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D J Tate

Publications and source records attributed to D J Tate.

7 recordsLinked to original sources

Pelvic relapse following subtotal lymphoid irradiation in early stage Hodgkin's disease--an analysis of risk, management, and outcome.

PURPOSE: To evaluate the time of onset, method of identification, management, and outcome of pelvic relapse following subtotal lymphoid irradiation (STLI) alone (mantle and paraaortic/spleen or splenic pedicle fields, excluding the pelvis) in supradiaphragmatic Stage I-II Hodgkin's disease. METHODS AND MATERIALS: A retrospective analysis was performed of the initial, relapse, and regular follow-up evaluations of patients with pelvic relapse following STLI alone from 1968 to the present for supradiaphragmatic Stage I-II Hodgkin's disease after pathologic staging (PS-laparotomy staging) and clinical staging (CS-no laparotomy staging). RESULTS: Following staging, which included bipedal lymphangiography, 482 patients (408 PS and 74 CS), were treated with STLI alone for supradiaphragmatic Stage I-II Hodgkin's disease. The actuarial freedom from relapse at 20 years was 75% in PS patients and 81% in CS patients. The actuarial pelvic failure at 20 years was 7% for PS patients and 3% for CS patients. Of the 29 patients with pelvic relapse, 97% (28 of 29) occurred within 5 years of treatment, including 1 patient who progressed during initial treatment. Pelvic relapse was most commonly initially identified by abnormalities involving patient symptoms (62%), physical examination (55%), erythrocyte sedimentation rate (48%), and bipedal lymphangiogram and/or abdominal radiograph (38%). Relapse was limited to previously unirradiated sites in 17 patients (58%). In addition to pelvic lymph node disease, 3 patients (10%) had involvement of bone, and 4 patients (14%) had bone marrow involvement. Following relapse, all patients were treated with chemotherapy (MOP[P], MOP[P]/ABV[D], ABVD, or PAVe) and 19 of 29 patients received involved field consolidative irradiation. Twenty-one of 29 (72%) remained relapse free at the time of last follow-up evaluation, including 15 of 19 (79%) treated with combined therapy. Eight patients experienced a second relapse despite salvage therapy, and all eight expired with recurrent Hodgkin's disease. Two patients died of complications related to prior treatment. Therefore, the actuarial risk of death at 20 years associated with pelvic failure in the entire cohort of 482 patients was 2%. CONCLUSION: Pelvic relapse occurred in 7% of patients following STLI alone and was effectively diagnosed by regular follow-up, which included a combination of patient history, physical examination, and radiographic laboratory evaluation. Seventy-two percent of patients remained relapse free following salvage treatment, which included chemotherapy, resulting in an overall survival rate associated with pelvic control of 98%. This approach, therefore, spared the majority of patients the long-term risks associated with pelvic irradiation and/or chemotherapy, such as infertility, but maintained an excellent prognosis.

Antineoplastic Combined Chemotherapy Protocols

Influence of zinc on selected cellular functions of cultured human retinal pigment epithelium.

Zinc is a necessary micronutrient, usually abundant in human RPE. Our study was undertaken to determine the effects of short-term, zinc deficiency on human retinal pigment epithelium (RPE) using a culture model of fetal human RPE cells. Human fetal RPE cells were isolated and cultured in Coon's modified Ham's F-12 medium. For zinc depletion studies, cells were cultured for 1 week in Chelex-treated Dulbecco's modified Eagle's medium containing low (0.25 microM) or physiologic (11 microM) total zinc concentrations as determined by flame atomic absorption spectroscopy. Protein synthesis was determined by incorporation of 35S-cysteine/methionine and labeled proteins analysed by polyacrylamide gel electrophoresis. Several cell parameters and enzymes were significantly reduced below control when cultured in low zinc: zinc content (40%), proliferation (63%), protein/well (50%), catalase activity (68%), alkaline phosphatase activity (61%), alpha-mannosidase activity (68%), and metallothionein (82%). No statistically significant decline was seen in acid phosphatase activity, superoxide dismutase activity, glutathione peroxidase activity and dexamethasone induction of metallothionein. Zinc repletion (100 microM, 1 h) increased catalase and alpha-mannosidase activities from 32% and 33% of control to 75% and 73%, respectively. Cycloheximide did not inhibit this short-term zinc-induced repletion of catalase or alpha-mannosidase. Protein synthesis in low zinc medium was depressed, but not significantly, as shown by incorporation of radiolabeled 35S-cysteine/methionine into newly synthesized proteins. The effects of zinc deficiency in cultured human RPE are selective. Adequate intracellular zinc was required for maximal activity of some enzymes. The dependence of catalase activity on zinc was not predicted and may help explain the observed decline in catalase activity seen with age in RPE. Our model of zinc deficiency should prove useful in elucidating the complex effects of zinc deficiency and repletion in human RPE.

