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Front Matter Sep 1992

Front Matter

Henry Ford Hospital Medical Journal

No abstract provided.


Prospective Screening In Multiple Endocrine Neoplasia Type 1, Britt Skogseid, Kjell Oberg Sep 1992

Prospective Screening In Multiple Endocrine Neoplasia Type 1, Britt Skogseid, Kjell Oberg

Henry Ford Hospital Medical Journal

To assess the age of clinically detectable onset of multiple endocrine neoplasia type 1 (MEN 1), 88 members of four families were invited to participate in a ten-year biochemical screening program. Evidence for clinically detectable MEN 1 was found in adolescence. Pancreatic endocrine dysfunction constituted the presenting lesion in a majority of these individuals. The age at diagnosis of pancreatic endocrine tumors averaged 25 years and was lowered by almost two decades by prospective investigation. Furthermore, the penetrance of the pancreatic endocrine and parathyroid lesions equaled the penetrance found in autopsy studies. The use of a standardized meal stimulation test ...


Practical Guidelines For Dna-Based Testing In Multiple Endocrine Neoplasia Type 1, Catharina Larsson, Magnus Nordenskjold, Britt Skogseid, Kjell Oberg Sep 1992

Practical Guidelines For Dna-Based Testing In Multiple Endocrine Neoplasia Type 1, Catharina Larsson, Magnus Nordenskjold, Britt Skogseid, Kjell Oberg

Henry Ford Hospital Medical Journal

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant predisposition to neoplastic lesions of the parathyroid glands, the neuroendocrine pancreas, and the anterior pituitary gland. The predisposing genetic defect was localized to the long arm of chromosome 11 by genetic linkage analysis in three affected families. By analyzing six MEN 1 families with 14 DNA marker systems located close to the MEN 1 gene, we have developed a method to identify carriers of the MEN 1 predisposition. We describe practical aspects of such DNA-based diagnostic procedures.


Parathyroid Tumor Biology In Familial Multiple Endocrine Neoplasia Type 1: A Model For Cancer Development, Maria Luisa Brandi Sep 1992

Parathyroid Tumor Biology In Familial Multiple Endocrine Neoplasia Type 1: A Model For Cancer Development, Maria Luisa Brandi

Henry Ford Hospital Medical Journal

Familial multiple endocrine neoplasia type 1 (FMEN 1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. Hyperplasia appears to be the typical histopathological lesion in FMEN 1 endocrine tumors. A circulating mitogen related to basic fibroblast growth factor was active on proliferation of clonal bovine and human parathyroid endothelial cells. Moreover, the FMEN 1 mitogen modulated differentiation of human parathyroid endothelial cell in vitro. All these facts suggested that an extrinsic factor was active on parathyroid endothelial cell growth and differentiation. The FMEN 1 gene maps to chromosome 11q13, and allelic ...


Surgical Treatment Of The Endocrine Pancreas And Zollinger-Ellison Syndrome In The Men 1 Syndrome, Norman W. Thompson Sep 1992

Surgical Treatment Of The Endocrine Pancreas And Zollinger-Ellison Syndrome In The Men 1 Syndrome, Norman W. Thompson

Henry Ford Hospital Medical Journal

Islet cell neoplasia is a frequent occurrence in multiple endocrine neoplasia type 1 (MEN 1). Sixteen of 27 patients with MEN 1 developed functioning endocrine pancreatic tumor syndromes. Eleven of the 16 developed Zollinger-Ellison syndrome and each was evaluated by a combination of computed tomography and hepatic angiography to exclude hepatic metastasis and percutaneous transhepatic catheterization to localize the tumor. Seven of the 11 patients were found to have duodenal gastrinomas with multiple duodenal tumors in three patients. Four of the 11 patients had only pancreatic gastrinomas. In addition to the gastrinomas, other types of islet tumors in the pancreatic ...


