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G Jaffe

Publications and source records attributed to G Jaffe.

18 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↗
PubMed1993

Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma. Tumor inhibition by IL-2 but not tumor necrosis factor.

Recent investigations have demonstrated that the in vivo growth of weakly immunogenic murine tumors can be inhibited by genetic manipulations that enable them to secrete a variety of cytokines. Inasmuch as most human tumors fail to elicit a detectable host immune response we questioned whether the growth of a nonimmunogenic murine tumor could be inhibited by the secretion of cytokines. We have thus inserted the cDNA encoding for human IL-2 or TNF into the nonimmunogenic murine fibrosarcoma MCA 102. Tumor cells secreting IL-2 failed to grow in vivo despite normal in vitro growth. This growth inhibition required an intact immune system as tumors grew progressively in mice sublethally irradiated before tumor injection. Tumor inhibition was abrogated by the in vivo depletion, by specific mAb before tumor injection, of either CD8+ T cells or NK cells, but not CD4+ T cells. IL-2 secretion by tumor afforded a significant survival benefit to the animal, and IL-2-secreting tumor limited the growth of admixed nonsecreting parental tumor. Histologic evidence and FACS analyses revealed a dense lymphocytic infiltration of IL-2-secreting tumors composed of both CD4+ and CD8+ T cells. In contrast, secretion of TNF failed to inhibit the growth of MCA 102, and similar lymphocyte subset depletions, or administration of specific anti-TNF mAb had no effect on the growth of TNF secreting MCA 102. In summary, these investigations demonstrated that the host response to this nonimmunogenic tumor can be markedly enhanced by the genetic manipulation of the tumor cells to secrete IL-2, but not TNF. This strategy has potential application for the development of immunotherapies for nonimmunogenic tumors.

Animals↗
PubMed1993

Age contrast in ovarian pathology.

BACKGROUND. Ovarian cancer accounts for approximately 23% of all gynecologic tumors and is the most common fatal gynecologic malignancy. These tumors can occur in women of all ages, but there are differences in the histologic types during various decades of life. CONCLUSIONS. During infancy and childhood, the predominant type of neoplasms are those of germ cell origin, such as teratomas, dysgerminomas, and endodermal sinus tumors. In adults, epithelial neoplasms, or tumors that originate from the epithelium that covers the ovarian surface, are the most common, accounting for almost 85% of all neoplasms after the age of 50 years. The peak incidence of benign epithelial tumors occurs between the ages of 20 and 40 years. Young women (30 to 40 years of age) are frequently affected by the so-called "tumors of low malignant potential," which have excellent prognosis. Older women, on the other hand, usually have the most aggressive forms of ovarian cancer, present with advanced disease, and have a dismal prognosis.

Adult↗
PubMed1993

Flow cytometry and Zollinger-Ellison syndrome: relationship to clinical course.

BACKGROUND: With successful means of controlling gastric acid secretion in patients with Zollinger-Ellison syndrome, the gastrinoma itself is becoming the major determinant of long-term survival. No methods have yet been described to predict which tumors will have more malignant courses thereby indicating which patients should undergo aggressive surgery or antitumor therapy. Because DNA analysis, using flow cytometry, has proved helpful in this regard in other tumors, the current study was designed to evaluate its utility in gastrinoma patients. METHODS: Flow cytometry was performed on 81 paraffin-embedded gastrinoma specimens from 59 patients. Results were compared with preoperative patient characteristics, findings at surgery, and postoperative follow up. RESULTS: Tumors were diploid in 54% of patients, near diploid in 15%, pure tetraploid in 0%, nontetraploid aneuploid in 25%, and multiple stem line aneuploid in 5%. All patients with multiple stem line aneuploid tumors had wide-spread metastases whereas all patients with nontetraploid aneuploid tumors had localized or regional disease. Median S phase percentage was 3.6. S phase percentages were higher in patients with widespread metastatic disease than in patients with localized or regional disease. Disease extent also correlated closely with fasting serum gastrin level. After removing this variable with logistic regression analysis, the significant correlation between disease extent and DNA analysis persisted. CONCLUSIONS: DNA analysis of gastrinoma tissue specimens correlates independently with the extent of disease and may be useful in planning therapeutic strategies for patients with Zollinger-Ellison syndrome.

Adult↗
PubMed1993

Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess.

An adrenal carcinosarcoma is reported in a 79-year-old woman presenting with clinical signs of hyperaldosteronism. The tumor weighed 199 g and consisted of areas typical of adrenal carcinoma and areas of sarcoma. The sarcomatous component of the tumor showed osteogenic and chondroid differentiation. Vimentin stained both the carcinomatous and sarcomatous regions. Four months after resection, the patient developed metastases. This is the third reported case of adrenal carcinosarcoma and the only case in which hyperaldosteronism or bony differentiation was observed.