Cell Division

Phagocytosis and H2O2 induce catalase and metallothionein gene expression in human retinal pigment epithelial cells.

PURPOSE: Reactive oxygen intermediates have been implicated in the aging process and degenerative diseases of the eye, including retinopathy of prematurity, cataractogenesis, and macular degeneration. The purpose of this study was to investigate the effect of phagocytosis of photoreceptor outer segments and the addition of exogenous H2O2 on catalase and metallothionein expression in human retinal pigment epithelial cells. METHODS: Confluent RPE cells were treated with bovine photoreceptor outer segments or H2O2 for either 6 or 18 hours. Slot blot hybridization was used to assess catalase and metallothionein gene expression after 6 hours. Catalase enzyme activity and metallothionein content were measured after 18 hours. RESULTS: Phagocytosis or the addition of H2O2 increased catalase enzyme activity and metallothionein twofold above control levels. The addition of n-acetyl cysteine abrogated the inductive effect caused by either stress. Catalase and metallothionein gene expression, measured by slot blot hybridization, also were measurably induced by either stress. Phagocytosis of photoreceptor outer segments increased extracellular H2O2 concentration nine times above control. CONCLUSIONS: The response of the retinal pigment epithelial cells to phagocytosis was indistinguishable from the response observed after the addition of exogenous H2O2. The generation of H2O2 during phagocytosis may act as an intracellular signal in retinal pigment epithelial cells that leads to increased levels of key antioxidant enzymes and other proteins important for protecting the cells from oxidative damage.

Adolescent

Age-dependent change in the hyaluronic acid content of the human chorioretinal complex.

OBJECTIVE: Hyaluronic acid (HA) has a key role in the structure and organization of the extracellular matrix. We sought to identify the distribution of HA in human eye tissue with regard to age using a biotinylated HA-binding protein. METHODS: Fetal and adult (from donors ranging from 28 to 94 years of age) eye tissues were fixed less than 24 hours post mortem and embedded in JB-4 medium (Polysciences, Warrington, Pa). Sections of 2-microns thickness were used. Control sections were pretreated either with Streptomyces hyaluronidase or HA-binding protein inactivated by HA. The binding of the protein to HA was detected with avidinbiotin alkaline phosphatase and developed by incubation with naphthol as-mx phosphate and Texas Red Salt (Pierce, Rockford, Ill). RESULTS: Specific staining for HA was observed in fetal eyes in the choroid, Bruch's membrane, sclera, retinal pigment epithelium, and developing retina from the vitreoretinal interface to the inner plexiform layer. Specific staining decreased with age in the choroid, retinal pigment epithelium, and Bruch's membrane. Hyaluronic acid-specific staining was undetectable in tissues from donors over 50 years of age. CONCLUSIONS: The localization of HA in the chorioretinal complex and its disappearance after the fifth decade of life may play a role in aging and age-related retinal disorders.

Adult

Metallothionein shows an age-related decrease in human macular retinal pigment epithelium.

PURPOSE: To investigate the possible role of zinc-metallothionein in human retinal pigment epithelium with regard to age-related changes. METHODS: A cadmium/heme assay was used to quantitate metallothionein in isolated macular and peripheral retinal pigment epithelium from donors ranging in age from 28 to 91 yr (n = 16, mean age = 68.6 yr). RESULTS: It was found that peripheral retinal pigment epithelium contained significantly more metallothionein and zinc than macular retinal pigment epithelium. Macular retinal pigment epithelium cells contained 17.6 +/- 2.2 micrograms metallothionein/mg cytosolic protein in donors younger than 70 yr, compared to 5.6 +/- 0.9 in macular retinal pigment epithelium from donors older than 70 yr, a 68% decline (P = 0.0007). In cultured retinal pigment epithelium, when we lowered the zinc concentration in the medium, metallothionein was reduced by 72% after 1 wk of incubation. CONCLUSIONS: It is suggested that lower levels of metallothionein in retinal pigment epithelium are caused by reduced metallothionein gene activity or a faster rate of protein degradation, both of which are known to be regulated, at least partly, by bioavailable zinc.

Adult

Metallothionein in human retinal pigment epithelial cells: expression, induction and zinc uptake.

The retinal pigment epithelium (RPE) plays several important roles in the continual support and renewal of photoreceptor outer segments. In the present study, we have demonstrated that RPE cells contain a low molecular weight protein with a high capacity for zinc binding that is dependent on available sulfhydryl groups. This protein is inducible by a 24 hour incubation of cultured RPE in medium supplemented with zinc, cadmium, or dexamethasone. The induction of this protein is correlated with an increased capacity for zinc-65 uptake into cultured RPE. Analysis with a cDNA probe specific for the human metallothionein II gene corroborated the existence and induction of metallothionein gene products in RPE cells. Based on these properties, we have identified this protein as metallothionein. The induction of metallothionein likely has a critical influence on the zinc economy of the RPE.

Cadmium