed preparation of acyl thioesters from unsaturated fatty acids and alkanethiols is accompanied by the formation of geometrical isomers via stereomutation and of thioether derivatives via addition at the olefinic bond, both induced by thiyl radicals. Therefore, a method was developed in order to inhibit radical generation by the addition of antioxidants and thus prevent the formation of geometrical isomers and thioether derivatives during the lipase-catalyzed preparation of unsaturated acyl thioesters. In the presence of antioxidants such as 2,6-di-t-butyl-4-methylphenol (BHT) and octyl gallate thioesterification of oleic and elaidic acids with 1-tetradecanethiol as well as transthioesterification of methyl linoleate with 1-tetradecanethiol led to the corresponding geometrically uniform thioesters without radical-induced side reactions. In the absence of antioxidants rapid stereomutation of unsaturated acyl moieties as well as formation of high proportions of thiyl radical-induced addition products such as isomeric 9(10)-S-tetradecyl stearic acids and 9(10)-S-tetradecyl stearic acid tetradecyl thioesters were observed.

Antioxidants↗
PubMed2000

Challenges in the development of an effective HIV vaccine: current approaches and future directions.

OBJECTIVE: The intent of this review is to investigate and discuss why developing a successful HIV vaccine has been so challenging, first by examining the molecular biology of the virus and how HIV interacts with the immune system, and then reviewing past viral vaccine successes as well as future directions for HIV vaccine research. BACKGROUND: Since HIV appeared in the United States in the early 1980s, an estimated 40 million people worldwide have been infected with the virus. Despite promising advances in the pharmacotherapy of HIV infection, it is apparent that the best, most cost-effective strategy for controlling the further spread of the virus is through synthesis of a protective vaccine. Almost 2 decades into the epidemic, there are few prospects for a truly effective vaccine entering the market in the foreseeable future. METHODS: MEDLINE was searched for articles written between 1966 and June 1999. Search terms used were AIDS, HIV vaccine, HIV-1, HIV-2, vaccines, and human immunodeficiency virus. RESULTS: Only 2 candidates for an HIV vaccine are currently in phase III clinical trials (1 in the United States and 1 in Thailand). The efficacy of these vaccines when applied to the population as a whole is widely questioned, largely because they induce protection by an antibody response only. Several studies have suggested that this approach will likely be ineffective in providing any real protection from viral infection. It appears that a strong cellular immune response is necessary in addition to a strong antibody response.

AIDS Vaccines↗
PubMed2000

Cutaneous gnathostomiasis in a woman from Bangladesh.

A woman from Bangladesh who had lived in Germany for more than 2 years presented with migratory, painful swellings on her left hand and arm of 5 months duration. Laboratory examinations yielded a marked eosinophilia and a grossly elevated IgE level in combination with an inflammatory reaction restricted to the subcutaneous tissues. A preliminary diagnosis of gnathostomiasis was established and confirmed by a positive gnathostoma serology by enzyme immunoassay (EIA). Treatment was initiated with albendazole, leading to the outward migration of a larva and complete resolution of clinical disease. Currently, there is no definitive therapy that has been proved to be both safe and highly effective. A wide range of potential agents has been used in clinical studies, but only albendazole has proved to be reliably effective to date, stimulating the outward migration of larvae in a proportion of cases of cutaneous disease, as observed in the present case.

Adult↗
PubMed2000

Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study.

Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIalpha (Topo IIalpha) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIalpha and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIalpha was consistently negative in normal ductal epithelium. Topo IIalpha-labeling index (Topo IIalpha-LI) was 0.7+/-0.6% for grade I, 4.3+/-3.9% for grade II, and 13.4+/-8.9 for grade III lesions (P<.01). For mixed nuclear grade DCIS, Topo IIalpha-LI was 6.8+/-4.8. There was no difference in Topo IIalpha-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIalpha-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIalpha-LI was significantly higher in c-erbB-2-positive lesions (Topo IIalpha-LI- 12.4+/-8.5) as compared with negative lesions (Topo IIalpha-LI- 3.9+/-4.5, P<. 0001). Overexpression of c-erbB-2 and Topo IIalpha is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions.

Antigens, Neoplasm↗
PubMed2000

A repetitive sequence of Epstein-Barr virus nuclear antigen 6 comprises overlapping T cell epitopes which induce HLA-DR-restricted CD4(+) T lymphocytes.

Most human adults carry the Epstein-Barr virus (EBV) and develop immunological memory against the structural and the virus-encoded cellular proteins. The EBV nuclear antigen 6 (EBNA6) elicits cytotoxic T cell responses and it also maintains a persistent antibody response. The majority of sera from EBV-seropositive individuals reacts with a synthetic peptide, p63, comprising 21 amino acids of a repetitive region of EBNA6. CD4(+) T lymphocytes, with specificity for p63, could be recalled from the T cell repertoire of EBV carriers that expressed certain HLA-DR allotypes which were identified as good binders of p63 by an in vitro flow cytometric assay. Analysis of the HLA-DR/p63 interaction by molecular mechanics calculations indicated the presence of multiple overlapping epitopes which were predicted to bind in a HLA-DRB1 allo- and subtype-specific manner. Specific activation of p63-selected long-term CD4(+) T cell cultures resulted in a proliferative response, in the production of IL-2 and in the secretion of high levels of tumor necrosis factor as measured by bioassays. Proliferation and cytokine production of p63-specific T cells could be induced by p63-loaded HLA-DR-matched antigen-presenting cells and by B cells co-expressing relevant HLA-DR molecules and EBNA6. Our results show that peptides of an EBNA6 repeat region induce CD4(+) T cells which can react with EBNA6-carrying cells in many individuals. We suggest that these T(h) cells may be important in conditioning dendritic cells for initiation potent virus-specific immune responses, provide help for EBV-specific B cells, drive IgG isotype switch and support the sustained effector function of memory cytotoxic T lymphocytes.

