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Biomedical subjects

L Fogelfeld

Publications and source records attributed to L Fogelfeld.

At least 19 recordsLinked to original sources
PubMed2002

RET expression in papillary thyroid cancer from patients irradiated in childhood for benign conditions.

Both external and internal exposure to radiation have been linked to the development of papillary thyroid cancer. Rearrangement of the gene for RET tyrosine kinase and subsequent expression of this protein has also been found to occur in many papillary thyroid cancers, and with increased frequency in radiation-related cancers following the Chernobyl accident. However, little has been reported on the frequency of RET rearrangements in cancers after exposure to external radiation. We here report on RET protein immunoreactivity in paraffin-embedded thyroid samples from 30 patients with papillary thyroid cancer who received radiation treatment during childhood for benign conditions at Michael Reese Hospital in Chicago, and in 34 patients identified from the tumor registry as having papillary thyroid cancer with no history of therapeutic radiation. The subjects were characterized by sex, age at surgery, and the following attributes of tumor pathology: size, number of lobes involved, number of foci, lymph node metastases, and soft tissue invasion. Representative tissue samples were reacted with an antibody against the RET tyrosine kinase domain whose expression has been shown to correlate highly with RET/PTC rearrangements. A greater percentage of cancers positive for RET immunoreactivity was found in the radiation-exposed group (86.7% vs. 52.9%, P = 0.006). Although the mean age at surgery of the exposed group was lower than the control group, there was no correlation of positive RET immunoreactivity with the age at surgery. No characteristics of the tumors were associated with positive RET immunoreactivity. In summary, the greater incidence of RET-immunopositives in the irradiated group indicates that the expression of RET immunoreactivity is strongly associated with radiation exposure, but the prognostic significance of this is not yet clear.

Adult↗
PubMed1996

p53 gene mutations in radiation-induced thyroid cancer.

Little is known about the role of specific oncogenes and tumor suppressor genes in radiation-induced thyroid cancer (RITC). In thyroid cancer, mutations in the p53 tumor suppressor gene have been largely confined to the more aggressive anaplastic forms. We studied point mutations in the p53 gene in 22 patients exposed in childhood to radiation in the head and neck area who later developed papillary thyroid cancers (RITC). Eighteen thyroid cancer patients without exposure to radiation, selected to match by gender and age the RITC group, were used as the control group. After histological identification, DNA was extracted from paraffin-embedded specimens. Exons 5-8 of p53 were PCR amplified and screened for mutations by single strand conformation polymorphism analysis and cycle sequencing. Four of 22 RITC patients (18%) showed missense point mutations. No missense mutations were found in the cancer control group. The missense mutations in the RITC group occurred at codon 208 in 2 patients, codon 177 in 1, and codon 217 in 1. The mutations were transitions from G to A and C to T. All patients with missense mutations were male and had lymph node involvement. Three of the 4 patients with p53 missense mutations had invasion of the cancer beyond the thyroid capsule compared to 2 of the 17 remaining RITC patients. None of the patients with p53 mutations had distant metastases or recurrence of the tumor. These results suggest that p53 gene point mutations may play a pathogenetic role in some radiation-induced, well differentiated thyroid cancers and in their local spread.

Adolescent↗
PubMed1992

Low-molecular-weight iodoproteins in the congenital goiters of cog/cog mice.

Previously we described sedimentation and immunologic abnormalities of thyroglobulin (Tg) in a strain of mice with inherited congenital goiter and hypothyroidism (cog/cog). The goals of the present study were to determine the extent to which thyroid gland stimulation by TSH accounts for the abnormal properties of cog/cog Tg and to characterize further the abnormally small iodoproteins found in cog/cog mice. Cog/cog and control +/cog and BALB/c mice were fed with either normal or thyroid-hormone-containing diets and were injected with Na125I. Sucrose density gradient centrifugation of labeled thyroid extracts from cog/cog mice on normal diet showed that 82% of the iodine was in iodoproteins smaller than Tg, with sedimentation rates of 3-8S. No 12S and 19S peaks, characteristic of normal Tg, were present, but distinct and stable 12S and 19S peaks emerged after recentrifugation of the 12S and 19S areas. In contrast, in cog/cog mice treated with T4, a smaller (55%) amount of 3-8S iodoproteins and distinct 12S and 19S peaks were present. In both groups of mice, the labeled 3-8S iodoproteins were composed of three fractions: 15% precipitated by antirat Tg serum, 38% precipitated by antimouse albumin serum, and 47% not precipitated by either serum. The 3-8S iodoproteins contained labeled MIT and DIT and no T4. On sodium dodecyl sulfate polyacrylamide gel electrophoresis the 3-8S iodoprotein fraction that reacted with anti-Tg serum contained a distinct electrophoretic band at 49K. The 3-8S nonreactive iodoproteins resolved into several bands of lower molecular weight. We conclude that the 3-8S iodoproteins in cog/cog mice are heterogeneous and that TSH stimulation contributes to the production of these low-molecular-weight iodoproteins.

