Biomedical subjects

J J Hoffmann

Publications and source records attributed to J J Hoffmann.

At least 19 recordsLinked to original sources

PubMed2002

Microbiological conversion of a beta- and gamma-eudesmol mixture by Rhizopus.

A mixture of beta- and gamma-eudesmols was microbiologically biotransformed by Rhizopus stolonifer ATCC 6227. Positions-2 and 3, in both substrates, proved to be accessible by hydroxylase enzyme. Four different metabolites were isolated and their structures were elucidated by different spectroscopic methods. The structures of these metabolites were established as eudesma-3-en-2 beta,11-diol; eudesma-4-en-3 beta,11-diol; eudesma-4(15)-en-2 beta,11-diol and eudesma-4(15)-en-3 beta,11-diol.

Antifungal Agents↗

PubMed2002

New terpenoids from Haplopappus multifolius.

The chemical investigation of the aerial parts of Haplopappus multifolius afforded the new monoterpene 2,9-epoxy-p-menth-6-en-8-ol (7, haplopappol), the new monoterpenoid ester 9-cis-p-coumaroyloxy-alpha-terpineol (8, haplofolin), the new diterpene 18-hydroxylabda-7,13Z-dien-15-oic acid (6) and its known E-isomer (5). In addition, the known dihydroflavones 3',5-dihydroxy-4',7-dimethoxydihydroflavone and 3',4',5-trihydroxy-7-methoxydihydroflavone and the known dihydroflavonols 3',5-dihydroxy-4',7-dimethoxydihydroflavonol and 3',4',5-trihydroxy-3-acetyl-7-methoxydihydroflavonol were also obtained. The structural assignments of these compounds were made possible by the different spectroscopic measurements.

Asteraceae↗

PubMed2001

Triterpenoid saponins from Acacia victoriae (Bentham) decrease tumor cell proliferation and induce apoptosis.

This report describes the isolation and partial purification of novel triterpenoid saponins [Fraction 35 (F035)] and two pure biologically active derivatives (termed avicins D and G) from Acacia victoriae, an Australian desert tree of the Leguminosae family. F035 and the avicins markedly inhibited the growth of several tumor cell lines with minimum growth inhibition in human foreskin fibroblasts, mouse fibroblasts, and immortalized breast epithelial cells at similar concentrations. F035 and the avicins induced cell cycle (G1) arrest of the human MDA-MB-453 breast cancer cell line and apoptosis of the Jurkat (T-cell leukemia) and the MDA-MB-435 breast cancer cell line. The triterpenoid saponins also partially inhibited phosphatidylinositol 3-kinase activity in Jurkat T cells in a time-dependent manner and phosphorylation in the downstream protein Akt, whereas no affect was seen on the Ras/mitogen-activated protein kinase cascade. These observations as well as other work from our laboratory demonstrating mitochondrial perturbation, chemoprevention, and inhibition of nuclear factor kappaB suggest that triterpenoid saponins from A. victoriae have potential as novel anticancer agents. Recent work linking Akt signaling with glucose metabolism, stress resistance, and longevity suggests other potential applications of these compounds.

Acacia↗

PubMed2001

[BIS monitoring may allow the detection of severe cerebral ischemia].

PURPOSE: To show that the bispectral index (BIS) is not only a monitor of the depth of anesthesia but that acute decreases of the index may be related to severe cerebral ischemia. CLINICAL FEATURES: Several clinical observations suggest that an unexplained fall of the BIS may be the result of cerebral ischemia. Somatosensory evoked potentials decreased in parallel to the decrease in BIS during carotid clamping in a 58-yr-old patient undergoing carotid endarterectomy. In a 62-yr-old patient undergoing resection of an aortic aneurysm, the BIS decreased from 40-50% to 8% as the cardiac index and central venous O(2) saturation decreased. The BIS returned to normal values when the low cardiac output was corrected pharmacologically. CONCLUSION: While the BIS is a well accepted monitor of the depth of anesthesia, several factors, unrelated to anesthesia, can modify the index. Thus, to adjust the level of anesthesia based solely on the BIS could be inappropriate. While the sensitivity and specificity of the BIS for this indication have not been determined, we suggest that the BIS may be useful to detect severe cerebral ischemia.

Brain Ischemia↗

PubMed2001

Inhibition of Mycobacterium tuberculosis growth by saringosterol from Lessonia nigrescens.

