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Biomedical subjects

S D Wilson

Publications and source records attributed to S D Wilson.

At least 55 records · Page 3Linked to original sources

Cloning and characterization of a novel T cell activation gene.

We have used the technique of subtractive hybridization to identify a T cell gene selectively expressed during activation via the antigen-receptor pathway. This gene, termed TCA3 (for T cell activation) encodes a mRNA which is expressed following concanavalin A (Con A) activation of T cell clones at levels of approximately 1% total poly(A)-containing mRNA. The cDNA isolate, termed TCA3.0, is 512 bases in length excluding poly(A) and encodes a predicted 92-amino acid protein having the characteristics of a secreted polypeptide of approximately 69 amino acids. The genomic organizations of TCA3 was determined for two lambda phage clones and was found to be a single copy gene containing at least three exons dispersed over less than 4.7 kb. The temporal appearance of TCA3 mRNA in response to several activating agents was examined. It is not transcribed in response to interleukin 2 stimulation, but is transcribed in response to either antigen or Con A stimulation and can be detected as early as 1 hr poststimulation. Expression TCA3 in response to Con A is blocked by cyclosporin A treatment. The combined data suggest that TCA3 may represent a new lymphokine.

Amino Acid Sequence↗

Enlarged parathyroid glands: high-resolution local coil MR imaging.

Twenty-two patients with primary hyperparathyroidism underwent high-resolution magnetic resonance (MR) imaging with local (surface) coils for preoperative localization of enlarged parathyroid glands. The MR studies were interpreted prospectively and the results compared with findings at surgery and the results of computed tomography (CT), ultrasonography (US), and thallium-technetium scintigraphy (TTS). The sensitivity and specificity of MR imaging were .74 and .88, respectively. The sensitivity/specificity for the other modalities were as follows: 74/.95 for CT, .59/.82 for US, and .82/.98 for TTS. Enlarged parathyroid glands displayed a medium-intensity signal on T1-weighted images and a marked increase in intensity on T2-weighted images, but the degree of increase varied considerably.

Adenoma↗

The effect of parathyroidectomy on the recurrence of nephrolithiasis.

Little information is available on the long-term influence of parathyroidectomy on the rate of renal stone formation in patients with primary hyperparathyroidism (pHPT) and nephrolithiasis. The reported occurrence of renal stone disease in untreated patients with pHPT is 15% to 30%. A registry of 258 pHPT patients who underwent parathyroidectomies at the Milwaukee Regional Medical Center has allowed continued follow-up of the 71 (28%) pHPT patients with associated renal stone disease. Patients have been followed up for an average of 5 years (range, 1 to 15 years) since surgery. The rate of renal stone formation before and after parathyroidectomy was compared. Identification of a "new" renal stone was defined as passage and collection, extraction, or radiographic visualization of stones. All 71 pHPT patients with stone disease had hypercalcemia and inappropriately elevated parathyroid hormone concentrations, and after parathyroidectomy these values returned to normal in 69 of 71 patients. Since undergoing parathyroidectomy, only 4 patients have passed renal stones. The rate of stone formation per patient per year was 0.36 before and 0.02 after surgery (p less than 0.001). Surgical correction of pHPT significantly reduced the rate of stone formation.

Adult↗

Pancreaticobiliary involvement in familial polyposis coli/Gardner's syndrome.

Adenomatous lesions and carcinoma of the upper gastrointestinal tract, biliary tree, and gallbladder are being reported with increasing frequency in patients with familial polyposis coli or Gardner's syndrome (FPC/GS). A patient with FPC/GS who developed polyps with carcinoma in situ of the common bile duct and ampulla of Vater, along with extensive adenomatous changes in the duodenum, gallbladder, extrahepatic bile ducts, and main pancreatic duct is presented. Proliferative lesions, adenomas, and carcinomas should always be considered in the differential in patients with FPC/GS who have symptoms of upper gastrointestinal, biliary or pancreatic disease.

Biliary Tract↗

Effect of nitrous oxide inactivation of vitamin B12 on the levels of folate coenzymes in rat bone marrow, kidney, brain, and liver.