Amino Acids↗
PubMed1991

Anionic carbohydrate groups of human thyroglobulin containing both phosphate and sulfate.

We showed previously that human thyroglobulin (hTG) contains anionic complex carbohydrate units with up to four sulfate groups, some containing both sulfate and sialic acid. Recent reports indicate that the carbohydrate units of hTG may also contain phosphate, but these reports are not all in accord. The purpose of this study was to confirm the presence of phosphate on the carbohydrate units of hTG and to determine whether phosphate coexists with other acidic moieties, such as sulfate and sialic acid, on the same carbohydrate units. Alkaline phosphatase and acid hydrolysis were used to detect phosphate on the sulfated carbohydrate units of hTG derived from normal and neoplastic tissues. Thyroid fragments from two patients were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified. Complex carbohydrates were released from hTG with endoglycosidase-F and analyzed at pH 2.2 on a HPLC ion exchange column. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing ones were identified by their reduced charge after neuraminidase or acid treatment. None of the sulfate-labeled carbohydrate peaks shifted after alkaline phosphatase treatment alone, indicating that none of them contained phosphomonoesters. Several of the sulfate-labeled peaks shifted after acid hydrolysis, some to positions of decreased charge, due to removal of sialic acid, and some to positions of increased charge, suggesting the presence of phosphodiesters. The latter was confirmed by the observation that some of the newly formed peaks were susceptible to alkaline phosphatase digestion. Thus, acid hydrolysis converted phosphodiesters into alkaline phosphatase-susceptible phosphomonoesters, most likely mannose-6-phosphate. We conclude that some anionic complex carbohydrate units of hTG contain exclusively sulfate, while others contain combinations of sulfate, sialic acid, and phosphodiesters. Phosphodiesters are present in the sulfated carbohydrate units of hTG from normal as well as neoplastic thyroid tissue.

Alkaline Phosphatase↗
PubMed1990

Inhibition of chondroitin sulfate incorporation into human thyroglobulin by p-nitrophenyl-beta-D-xylopyranoside.

Human thyroglobulin (TG) is unique among glycoproteins and TGs of other species in having a chondroitin sulfate chain. We studied the effects of p-nitrophenol-beta-D-xylopyranoside (PNXP), an inhibitor of chondroitin sulfate incorporation into core protein of proteoglycans, on the synthesis of human TG. Fragments of normal thyroid tissue from two patients were preincubated for 1 h with PNXP before adding [35S] sulfate and [3H]leucine. TG was purified by ammonium sulfate precipitation, sucrose gradient centrifugation, and CsCl equilibrium density gradient centrifugation. Chondroitin ABC lyase released 38-42% of the [35S]sulfate from control TG, synthesized in the absence of inhibitor, demonstrating the presence of chondroitin sulfate units. In the samples incubated with increasing concentrations of PNXP (0.2 and 1 mM), the fraction of [35S] sulfate released by ABC lyase decreased progressively (14-23% and 8-11%, respectively). This confirms that, as in chondroitin sulfate proteoglycans, chondroitin sulfate synthesis in TG is initiated by the transfer of a galactose unit, by galactosyltransferase, to a xylosyl-serine in the TG peptide backbone. This step is prevented by PNXP, which is a competitive acceptor of galactose. The density of TG synthesized in the presence of PNXP was determined by CsCl equilibrium density centrifugation. [3H] leucine-labeled TG from the samples incubated with PNXP was less dense than [3H]leucine-labeled TG from the control specimen. The newly synthesized TG was less dense either because of the lack of the chondroitin sulfate chain or because further processing of the TG was impaired. To differentiate these possibilities, we treated control, [3H]leucine-labeled TG with chondroitin ABC lyase and compared its density to that of [3H] leucine-labeled TG synthesized in the presence of 1 mM PNXP. The decrease in density produced by PNXP was greater than the decrease brought about by chondroitin ABC lyase (4.3-5.2 x 10(-3) and 2.4-2.8 x 10(-3) g/cm3, respectively). Therefore, the density contributed by the chondroitin chain was insufficient to account for the entire density shift seen with PNXP. We conclude that 1) chondroitin sulfate synthesis is initiated by the transfer of a galactosyl unit to xylosyl-serine in the TG peptide backbone; and 2) inhibition of this step decreases the density of TG by preventing the addition of the chondroitin chain and interfering with the further processing of TG.

Centrifugation, Density Gradient↗
PubMed1990

Anionic complex-carbohydrate units of human thyroglobulin.

