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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 289 records · Page 16Linked to original sources

New direct assay of free protein S antigen using two distinct monoclonal antibodies specific for the free form.

Monoclonal antibodies (mAbs) specific for free protein S and devoid of reactivity with protein S-C4b-BP complexes, have been produced. A one-step sandwich-type enzyme-linked immunoassay (ELISA) has been developed with two mAbs reacting with distinct epitopes of free protein S. F(ab')2 fragments from mAb 15C4 were coated on microplates and mAb 34G2 conjugated with horseradish peroxidase (HRP) was added immediately before diluted plasma. The presence of calcium in the sample diluent prevented dissociation of complexes during the assay. This assay was specific as demonstrated by good recovery of purified protein S added to plasma and the lack of influence of C4B-BP-protein S complexes. Thus, addition of increasing amounts of purified C4B-BP to human citrated plasma induced a dose-dependent decrease of free protein S. The assay was sensitive, allowing measurement of 5-500 ng/ml of free protein S, with a detection threshold of 2 ng/ml. It was also reproducible with inter-assay and intra-assay variation coefficients of 2.5-5.1% and 3.1-5.0%, respectively. Thus, this new ELISA of free protein S antigen in plasma has the advantages of being fast, accurate and reproducible. It appears to be extremely useful for routine studies as no preliminary treatment of plasma is required.

Antibodies, Monoclonal↗

Clinical applications of a direct assay of free protein S antigen using monoclonal antibodies. A study of 59 cases.

A new one-step ELISA using two monoclonal antibodies specific for distinct epitopes of the free form of protein S (ELISA-m) has been developed for the direct measurement of free protein S in untreated plasma. This assay has been compared with the classic method using polyclonal antibodies to protein S (ELISA-p). The latter method has the drawback of requiring PEG precipitation of plasma which is time-consuming, difficult to perform with accuracy and therefore poorly reproducible in most laboratories. Results of both ELISAs were compared with those of a functional assay. In 30 normal subjects, there was an excellent correlation between ELISA-m and ELISA-p (r = 0.95) as well as between ELISA-m and the functional assay (r = 0.96). In twelve patients with a congenital deficiency, the levels of free protein S antigen were similarly decreased with ELISA-m and ELISA-p and in good agreement with those of protein S activity. In 20 patients with miscellaneous inflammatory diseases, the levels of free proteins S were normal with good correlation between both ELISAs and PS activity, despite high levels of C4bBP-protein S complexes. As expected, in 15 dicoumarol-treated patients, there was a significant and parallel decrease of free protein S antigen with both ELISAs, with even lower levels of protein S activity. In 14 patients with liver cirrhosis, the mean values for free protein S antigen were normal using both assays, but with wide extreme values, whereas protein S activity was significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Matutinal vertigo--a chronobiological phenomenon.

Matutinal vertigo, characterized by vertiginous attacks occurring in the morning, has been noted in a significant percentage of patients with vestibular disorders and is considered to be precipitated by the patient's movements preparatory to arising from bed. Chronobiological studies of the variations of positional nystagmus in 10 patients with acute vertigo revealed rhythms of circadian periodicities in eight. The acrophases (i.e. computed peak hour), of nearly 40% of the circadian rhythms were found between 02.00 and 07.00 hours. Chronobiological characteristics of the vestibular system are postulated to play a part in the development of this clinical phenomenon.

Adult↗

Shuttle mutagenesis of Legionella pneumophila: identification of a gene associated with host cell cytopathicity.

We performed shuttle mutagenesis of Legionella pneumophila. Mutants were screened for reduced cellular infectivity. Approximately 10% of the mutants had decreased cytopathicity. The DNA sequence of one locus was determined; the inferred amino acid sequence revealed homology with transport proteins including Escherichia coli TolC, Bordetella pertussis CyaE, and Alcaligenes eutrophus CzcC and CnrC.

Amino Acid Sequence↗

Peritonsillar abscess: repeated needle aspiration versus incision and drainage.

