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Biomedical subjects

R Finke

Publications and source records attributed to R Finke.

At least 19 recordsLinked to original sources
PubMed1995

Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis.

It is unknown whether in chronic lymphocytic thyroiditis the goitrous (Hashimoto's thyroiditis) and atrophic forms (primary myxedema) are variants of the same disease or different pathogenic entities. Conventional thyroid-related autoimmune parameters are unable to separate both diseases serologically. It is assumed that cellular and humoral cytotoxic events induce gland atrophy and thus should be detectable more often in non-goitrous than goitrous autoimmune thyroiditis. We determined antibody-dependent cell-mediated cytotoxicity in 67 patients with autoimmune thyroiditis, using a 51chromium-release assay against human thyroid cells. Thyroid volume had been measured by ultrasonography. Other thyroid-specific antibodies, like TSH binding-inhibiting antibodies, TSH function-blocking antibodies, thyroglobulin antibodies and thyroid peroxidase antibodies, were determined. Cytotoxic antibody activity was 20.5% (median, range 0-54.5%) in patients with autoimmune thyroiditis and 8.3% (median, range 0-18.4%) in controls (p < 0.0001). Analysis of cytotoxicity regarding thyroid size showed a high incidence of cytotoxic antibodies in atrophic disease (median thyroid volume 6 ml), where cytotoxic antibodies were detectable in 80% versus 39% (x2 = 9.6; p < 0.0001) in goitrous disease (median thyroid volume 36 ml). The specific lysis of 30% (median; 95% confidence limit 23.9-32.9) in non-goitrous thyroiditis patients was significantly higher than in goitrous patients (16.9%; 95% confidence limit 13.2-20.4) (p = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Importance of the carboxyl terminus of human thyroid peroxidase in the efficient expression of the protein in eukaryotic cells.

Carboxyl terminal truncation of membrane-associated human thyroid peroxidase (hTPO), with the elimination of its single membrane-spanning and short intracytoplasmic regions, generates a soluble, secreted, enzymatically active protein (amino acids 1-848). In order to determine the effects of further carboxyl terminal deletions on the expression of hTPO, Chinese hamster ovary cells were stably transfected with plasmids constructed to express amino acids 1-771, 1-636, 1-539 and 1-382 of the 933 amino acid TPO protein, respectively. Unlike hTPO1-848, the more severely truncated TPO mutant proteins could not be detected in conditioned media by polyclonal anti-TPO antibodies. Using detergent-solubilized microsomal proteins from these cells, very low levels of hTPO1-771 (approximately 90 kDa), but not the more extensive deletion mutations, were detected by these anti-TPO antibodies. Confirmation of the loss of efficient expression of more severely truncated hTPO was obtained using a anti-hTPO monoclonal antibody with an epitope near the amino terminus and which recognizes only the denatured protein. The mRNA for all hTPO mutants was detected in the stably-transfected Chinese hamster ovary cells. In summary, the present study indicates that a largely intact extracellular portion of hTPO is required for expression in eukaryotic cells.

Animals↗
PubMed1992

Effect of storage time of pleural effusions on immunocytochemical cell surface analysis of tumor cells.

To determine how long tumor cells can be stored without losing their immunocytochemical reactivity, five malignant pleural effusions in EDTA-coated tubes were analyzed after different storage times at either 4 degrees C or room temperature. Only minor differences were observed between the cells from the two storage conditions. Though there was a considerable decrease in the number of tumor cells attached to the slides from day 0 to 1, the number of tumor cells was still sufficient to allow their clear detection with the monoclonal antibody HEA-125 even on day 4 of storage in all cases. Therefore, for routine purposes, pleural fluids in EDTA-coated tubes can be stored for at least one day prior to immunocytochemical staining if the cells are gently handled during preparation. Pleural fluid is a richly nutritious medium not only for keeping cells alive but also for preserving their immunoreactivity.

Antigens, Neoplasm↗
PubMed1991

Determination at the molecular level of a B-cell epitope on thyroid peroxidase likely to be associated with autoimmune thyroid disease.