Expression Of The Ret Proto-Oncogene In Human Medullary Thyroid Carcinomas And Pheochromocytomas Of Men 2a, Akihiro Miya, Masayuki Yamamoto, Hideki Morimoto, Norifumi Tanaka, Esei Shin, Katsu Karakawa, Kumao Toyoshima, Yukihito Ishizaka, Takesada Mori, Shin-Ichiro Takai Sep 1992

Expression Of The Ret Proto-Oncogene In Human Medullary Thyroid Carcinomas And Pheochromocytomas Of Men 2a, Akihiro Miya, Masayuki Yamamoto, Hideki Morimoto, Norifumi Tanaka, Esei Shin, Katsu Karakawa, Kumao Toyoshima, Yukihito Ishizaka, Takesada Mori, Shin-Ichiro Takai

Henry Ford Hospital Medical Journal

We studied the expression of the ret proto-oncogene (proto-ret) in human medullary thyroid carcinomas (MTCs) and pheochromocytomas of multiple endocrine neoplasia type 2A (MEN 2A) by Northern blot analysis. Expression of the normal-sized transcripts was detected in all 12 MTCs and in 6 of 8 pheochromocytomas. In situ localization of proto-ret mRNA revealed that the signal was confined to the cytoplasm of MTC cells. By Southern blot analysis neither amplification nor gross genetic changes of proto-ret were found in the tumors. Although no transcripts were detected in the normal portion of the thyroid from one MEN 2A patient,faint signals ...


Medullary Thyroid Carcinoma: Australian Experience With Genetic Testing, Janet L. Ward, Valentine J. Hyland, David S. Andrew, Debbie J. Marsh, Bruce G. Robinson Sep 1992

Medullary Thyroid Carcinoma: Australian Experience With Genetic Testing, Janet L. Ward, Valentine J. Hyland, David S. Andrew, Debbie J. Marsh, Bruce G. Robinson

Henry Ford Hospital Medical Journal

Linkage analysis has been performed in four pedigrees with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (MTC) using pericentromeric chromosome 10 probes. Important information regarding carrier status has been provided in 10 individuals, many of whom would not have been identified by pentagastrin stimulation testing. We have also used pulsed field gel electrophoresis (PFGE) to link the probes H4JRBP and pMCK2 to a 150 kb fragment. Using PFGE, no evidence was found in DNA from lymphocytes of a major DNA rearrangement in two individuals affected with MEN 2A and an individual with MEN 2B compared ...


Multiple Endocrine Neoplasia Type 2b: Eighteen-Year Follow-Up Of A Four-Generation Family, Glen W. Sizemore, J. Aiden Carney, Hossein Gharib, Charles C. Capen Sep 1992

Multiple Endocrine Neoplasia Type 2b: Eighteen-Year Follow-Up Of A Four-Generation Family, Glen W. Sizemore, J. Aiden Carney, Hossein Gharib, Charles C. Capen

Henry Ford Hospital Medical Journal

Seven members with multiple endocrine neoplasia type 2B from a 15-member family have been followed for 18 years. All affected had the neuroma phenotype in a distribution compatible with autosomal dominant inheritance. The phenotype features have allowed 100% initial and continuing prediction of affected versus nonaffected status in as early as 1.5 years. Among the affected: immunoreactive plasma calcitonin (iCT) concentration was high in 100%; thyroid palpation was false-negative in 71%; and thyroid scintiscan was false-negative in 83%. All had total thyroidectomy, plus lymphadenectomy in three, for bilateral medullary thyroid carcinoma (MTC) or C-cell hyperplasia (in the youngest). None ...


