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S Self

Publications and source records attributed to S Self.

18 recordsLinked to original sources
PubMed1995

Immunological function in post-traumatic splenosis.

A 28-year-old male medical student underwent splenectomy at 8 years of age due to traumatic rupture of the spleen sustained in a motor vehicle accident. Eighteen years later the patient had major abdominal surgery performed for an unrelated condition and, at the time of surgery, over 100 splenic nodules were found embedded throughout the patient's omentum, small bowel, and mesentery. An extensive study of immunological functions was carried out during the following 2 years. Through the course of this investigation, it was determined that the patient's peripheral blood smear lacked Howell-Jolly bodies and deformed or damaged erythrocytes, indicating that the splenotic tissue had the capacity to remove intranuclear inclusions from circulating red cells and to phagocytose old erythrocytes. The patient's levels of complement, serum immunoglobulins and the numbers of circulating T and B lymphocytes, helper T cells, and cytotoxic/suppressor T cells all were within the normal range. The response to Streptococcus pneumoniae polysaccharides was also normal, with increased levels of specific antibodies to all serotypes included in the vaccine 4 months after immunization. Finally, histological examination of his biopsied splenotic nodules revealed tissue that was indistinguishable from normal spleen.

Adult↗
PubMed1995

Comparative in vitro cytotoxic effects of taxol and its major human metabolite 6 alpha-hydroxytaxol.

Taxol is metabolized by the liver microsomal cytochrome P450 enzyme system into its principal metabolite 6 alpha-hydroxytaxol (6HT). In the present in vitro studies 6HT was compared to taxol with respect to its effects on tubulin depolymerization, mitotic arrest, clonogenic survival and apoptosis in HL-60 cells. 6HT was generated by incubating taxol with human liver microsomes in a NADPH-generating system. HL-60 cells were incubated for 24 h with either taxol or 6HT, washed and placed in drug-free suspension or cultured for colony growth in agarose. For the suspension and colony culture growth of the cells, the IC50 concentrations of 6HT were 500 +/- 46 and 350 +/- 37 nM, while those of taxol were 3.2 +/- 0.2 and 2.8 +/- 0.5 nM, respectively. Immediately after a 24-h exposure of HL-60 cells to 50 nM taxol, electrophoresis of genomic DNA from HL-60 cells revealed an internucleosomal DNA fragmentation 'ladder'. In addition, 39% of the cells were arrested in mitosis and 16% showed the morphologic features of apoptosis. In contrast, an identical treatment with 6HT resulted in the mitotic arrest of only 2.8% of the cells, with 4.0% displaying apoptosis (P < 0.01); internucleosomal DNA fragmentation was not observed. 6HT was also significantly less effective than taxol in inhibiting the temperature-induced depolymerization of microtubules in a cell-free system. However, at equipotent concentrations, the effect of 6HT on tubulin depolymerization, mitotic arrest or apoptosis was similar to that of taxol. In addition, at concentrations of taxol or 6HT at or below their IC50, there was little tubulin depolymerization, mitotic arrest or apoptosis. The results presented here show that the biotransformation of taxol to 6HT substantially detoxifies taxol.

Apoptosis↗
PubMed1994

Characterization of a human myeloid leukemia cell line highly resistant to taxol.

