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Biomedical subjects

C E Jackson

Publications and source records attributed to C E Jackson.

At least 127 records · Page 7Linked to original sources
PubMed1987

Chromosome 20 deletion in multiple endocrine neoplasia type 2: expanded double-blind studies.

Multiple endocrine neoplasia (MEN) type 2A and 2B are autosomal dominant syndromes in which medullary thyroid cancers are associated with adrenal pheochromocytomas. We have expanded our double-blind studies of high-resolution G-banded chromosomes from lymphocytes to a total of 12 MEN-2A families, 7 MEN-2B (mucosal neuroma phenotype) families and 23 non-MEN control subjects. Eighteen of 23 different control subjects were scored as having normal chromosomes 20, and 15 of 21 MEN-2A and 4 of 8 MEN-2B patients were scored as having an interstitial deletion: del(20) (p12.2p12.2). These findings suggest that the dominant mutation in many MEN-2A and MEN-2B families is a visible deletion within band 20p12.2. Combining the results of these double-blind studies with those of the only other comparable reported double-blind series provides a statistical probability of less than 1/1000 that the association between MEN-2A and the deletion was observed by chance alone. However, the occasional discrepancies in classification using presently available techniques preclude the use of high resolution chromosome studies for the diagnosis of MEN-2.

Chromosome Deletion↗
PubMed1987

Gastric cancer in San Marinese and their first degree relatives in San Marino and the United States. Gastroscopic biopsy as an epidemiological tool.

The Republic of San Marino, a small, 23-square mile, independent country near the Adriatic Coast within Italy, has been noted to have a high incidence of gastric cancer in its 22,000 population (9% of all deaths from 1969-1983 with 33% of all cancer deaths attributed to gastric cancer). Gastroscopic biopsy studies on 284 first degree relatives of San Marinese gastric cancer patients in the Republic of San Marino and in Detroit, where 2,000-2,500 San Marinese reside, have allowed detection of six gastric malignancies. Intestinal metaplasia of gastric mucosa was found in 16 (52%) of 31 Detroit first degree relatives and 51 (36%) of 143 San Marino first degree relatives. Gastroscopy provides an important tool not only for the early detection of gastric cancer in populations of high risk (such as that of San Marino), but also for providing clues to the genetic and environmental factors in gastric neoplasia.

Aged↗
PubMed1985

Characterization of calcium-dependent membrane binding proteins of brain cortex.

Proteins of Mr 68 000, 34 000 and 32 000 were selectively extracted by EGTA from brain cortex. The three proteins that were extracted along with calmodulin were acidic, monomeric, and did not exhibit structural homology, as demonstrated by one-dimensional peptide mapping. The Mr-68 000 protein was purified to homogeneity and had a Stokes radius of 3.54 nm and S20,W value of 5.1S. Purified calmodulin, Mr-68 000 protein and two proteins of Mr 34 000 and Mr 32 000, interacted with the brain particulate fraction, with half-maximal binding occurring at 3.5 microM, 8.3 microM and 150 microM-Ca2+ respectively. Proteins were bound independently of each other and calmodulin. Pretreatment of the particulate fraction with trypsin prevented the Ca2+-dependent binding of calmodulin; however, the binding of the Mr-68 000 protein or the Mr-32 000 and -34 000 proteins was unaffected. The Mr-68 000 protein of bovine brain did not cross-react immunologically with Mr-67 000 calcimedin from chicken gizzard.

Animals↗
PubMed1985

The two-hit theory of neoplasia: implications for the pathogenesis of hyperparathyroidism.

Knudson's two-hit or two-mutational-event hypothesis for the initiation of neoplasia suggests that two somatic mutations are necessary for initiation of sporadic neoplasms, and that a genetic plus a somatic mutation are required for hereditary neoplasms. Glucose-6-phosphate dehydrogenase (G6PD) studies of parathyroid tumors of 11 heterozygotes with hyperparathyroidism (HPT), including one with hereditary HPT, have shown both A and B isoenzymes. These findings suggest multicellular development of parathyroid tumors and are compatible with tumors being manifestations of either nonneoplastic hyperplasia or a genetic first mutational event. Parathyroid carcinoma may be the result of a second mutation in cells made susceptible by previous genetic or somatic mutations. Comparison of parathyroid cancer in families with hereditary HPT with sporadic cases from the literature reveals a generally younger onset with hereditary HPT compatible with the two-hit theory. Consideration of these age-of-onset and G6PD findings suggest that hyperparathyroidism may result from either non-neoplastic or mutational-induced processes even though no histologic distinctions have been observed in the hyperplasia associated with these processes.

Glucosephosphate Dehydrogenase↗
PubMed1985

Localization of residual medullary thyroid cancer by thallium/technetium scintigraphy.