Cutaneous Lesion Associated With Multiple Endocrine Neoplasia Type 2a: Lichen Amyloidosis Or Notalgia Paresthetica?, O. Chabre, F. Labat, N. Pinel, F. Berthod, V. Tarel, I. Bachelot Sep 1992

Cutaneous Lesion Associated With Multiple Endocrine Neoplasia Type 2a: Lichen Amyloidosis Or Notalgia Paresthetica?, O. Chabre, F. Labat, N. Pinel, F. Berthod, V. Tarel, I. Bachelot

Henry Ford Hospital Medical Journal

Three patients of a French family demonstrated an association of multiple endocrine neoplasia type 2A (MEN 2A) with a pruritic scapular skin lesion. The lesions are similar to those described as familial cutaneous lichen amyloidosis in unrelated MEN 2A and medullary thyroid carcinoma families, but histological, immunohistochemical, and ultrastructural analysis of skin biopsies from each patient in the French family did not show amyloid deposition. The topography of the lesion follows dermatomes C8-D3. The patients report not only pruritus but also paresthesia and hyperalgesia, and one showed touch hypoesthesia and pain hyperesthesia in the area of the lesion. Such an ...


Long-Term Follow-Up In Four Large Men 2 Families In The Netherlands, C. J. M. Lips, M. J. H. Berends, J. Brouwers-Smalbraak, R. A. Geerdink, W. H. L. Hackeng, J. M. Jansen-Schillhorn Van Veen, A. Struyvenberg, Th. J. M. V. Van Vroonhoven Sep 1992

Long-Term Follow-Up In Four Large Men 2 Families In The Netherlands, C. J. M. Lips, M. J. H. Berends, J. Brouwers-Smalbraak, R. A. Geerdink, W. H. L. Hackeng, J. M. Jansen-Schillhorn Van Veen, A. Struyvenberg, Th. J. M. V. Van Vroonhoven

Henry Ford Hospital Medical Journal

Results of follow-up studies in four large multiple endocrine neoplasia type 2A families (total of 95 patients affected) have shown a positive effect on the course of the disease since early screening and intervention were initiated in 1974.


Mineral Metabolic Effects Of Thyroidectomy And Long-Term Outcomes In A Family With Men 2a, Henry G. Bone Iii, Leonard J. Deftos, William H. Snyder, Charles Y. C. Pak Sep 1992

Mineral Metabolic Effects Of Thyroidectomy And Long-Term Outcomes In A Family With Men 2a, Henry G. Bone Iii, Leonard J. Deftos, William H. Snyder, Charles Y. C. Pak

Henry Ford Hospital Medical Journal

We have followed a family with multiple endocrine neoplasia type 2A for 18 years. Four members have undergone total thyroidectomy for medullary thyroid carcinoma or C-cell hyperplasia, and one has required bilateral adrenalectomy for pheochromoctyoma. None has developed hypercalcemic hyperparathyroidism, although parathyroid hormone levels were relatively high prethyroidectomy and fell postoperatively in the patients with high calcitonin levels. In three of the four cases, intestinal calcium absorption decreased following thyroidectomy.


Oncogene And Growth Factor Expression In Men 2 And Related Tumors, Jeffrey F. Moley, Göran K. Wallin, Michele B. Brother, Michael Kim, Samuel A. Wells Jr., Garrett M. Brodeur Sep 1992

Oncogene And Growth Factor Expression In Men 2 And Related Tumors, Jeffrey F. Moley, Göran K. Wallin, Michele B. Brother, Michael Kim, Samuel A. Wells Jr., Garrett M. Brodeur

Henry Ford Hospital Medical Journal

Pheochromocytomas occur sporadically or in individuals affected by inherited syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B, neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and familial MTC. Little is known of the molecular genetic background of these tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras oncogenes does not occur in these tumors, but that deletions of the short arm of chromosome 1 are extremely common (> 60%) and may indicate loss of a suppressor gene in the chromosomal region ...