Assay-guided fractionation of an antitubercular extract obtained from Lessonia nigrescens yielded the phytosterol saringosterol as its active component. No appreciable toxicity against Vero cells was observed for this compound. Saringosterol was also synthesized by oxidation of fucosterol. The MIC values for antitubercular activity of saringosterol and its 24S and 24R epimers were determined as 0.25, 1, and 0.125 microg/mL.

Animals↗

PubMed2001

EDTA-induced pseudo-neutropenia resolved with kanamycin.

This report describes a case of spurious neutropenia caused by EDTA-dependent in vitro agglutination of neutrophils. After raising the temperature of the sample to 37 degrees C the agglutination was irreversible, but it resolved completely after addition of kanamycin. Previously this method has been shown to be effective in EDTA-dependent pseudo-thrombocytopenia, but this is the first report demonstrating successful application in EDTA-dependent pseudo-neutropenia.

Anti-Bacterial Agents↗

PubMed2001

Comparison of three methods for measuring PEG-hirudin in blood.

Three methods for measuring pegylated hirudin (PEG-hirudin), a new antithrombotic agent, in blood were compared using clinical samples. The ecarin clotting time (ECT) was performed in whole blood using a point-of-care device (TAS analyzer). The ECT was also performed in plasma, using a clotting assay in a conventional automated coagulation analyzer. Finally, a chromogenic method was used, based on thrombin inhibition and the substrate S-2238. Both clotting assays showed a linear relationship between the ECT and the PEG-hirudin concentration up to 3.0 microg/ml. The chromogenic substrate method was linear only between 0.1 and 1.0 microg/ml PEG-hirudin. The intra-assay coefficient of variation was 3.0% for the automated ECT method, 6.4% for the point-of-care ECT method and 3.4% for the chromogenic method. The inter-assay coefficient of variation was approximately 10% for both clotting methods and 3.2% for the chromogenic method. There was a high correlation (r = 0.954) in PEG-hirudin concentration between both ECT methods over the entire measuring range. The correlation of the chromogenic method with any ECT was significantly less (r < 0.89), even if only PEG-hirudin concentrations < 1.0 microg/ml were taken into account (r < 0.92). Although we clearly prefer the conventional ECT, any of the other methods may be used for monitoring PEG-hirudin in patients treated with this drug, depending on the specific application and local circumstances.

Antithrombins↗

PubMed2000

[Two patients with chronic lymphocytosis of large granular lymphocytes; benign or premalignant?].

In two female patients aged 44 and 86 years, a chronic lymphocytosis was observed caused by a proliferation of large granular lymphocytes (LGL). The first one had been successfully treated for Hodgkin lymphoma long before, the second had diabetes mellitus type 2. Immunophenotyping showed the proliferating lymphocytes to be natural killer (NK) cells. In contrast to the proliferation of B- and T-lymphocytes, data on the prognosis and treatment of NK-lymphocytosis are very scarce. A literature search revealed three major clinical entities in which LGL proliferate: at one end of the spectrum we see the very aggressive NK-LGL leukaemia, at the other, NK-lymphocytosis, a benign chronic disorder, in between is the relatively indolent chronic T-LGL leukaemia. Both patients suffered from chronic NK-lymphocytosis with a favourable course; there were no further symptoms 4 and 2 years, respectively, after the diagnosis. In cases of prolonged lymphocytosis of unknown origin, immunophenotyping of the lymphocytes is essential. Only in this way can one arrive at the proper diagnosis and reach conclusions as to the prognosis and the possible methods of treatment.

Adult↗

PubMed2000

Haemostatic effects of low osmolar non-ionic and ionic contrast media: a double-blind comparative study.

In this prospective, double-blind, randomized study the effects of a non-ionic contrast medium (Iopromide) on the haemostatic system were compared with those of a low osmolar ionic medium (Ioxaglate). The aim was to investigate in vivo whether a non-ionic contrast agent is less anticoagulant or more pro-thrombotic than an ionic medium. A large number of haemostatic parameters, including activation markers, were measured. Either Iopromide (n = 16; median volume 102 ml; 95% confidence interval 90-108 ml) or Ioxaglate (n = 15; median 105 ml; 95% confidence interval 95-114 ml) was given to 31 patients scheduled for abdominal and femoral arteriography. Blood for laboratory investigations was collected before, and 5 and 30 min after, administering the contrast medium. Indications for activation of coagulation and platelets were already found in nearly 50% of the patients before any contrast medium was given. Both Iopromide and Ioxaglate caused further increases in thrombin-antithrombin complex, prothrombin fragments 1 + 2 and beta-thromboglobulin. The degree of activation was similar for both agents. Anticoagulant effects were not observed. The haemorheological effects were compatible with haemodilution by 5-8%, again without differences between the contrast agents. Contrary to the findings from in vitro studies, we found no significant differences between the effects of the non-ionic Iopromide and the ionic Ioxaglate on coagulation and platelets. Both agents activated these systems to a limited, but identical, degree. Our results support the notion that the catheterization procedure per se may represent a source of haemostatic activation and that the ionic contrast agent studied has insufficient anticoagulant effect to prevent clotting activation being induced by the contrast medium.