Taxol-resistant sublines of HL-60 myeloid leukemia cells (HL-60/TAX100 and HL-60/TAX1000) have been isolated in vitro by subculturing in progressively higher concentrations of taxol. HL-60/TAX100 and HL-60/TAX1000 cells are capable of continuous growth in the presence of 0.1 microM and 1.0 microM taxol, respectively, and the IC50 (50% growth inhibitory dose) values for taxol for the two sublines are 0.34 and 2.44 microM as compared to 3.1 nM for the parent HL-60 cells. HL-60/TAX100 and HL-60/TAX1000 cells display a variable degree of cross-resistance to taxotere, vincristine and doxorubicin, but are sensitive to the antimetabolite Ara-C. Both HL-60/TAX100 and HL-60/TAX1000 cells over-express MDR-1 m-RNA and the membrane efflux multidrug transporter P-glycoprotein (PGP), as determined by Western blot and immunofluorescence labeling with anti-PGP antibodies. Consequently, exposure of the taxol-resistant cells to [3H]taxol or daunomycin results in the accumulation of significantly lower levels of the two drugs. Co-treatment with cyclosporine (0.5 microgram/ml) or verapamil (10 microM) partially overcomes taxol resistance in HL-60/TAX1000 cells. Following treatment with clinically relevant concentration of taxol (1.0 microM for 24 h), HL-60 but not HL-60/TAX1000 cells display intracellular microtubular bundling, markedly enhanced accumulation of the cells in G2/M phase of cell-cycle and internucleosomal DNA fragmentation associated with apoptosis which is independent of bcl-2 gene expression. These taxol-resistant myeloid leukemia cells may serve as in vitro experimental models for examinating strategies which may have potential applicability for overcoming taxol resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Carbon dioxide gas as an arterial contrast agent.

OBJECTIVE: To investigate the clinical utility of CO2 gas as an arterial contrast agent, the experience with CO2 arteriography at the University of Florida was reviewed. SUMMARY BACKGROUND DATA: Preliminary studies have demonstrated the feasibility of CO2 arteriography and shown that arterial injection of CO2 gas appears non-toxic (which could limit the risks of contrast induced renal injury and allergic reaction). However, numerous technical problems make CO2 arteriography a demanding technique and recent studies have suggested that distal lower extremity vessels are difficult to image using CO2 arteriography, especially when significant arterial occlusive disease is present. METHODS: One hundred twenty-eight CO2 arteriograms done in 115 patients were reviewed. CO2 arteriograms were graded as excellent, good, poor, or inadequate by two blinded observers and results of CO2 studies compared to results of standard contrast studies (done in 98 patients for image comparison). In addition, a therapeutic plan based on the CO2 arteriograms was compared with the therapy each patient received. RESULTS: One hundred-seventeen (91%) of the CO2 arteriograms were of good or excellent quality and agreement between CO2 studies and standard contrast studies was seen in 93 of 98 cases (95%). Accurate therapeutic plans based on CO2 studies were possible in 92% of cases with inadequate visualization of infrapopliteal arteries being the major limitation (7 cases). No allergic reactions occurred and only one patient potentially had contrast-induced nephrotoxicity. CONCLUSIONS: CO2 arteriography provides accurate, clinically useful arterial imaging with minimal risk. Thus, this new technology significantly increases the utility of arteriography in patients with peripheral vascular disease.

Adult↗
PubMed1990

Analysis of the costs of a large prevention trial.

Total direct costs of the Women's Health Trial (WHT), a large multicenter prevention trial, were reduced by more than 50% by means of research cost analysis conducted during the trial design phase. The unit costs of specific trial activities were estimated so that total direct costs of the trial could be predicted from design parameters. The relative costs of screening, treatment, and follow-up, and the fixed costs associated with each clinical center in a multicenter prevention trial were taken into account. Direct costs of the WHT were reduced from +195 million to +95 million by refinement of the trial protocol, selection of an efficient design, and consideration of trial logistics. The analyses suggest several ways to reduce costs in a prevention trial. Use of the case-cohort approach can reduce costs substantially when the protocol includes collection of specimens or data that are costly to process. When establishing and maintaining a clinical center represents a significant proportion of a clinical center's costs, use of a smaller number of larger clinical centers offers important cost savings. Because restrictive eligibility requirements reduce the recruitment potential of each clinical center, use of high-risk participants may not improve the efficiency of a prevention trial; its favorable impact on sample size may fail to compensate for its cost in terms of additional clinical centers and higher recruitment costs.

Aged↗
PubMed1989

Polychlorinated biphenyl congeners in adipose tissue lipid and serum of past and present transformer repair workers and a comparison group.