Biologic And Cytogenetic Characterization Of Three Human Medullary Thyroid Carcinomas In Culture, R. Pfragner, G. Wirnsberger, A. Behmel, B. Niederle, F. Längle, R. Roka, A. Mandl, P. Pürstner, J. Auner, F. Tatzber Sep 1992

Biologic And Cytogenetic Characterization Of Three Human Medullary Thyroid Carcinomas In Culture, R. Pfragner, G. Wirnsberger, A. Behmel, B. Niederle, F. Längle, R. Roka, A. Mandl, P. Pürstner, J. Auner, F. Tatzber

Henry Ford Hospital Medical Journal

Neuroendocrine features and cytogenetic abnormalities of one continuous cell line (MTC-SK) and two long-term cultures (GER, STAH) derived from three sporadic cases of human medullary thyroid carcinomas (MTCs) were studied. Specific neuroendocrine markers (NSE, chromogranins, calcitonin, calcitonin gene-related peptide) were identified by electron microscopy and immunocytochemistry. In situ hybridochemistry and Northern blot analysis confirmed endocrine activity. Cytogenetic studies of the cell line MTC-SK revealed three consistent marker chromosomes, t(3;10), 11p+, and 22p+. Cells of long-term cultures GER and STAH exhibited a consistent translocation t(2;18), a trisomy 7, and two consistent marker chromosomes der3 and 5p+, respectively ...


Proceedings Of The Fourth International Workshop On Multiple Endocrine Neoplasia: Introduction, Robert F. Gagel, Charles E. Jackson Sep 1992

Proceedings Of The Fourth International Workshop On Multiple Endocrine Neoplasia: Introduction, Robert F. Gagel, Charles E. Jackson

Henry Ford Hospital Medical Journal

No abstract provided.


Sublocalization Of The Multiple Endocrine Neoplasia Type 1 Gene, Catharina Larsson, Gunther Weber, Marie Janson Sep 1992

Sublocalization Of The Multiple Endocrine Neoplasia Type 1 Gene, Catharina Larsson, Gunther Weber, Marie Janson

Henry Ford Hospital Medical Journal

Tumorigenesis in multiple endocrine neoplasia type 1 (MEN 1) involves the unmasking of a recessive mutation at the MEN 1 locus which has been mapped to chromosomal region 11q11-13. By analyzing 58 DNA markers on a panel of radiation-reduced somatic cell hybrids, the region encompassing the MEN 1 gene was divided into nine subregions. Pulsed field gel electrophoresis analysis of markers within subgroups showed that the recombination rate around the MEN 1 locus is high. Combined linkage analysis in MEN 1 families and deletion mapping in MEN 1-related tumors suggest the MEN 1 gene is located centromeric to D11S807 and ...


The Importance Of Screening For The Men 1 Syndrome: Diagnostic Results And Clinical Management, C. J. M. Lips, H. P. F. Koppeschaar, M. J. H. Berends, J. M. Jansen-Schillhorn Van Veen, A. Struyvenberg, Th. J. M. V. Van Vroonhoven Sep 1992

The Importance Of Screening For The Men 1 Syndrome: Diagnostic Results And Clinical Management, C. J. M. Lips, H. P. F. Koppeschaar, M. J. H. Berends, J. M. Jansen-Schillhorn Van Veen, A. Struyvenberg, Th. J. M. V. Van Vroonhoven

Henry Ford Hospital Medical Journal

No abstract provided.


Hyperparathyroidism With Normal Albumin-Corrected Total Calcium In Patients With Multiple Endocrine Neoplasia Type 1, J. J. Shepherd, Bin Tean Teh, V. Parameswaran, R. David Sep 1992

Hyperparathyroidism With Normal Albumin-Corrected Total Calcium In Patients With Multiple Endocrine Neoplasia Type 1, J. J. Shepherd, Bin Tean Teh, V. Parameswaran, R. David

Henry Ford Hospital Medical Journal

In the largest reported family of patients with multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism was expressed at first screening in 33 patients by elevation of ionized calcium (IC) (30 cases) or parathyroid hormone (three cases) without elevation of albumin-corrected total calcium (ACTC). Three of these 33 patients have shown a progressive rise in IC and later an elevation of ACTC. However, the age distribution suggests that in others the level of IC may remain stable at a minimally elevated level throughout life with ACTC remaining normal except for transient rises at the times of intercurrent illness or surgical ...


