Medicine and Health Sciences Commons^™

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

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 …

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 …

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 …

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 were …

Screening For Multiple Endocrine Neoplasia Type 2a With Dna-Polymorphism Analysis, Estelle M.-F. Lamothe, Steven A. Narod, Shari Miller, Paul J. Goodfellow, David E. C. Cole, Dawna Gilchrist, Zdenka Pausova, David Goltzman, Geoffrey N. Hendy

Henry Ford Hospital Medical Journal

Nine chromosome 10 DNA markers (FNRB, D10S34, D10Z1, MEN203, D10S94, RBP3, D10S15, MBP [48.11], D10S22) were typed in two large Canadian pedigrees with multiple endocrine neoplasia type 2A (MEN 2A). These markers and the gene for MEN 2A (MEN2A) are believed to be in one linkage group spanning approximately 15 cM (male). MEN203 and D10S94 were informative and tightly linked to MEN2A with no recombinants observed in 26 meiotic events. D10S15 (MCK2), widely used in DNA genotyping predictions, demonstrated two recombinants in these two families. The use of multiple flanking markers increases both the likelihood of informativeness and the accuracy …

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 has …

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 these …

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.

Frequency And Significance Of Cervicomediastinal Lymph Node Metastases In Medullary Thyroid Carcinoma: Results Of A Compartment-Oriented Microdissection Method, Henning Dralle, Iris Damme, Georg Friedrich Wilhelm Scheumann, Jorg Kotzerke, Eckhart Kupsch

Henry Ford Hospital Medical Journal

The frequency and significance of cervicomediastinal lymph node metastases have been investigated in 82 medullary thyroid carcinoma (MTC) patients retrospectively comparing two surgical techniques of lymph node dissection: selective lymphadenectomy (n = 63) versus compartment-oriented microdissection (n = 35). No positive correlation was observed between primary tumor size and the number of lymph node metastases. Inpatients with lymph node metastases proven histologically, 42% showed only cervical involvement (35% unilateral—type A, 7% bilateral—type B, and 22% cervicomediastinal lymph node involvement (15% cervico-unilateral and mediastinal—type C, 7% cervicobilateral and mediastinal—type D). Biochemical cure was 83% in node-negative patients but only 21% in …

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 in …

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

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

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

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 serum-free …

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. Recently, we have isolated …

Extracellular Ca2+ Sensing In C-Cells And Parathyroid Cells, Hans Scherubl, Maria Luisa Brandi, Jurgen Hescheler

Henry Ford Hospital Medical Journal

An essential function of C-cells and parathyroid cells is to monitor the extracellular Ca²⁺ concentration. The Ca²⁺-dependent secretion of calcitonin (CT) and parathyroid hormone is known to be mediated by corresponding changes in the intracellular Ca²⁺ concentration. To address the question of whether Ca²⁺ influx through voltage-dependent Ca²⁺ channels couples the extracellular to the intracellular Ca²⁺, we applied the patch clamp technique to C-cells of the rMTC 44-2 cell line and to parathyroid cells of the PT-r cell line. The rMTC cells displayed dihydropyridine-sensitive, voltage-dependent, high-threshold Ca²⁺ channels which allowed ion …

Back Matter

Henry Ford Hospital Medical Journal

No abstract provided.

On The Mechanism Of Parathyroid Hormone Stimulation Of Calcium Uptake By Mouse Distal Convoluted Tubule Cells, F A. Gesek, A. Friedman

Dartmouth Scholarship

PTH stimulates transcellular Ca2+ absorption in renal distal convoluted tubules. The effect of PTH on membrane voltage, the ionic basis of the change in voltage, and the relations between voltage and calcium entry were determined on immortalized mouse distal convoluted tubule cells. PTH (10(-8) M) significantly increased 45Ca2+ uptake from basal levels of 2.81 +/- 0.16 to 3.88 +/- 0.19 nmol min-1 mg protein-1. PTH-induced 45Ca2+ uptake was abolished by the dihydropyridine antagonist, nifedipine (10(-5) M). PTH did not affect 22Na+ uptake. Intracellular calcium activity ([Ca2+]i) was measured in cells loaded with fura-2. Control [Ca2+]i averaged 112 +/- 21 nM. …

Fixed-Ratio Size As A Determinant Of The Development Of Tolerance To Morphine, Mark J. Nickel

Masters Theses

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.

The R Value At Vo2 Max During Maximal Graded Exercise Treadmill Tests Of Coronary Artery Diseased And Nondiseased Subjects, Sherry S. Williams

Masters Theses

This study examined the R value at VO2 max during maximal graded treadmill exercise tests to determine if it was a reliable indicator of VO2 max and could therefore be used as a test termination criterion. The subjects in this study were 160 coronary artery diseased (CAD) patients and 170 nondiseased individuals. Data were collected from existing stress test records. The R value was also analyzed to determine if proportions of diseased and nondiseased subjects were the same. The time it took 100 CAD patients to reach VO2 max and exhaustion once R rose above 1.00 was also examined.

