PubMed Health⌕ Search

Biomedical subjects

T A Victor

Publications and source records attributed to T A Victor.

At least 19 recordsLinked to original sources

Modulation of alloreactivity in transplant recipients by phenotypic manipulation of donor endothelium.

Phenotypic manipulation of allograft endothelium to reduce immunogenicity would have a significant impact on transplantation. In this study we have demonstrated that random seeding of a heart allograft with endothelium, of host origin, not only promotes long-term survival, but reduces the requirement for pharmacologic immunosuppression. We propose that this simple technology could easily be extrapolated to the clinical arena where hypothermia and preservation solutions have allowed allografts to remain ex vivo for extended periods.

Animals↗

Diversity in the ability of cultured cells to elongate and desaturate essential (n-6 and n-3) fatty acids.

Essential fatty acids (EFAs) cannot be synthesized by mammalian cells. Once taken in with the diet, they can undergo desaturations/saturations and chain elongations/shortenings to yield a variety of polyunsaturated fatty acids of the same family. Cells in vitro from a variety of tissues are capable of processing EFAs to varying extents. Conversion of the parent EFAs, linoleic (LA, n-6) and alpha-linolenic (LNA, n-3) acids, to the 20-carbon polyunsaturated fatty acids, arachidonic (AA, n-6) and eicosapentanoic (EPA, n-3), requires chain elongation and delta 6 and delta 5 desaturations. AA and EPA are required by many tissues for optimal biological function and are precursors of biologically active eicosanoid hormones. All cultured cells are able to elongate exogenous LA and LNA, and most can perform delta 5 desaturation, so delta 6 desaturation is the limiting step in AA and EPA production. Longer fatty acids that have more double bonds than AA or EPA are less frequently produced due to a deficiency in delta 4 desaturating ability. The process of retroconversion (chain shortening) is less extensively studied, but evidence from a variety of cells suggests that this type of metabolic conversion is normally active. The example of MCF-7 (human breast cancer cell line) and MCF-10A cells (human noncancerous breast cell line) is discussed in order to emphasize the diversity in EFA processing ability of cultured cells. Under identical culture conditions, MCF-10A cells perform extensive desaturations, elongations, and retroconversions, whereas MCF-7 cells can only elongate and retroconvert exogenous EFAs. Given the great diversity in the ability of cultured cells to process EFAs, no conclusions can be drawn regarding the mechanisms responsible for the effects of exogenous EFAs on a particular cell until that cell's EFA processing patterns have been evaluated.

Animals↗

Diverse effects of essential (n-6 and n-3) fatty acids on cultured cells.

Fatty acids (FAs) have long been recognized for their nutritional value in the absence of glucose, and as necessary components of cell membranes. However, FAs have other effects on cells that may be less familiar. Polyunsaturated FAs of dietary origin (n-6 and n-3) cannot be synthesized by mammals, and are termed 'essential' because they are required for the optimal biologic function of specialized cells and tissues. However, they do not appear to be necessary for normal growth and metabolism of a variety of cells in culture. The essential fatty acids (EFAs) have received increased attention in recent years due to their presumed involvement in cardiovascular disorders and in cancers of the breast, pancreas, colon and prostate. Many in vitro systems have emerged which either examine the role of EFAs in human disease directly, or utilize EFAs to mimic the in vivo cellular environment. The effects of EFAs on cells are both direct and indirect. As components of membrane phospholipids, and due to their varying structural and physical properties, EFAs can alter membrane fluidity, at least in the local environment, and affect any process that is mediated via the membrane. EFAs containing 20 carbons and at least three double bonds can be enzymatically converted to eicosanoid hormones, which play important roles in a variety of physiological and pathological processes. Alternatively, EFAs released into cells from phospholipids can act as second messengers that activate protein kinase C. Furthermore, susceptibility to oxidative damage increases with the degree of unsaturation, a complication that merits consideration because lipid peroxidation can lead to a variety of substances with toxic and mutagenic properties. The effects of EFAs on cultured cells are illustrated using the responses of normal and tumor human mammary epithelial cells. A thorough evaluation of EFA effects on commercially important cells could be used to advantage in the biotechnology industry by identifying EFA supplements that lead to improved cell growth and/or productivity.

Animals↗

n-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines.

The type rather than the amount of dietary fat may be more important in breast carcinogenesis. While animal studies support this view, little is known about the effects of essential fatty acids (EFAs) at the cellular level. The MCF-7 breast cancer and the MCF-10A non-cancerous human mammary epithelial cell lines are compared in terms of growth response to EFAs and ability to incorporate and process the EFAs. Eicosapentaenoic (EPA, n-3) and docosahexaenoic (DHA, n-3) acids, presented bound to albumin, inhibited the growth of MCF-7 cells by as much as 50% in a dose-dependent manner (6-30 microM) in medium containing 0.5% serum. alpha-Linolenic (LNA, n-3) and arachidonic (AA, n-6) acids inhibited growth less extensively, while linoleic acid (LA, n-6) had no effect. In contrast, MCF-10A cells were not inhibited by any of the EFAs at levels below 24 microM. The differential effects of AA, EPA and DHA on MCF-7 and MCF-10A cells support a protective role of highly unsaturated essential fatty acids against breast cancer. The EFAs were primarily incorporated into phosphoglycerides. MCF-7 cells showed chain elongations and possibly delta 8 desaturation, but no AA was formed from LA, nor EPA or DHA from LNA. In contrast, MCF-10A cells desaturated and elongated the exogenous EFAs via all the known pathways. These findings suggest defects in the desaturating enzymes of MCF-7 cells. LNA, DHA and AA presented to MCF-7 cells in phospholipid liposomes inhibited growth as extensively as albumin-bound free acids, but were less extensively incorporated, suggesting different mechanisms of inhibition for the two methods.