Primary Hyperparathyroidism In Patients With Multiple Endocrine Neoplasia Type 1: Experience By A Single Surgical Team In Japan, Takao Obara, Yoshihide Fujimoto, Yukio Ito Sep 1992

Primary Hyperparathyroidism In Patients With Multiple Endocrine Neoplasia Type 1: Experience By A Single Surgical Team In Japan, Takao Obara, Yoshihide Fujimoto, Yukio Ito

Henry Ford Hospital Medical Journal

Nineteen patients were surgically treated for hyperparathyroidism associated with multiple endocrine neoplasia type 1 syndrome. Fourteen patients (74%) had removal of three or more parathyroid glands at the first operation, and five (26%) by removal of 2 1/2 or fewer glands. Two patients had recurrent hypercalcemia during the mean follow-up period of 65 months. One had a recurrence 10 years after subtotal parathyroidectomy. Reexploration in this patient revealed enlargement of the remaining tissue in the neck and an enlarged supernumerary gland in the aorticopulmonary window. The other patient had persistent hypercalcemia after removal of two hyperplastic parathyroid glands until ...


Isolation Of Yac Clones From The Pericentromeric Region Of Chromosome 10 And Development Of New Genetic Markers Linked To The Multiple Endocrine Neoplasia Type 2a Gene, Terry C. Lairmore, James R. Howe, Shenshen Dou, Rosalie Veile, Jennifer A. Korte-Sarfaty, Samuel A. Wells Jr., Helen Donis-Keller Sep 1992

Isolation Of Yac Clones From The Pericentromeric Region Of Chromosome 10 And Development Of New Genetic Markers Linked To The Multiple Endocrine Neoplasia Type 2a Gene, Terry C. Lairmore, James R. Howe, Shenshen Dou, Rosalie Veile, Jennifer A. Korte-Sarfaty, Samuel A. Wells Jr., Helen Donis-Keller

Henry Ford Hospital Medical Journal

Genetic linkage mapping and contig assembly using yeast artificial chromosome (YAC) technology form the basis of our strategy to clone and define the genomic structure of the pericentromeric region of chromosome 10 containing the multiple endocrine neoplasia type 2A gene. Thus far YAC walks have been initiated from five chromosome 10 pericentromeric loci including RBP3, D10S94, RET, D10Z1, and FNRB. Long range pulsed-field gel electrophoresis maps are constructed from the YACs isolated to define clone overlaps and to identify putative CpG islands. Bidirectional YAC walks are continued by rescreening the YAC library with sequence-tagged site assays developed from endclones. Several ...


High-Sensitivity Serum Calcitonin Assays Applied To Screening For Thyroid C-Cell Disease In Multiple Endocrine Neoplasia Type 2a, Michael M. Kaplan, Glenn M. Stall, Timothy Cummings, Andrew Macaulay, Philippe Motté, Hubert J. Wolfe, Seymour Reichlin, Arman J. Tashjian Jr. Sep 1992

High-Sensitivity Serum Calcitonin Assays Applied To Screening For Thyroid C-Cell Disease In Multiple Endocrine Neoplasia Type 2a, Michael M. Kaplan, Glenn M. Stall, Timothy Cummings, Andrew Macaulay, Philippe Motté, Hubert J. Wolfe, Seymour Reichlin, Arman J. Tashjian Jr.

Henry Ford Hospital Medical Journal

Two serum calcitonin assays with sensitivities ≤ 10 pg/mL were compared to our standard radioimmunoassay (sensitivity 100 pg/mL) in multiple endocrine neoplasia type 2A (MEN 2A) screening. Values from the Nichols displacement radioimmunoassay averaged 38% higher than values from the CIS immunoradiometric assay; values from both were highly correlated, r = 0.845. In three individuals, both of the newer assays revealed abnormalities in pentagastrin tests three to four years before abnormalities were detected by the standard assay. Pentagastrin tests after total thyroidectomy were assayed by the newer methods in patients with medullary thyroid carcinoma (MTC) diagnosed at initial testing ...