The concentrations of individual PCB's were determined in both serum and adipose tissue lipid from 35 transformer repair workers currently exposed to PCBs, mainly Aroclor 1260, 17 previous transformer repair workers, and 56 comparison workers never occupationally exposed to PCBs. The analysis used fused-silica capillary gas chromatography with electron capture detector (FSCGC/ECD) and FSCGC with negative ion chemical ionization mass spectrometry to verify PCB congener levels. Eighty-nine PCB peaks were identified and confirmed. More congeners were detected in adipose tissue. In serum approximately 50% of peaks were below the level of detection. Statistical techniques to account for left and interval censoring allowed comparison of concentration distributions even where data were incomplete. We found that unquantifiable levels were unlikely to contribute substantially to the true values for total [PCBs] over and beyond the contribution of the measured values. However, the total serum [PCBs] determined by FSCGC/ECD greatly exceeded that from standard packed cell gas chromatography (PCGC/ECD). The underestimation was less marked for adipose samples. In serum the total [PCBs] was highest in currently exposed workers and lowest in unexposed workers, with past-exposed workers clearly intermediate. In adipose tissue [PCBs] in the currently exposed group was much higher than in the other two groups, in whom the distribution of results was broadly similar. In all worker groups hexachlorinated and heptachlorinated species predominated followed by octachlorinated and pentachlorinated. The relative distribution of individual PCB congeners in the three groups was similar although the amounts varied. The seven major peaks in serum and adipose tissue were 2,3,5,6,3',4',5'/2,3,4,5,2',4',5' hepta-CB; 2,3,4,2',3',5' hexa-CB; 2,4,6,3',4',5'/2,4,5,2',4',5'/2,3,4,5,2',5' hexa-CB; 2,3,4,5,2',3',4' hepta-CB; 2,3,4,5,2',3',5',6'/2,3,4,5,6,2',3',5', octa-CB; 2,4,5,3',4',/3,4,5,2',3' penta-CB; and 2,3,4,2',3',4'/2,3,5,6,2',4',5'/2,3,4,5,2',4',6' multi-CB. The distribution of PCB peaks in our populations differs from that in capacitor workers (exposed to less highly chlorinated PCBs) and from Yu-Cheng patients suggesting differing toxic potentials from PCBs in these three circumstances.

Adipose Tissue↗
PubMed1988

Statistical design of the Women's Health Trial.

The National Cancer Institute has initiated a randomized trial to determine whether a low fat diet can reduce the incidence of breast cancer among women at increased risk for this disease. A feasibility trial involving 303 women has been conducted to examine recruitment strategies, study short-term compliance and, more generally, develop and refine trial procedures. The feasibility trial group also developed a detailed full-scale trial design plan, and randomization of participants to such a trial is currently underway. The purpose of this report is to describe the major design features of this Women's Health Trial, with particular emphasis on the statistical aspects of the design. The trial is planned to last 10 years and to include 32,000 participants. Of these 32,000 women, 12,800 will be assigned to a low fat diet intervention, and the other 19,200 will constitute a control group. The sample size of 32,000 arises from a range of estimates and assumptions pertaining to (a) the incidence of breast cancer at enrollment corresponding to selected eligibility criteria, (b) the relative risk of breast cancer as a function of a woman's history of dietary fat intake, (c) compliance assumptions in terms of average percent fat in the intervention and control groups as a function of time from randomization, and (d) rates of competing causes of death. These estimates and assumptions will be discussed, as will the robustness of the intended sample sizes to departures from such design assumptions.

Aged↗
PubMed1988

The occurrence of a peripheral T-cell lymphoma in a chronically immunosuppressed renal transplant patient.