Breast↗

Detecting fatty acids of dietary origin in normal and cancerous human breast tissue by 13C nuclear magnetic resonance spectroscopy.

Natural abundance 13C NMR was used to determine relative amounts of fatty acid subclasses present in fibroadipose tissue from the human breast in healthy and cancer patients and in breast carcinoma tissue. Resonances corresponding to the carbon atoms of triacylglycerides were obtained when adipose tissue constituted more than 10% of the carcinoma. Resonances corresponding to phospholipids and proteins were also observed when the percentage of adipose tissue was lower. No significant difference between the levels of unsaturated fatty acids in adipose tissue from cancer and non-cancer patients was found. However, significant differences in the levels of monounsaturated and saturated fatty acids of carcinoma compared to non-cancerous tissue was found, as was a nearly significant difference for the levels of polyunsaturated fatty acids in these two tissue types. These findings suggest an alteration of cellular lipid composition in neoplastic mammary tissue.

Breast↗

Intercostal hemangioma presenting as a chest wall tumor.

Skeletal muscle hemangiomas are uncommonly described in a variety of locations. This report details the diagnosis and management of a 39-year-old woman with a right chest wall mass detected on physical examination. After a negative diagnostic evaluation, exploratory thoracotomy revealed an intercostal hemangioma, undescribed in recent literature. The lesion was excised.

Adult↗

Evolution of pulmonary pseudolymphomas: clinical and radiologic manifestations.

Solitary or multifocal pulmonary pseudolymphoma developed in two men and two women between 59 and 76 years of age. The lesions were detected incidentally in three patients and following a respiratory infection in the fourth. Follow-up radiographs and chest CT revealed gradual expansion of the opacities without cavitation, calcification, or pleural involvement. Histopathologic sections from open lung biopsies or resected segments showed dense alveolar and peribronchial infiltration by numerous mature lymphocytes and plasma cells surrounding reactive lymphoid follicles with true germinal centers. Their benign nature was confirmed by immunofluorescent studies showing polyclonal cell populations. No recurrence or malignant change occurred during 4- to 9-year periods of observation. The clinical and radiologic features of pulmonary pseudolymphoma are presented with a brief review of 54 previously reported cases.

Aged↗

Effects of 17 beta-estradiol on high energy phosphate concentrations and the flux catalyzed by creatine kinase in immature rat uteri: 31P nuclear magnetic resonance studies.

31P nuclear magnetic resonance (NMR) was used to study the effects of 17 beta-estradiol on the content of phosphates and on the flux catalyzed by creatine kinase in immature rat uteri. Perifusion with oxygenated medium at 36 C maintained the uteri in a viable state for at least 10 h in vitro during 31P NMR measurements. In vitro administration of 17 beta-estradiol to the perifused uteri induced changes in the concentration of the high energy phosphates similar to those found after in vivo stimulation: a rapid fall in the concentrations of ATP, phospho-creatine, and the phosphomonoesters during the first 2 h, followed by a slower return to initial concentrations by approximately 6 h. Analysis of the time course of this modulation indicated that after estrogen stimulation, the energy utilization rate was about twice the production rate. The flux through the creatine kinase (CK) reaction was measured independently using 31P magnetization transfer techniques; it was found to increase in uteri 24 h after estradiol injection by the same extent (65%) as the specific activity of CK measured by a spectrophotometric assay. The congruence between the results of these two techniques (in the absence of increased substrate concentrations) provides evidence that the early stimulation of brain-type CK synthesis by estrogen results in a net increase in the concentration of this enzyme.

Algorithms↗

Heterotopic gastric mucosa in the duodenum: radiographic findings.

Heterotopic gastric mucosa in the duodenal bulb was detected by endoscopic examination in 25 adult patients and was confirmed by biopsy in 17 of these patients. The endoscopic findings were correlated with the radiographic features of the lesion on upper gastrointestinal barium studies. On radiographs, this entity usually presented as clusters of 1- to 3-mm plaques raised above the smooth and featureless duodenal mucosa; this was seen in 17 (68%) of 25 patients. A less frequent finding was patches of coarse nodular mucosa with superficial erosions or an ulcer crater (five cases [20%]). The heterotopic gastric mucosa was visible as polypoid masses in two patients and as prominent areae gastricae covering the base of duodenal bulb in another.

Adult↗

Lung cancer classification: the relationship of disease extent and cell type to survival in a clinical trials population.