Whole-body thallium/technetium subtraction scintiscans, with thallium 201 chloride and technetium 99m pertechnetate, were obtained on 10 patients with medullary thyroid cancer with postoperative elevations of serum calcitonin values. Seven patients had the hereditary variant of medullary thyroid cancer (the multiple endocrine neoplasia, type II syndrome) while three patients had the sporadic form. Negative scans were obtained on five patients with basal calcitonin levels less than 3 ng/ml (normal less than 0.35 ng/ml). Five other patients with elevated calcitonin levels (range 3.6 to 69.2 ng/ml; mean 28.3 ng/ml) had positive scans that have guided further surgical approaches. Serum calcitonin appears to remain the most sensitive indicator of residual medullary thyroid cancer while localization of this residual tumor tissue frequently can be obtained through thallium/technetium subtraction imaging in both the hereditary and sporadic forms of the disease.

Adolescent↗
PubMed1984

Multiple cell origin of traumatically induced keloids.

Six keloids from five patients heterozygous for the X-linked glucose-6-phosphate dehydrogenase (G6PD) locus were studied. Both the B and A enzymes were found in the keloids in similar proportions to the normal tissues. This finding indicates that keloids have a multicellular origin and that they do not develop clonally as do most neoplasms.

Adolescent↗
PubMed1984

Chromosome 20 deletion in human multiple endocrine neoplasia types 2A and 2B: a double-blind study.

Multiple endocrine neoplasia type 2A and 2B (MEN-2A and MEN-2B) are autosomal dominantly inherited syndromes in which medullary thyroid cancers are associated with adrenal pheochromocytomas. A double-blind analysis of high-resolution G-banded chromosomes was performed on blood specimens from patients in four MEN-2A families and five MEN-2B (mucosal neuroma phenotype) families and from control subjects. Excluding studies on duplicate blood specimens, 9 of 11 control subjects were scored as having normal chromosomes 20, and 11 of 14 MEN-2 patients were scored as having chromosomal deletion: del(20)(p12.2p12.2) (phi 2 = 9.00; P less than 0.001). Two new mutant MEN-2B patients had apparently normal chromosomes 20. These findings demonstrate that the dominant mutation in most MEN-2A and MEN-2B families is a visible chromosome deletion within band 20p12.2.

Adrenal Gland Neoplasms↗
PubMed1984

Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia.

Adolescent↗
PubMed1983

Phenotype mapping of the multiple endocrine neoplasia type II syndrome.

The multiple endocrine neoplasia (MEN) IIb syndrome has been differentiated from MEN IIa by the presence of various phenotypic characteristics such as mucosal neuromas, marfanoid habitus, congenital skeletal anomalies, and prominent corneal nerves, as well as the lack of parathyroid involvement. Analysis of a kindred with some characteristics of both syndromes (including an associated chromosomal deletion) tends to unify the MEN II syndromes as a single disorder with variable expressivity. The linear map of the genetic determinants is postulated to conform with the following phenotype order: parathyroid tumors, medullary thyroid cancer, pheochromocytomas, skeletal changes, prominent corneal nerves, mucosal neuromas, and marfanoid habitus. Appreciation of this sequence can allow earlier identification and treatment of affected individuals.

Acetabulum↗
PubMed1983

The clinical course after definitive operation for medullary thyroid carcinoma.

Thorough family studies that used the radioimmunoassay procedure for calcitonin (CT) during the past 12 years have provided data on 70 patients from 12 kindreds with hereditary medullary thyroid cancer (hereditary group) and 28 patients with sporadic or nonhereditary medullary thyroid cancer (sporadic group). Serum CT elevations after total thyroidectomy as evidence of residual tumor have been encountered in 21 of 25 patients in the hereditary group with palpable tumors preoperatively (84%) and in 13 of 24 in the sporadic group (54%). However, none of 26 patients with hereditary nonpalpable lesions found by family screening studies have been found to have postoperative CT elevations. Both cervical lymphadenectomy in patients with lymph node involvement at initial operation and reexploration in those with CT elevations after total thyroidectomy have been unsuccessful in the eradication of metastatic disease. These data emphasize the value of thorough family studies that use stimulated CT measurements in the detection of early and curable neoplasms. Involvement of the parathyroid glands or the adrenal medulla that occurred in the hereditary multiple endocrine neoplasia syndromes varied from family to family; it influenced the clinical course and required regular surveillance with calcium and catecholamine studies. Separation of hereditary from sporadic cases has practical value in the identification of family members at risk and also in the provision of prognostic data.

Adult↗
PubMed1982

Age-related probability of development of hereditary medullary thyroid carcinoma.

Hereditary medullary thyroid carcinoma is inherited as an autosomal dominant trait; at birth each child of an affected parent has a 50% chance of developing the disease. Measurement of plasma calcitonin concentrations after provocative calcium or pentagastrin stimulation has proved useful in the early diagnosis of this disease. To determine the age-related risk of conversion from a negative to a positive provocative test, 445 members of 11 kindreds were studied with sequential tests. Of 159 family members with a 50% risk at birth of developing medullary thyroid carcinoma 38 converted from a negative to a positive test result (mean age of conversion was 15 years). By means of methods previously described for determining the age-related probability for developing Huntington chorea, we present a method for determining the probability of development of medullary thyroid carcinoma. An individual at risk whose test result was negative had the following probability of converting to a positive test result at a later date: age (years)/probability, 0/0.5; 5/0.49; 10/0.41; 15/0.25; 20/0.16; 25/0.10, 30/0.05; and 35/0. We conclude that hereditary medullary thyroid carcinoma is regularly detectable in the pediatric age group and that screening should begin by age 5 years and be continued at regular intervals until age 35.