The …

F Response Frequency For The Median And Ulnar Nerves In A Normal Population, Patricia J. Killea

Rehabilitation Sciences Theses & Dissertations

The F wave or F response results form the recurrent discharge of antidromically activated anterior horn cells. F response latency represents an impulse which travels to and from the spinal cord through the central segment of a nerve. Study of the F wave is commonly done to assess proximal conduction in motor nerves, to measure motor nerve conduction velocity over a longer pathway than in orthodromic motor studies, and to assess motor neuron excitability. F response characteristics less commonly studied include duration, chronodispersion, shape, amplitude, and frequency. The primary purpose of this study was to determine F response frequencies of …

Development Of Periapical Lesions In Immunosuppressed Rats, Phillip A. Waterman Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

The pathogenesis of periapical lesions is the interaction of the oral flora with the existing host defenses. The role of bacteria has been established in endodontic disease but the contribution of the host defenses in periapical lesion formation is less clear. The purpose of this study was to compare periapical lesion development in immunosuppressed rats with that in normal rats. Thirty-five, eight-week old Sprague-Dawley rats were equally divided into seven groups. Groups 1, 2, and 3 were given weekly injections of Cytoxan, an immunosuppressive agent. Groups 4, 5, and 6 received no immunosuppressive therapy. Group 7 served as a control, …

Transforming Growth Factor-Beta 1 Expression In Developing Ovine Teeth As Visualized By In Situ Hybridization, Søren Jepsen

Loma Linda University Electronic Theses, Dissertations & Projects

Recently we demonstrated that human dentin contained relatively high amounts of transforming growth factor beta (TGF-ß) and proposed that dentin TGF-ß originated from odontoblasts. Because of the suggested role of TGF-ß in mediating cellular interactions in dental cell development by paracrine mechanisms, we studied the expression of TGF-ß message in developing teeth by in situ hybridization. 5 µm serial sections of neonatal sheep mandibular third molars that had been fixed in glutaraldehyde and paraffin-embedded were used for in situ analysis. An [³⁵S]-labeled cRNA probe, complementary to TGF-ß1 mRNA, was constructed from human TGF-ß1 cDNA. Northern analysis of total …

Appearance Of A Methotrexate Binding Plasma Protein During High Dose Methotrexate Therapy, M P. Iqbal, I Malik, N Mehboobali

Department of Biological & Biomedical Sciences

No abstract provided.

Santa Clara Magazine, Volume 34 Number 4, Summer 1992, Santa Clara University

Santa Clara Magazine

12 - SQUEEZING THE MIDDLE CLASS Gone, in the face of staggering recessionary losses, is the peace of mind that once seemed the virtual birthright of the middle class. By Elizabeth Fernandez '79

18 - A FRAGILE PEACE El Salvador shows a ravaged but hopeful face to a delegation from SCU, Stanford, and the Diocese of San Jose. By Thomas Shanks, S.J.

24 - IT TAKES TEAMWORK Facing fierce global competition, more and more U.S. companies are exploring work teams. By Lisa Agrimonti '87

28 - GIVING TO SANTA CLARA: IT RUNS IN THE FAMILY A tradition of giving and …

Kinetic Characterization Of A Recombinant C-Terminal Mutant Of Reverse Transcriptase From The Human Immunodeficiency Virus, Thomas S. Heard

Chemistry & Biochemistry Theses & Dissertations

The human immunodeficiency virus (HIV) reverse transcriptase (RT) (EC 2.7.7.49) is the central replication enzyme for HIV. In general, the kinetic mechanism for this and all other polymerases involves the ordered binding of two substrates: a primer-template (PT) followed by a deoxyribonucleoside triphosphate (dNTP). Previous investigations prompted this research when it was discovered that the substrate dNTP, in absence of PT, could protect a recombinant c-terminal mutant HIV-1 RT from inhibition by pyridoxal-5'-monophosphate (PLP), an active-site dNTP inhibitor. In contrast, the non-mutant recombinant HIV-1 RT required both substrates for protection from PLP inhibition. This investigation sought to determine if this …

Biochemical Investigation Of Gout And Its Familial Incidences, Chin-Ling Hsu

Chemistry & Biochemistry Theses & Dissertations

Gout is a chronic metabolic disorder caused by deposition of uric acid on the joint. It is categorized into two types: primary and secondary. Primary gout is uric acid overproduction, caused by excessive synthesis of the purine precursors. Secondary gout occurs also as the result of overproduction or decreased renal excretion of uric acid resulting from other disease processes or medication.

The two purine bases, hypoxanthine and xanthine, liberated from ribosides by the action of nucleoside phosphorylase, are degraded to uric acid as the final excretory product in the purine degradation pathway. Hypoxanthine and xanthine are the physiological substrates of …

Book Review, Gianna Julian-Arnold

RISK: Health, Safety & Environment (1990-2002)

Review of the following: BIOMEDICAL POLITICS. (Kathi E. Hanna, ed., National Academy Press 1991) [352 pp.] Preface and acknowledgements, Carl W. Gottschalk, Chair, Institute of Medicine Committee to Study Biomedical Decision Making. Appendices, biographical notes on authors and commentators, index, notes, references. LC 91- 18394, ISBN 0-309-04486-3. [Cloth $29.95. Export $36.00. 2101 Constitution Ave., NW, Washington DC 20418.]

Old Remedies In The Biotechnology Age: Moore V. Regents, Michelle J. Burke, Victoria M. Schmidt

RISK: Health, Safety & Environment (1990-2002)

The California Supreme Court, by excluding a potential remedy, has eliminated many concerns generated by a lower court decision resolving rights to the cell line derived from John Moore's spleen. Yet, the Supreme Court gave little attention to remedies that remain. The authors argue that a constructive trust, a remedy of considerable vintage and great flexibility, could be applied to achieve a just result in such circumstances without affecting the biotechnology world at large.