The study evaluates the management of peritonsillar abscess (PTA) by comparing needle aspiration versus incision and drainage of the abscess. Twenty-four of 86 patients treated by needle aspiration underwent a single aspiration, and 38 had 2, 19 had 3, and 5 had 4 aspirations before the abscess resolved. A significant amount of pus, up to 8, 5, and 3 mL, respectively, was detected in the subsequent aspirations. Recurrent PTA was noted in 20 patients (23.26%). In 9 of these patients (10.47%) the recurrent episode occurred immediately (in less than 1 month) and was considered residual disease. Seventy-four patients were treated by incision and drainage, and none had an immediate recurrence. Only 3 (4.05%) patients developed a late recurrent episode. The difference in the recurrence rate between the two groups is statistically significant. A history of recurrent tonsillitis prior to abscess formation did not show a significant influence on the recurrence rate. A high incidence of streptococcal infections was noted in both groups, with anaerobes detected in only 15% of samples. There was a good response to penicillin-resistant organisms. Although needle aspiration is a tempting modality for treating PTA in community clinics, one should be aware of the risks of a higher incidence of residual and recurrent disease in comparison to incision and drainage, as well as the need for repeated aspirations.

Adolescent↗

Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report.

PURPOSE: To assess the impact of prognostic factors, including continued (orchiectomy) versus discontinued androgen-suppression (nonorchiectomy) therapy, on chemotherapy response and survival of patients with hormone-refractory prostate cancer. METHODS: Analysis of five consecutive Southwest Oncology Group (SWOG) phase II chemotherapy trials was undertaken. RESULTS: Two hundred five hormone-refractory patients were evaluated. Eighty-four percent had been orchiectomized. The median survival durations for the nonorchiectomy and orchiectomy patients were 6 and 7 months, respectively (P = .73). In a univariate analysis, orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy (1.1 v 0.1 years, P = .003), were more likely to have had chemotherapy initiated > or = 2 years from diagnosis (75% v 56%, P = .03), had a lower incidence of liver metastases (16% v 30%, P = .05), and had lower likelihood of being black (8% v 18%, P = .05) when compared with the nonorchiectomy group. Orchiectomy patients had a marginally significant longer median time from initial hormone treatment, more prior endocrine manipulations, lower median baseline alkaline phosphatase levels, and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group. Absence of liver metastases (P = .004), hemoglobin level > or = 10 g/dL (P < .001), acid phosphatase level > or = 1.2 IU/L (P = .05), response to chemotherapy (P = .001), and > or = 2 years from initial hormone treatment (P = .01) are important factors for survival. CONCLUSION: This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression. A prospective randomized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy.

Acid Phosphatase↗

Interleukin 1 beta, tumor necrosis factor-alpha and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line.

Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6). Furthermore, these cytokines are involved in mediating the characteristic changes of thyroid function during acute disease known as non-thyroidal illness. In the present studies we investigated in vitro whether TNF-alpha, IL-1 beta and IL-6 modify nuclear thyroid hormone receptor (TR) capacity and/or affinity. Regulation of TR synthesis was studied in the human hepatoma cell line Hep-G2. Subconfluent cells were incubated with recombinant cytokines in serum-free medium. Nuclear extracts were prepared by high-salt extraction of cell nuclei. Binding assays were performed with [125I]-triiodothyronine; bound and free hormone were separated by filtration. Interleukin 1 beta decreased TR capacity in a dose-dependent manner. Compared with unstimulated cells, the TR capacity was reduced to 87.9 +/- 3.9% (p < 0.05), 80.1 +/- 3.9% (p < 0.01) and 72.1 +/- 5.1% (p < 0.01) after incubation with 0.1, 1.0 and 100 micrograms/l IL-1 beta, respectively. Interleukin 6 and TNF-alpha significantly reduced receptor capacity only at concentrations of 10 micrograms/l or higher and the magnitude of the reduction was lower than with IL-1 beta. The TR capacity was reduced to 81.2 +/- 2.3% (p < 0.01) and 83.2 +/- 6.6% (p < 0.05) after stimulation with 10 micrograms/l IL-6 or TNF-alpha, respectively. TR affinity was not altered significantly after stimulation with any of the cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗

Peripheral blood lymphocyte surface antigen expression and prognosis in myeloma: Australian Leukaemia Study Group Study.

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (beta 2M) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of beta 2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Secondary myelodysplastic syndrome following bone marrow transplantation: report of two cases.

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

Adult↗