In a panel of 13 mouse monoclonal antibodies generated against native (nondenatured) human thyroid peroxidase (TPO), only 1 (monoclonal antibody 47) recognized TPO protein fragments expressed in a human TPO cDNA sublibrary. Determination of the nucleotide sequences of 18 clones recognized by monoclonal antibody 47 localized its epitope to 9 amino acids (residues 713-721) in the human TPO protein. On Western blot analysis, only TPO monoclonal antibody 47 recognized the 933-amino acid TPO molecule after denaturation and reduction of the latter, supporting the concept that the major part of the epitope is represented by a continuous portion of the TPO sequence. The binding of TPO monoclonal antibody 47 to native TPO is inhibited by immunoglobulin G in the serum of patients with autoimmune thyroid disease. The epitope for monoclonal antibody 47 defined in the present study is, therefore, part of or in the vicinity of an epitope for autoimmune thyroid disease-associated TPO antibodies.

Amino Acid Sequence↗
PubMed1990

Evidence for the highly conformational nature of the epitope(s) on human thyroid peroxidase that are recognized by sera from patients with Hashimoto's thyroiditis.

To define the epitope(s) on human thyroid peroxidase (TPO) recognized by antibodies in the sera of patients with autoimmune thyroid disease, we constructed and screened a human TPO cDNA sublibrary containing 3.8 million random fragments of human TPO cDNA, each 200-500 basepairs in length. These fragments would code for TPO polypeptides of 66-166 amino acid residues. The validity of this approach was first tested with a murine monoclonal antibody against the denatured human thyroid microsomal antigen (TPO). Analysis of the nucleotide sequence of 14 clones selected from this library enabled molecular identification of the epitope recognized by this monoclonal antibody. In contrast to the data obtained with the monoclonal antibody, sera from patients with Hashimoto's thyroiditis containing polyclonal antimicrosomal/TPO antibodies did not recognize the TPO protein fragments generated by this library. These results differ from previous data obtained with recombinant human TPO fragments generated as bacterial fusion proteins. Our data suggest that, contrary to previous concepts, the natural B-cell epitope(s) on human TPO may be highly conformational (requiring a complex 3-dimensional structure) or may be discontinuous (formed by distant regions of the linear polypeptide chain being brought into apposition by protein folding).

Amino Acid Sequence↗
PubMed1990

[Comparison of oral fluconazole and amphotericin B prophylaxis against fungal infections in the neutropenic phase of patients treated with antileukemic agents].

Forty patients with acute leukemia (age 16-71 years, 13 females, 27 males) with induced neutropenia due to chemotherapy received either 50 mg fluconazole or 800 mg amphotericin B per day orally as prophylaxis against fungal infection. Nasal and genital swabs, mouth washings, urine, stool and blood serum were taken for mycological and serological examination before and weekly during one episode of neutropenia (less than 10(9) granulocytes/l) per patient. The quantitative determination of the yeast concentration in stool specimens demonstrated that amphotericin B led to intestinal yeast count reduction in only one third of the patients and could not prevent the increase of the intestinal yeast flora in another third of the patients. Beyond that the quantitative determination of yeast colonization in oropharynx, genital region, blood and stool did not prove to be a reliable tool for evaluating the host-fungus relationship during neutropenia. On the other hand mycoserology reflected episodes of candidosis well. 19 patients treated with fluconazole showed only minor titer increases. In 21 patients treated with amphotericin B, four fungemias were found: two by both hemagglutination (HAT) and immunofluorescence (IFT), one by IFT and one by antigen detection (Ramco Cand-Tec) alone. In only one of these cases yeast cells were released in urine. From these results is concluded that control of serology is essential in studies of that type and that fluconazole seems to provide better protection from candidosis than amphotericin B during induced neutropenia.

Administration, Oral↗
PubMed1989

Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease.

Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective [corrected] and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P less than 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P less than 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P less than 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

Follow-Up Studies↗
PubMed1989

Appearance of thyroid diseases using colour-coded duplex sonography.

One hundred and seventeen patients with various thyroid diseases were examined with colour-coded duplex ultrasonography permitting simultaneous real-time display of soft tissue and blood flow. Twenty-four out of 25 patients with an autonomous adenoma, all six patients with thyroid carcinoma and five out of 61 patients with simple nodular goitre showed increased vascularity. Absence of increased vascularity would seem an important parameter for the exclusion of autonomous adenoma and thyroid carcinoma in patients with nodular goitre.

Adolescent↗
PubMed1989

[Diagnostic strategy in primary malignant bone tumors in children].