The staging and histologic cell type of patients in the Lung Cancer Study Group (LCSG) clinical trials program are reviewed and confirmed or resolved at the reference center for anatomic and pathologic classification of lung cancer. A high level of consistency in classification has been achieved through the use of criteria that minimize intraobserver variability. The data obtained from the review project have been used to characterize the relationship of disease extent and cell type to survival in the clinical trials population. Survival characteristics were generated for 1,121 patients who underwent apparent complete resection of nonsmall cell lung cancer and were subsequently entered into various protocols to receive either adjuvant treatment or no further therapy. The end results study provides some insight regarding the biological behavior of squamous cell carcinoma and adenocarcinoma of the lung in terms of the anatomic extent of disease at the time of apparent complete resection. Patients with squamous cell carcinoma had an outcome superior to that of patients with adenocarcinoma in every TNM subset. The differences in survival according to these major cell types were significant overall and in the T1 N0, T1 N1, and T2 N1 subsets but not in the TNM subsets in stage III disease. Histologic cell type and extent of disease are important factors in survival expectations; thus the accuracy and reproducibility of these classifications plays a significant role in the evaluation of differing modalities of treatment.

Actuarial Analysis↗

Estrogen-induced changes in high-energy phosphate metabolism in rat uterus: 31P NMR studies.

Changes in the concentrations of high-energy phosphate metabolites were measured by 31P NMR spectroscopy of surviving rat uteri from 0-48 h following estrogen administration. Concentrations (millimoles per kilogram wet weight) of these metabolites in the untreated immature uterus, measured at 4 degrees C, were found to be the following: creatine phosphate (CP), 2.1 +/- 0.2; nucleoside triphosphates, mainly adenosine 5'-triphosphate (ATP), 4.6 +/- 0.4; phospho monoesters, primarily sugar phosphates (SP), 5.4 +/- 0.7; and inorganic phosphate (Pi), 0.8 +/- 0.4. Adenosine 5'-diphosphate (ADP) concentration was estimated to be approximately 40 mumol/kg wet weight from the assumed equilibrium of the creatine kinase reaction. The concentration of CP, and to lesser extent ATP and SP, declined within the first 1.5-3 h after injection of 17 beta-estradiol, returned to control values between 6 and 12 h, and then increased, reaching maximal concentrations at 24 h. From the fractions of the total soluble ATP in free and Mg2+-bound forms, [free Mg2+] in the untreated uterus was estimated to be 0.2-0.4 mmol/kg wet weight. An increase in [free Mg2+] in the uterus was detected 1.5 h after estrogen injection. A subsequent parallel increase in the ratio of ATP to CP concentrations suggests that estrogen can also affect the apparent creatine kinase equilibrium by modulating [free Mg2+].

Adenosine Diphosphate↗

Bilateral intrathyroidal hyperplastic parathyroid glands.

A patient with secondary hyperparathyroidism was found to have two intrathyroidal parathyroid glands. Parathyroid glands are found completely within the substance of the thyroid in approximately 2 to 8% of all cases. The surgical approach to hyperparathyroidism is discussed.

Functional Laterality↗

Pleomorphic xanthoastrocytoma. Ultrastructural and immunohistochemical study of a case with a rapidly fatal outcome following surgery.

In 1979, researchers described a series of young patients with clinically and histologically distinctive supratentorial gliomas which were designated pleomorphic (meningocerebral) xanthoastrocytomas (PXA). Significantly, patients with these neoplasms were reported to have a relatively favorable prognosis. The authors present a new case of PXA in a 32-year-old man. This case is unique for two reasons: (1) a relatively rapid fatal outcome with death 21 months after diagnosis; and (2) the presence, at autopsy, of extensive recurrent tumor with features of a malignant astrocytoma. Detailed electron microscopic and immunohistochemical studies, supporting the proposed subpial astrocytic origin of PXA, are presented. Literature pertaining to PXA is reviewed. This report illustrates the unique features of PXA and demonstrates its potential for aggressive behavior.

Astrocytoma↗

Malignant Brenner tumor of the ovary. Electron microscopic study of a case responsive to radiation and chemotherapy.

A patient with malignant Brenner tumor of the ovary is presented. The tumor responded to combined therapy with radiation plus doxorubicin + cyclophosphamide despite earlier failure on a single alkylating agent (levophenylalanine mustard). The patient next exhibited a brief response to chemotherapy with hexamethylmelamine + cyclophosphamide + amethopterin + 5-fluorouracil. The histologic findings and ultrastructure of the tumor are discussed in detail. The morphologic features are consistent with the proposed origin of Brenner tumors from coelomic epithelium through a process of secondary urothelial metaplasia.

Aged↗

Infective endocarditis caused by Paecilomyces varioti.

The first reported case of Paecilomyces varioti endocarditis occurring on a porcine heterograft prosthesis is presented and the clinical and pathological features described in the four previously reported cases of prosthetic valvular endocarditis caused by this organism are reviewed. In each case, infection became apparent more than two months after cardiac surgery. Three of the four patients with infected aortic prosthesis developed outflow obstruction secondary to valvular vegetations. All patients died regardless of medical or surgical intervention. Appropriate therapy remains unknown.

Adult↗