The effects of nitrous oxide inactivation of the vitamin B12-dependent enzyme, methionine synthetase, on the distribution of folic acid derivatives in rat bone marrow cells, kidney, brain, and liver were determined. Methionine synthetase activity was decreased by about 90% in bone marrow cells, kidney, and brain and by 83% in liver. The proportion of 5-methyltetrahydrofolate (5-CH3-H4PteGlu) in N2O-exposed rats increased from 1.4- to 1.9-fold depending on the tissue examined. This increase was at the expense of a decrease in different folate derivatives in different tissues--in bone marrow cells, kidney, and liver 5-HCO-H4PteGlu, 10-HCO-H4PteGlu, and H4PteGlu decreased; in brain only H4PteGlu decreased significantly. Total endogenous folates, as measured by Lactobacillus casei after conjugase treatment, were unchanged in all tissues after nitrous oxide exposure. The results are interpreted as direct support of the methyl trap hypothesis as the explanation of the interrelationship of folate and vitamin B12 metabolism in bone marrow cells, kidney, and brain, as well as in liver.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

The tip-E mutation of Drosophila decreases saxitoxin binding and interacts with other mutations affecting nerve membrane excitability.

A recessive temperature-sensitive paralytic mutation, tip-E, is associated with reduced binding of [3H]saxitoxin to voltage-sensitive sodium channels in membranes from adult Drosophila heads. There is a decrease of 30-40% in the number of [3H]saxitoxin-binding sites per mg protein (Bmax), but the dissociation constant (Kd) for [3H]saxitoxin binding is normal in the remaining population of binding sites. This decrease is not due to a general hypotrophy of neural tissue since the number of alpha-bungarotoxin binding sites is normal in tip-E mutants. Although saxitoxin binding is reduced in vitro, pharmacological experiments suggest that tip-E mutants have close to the wild-type number of sodium channels in vivo. This suggestion is supported by the observation that at permissive temperatures tip-E only marginally suppresses a mutation which causes enhanced membrane excitability. However, even at permissive temperatures tip-E interacts synergistically with mutations that decrease membrane excitability. In this case, the double mutants exhibit reduced viability and/or longevity. We postulate that either the structure of sodium channels or their microenvironment is altered in tip-E mutants resulting in an increased liability of binding sites in vitro.

Amphibian Proteins↗

Total or near total thyroidectomy versus limited resection for radiation-associated thyroid nodules: a twelve-year follow-up of patients in a thyroid screening program.

Controversy continues regarding the extent of thyroidectomy appropriate for patients with radiation-associated thyroid nodules. The incidence of cancer in this group of patients is more than 50% when near total or total thyroidectomy is done and all thyroid tissue is serially sectioned and examined. Tumor multicentricity is common. Is total or near total thyroidectomy warranted in all of these patients? A prospective study and follow-up program of 2118 patients with prior low-dose head and neck irradiation who entered into a thyroid screening program allowed us to examine how the extent of thyroidectomy influenced the clinical course of these patients. Near total or total thyroidectomy was performed in 59 patients (36 had cancer), and limited thyroid resection, that is, lobectomy or less, was done in 78 patients (four of whom had cancer). During follow-up, only three patients have developed recurrent cancer; two had near total thyroidectomy and one had total thyroidectomy at first operation. Two patients with limited thyroid resection have had reoperation for new thyroid nodules, both of whom had benign nodules. We conclude that although limited thyroid resection may leave occult malignancies in unresected thyroid tissue, there is no significant difference in outcome between patients with limited resection and those with near total or total thyroidectomy after a 12-year follow-up of the program. Significant differences in cancer recurrence rats may occur with longer follow-up.

Follow-Up Studies↗

Elevated plasma vasopressin (AVP) levels during resection of pheochromocytomas.