Genetics Of The Multiple Endocrine Neoplasia Type 2b Syndrome, Charles E. Jackson, Robert A. Norum Sep 1992

Genetics Of The Multiple Endocrine Neoplasia Type 2b Syndrome, Charles E. Jackson, Robert A. Norum

Henry Ford Hospital Medical Journal

Multiple endocrine neoplasia type 2B (MEN 2B) is similar to MEN 2A in that both autosomal dominant syndromes include medullary thyroid cancers and pheochromocytomas. It is distinct in that MEN 2B patients have much earlier age of onset with more aggressive tumors and mucosa/neuromas of the lips and tongue. The neuromas allow ascertainment generally before age 5. Studies of two and three generations of 14 MEN 2B families disclosed close linkage of the MEN 2B gene to DNA markers to which MEN2A had been linked. Multipoint analysis utilizing additional results in three generations of a 15th family have disclosed ...


Unusual Features Of Multiple Endocrine Neoplasia, Andrea Frilling, Heinz Becker, Hans-Dietrich Roeher Sep 1992

Unusual Features Of Multiple Endocrine Neoplasia, Andrea Frilling, Heinz Becker, Hans-Dietrich Roeher

Henry Ford Hospital Medical Journal

In addition to the common presentations of the multiple endocrine neoplasia (MEN) syndromes, unusual organ involvement as rare manifestations of a single disease may occur. Among our patients we have identified four cases in which unusual features of MEN were present. In the first patient, bilateral adrenal cortical adenoma, parathyroid adenoma, multiple pancreatic tumors, and follicular thyroid carcinoma were observed. The second patient suffered from thymic carcinoid, parathyroid hyperplasia, gastrinoma, and pituitary adenoma. Additionally, one family was discovered in which medullary thyroid carcinoma (MTC), Hirschsprung's disease, and pheochromocytoma occurred and another family had MTC and ovarian cancer. Based on ...


Should Patients With Medullary Thyroid Carcinoma Undergo Extensive Lymph Node (Re)Operation To Improve Long-Term Survival?, Caro Brumsen, Harm R. Haak, Bernard M. Goslings, Cornelis J. H. Van De Velde Sep 1992

Should Patients With Medullary Thyroid Carcinoma Undergo Extensive Lymph Node (Re)Operation To Improve Long-Term Survival?, Caro Brumsen, Harm R. Haak, Bernard M. Goslings, Cornelis J. H. Van De Velde

Henry Ford Hospital Medical Journal

To investigate the role of primary and/or secondary modified radical neck dissection (MRND) in patients with medullary thyroid carcinoma (MTC), follow-up data on 43 patients operated on between 1972 and 1983 were analyzed retrospectively; patients included 16 with sporadic MTC (group 1) and 27 with multiple endocrine neoplasia type 2 (group 2). Primary surgical therapy consisted of (near-) total thyroidectomy and limited lymph node dissection: one patient in group 1 and two in group 2 underwent primary MRND. Positive nodes were found in nine patients of group 1 and in 12 of group 2. Calcitonin (CT) was raised postoperatively ...


Pheochromocytoma: A Frequent Indicator For Men 2, Claude Calmettes, Myriam Rosenberg-Gourgin, Jean Caron, Nicole Feingold Sep 1992

Pheochromocytoma: A Frequent Indicator For Men 2, Claude Calmettes, Myriam Rosenberg-Gourgin, Jean Caron, Nicole Feingold

Henry Ford Hospital Medical Journal

Pheochromocytoma is a frequent indicator of multiple endocrine neoplasia type 2A (MEN 2A); in the 35 French MEN 2A families in which a pheochromocytoma occurred first in some affected members, 30% of the patients had a pheochromocytoma as the first manifestation constituting 45% of all patients with pheochromocytomas. The finding of a pheochromocytoma is a strong indication for a search for medullary thyroid carcinoma and for initiating family screening.