Adult↗

PubMed1999

Antibacterial and antifungal flavanones from Eysenhardtia texana.

An activity-guided fractionation of a methanol-dichloromethane extract obtained from the aerial parts of Eysenhardtia texana led to the isolation of two novel antibacterial and antifungal flavanones together with a known flavanone. Their structures were established as 4',5,7-trihydroxy-8-methyl-6-(3-methyl-[2-butenyl])-(2S)-flavanone, 4',5,7-trihydroxy-6-methyl-8-(3-methyl-[2-butenyl])-(2S)-flavanone and 4',5-dihydroxy-7-methoxy-6-(3-methyl-[2-butenyl])-(2S)-flavanone on the basis of their UV, 1D and 2D-NMR spectra.

Anti-Bacterial Agents↗

PubMed1999

Antibacterial diterpenoid acids from Azorella compacta.

The two novel diterpenoid acids mulin-12,14-dien-11-on-20-oic acid (1) and mulin-12-ene-11,14-dion-20-oic acid (2) have been isolated from Azorella compacta. Their structures have been elucidated by 1D and 2D NMR methods. In contrast to the closely related known mulinolic acid (3) and its dehydration product (4) these new natural products have been shown to exhibit antimicrobial activity.

Anti-Bacterial Agents↗

PubMed1999

Performance characteristics of blast flagging on the Cell Dyn 4000 haematology analyser.

This study investigated the performance characteristics of blast flagging on the Abbott Cell Dyn 4000 (CD4000) haematology analyser. Our special interest was focused on the usability and prognostic value of the confidence fraction (CF), accompanying blast flagging. From our routine patient samples, 100 with blast flagging on the CD4000 were selected and examined microscopically for the presence of blasts. Blast flagging on the CD4000 resulted in a high number of false positive events. The results indicate that the blast flag confidence fraction (CF) of the CD4000 can be useful as a parameter for the prediction of the presence of blasts in samples with normal and increased white blood cell count. A model with criteria for blood smear examination following blast flagging was developed, using the blast flag CF combined with the WBC count. The model was tested and validated in a new set of 100 samples with blast flagging. Implementation of the criteria of the model resulted in a total reduction of the number of microscopic smear examinations of 45%, without losing clinically significant sensitivity.

Hematologic Tests↗

PubMed1999

Pseudo-reticulocytosis as a result of malaria parasites.

Recently fully automated methods for enumerating reticulocytes have become available as an integral function in routine haematology analysers. In such methods, all intraerythrocytic nucleic acid is stained and can be regarded as representing reticulocytes. It has previously been shown that Howell-Jolly bodies may be counted as reticulocytes in automated flow cytometric methods. In the present paper, data from two patients are described indicating that severe malaria infection may lead to falsely increased reticulocyte counts, at least in the CELL-DYN(R) 4000 haematology analyser. In this instrument, the intraerythrocytic nuclear material of the parasites will be stained and counted as reticulocytes. This phenomenon appears to be independent of the type of Plasmodium infection. Clinical haematology laboratories should be aware of this potential source of pseudo-reticulocytosis.

Afghanistan↗

PubMed1999

VO(2) kinetics of mild exercise are altered by RER.

We propose that variations in fat and carbohydrate (CHO) oxidation by working muscle alter O(2) uptake (VO(2)) kinetics. This hypothesis provides two predictions: 1) the kinetics should comprise two exponential components, one fast and the other slow, and 2) their contribution should change with variations in fat and CHO oxidation, as predicted by steady-state respiratory exchange ratio (RER). The purpose of this study was to test these predictions by evaluating the VO(2) kinetic model: VO(2)(t) = alpha(R) + alpha(F)(1 - exp[(t - TD)/-tau(F)]) + alpha(C)(1 - exp[(t - TD)/-tau(C)]) for short-term, mild leg cycling in 38 women and 44 men, where VO(2)(t) describes the time course, alpha(R) is resting VO(2), t is time after onset of exercise, TD is time delay, alpha(F) and tau(F) are asymptote and time constant, respectively, for the fast (fat) oxidative term, and alpha(C) and tau(C) are the corresponding parameters for the slow (CHO) oxidative term. We found that 1) this biexponential model accurately described the VO(2) kinetics over a wide range of RERs, 2) the contribution of the fast (alpha(F), fat) component was inversely related to RER, whereas the slow (alpha(C), CHO) component was positively related to RER, and 3) this assignment of the fast and slow terms accurately predicted steady-state respiratory quotient and CO(2) output. Therefore, the kinetic model can quantify the dynamics of fat and CHO oxidation over the first 5-10 min of mild exercise in young adult men and women.