During the evaluation of epidural blockade with light general anesthesia for pheochromocytoma resection, increases in plasma arginine vasopressin (AVP) concentrations were noted. We measured AVP levels in conjunction with plasma catecholamines during perioperative maneuvers in eight consecutive patients undergoing resection of pheochromocytomas. Hormonal responses (mean +/- SE) for preoperative baseline and peak values during tumor manipulation were as follows: AVP, 5 microgram/ml or picogram/ml (+/- 1.7) to a peak of 129 pg/ml (+/- 44) pg/ml; norepinephrine, 5,834 pg/ml (+/- 2,564) to 72,422 (+/- 31,433) pg/ml; epinephrine, 1,033 pg/ml (+/- 405) to 56,444 (+/- 23,542) pg/ml; and dopamine, 165 pg/ml (+/- 35) to 4,231 (+/- 1,318) pg/ml. Maximal AVP values occurred with tumor manipulation and remained elevated for 24 hours postoperatively. Neither epidural placement, induction of anesthesia, nor epidural narcotics used for postoperative pain control had any effect on AVP or catecholamine levels. These extraordinarily high concentrations of plasma AVP found during tumor manipulation may contribute to hemodynamic lability and fluid problems in patients undergoing surgery for the treatment of pheochromocytoma.

Adolescent↗

High-performance liquid chromatographic determination of the distribution of naturally occurring folic acid derivatives in rat liver.

Procedures which allow extraction and quantitation of labile, reduced folic acid derivatives in rat liver have been developed. These procedures entail extraction of hepatic folates at 100 degrees C in 2% (w/v) sodium ascorbate, 0.2 M 2-mercaptoethanol, pH 7.85. The extract was treated with conjugase to hydrolyze folate polyglutamates and reverse-phase, ion-pair high-performance liquid chromatography was used to separate the resulting monoglutamates which were measured by microbiological assay using Lactobacillus casei. Experiments with HPLC-purified standard derivatives, so treated, showed excellent stability of tetrahydropteroylglutamic acid (H4PteGlu), 10-formyl-H4PteGlu, 5-formyl-H4PteGlu, 5-methyl-H4PteGlu, and pteroylglutamic acid (PteGlu). Under these conditions, approximately 56% of H2PteGlu was recovered unchanged while about 27% was converted to PteGlu; 5,10-methylene-H4PteGlu was quantitatively recovered as H4PteGlu. These procedures were applied to the task of measuring the distribution of naturally occurring folate cofactors in rat liver. These results indicated that rat liver folates have the following compositions: 5-methyl-H4PteGlu, 37.2%; H4PteGlu, 32.7%; 10-formyl-H4PteGlu, 22.6%; and 5-formyl-H4PteGlu, 7.7%. Experiments with [3H]PteGlu injection showed that all hepatic folates had the same specific radioactivity as determined by radioassay and L. casei assay, indicating that L. casei exhibited the same growth response to all the folates detected in rat liver.

Animals↗

A genetic variant of beta-glucuronidase in Drosophila melanogaster.

The beta-glucuronidase activity of Drosophila melanogaster exists as two chromatographically separable forms, both of which are glycoproteins. Form I is membrane-bound in vivo, has a pI of 8.0-8.5, and can be irreversibly inactivated either by incubation at 55 degrees C for 20 min or by incubation at 37 degrees C in the presence of 6 M urea. Form II exists both membrane-bound as well as membrane-free, has a pI of 4.5, and is resistant to the conditions which inactivate form I. The two forms are similar in Km and Vmax for the artificial substrate 4-methylumbelliferyl-beta-D-glucuronide and both forms are precipitated by antibody to form II. A natural genetic variant, beta-GluL1, completely lacks from I beta-glucuronidase. This variant behaves in a co-dominant fashion for the determination of the presence of form I and has been localized to the extreme distal portion of chromosome 3R. Other data indicate that at least one genetic determinant for the amount of form II is also localized to this portion of chromosome 3R.

Animals↗

Evaluation of ascorbic acid in protecting labile folic acid derivatives.

The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives.

Ascorbic Acid↗

Inferences of mental illness from noninvolvement.

These studies continue the exploration of variables related to a person's use of the mental illness categorization. The central concern in the present studies was the effect of perceived variation in a target person's level of involvement in a social situation. While a low level of involvement, as portrayed in videotaped scenarios, prompts attribution of mental illness, other features of implicit personality theories also relate to greater or lesser attribution of mental illness. Those participants who gave evidence of having attributed lower levels of involvement, regardless of filmed information, also attributed higher levels of mental illness. Social workers, compared to general population participants, attributed higher levels of mental illness at all levels of target involvement. We discuss the implications of these findings for dissemination and assignment of the mentally ill role.