Evaluation Of Children With Medullary Thyroid Carcinoma, Alfonso Libroia, Fabrizio Muratori, Uberta Verga, Gianleone Di Sacco, Anna Grattieri, Dario Gelli Sep 1992

Evaluation Of Children With Medullary Thyroid Carcinoma, Alfonso Libroia, Fabrizio Muratori, Uberta Verga, Gianleone Di Sacco, Anna Grattieri, Dario Gelli

Henry Ford Hospital Medical Journal

Early diagnosis and surgical treatment of medullary thyroid carcinoma (MTC) in children is essential to decrease the likelihood of metastatic spread. From 1981 to 1991, eight children under 18 years of age (five girls and three boys) with MTC were seen and seven underwent total thyroidectomy. Followup ranged from 14 months to 10 years after surgery. Four of the seven presented with a neck mass and elevated basal levels of calcitonin (CT). After surgery, three had recurrent disease. In the other three, the diagnosis was made after several years of screening (normal basal values of CT but increased CT levels ...


Somatostatin Acts Via A Pertussis Toxin-Sensitive Mechanism On Calcitonin Secretion In C-Cells, Angela Zink, Hans Scherubl, Friedhelm Raue, Reinhard Ziegler Sep 1992

Somatostatin Acts Via A Pertussis Toxin-Sensitive Mechanism On Calcitonin Secretion In C-Cells, Angela Zink, Hans Scherubl, Friedhelm Raue, Reinhard Ziegler

Henry Ford Hospital Medical Journal

The effect of the somatostatin analog octreotide on cAMP-mediated calcitonin (CT) secretion and cAMP accumulation in C-cells was investigated. Glucagon stimulated cAMP accumulation and CT secretion with a maximal effect at a concentration of 10-6 M. The cAMP antagonist RpcAMPs blocked the glucagon-induced CT secretion down to control levels. Therefore, no other second messengers seem to be involved in glucagon-stimulated CT secretion. Octreotide in increasing doses (10-9 to 10-6 M) inhibited cAMP accumulation and CT secretion with a maximal effect at a concentration of 10-7 (40% and 29% of control values, respectively). Pretreatment of the cells ...


Role Of Insulin-Like Growth Factor-I In The Autocrine Regulation Of Cell Growth In Tt Human Medullary Thyroid Carcinoma Cells, Kuo-Pao P. Yang, Naguib A. Samaan, Yi-Fan Liang, Socorro G. Castillo Sep 1992

Role Of Insulin-Like Growth Factor-I In The Autocrine Regulation Of Cell Growth In Tt Human Medullary Thyroid Carcinoma Cells, Kuo-Pao P. Yang, Naguib A. Samaan, Yi-Fan Liang, Socorro G. Castillo

Henry Ford Hospital Medical Journal

Since the TT human medullary thyroid carcinoma cell line required fewer exogenous growth factors (serum), we investigated whether this line has an autocrine mechanism by examining the effects of antibodies directed toward insulin-like growth factor I (IGF-I) and its receptor on TT cell growth in serum-free conditions. Treating cells with anti-IGF-I antibody for four days reduced the cell number by more than 50% compared with a nonimmune IgG control. Furthermore, a monoclonal antibody to the IGF-I receptor suppressed DNA synthesis when determined by a [3H]thymidine incorporation assay. Exogenous IGF-I (20 ng/mL) stimulated [3H]thymidine incorporation in ...