Human thyroglobulin (hTG) contains sulfate in chondroitin 6-sulfate chains and in complex carbohydrates. In this study the sulfate-containing complex carbohydrates were characterized by the number of sulfate and sialic acid residues that they contain. Samples of normal and nodular thyroid tissue were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified from the tissues and the media. Complex carbohydrates were enzymatically removed from hTG. Subsequent analysis on an HPLC anion exchange column at pH 2.2 separated the carbohydrate units according to their number of negative charges. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing peaks were identified by their shift to lower charge after treatment with neuraminidase. Peaks corresponding to sialic acid-free carbohydrate units with one to four sulfates were identified. Also, carbohydrate units with two and three negative charges containing both sulfate and sialic acid were present. In the nodular tissue of one patient there were more sulfated units with higher charge, especially units containing sialic acid. In this patient the proportion of sulfated polyvalent units with sialic acid was 22.4% for normal and 64.6% for nodular tissue. No difference in the composition of the charged units between the tissues and their corresponding media was seen, making it unlikely that the sulfate-containing carbohydrates play a role in hTG release. It is concluded that hTG contains complex carbohydrate units with up to four sulfate groups and units with both sulfate and sialic acid. In some patients, the sulfate-containing anionic carbohydrate units of hTG from normal and nodular thyroid tissue are different.

Anions↗
PubMed1990

Phosphofructokinase deficiency (Tarui disease) associated with hepatic glucuronyltransferase deficiency (Gilbert's syndrome): a case and family study.

Tarui disease is a rare, genetically determined glycogen storage myopathy caused by the total lack of phosphofructokinase (PFK) enzymatic activity in the muscles and partially deficient enzymatic activity in the erythrocytes. We describe a patient with this disorder, who presented with exercise intolerance, painful cramps, elevation of muscle enzyme levels in the serum, compensated hemolysis with paradoxically elevated hemoglobin levels and gout with overproduction of uric acid. This patient had a partial hepatic uridine diphosphoglucuronate-glucuronyltransferase deficiency (Gilbert's syndrome). The coexistence of these two enzymatic deficiencies resulted in a complex clinical picture, especially during and after muscular effort. Screening of the patient's family revealed asymptomatic PFK deficiency in the erythrocytes of both parents and sister.

Adult↗
PubMed1989

[Well-differentiated thyroid carcinoma].

18 cases of well-differentiated thyroid carcinoma are described, of which 5 were papillary or mixed carcinomas and 3 were follicular. In 12 of 14 in whom radio-isotope scanning was performed, a cold or indeterminate nodule was found. Fine needle aspiration was positive and concordant with the operative histological findings in half the cases examined. In 4 hemithyroidectomy was performed, and in 14 total thyroidectomy. Thyroid remnants were found on scanning in all of the 14. These remnants were ablated with radioactive iodine (131I). An ablative dose of 30 millicurie was insufficient in almost all cases and a second dose was required. 3 cases with regional spread of the tumor were reoperated, and large ablative doses of 131I(150-170 mCi) were given. In 14 cases clinical remission was achieved. Followup included ultrasonography and total body 131I scans.

Adenocarcinoma↗
PubMed1989

Recurrence of thyroid nodules after surgical removal in patients irradiated in childhood for benign conditions.

To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P less than 0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patient's sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologic analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer.

Adult↗
PubMed1989

Nesidioblastosis in adults.

A 75-year-old woman with hyperinsulinemic hypoglycemia who died of acute myocardial infarction with ventricular rupture is reported. The microscopic examination of the pancreas revealed that the cause of hyperinsulinemic hypoglycemia was nesidioblastosis characterized by the presence of enlarged, irregular islets of Langerhans and clusters of islet cells in close proximity to the ducts. To our knowledge, nesidioblastosis in adults has not been previously reported in Israel.

Aged↗
PubMed1986

Severe thyrotoxicosis caused by an ectopic intrathoracic goiter.

The case of a 71-year-old woman with severe thyrotoxicosis due to an ectopic multinodular intrathoracic goiter is described. Previously reported cases with intrathoracic ectopic thyroid tissue were either nontoxic, or, if thyrotoxic, were a direct continuation of the tissue of the normally located gland. This mass was proved to be of thyroid origin using Tc-99m sodium pertechnetate scanning.

Aged↗
PubMed1983

Antibodies to spiroperidol and their anti-idiotypes as probes for studying dopamine receptors.

Spiroperidol was covalently conjugated to bovine serum albumin (BSA). Conjugated spiroperidol was almost as efficient as free spiroperidol in its binding capacity to dopamine receptor. Antibodies to spiroperidol were produced in rabbits following repeated immunizations with the conjugate of spiroperidol and BSA. The obtained antibodies have an apparent KD of 0.02 nM for [3H]-spiroperidol. These antibodies bind also to other butyrophenones with IC50 values three to four orders of magnitude higher than the IC50 obtained with unlabeled spiroperidol. Antibodies were purified from anti-spiroperidol sera by affinity chromatography. Anti-idiotypic antibodies were raised in rabbits by immunization with the purified anti-spiroperidol antibodies. Some rabbits produced anti-idiotypic antibodies which bind to rat and calf striatum.

Animals↗