Attitude of Health Personnel↗

Radiation-associated thyroid tumors: extent of operation and pathology technique influence the apparent incidence of carcinoma.

A prospective study and follow-up program of 2,118 patients with prior low-dose head and neck irradiation, entered into a thyroid screening project, allowed us to examine how the extent of operation and pathology technique influenced the incidence of thyroid carcinoma. Patients with palpable nodular thyroid disease were referred to their physicians with a recommendation for surgery: 107 patients had thyroid surgery in community hospitals (CHs) where enucleation of the nodule or lobectomy was the usual operation, and 29 patients had surgery at Milwaukee County Medical Complex (MCMC) where near-total thyroidectomy was routine. Lymph nodes were sampled in 69% of MCMC operations but in only 16% of CH operations. The pathologist's usual method at MCMC was to submit the total surgical specimen and to do serial sections. Less than total specimen examination and random sections typically were done in community hospitals. The mean age and sex ratio of the patients and size of thyroid lesions in the two groups were not different. Cancer was found in 59% (17/29) of patients who underwent operation at MCMC, while only 21% (22/107) of patients who underwent operation in CHs were found to have carcinoma (P less than 0.001). Surprisingly, there was nearly uniform agreement (99%) in the diagnoses made by MCMC and CH pathologists, and the incidence of microscopic foci of carcinoma was similar in both groups. We conclude that the incidence of thyroid carcinoma found in patients with prior head and neck irradiation who have had operation for thyroid nodules is related to the extent of thyroidectomy, routine lymph node sampling, the amount of resected thyroid tissue processed for histologic examination, and the absolute number of sections examined by the pathologist.

Adult↗

Thyroid gland morphology in young adults: normal subjects versus those with prior low-dose neck irradiation in childhood.

Thyroid glands obtained at autopsy from young adults were studied to establish more accurately the "normal" morphology in the groups 20 to 40 years of age. A total of 56 autopsy specimens (many obtained from trauma victims) were examined in detail by totally embedding and sectioning the thyroid glands. The morphology of these thyroid glands also was compared to that of surgically removed thyroid glands from 47 young adult patients with prior low-dose neck irradiation. The "normal" thyroid specimens frequently showed morphologic features, such as thyroid tissue outside the recognizable capsule of the gland (40 of 56 patients) and in the strap muscles of the neck (six of 56 patients), which are conditions commonly considered as evidence for invasive thyroid carcinoma. The thyroid glands from the "normal" young adult population were significantly different from those thyroid glands surgically removed from patients who had received irradiation. The irradiated thyroid glands invariably showed multiple nodules of a wide variety of histologic types, extensive lymphocytic infiltrates, and distorting fibrosis as well as a high incidence of malignancy (27 of 47 patients). A single 0.1 cm focus of papillary carcinoma was found in one specimen in the nonirradiated thyroid group. This study suggests that "occult" thyroid carcinomas in the group 20 to 40 years of age are rare and are significantly fewer in number than in the older population (P less than 0.02).

Adult↗

Intraoperative biliary endoscopy.

We examined the incidence of "missed" biliary calculi in a teaching center where intraoperative biliary endoscopy is performed routinely. During a six-year period, 1,280 procedures were performed for benign biliary disease. Two hundred eight patients (16%) underwent common duct explorations with choledocholithiasis discovered in 152 patients (73%). Choledochoscopy, using a rigid endoscope equipped with the Hopkins rod-lens system, was performed in 148 patients. When the scope was used, missed stones were seen on a follow-up T-tube cholangiogram in only 2.3% of the patients undergoing choledocholithotomy. More than 90% of the procedures were performed by supervised resident surgeons who had had no specialized training in biliary endoscopy. The incidence of retained stones after choledocholithotomy and choledochoscopy was lower than those of other reported series in which the choledochoscope was not used. We recommend routine use of intraoperative biliary endoscopy in all patients who undergo common duct exploration.

Common Bile Duct↗