Pdn-21 (Katacalcin) And Chromogranin A: Tumor Markers For Medullary Thyroid Carcinoma, Friedhelm Raue, Eberhard Blind, Andreas Grauer Sep 1992

Pdn-21 (Katacalcin) And Chromogranin A: Tumor Markers For Medullary Thyroid Carcinoma, Friedhelm Raue, Eberhard Blind, Andreas Grauer

Henry Ford Hospital Medical Journal

The malignant C-cell releases several markets of potential clinical significance into the circulation. To determine the usefulness of these markers for management of medullary thyroid carcinoma (MTC), it is necessary to compare the usefulness of these markers with calcitonin (CT), the classical tumor marker for MTC. Measurement of serum concentrations of the peptide PDN-21 (katacalcin), a carboxyterminal cleavage product of procalcitonin. showed a high correlation with serum CT levels (r = 0.99, P < 0.01, n = 65 patients with MTC). The presence of equimolar concentrations of CT and PDN-21 (CT/PDN-21 molar ratio = 0.95 ± 0.33) indicates the peptide is cosecreted with CT. Stimulation of CT release by intravenous pentagastrin was associated with a parallel increase of PDN-21, providing further evidence of cosecretion of these two peptides. Finally, measurement of either PDN-21 or CT in selective venous catheterization specimens was useful for localization of MTC. Chromogranin A (CgA) levels were also measured in patients with MTC. Circulating levels were elevated in most patients with advanced disease. There was a moderate correlation between CgA and CT serum levels (r = 0.87, P < 0.01. n = 61 patients with MTC). Pentagastrin did not stimulate CgA, and the long half-life of CgA in the circulation did not make it possible to use this peptide for tumor localization by selective venous catheterization. We conclude that measurement of PDN-21 provides an independent assay system for diagnosis, localization, and postoperative management of MTC. whereas CgA measurement is not useful in early diagnosis of MTC and is of limited value for localization or management of progressive disease.


Molecular Genetic Mapping Of The Multiple Endocrine Neoplasia Type 1 Locus, Joanna T. Pang, Mark A. Pook, James H. Eubanks, Carol Jones, Veronica Van Heyningen, Glen A. Evans, Rajesh V. Thakker Sep 1992

Molecular Genetic Mapping Of The Multiple Endocrine Neoplasia Type 1 Locus, Joanna T. Pang, Mark A. Pook, James H. Eubanks, Carol Jones, Veronica Van Heyningen, Glen A. Evans, Rajesh V. Thakker

Henry Ford Hospital Medical Journal

Familial multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by the combined occurrence of tumors of the parathyroid glands, the endocrine pancreas, and the pituitary gland. MEN 1 tumors have previously been shown to be associated with the loss of alleles on chromosome 11, and deletion mapping studies together with family linkage studies have localized the MEN 1 gene to 11q13. A detailed genetic map around the MEN 1 locus is required to facilitate further characterization and cloning of the gene (MEN1). We have characterized a panel of seven rodent-human somatic cell hybrids which contain ...


Prad1 (Cyclin D1): A Parathyroid Neoplasia Gene On 11q13, Andrew Arnold, Toru Motokura, Theodora Bloom, Carol Rosenberg, Allen Bale, Henry Kronenberg, Joan Ruderman, Milton Brown, Hyung Goo Kim Sep 1992

Prad1 (Cyclin D1): A Parathyroid Neoplasia Gene On 11q13, Andrew Arnold, Toru Motokura, Theodora Bloom, Carol Rosenberg, Allen Bale, Henry Kronenberg, Joan Ruderman, Milton Brown, Hyung Goo Kim

Henry Ford Hospital Medical Journal

Hyperparathyroidism is a central component of multiple endocrine neoplasia type 1 (MEN 1), and both sporadic and familial forms of parathyroid disease may share certain pathogenetic features. We recently identified a gene that is clonally rearranged with the PTH locus in a subset of sporadic parathyroid adenomas. This candidate oncogene, PRAD1 (previously D11S287), appears to contribute to parathyroid tumorigenesis in a fashion analogous to activation of C-MYC or BCL-2 by rearrangement with tissue-specific enhancers of the immunoglobulin genes in B-lymphoid neoplasia. The PRAD1 gene maps to 11q13 and has been linked to the BCL-1 breakpoint locus, although not to the ...