Adult↗

PubMed1999

Three-colour, one-tube flow cytometric method for enumeration of CD4+ and CD8+ lymphocytes.

We investigated the usefulness of a one-tube, three-colour flow cytometric method for enumerating CD4+ and CD8+ lymphocytes. This method does not use any control antibodies and we compared it to the standard methods using either control and CD14/CD45 antibodies or control antibodies only on 38 blood samples from healthy and human immunodeficiency virus-infected patients. The one-tube method showed good agreement with the other, more complicated methods and is therefore suitable for reliable enumeration of CD4+ and CD8+ T-lymphocytes.

CD4-Positive T-Lymphocytes↗

PubMed1998

Factor V inhibitor associated with cold agglutinin disease.

An 81-year-old man known to have a stable cold agglutinin syndrome presented with a progressive cerebral hemorrhage. Coagulation tests revealed prolonged APTT and prothrombin time and severely decreased factor V activity, which could not be normalized by mixing with normal plasma. The patient appeared refractory to substitution with fresh-frozen plasma, suggesting the presence of a circulating inhibitor specific for factor V. To our knowledge, this is the first case of a lymphoproliferative disease leading to a cold agglutinin syndrome and a putative inhibitor of factor V. In patients with paraproteinemia presenting with bleeding diathesis, the presence of a circulating inhibitor of a specific coagulation factor must be considered.

Aged↗

PubMed1997

Evaluation of an automated photometric fibrinogen assay.

A recently-introduced automated method for the determination of plasma fibrinogen is based on the principle of von Clauss, combined with photometric detection: after addition of thrombin, the coagulation time is determined by measuring the change in absorption at 405 nm. This method was evaluated and compared with the original coagulometric Clauss assay and with the prothrombin time (PT)-derived automated method. The inter-assay coefficient of variation of the Clauss-derived assay was lower (14.1, 3.8 and 4.6%) than the PT-derived assay (16.1, 7.5 and 10.5%, respectively) at all three fibrinogen levels tested (1.2, 4.0 and 7.5 g/l). The correlation between the assays was investigated according to the method of Passing and Bablok and could be described as follows: Clauss-derived = 0.79 (PT-derived) + 0.66; Clauss-derived = 1.12 (Clauss) + 0.143. The interference of heparin (< 1.5 U/ml), haemoglobin (< 30 micromol/l), bilirubin (< 200 micromol/l) and triglycerides (< 5.5 mmol/l) in the Clauss-derived assay was negligible. The effects of fibrinogen degradation products on the Clauss-derived assay were comparable with the effects on the Clauss assay, in contrast to the effects on the PT-derived assay. In conclusion, the Clauss-derived assay is a specific and precise automated method to determine fibrinogen concentrations in plasma, which is not liable to interference from different pathophysiological substances.

Autoanalysis↗

PubMed1997

HLA-B27 phenotyping with flow cytometry: further improvement by multiple monoclonal antibodies.

To establish the optimal flow cytometric method for HLA-B27 phenotyping, we compared several strategies, using three monoclonal anti-B27 antibodies (from the HLA-ABC-m3, GS145.2, and FD705 clones). We used a triple-color direct immunofluorescence assay, including a T-lymphocyte-specific antibody as an internal control and an anti-HLA-Bw4 antibody. Blood samples from >400 subjects were tested. From ROC curve analysis none of the three antibodies appeared to be suitable for use as a single typing reagent. The efficiency of the test was affected by cross-reactions with other HLA antigens, notably the HLA-B7 antigen. Preincubation with anti-B7 serum efficiently inhibited this cross-reaction and raised the test efficiency considerably. We concluded that none of the anti-B27 antibodies investigated is suitable for use as a single typing reagent. Additional typing of Bw4 is not valuable, whereas inhibition of cross-reactions due to the B7 antigen will considerably improve the performance of the test. We recommend that two different monoclonal anti-B27 antibodies be used for accurate and reliable HLA-B27 phenotyping with flow cytometry.

Antibodies, Monoclonal↗