Adolescent↗
PubMed1982

Preparation and in vitro evaluation of a new extracorporeal dialyzer with immobilized insulin.

A specific extracorporeal immunoadsorbent system has been developed that has potential application for the treatment of complications related to the presence of plasma insulin antibodies, namely severe insulin resistance and autoimmune hypoglycemia. The immunoadsorbent system described here makes use of a commercially available cellulose-based, hollow-fiber hemodialyzer. Optimal conditions for the coupling of insulin to cellulose matrices were found to involve activation with 1,4-butanediol diglycidyl ether and reaction with insulin at pH 7.4. The insulin-dialyzer prepared under these conditions contained 35.5 mg to 37.9 mg of insulin which correspond to a theoretical binding capacity of 887.5 to 947.5 units of insulin. Recirculation of human plasma with high insulin antibody titers through the insulin-dialyzer resulted in the clearance of 82-99% and 50-83% of high affinity and total insulin antibodies, respectively. The clearance of insulin antibodies approached a steady state after 15 minutes of recirculation at a flow rate of 50 ml/min. Regeneration of used insulin-dialyzers was accomplished by treatment with 0.02 M citrate buffer pH 3.2, which restored their ability to clear 90% and 40% of high affinity and total insulin antibodies, respectively. The principle of the insulin-dialyzer may find application in other disease states where removal of specific antibodies or other high molecular weight species may be of therapeutic value.

Animals↗
PubMed1982

Pheochromocytoma in multiple endocrine neoplasia type II: an example of the two-hit theory of neoplasia.

Six kindreds in which pheochromocytomas were present as manifestations of the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type II were studied. The patients underwent bilateral total adrenalectomy with the finding that the pheochromocytomas were bilateral, multifocal, and associated with distinct medullary hyperplasia and reduction in the normal corticomedullary ratio-- features not usually seen in patients with sporadic pheochromocytoma. These findings were exemplified in recent cases of a 34-year-old woman and a 40-year-old man who both had undergone total thyroidectomy for medullary carcinoma of the thyroid. Diagnoses of pheochromocytoma were made by catecholamine studies, computerized tomography, and 131I meta-iodobenzylguanidine (MIBG) scan. Bilateral adrenalectomy was performed with the finding of multiple bilateral pheochromocytomas and adrenal medullary hyperplasia. As in hereditary medullary carcinoma of the thyroid, the histologic findings in pheochromocytomas of the MEN II syndrome are consistent with Knudson's two-mutational-event theory for the initiation of neoplasia, with adrenal medullary hyperplasia representing the manifestation of the first or genetic mutational event and being present invariably in the hereditary cases.

Adrenal Gland Neoplasms↗
PubMed1982

A reagent strip for measuring the specific gravity of urine.

A solid-phase reagent for determination of urinary specific gravity (relative density) is described. This reagent strip, similar to others in the "N-Multistix" series (Ames), contains a polyacid whose acidity is sensitive to the ionic concentration in the urine in which it is immersed. As the acidity of the polyacid changes, pH changes are detected by a pH indicator within the reagent strip. In comparison studies, 84.4% of relative densities as measured with these reagent strips were within 0.005 of the corresponding results with a total-solids meter, and 89.9% were within 0.005 of the corresponding urinometer results. Adding a correction of +0.005 to the reagent-strip results for urines with high pH increased the percentage of results within 0.005 of the comparison method to 90.7% (TS meter) and 92.9% (urinometer). Lot-to-lot variability and reader-to-reader variability were both low. Reagent strip results are not affected by glucose, may be increased by albumin, and correlate with urea concentrations.

Equipment and Supplies↗
PubMed1982

Probable clonal origin of aldosteronomas versus multicellular origin of parathyroid "adenomas".

Adrenocortical adenomas causing hyperaldosteronism in two women heterozygous at the X chromosome-linked glucose-6-phosphate dehydrogenase (G-6-PD) locus exhibited only one G-6-PD isoenzyme. This finding suggests a clonal development for these benign tumors and contrasts with the multicellular origin of parathyroid adenomas reported in three patients from our institution in 1977 and found subsequently in seven other hyperparathyroid women whose cases are reported here. One of these seven patients had hereditary hyperparathyroidism. In this case each of three glands removed showed both A and B G-6-PD isoenzymes in similar ratios as were found in normal tissues. The multicellular origin of hereditary hyperparathyroidism is compatible with the concept of parathyroid lesions being manifestations of the first genetic event in Knudson's two-mutational-event theory for the initiation of cancer. The multicellular origin of sporadic parathyroid tumors suggest that they are caused by some factors stimulating many cells in the parathyroid glands. The young average age of onset of eight cases of parathyroid cancer from five families with hereditary hyperparathyroidism in the literature is also compatible with Knudson's theory. G-6-PD studies of other aldosteronomas, parathyroid tumors, and other endocrine neoplasms may provide important information about the pathogenesis of these conditions.

Adenoma↗