Adult↗
PubMed2000

Rapid hypothermic aortic flush can achieve survival without brain damage after 30 minutes cardiac arrest in dogs.

BACKGROUND: Neither exsanguination to pulselessness nor cardiac arrest of 30 min duration can be reversed with complete neurologic recovery using conventional resuscitation methods. Techniques that might buy time for transport, surgical hemostasis, and initiation of cardiopulmonary bypass or other resuscitation methods would be valuable. We hypothesized that an aortic flush with high-volume cold normal saline solution at the start of exsanguination cardiac arrest could rapidly preserve cerebral viability during 30 min of complete global ischemia and achieve good outcome. METHODS: Sixteen dogs weighing 20-25 kg were exsanguinated to pulselessness over 5 min, and circulatory arrest was maintained for another 30 min. They were then resuscitated using closed-chest cardiopulmonary bypass and had assisted circulation for 2 h, mild hypothermia (34 degrees C) for 12 h, controlled ventilation for 20 h, and intensive care to outcome evaluation at 72 h. Two minutes after the onset of circulatory arrest, the dogs received a flush of normal saline solution at 4 degrees C into the aorta (cephalad) via a balloon catheter. Group I (n = 6) received a flush of 25 ml/kg saline with the balloon in the thoracic aorta; group II (n = 7) received a flush of 100 ml/kg saline with the balloon in the abdominal aorta. RESULTS: The aortic flush decreased mean tympanic membrane temperature (Tty) in group I from 37.6 +/- 0.1 to 33.3 +/- 1.6 degrees C and in group II from 37.5 +/- 0.1 to 28.3 +/- 2.4 degrees C (P = 0.001). In group 1, four dogs achieved overall performance category (OPC) 4 (coma), and 2 dogs achieved OPC 5 (brain death). In group II, 4 dogs achieved OPC 1 (normal), and 3 dogs achieved OPC 2 (moderate disability). Median (interquartile range [IQR]) neurologic deficit scores (NDS 0-10% = normal; NDS 100% = brain death) were 69% (56-99%) in group I versus 4% (0-15%) in group II (P = 0.003). Median total brain histologic damage scores (HDS 0 = no damage; > 100 = extensive damage; 1,064 = maximal damage) were 144 (74-168) in group I versus 18 (3-36) in group II (P = 0.004); in three dogs from group II, the brain was histologically normal (HDS 0-5). CONCLUSIONS: A single high-volume flush of cold saline (4 degrees C) into the abdominal aorta given 2 min after the onset of cardiac arrest rapidly induces moderate-to-deep cerebral hypothermia and can result in survival without functional or histologic brain damage, even after 30 min of no blood flow.

Animals↗
PubMed2000

Echo-enhanced color Doppler sonography in children and adolescents.

Fifty-one patients, with a range of underlying pathologic conditions, were studied prospectively to assess the diagnostic value of echo-enhanced color Doppler sonography in the pediatric and adolescent population Their diagnoses included various tumors, vascular disorders, cerebral bleeding, pathologic conditions of small parts, and focal lesions of parenchymal organs. All patients underwent color Doppler sonography before proceeding to echo-enhanced color Doppler sonography. Diagnoses were confirmed by additional imaging (computed tomography, magnetic resonance imaging, angiography, and scintigraphy) performed as appropriate, with or without histologic study. An additional 20 children did not proceed to echoenhanced color Doppler sonography as color Doppler sonography alone was found to be sufficiently diagnostic. Levovist (SHU 508A), a contrast agent based on galactose-encapsulated air microbubbles, is approved for pediatric applications in Austria and was used as the echo-enhancing agent. Echo-enhanced color Doppler sonography was performed a total of 63 times in 51 patients (mean age, 9.8 years). Compared to color Doppler sonography, echo-enhanced color Doppler sonography either detected or enhanced visualization of pathologic conditions in 55 investigations (87.3%), yielding an overall accuracy of 95.2% (sensitivity, 95%), versus 65.7% with color Doppler sonography. One spinal arteriovenous malformation, one cerebral cavernoma, and one liver lesion were missed. The contrast material was easy to administer; no adverse reactions were observed. We conclude that echoenhanced color Doppler sonography is beneficial in pediatric sonography. It enhances visualization of vessels and perfusion, thus offering a nonionizing imaging tool for detection and follow-up evaluation of pathologic conditions with disturbed vasculature in specific cases. In infants and in persons with superficial lesions it did not offer significant advantages over color Doppler sonography.

Adolescent↗