Adrenal Cortex Neoplasms↗
PubMed1992

Studies in a kindred with parathyroid carcinoma.

We report a family with primary hyperparathyroidism in four patients in two generations with apparent autosomal dominant transmission. A fifth member was probably affected. Two cases had definite parathyroid carcinoma (PC), and two had parathyroid adenoma with atypical features that could represent an early stage of cancer. In each of our patients, one parathyroid gland was abnormal. Five other parathyroid glands (in two patients) were normal in histology and size. There was no evidence of neoplasia in other tissues. Constitutional karyotypes were normal in all four patients. We identified three chromosomal abnormalities (a reciprocal translocation between chromosomes 3 and 4, trisomy 7, and a pericentric inversion in chromosome 9) in cultured PC tissue from one patient. These chromosomal changes are of unclear significance. Analyses on tumor DNA from one case of PC and one of atypical adenoma showed no evidence of ras gene mutations, PTH gene rearrangement, or allelic loss from chromosome 11q13 (locus of the gene for multiple endocrine neoplasia type 1). This family shows susceptibility to cancer without antecedent hyperplasia in all parathyroids. It could help identify a novel tumor susceptibility gene.

Adenoma↗
PubMed1991

Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors.

Studies of the anti-tumor activity of TNF-alpha in vivo have been hampered by the need to administer systemically toxic doses of the cytokine to obtain a curative response. To facilitate studies of the effect of high local concentrations of TNF-alpha on tumor growth and host immunity, a newly induced murine sarcoma was transduced with the gene for human TNF-alpha and the biologic characteristics of these cells were examined. We identified high and low TNF-producing tumor clones which exhibited stable TNF secretion over time. Significant amounts of membrane associated TNF were found in a high-TNF producing clone as well. No difference in the in vitro growth rates between TNF-producing and nonproducing cell lines was observed. In contrast, in vivo studies demonstrate that although unmodified parental tumor cells grew progressively when implanted s.c. in animals, tumor cells transduced with the TNF gene were found to regress in a significant number of animals after an initial phase of growth. This effect correlated with the amount of TNF produced and could be blocked with a specific anti-TNF antibody. Regressions of TNF-producing cells occurred in the absence of any demonstrable toxicity in the animals bearing these tumors. TNF-producing tumor cells could function in a paracrine fashion by inhibiting the growth of unmodified, parental tumor cells implanted at the same site. The ability of tumor cells to regress was abrogated by in vivo depletion of CD4+ or CD8+ T cell subsets and animals that had experienced regression of TNF-producing tumors rejected subsequent challenges of parental tumor. Our studies thus show that tumor cells elaborating high local concentrations of TNF regress in the absence of toxicity in the host and that this process requires the existence of intact host immunity. Studies of the lymphocytes infiltrating the gene modified tumors and attempts to use TNF gene modified tumor infiltrating lymphocytes to deliver high local concentrations of TNF to the tumor site without inducing systemic toxicity are underway.

Animals↗
PubMed1991

Skeletal involvement in children who have chronic granulomatous disease.

Chronic granulomatous disease is a rare disorder of the oxidative metabolism of the white blood cells that results in immunodeficiency. In a retrospective review of the records of forty-two patients who had chronic granulomatous disease, we identified thirteen patients who had a total of twenty skeletal infections. Two types of infection were noted: Type 1, which resulted from a direct spread of the infection from an adjacent focus, usually of fungus or mycobacteria, and Type 2, which resulted from hematogenous spread, usually of Nocardia or more common bacteria. The thoracic vertebrae, ribs, and metatarsals were the most commonly involved bones. All four patients in whom the vertebrae were involved had a Type-1 fungal infection. Paresis developed in three of these patients, and two of them died. Antibiotics alone effectively eradicated the infection in only one patient. Wide operative débridement combined with administration of antibiotics was the most successful treatment. Comprehensive preoperative imaging and several cultures are necessary to locate the infection in the bone and to identify the organism.

Adolescent↗
PubMed1990

Histologic changes induced by intraperitoneal chemotherapy with 5-fluorouracil and mitomycin C in patients with peritoneal carcinomatosis from cystadenocarcinoma of the colon or appendix.

Intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil has been used to rescue patients from peritoneal carcinomatosis after perforated cystadenocarcinoma of the large bowel or appendix. A staging celiotomy was used to asses the results of therapy. In nine patients tumor was recovered from the abdominal cavity and was subjected to careful histopathologic examination. The posttreatment appearance of the tumor was compared with that before treatment. Also, tumor deposits harvested from these same patients, but from anatomic sites not directly exposed to chemotherapy were examined. The most striking findings observed in treated patients were as follows: (1) the marked reduction in the number of foci of atypical neoplastic epithelium lining the mucin globules, and (2) atrophy and degeneration of the atypical neoplastic epithelium. All treated patients showed these effects but they were not in all sampled tumor specimens, suggesting nonuniform drug distribution in the abdominal cavity and limited penetration of chemotherapy into tumor. The authors conclude that intraperitoneal chemotherapy produces marked histologic changes in mucinous tumors when there is direct contact between tumor and intracavitary drugs.

Adult↗
PubMed1990

Bilateral orbital involvement in fatal giant cell polymyositis.

The case of a young woman with giant cell polymyositis is described. She had bilateral, severe, midly painful proptosis and ophthalmoplegia. Extensive pharyngeal, laryngeal, and cardiac muscle involvement occurred 18 months later coincident with fatal cardiac arrhythmia. At autopsy, extensive muscle necrosis and giant cells were noted in extraocular, pharyngeal, laryngeal, and cardiac muscle with only minimal involvement of other striated muscles.

Adult↗
PubMed1987

Ocular manifestations of preeclampsia.

We performed a prospective, controlled, masked study designed to evaluate the ocular manifestations of preeclampsia in 56 patients, including 25 control, 17 mild preeclamptic, and 14 severe preeclamptic patients. There was a statistically significant correlation between the reduction in arteriole to vein ratio and a diagnosis of severe preeclampsia (r = -.32, P = .004). There was also a significant correlation between the number of focal constrictions and a diagnosis of severe preeclampsia (r = .34, P = .005). The arteriole to vein ratio and number of focal constrictions did not differ significantly between normal and mild preeclamptic patients. None of the patients showed background changes of hemorrhages, cotton-wool spots, and exudates, or evidence of choroidal ischemia (including Elschnig's spots and retinal detachment). In contrast to previous reports, the role of the ophthalmologist in the diagnosis and management of preeclampsia appears to be limited.

Arterioles↗
PubMed1982

Do all diuretics have equal hypotensive efficacy?

An open parallel study was carried out in general practice on 70 patients with uncomplicated mild to moderate hypertension to compare the hypotensive efficacy of hydrochlorothiazide/amiloride with that of cyclopenthiazide/potassium. After a 2-week baseline period on placebo, patients were allocated at random to receive treatment with one or other of the diuretics starting with 1 tablet per day and increasing up to a maximum of 4 tablets per day or until their supine diastolic blood pressure was 90 mmHg or less. They were then continued at their optimum dose for a further 4 weeks. Analysis of the results from 62 patients showed that the hydrochlorothiazide/amiloride preparation produced both a greater decrease and better control of blood pressure in a greater percentage of patients that did the comparison diuretic. In addition, the beneficial effects were attained with fewer tablets, of importance for patient compliance.

Adult↗
PubMed1974

Clinical study of the use of the new aminoglycoside tobramycin for therapy of infections due to gram-negative bacteria.

Tobramycin, a new aminoglycoside antimicrobial, was evaluated as therapy for infections due to gram-negative bacilli in 15 seriously ill patients with underlying diseases. Three of 10 patients with gram-negative bacteremias also had urinary tract infections. Two patients had respiratory tract infections, one had cellulitis, one had a urinary tract infection, and another had septic phlebitis. Twelve patients were cured of their infections. Eosinophilia was observed in one patient and another developed superinfection with Staphylococcus aureus after 6 days of tobramycin therapy. There were five isolates of Escherichia coli, five of Klebsiella sp., two of Pseudomonas sp., and one each of Enterobacter agglomerans, Serratia marcescens, and Enterobacter cloacae. The average serum concentration of tobramycin 2 h after a parenteral dose of 1.0 to 1.5 mg/kg was 5.1 mug/ml; higher concentrations of tobramycin were present in urine. Tobramycin proved to be an effective antimicrobial in these patients.

Aminoglycosides↗
PubMed1974

Pharmacokinetics of tobramycin in patients with stable renal impairment, patients undergoing peritoneal dialysis, and patients on chronic hemodialysis.

The pharmacokinetics of tobramycin were studied in five patients with stable renal impairment, four patients requiring peritoneal dialysis, and four patients on chronic hemodialysis. The half-life of the drug varied with the level of the serum creatinine in the first group of patients, and the average volume of distribution was 15 liters. Only 49% of the administered dose of tobramycin was recovered during 36 h of peritoneal dialysis. The average clearance of tobramycin during hemodialysis was 49.1 ml/min, and 51.5% of the administered dose was recovered during a 6-h dialysis.

Anti-Bacterial Agents↗
PubMed1972

Wearing tights.

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Adolescent↗