Our experience concerning the diagnostic proceeding for primary malignant bone tumours in children and their often difficult differentiation from osteomyelitis are discussed. A retrospective evaluation of patient records of 66 children showed, that in 53 cases (41 with osteomyelitis, 12 malign tumours) diagnosis was immediately obtained from clinical and radiological results. For five more children osteomyelitis was proven by short term monitoring and paraclinical investigations, while in 8 cases final diagnosis required biopsy. CT was relevant for the evaluation of intraosseous and intramedullary extending tumours and mandatory for therapy planning. Conventional radiography, however, remains the most important method within the diagnostic strategy, but the need for close cooperation of radiologists and clinicians and a synoptic evaluation of clinical results, radiography and anamnestic data must be stressed.

Adolescent↗
PubMed1988

[Etiology and pathogenesis of autoimmune diseases of the thyroid gland].

As for other autoimmune diseases it is discussed also for immune hyperthyroidism (Basedow's disease) and immune thyroiditis, whether factors such as stress and infections with viruses and bacteria may lead to a disturbance of the immune tolerance in persons genetically predisposed. In Basedow's disease antibodies against the TSH-receptor cause an uncontrolled stimulation of the function of the thyroid gland. One year after the end of an antithyroid drug treatment, e.g. with thiamazol, a recidivation rate of circa 50% develops. There are no criteria which may predict the clinical development of an individual after the end of the treatment with a sufficient reliability. This applies particularly also to the measurement of the TSH receptor antibodies and the suppression test at the end of treatment (Alexander's test). According to the experiences of author moreover patients with small and large goitres and with different degrees of Basedow's orbitopathy do not show any difference in the frequency of the recidivations. In the immune thyroiditis a series of antibody-dependent and lymphocyte-dependent processes may lead to a decreased function of the thyroid gland. This includes the interaction of antibodies with the complement system or with the killer cells (ADCC), the direct decomposition of the cells of the thyroid gland by certain subgroups of lymphocytes and the occurrence of blocking antibodies against the TSH receptor. In patients in whom antibodies were made evident may develop a hypothyroidism. But many patients also for ever remain euthyroid. These observations and experimental data suggest that the cell of the thyroid gland also itself must be "susceptible" to the destruction by the antibodies and lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1987

An epidemiological study of high school ice hockey injuries.

Between 1976 and 1983, 42 spinal cord injuries among ice hockey participants were documented in Canada; within a recent 3-week period, three cases involving fractured necks were reported in a metropolitan area of Minnesota. The purpose of this comprehensive epidemiological study was to document rates, types, and severities of injuries incurred among high school varsity hockey players in Minnesota, as a result of participation in the 1982-1983 season, and to determine the variables associated with these injuries. Within a 30-mile radius of the state's major metropolitan area, 12 high school varsity hockey teams were selected for participation. Specific techniques were used to ensure confidentiality, high response rates, and validation of information. Among the players an injury rate of 75 injuries per 100 players was documented. Head and neck injuries accounted for 22% of the total injuries. Increased risks of injury were associated with multiple health-care provision variables and equipment utilized. Potential strategies are identified as a result of these findings.

Adolescent↗
PubMed1987

Do HLA-DR-typing and measurement of TSH-receptor antibodies help in the prediction of the clinical course of Graves' thyrotoxicosis after antithyroid drug treatment?

In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.

Antithyroid Agents↗
PubMed1987

Pharmacokinetics and urinary excretion of orally administered diiodotyrosine.

Serum levels of diiodotyrosine (DIT) and urinary excretion rates of DIT and iodine were measured in 10 normal subjects after oral administration of 1.57 mumol of DIT corresponding to 400 micrograms of iodine. Serum DIT concentrations rose promptly from a mean endogenous basal level of 0.23 nmol/l to maximum values between 6.0 and 20 nmol/l within 30 min to 1 h after DIT ingestion. Decreasing DIT levels were found in all subjects 2 h after DIT intake. Urinary excretion of intact DIT was low, being less than 1% of the administered dose of exogenous DIT within 2 days. In contrast, 52% of the iodine administered in the form of DIT was excreted in the urine in the same time interval. The rapid absorption of DIT from the gastrointestinal tract combined with rapid and almost complete metabolic degradation by deiodination make orally applied DIT seem a suitable iodine carrier compound for therapeutic purposes.

Administration, Oral↗
PubMed1986

Sarcoidosis and immunocytoma.

The current literature contains reports of sarcoidosis with polyclonal increases in immunoglobulins. There are also reports of lymphoma in patients with pre-existing sarcoidosis. This is believed to be the first report of a patient in whom a monoclonal IgM kappa paraproteinemia developed after the diagnosis of sarcoidosis. This paraproteinemia was linked with a histologically proved non-Hodgkin's lymphoma. The possible relationships between the two disease entities are discussed.

Biopsy↗