A 32-year-old man received a cadavaric renal transplant in 1975 for end-stage renal disease and, thereafter, was treated with azathioprine and methylprednisolone for chronic immunosuppression. In 1985, he presented with fever and pancytopenia that persisted despite withdrawal of the immunosuppressive agents. Lymph node and liver biopsies demonstrated malignant lymphoma within the sinuses of the node and the sinusoids of the liver. A splenectomy was performed for persistent pancytopenia, and the spleen demonstrated malignant lymphoma of the diffuse mixed large and small cell type exclusively within the cords of the red pulp. The immunophenotype of the tumor cells was obtained by frozen section immunoperoxidase staining with monoclonal antibodies and flow cytometric analysis. The tumor cells were positive for the Pan T cell markers CD3 and CD2, but were negative for the subset markers CD4 and CD8. A DNA hybridization study conducted on the splenic tissue conclusively identified the clonal nature of the malignant T cells by demonstrating rearrangement of the T cell receptor beta gene. In spite of multiple chemotherapeutic regimens, the patient developed increasing peripheral blood involvement and died with disseminated lymphoma. This case appears to be unique in that it is the first report of a chronically immunosuppressed transplant recipient to develop a malignant lymphoma of the mature T cell type, and several of the pathologic features of the tumor have not been observed previously.

Adult↗
PubMed1987

Treatment of preleukemic syndromes with marrow transplantation.

Thirty patients with advanced preleukemic syndromes were treated with marrow transplantation. Most cases were diagnosed by the presence of peripheral pancytopenia and a diagnostic marrow examination but in 6 of the 30 patients pretransplant chromosome studies were instrumental in establishing the diagnosis. Three patients prepared for transplantation with cyclophosphamide alone recurred with their disease within 6 months of transplantation. The other 27 patients were treated with cyclophosphamide and total body irradiation. Twenty of these 27 patients had preleukemia not associated with prior therapy or severe marrow fibrosis. Thirteen of these 20 are alive and well 9 to 56 months from transplant and 7 died, 4 of interstitial pneumonia, 2 of candida septicemia, and 1 of disseminated zoster. There have been no disease recurrences in this group. The remaining preleukemic patients, which include 3 patients transplanted for preleukemia secondary to prior therapy and 4 patients transplanted for preleukemia associated with severe marrow fibrosis, have all died. Major problems in these patients included disease recurrence (2 cases) and, in those with severe marrow fibrosis, graft failure (2 cases). These results suggest that for patients with life-threatening pancytopenia due to spontaneous preleukemia without severe marrow fibrosis, marrow transplantation can prolong disease-free survival and may result in cure of the disease.

Bone Marrow Transplantation↗
PubMed1987

Refractoriness to random donor platelet transfusions in patients with aplastic anaemia: a multivariate analysis of data from 264 cases.

Frequent platelet support is an essential part of the management of patients with severe aplastic anaemia and platelet transfusions from random donors are usually given as initial therapy. To evaluate those parameters that might correlate with the development of refractoriness to platelets from random donors, we performed a retrospective multivariate analysis in 264 patients with severe aplastic anaemia who presented for allogeneic bone marrow transplantation. Two hundred and ten (79.5%) of these patients had received multiple platelet and red cell transfusions, and 71 (34%) were refractory to random donor platelets. The strongest factor correlating with refractoriness was the presence of lymphocytotoxic antibodies, followed by the number of platelet units previously transfused. However, the latter variable attained significance only when the number of platelet units transfused exceeded 40. When given HLA-compatible platelet transfusions, only five (7%) of the refractory patients did not show a reasonable post-transfusion platelet increment. Measures which would delay or prevent platelet alloimmunization might include a policy of therapeutic rather than prophylactic platelet transfusions, and referring patients early in the course of their disease for marrow grafting if a suitable donor is available.

Adolescent↗
PubMed1986

Is race a risk factor for allogeneic marrow transplantation?

We investigated the influence of race as a risk factor for the outcome of HLA-identical marrow transplantation. The actuarial survival at 2 years after grafting of Blacks, Hispanics and Asians was compared with that of Caucasians transplanted between 1971 and 1985 for aplastic anaemia, acute non-lymphocytic leukaemia and acute lymphoblastic leukaemia. Among patients with aplastic anaemia, there was no difference with regard to engraftment or actuarial survival among different racial groups. Among patients with acute non-lymphocytic leukaemia, Blacks had a lower survival (P = 0.03) than other groups, although there was no obvious single factor accounting for this difference. In patients with acute lymphocytic leukaemia, survival was comparable among the different races. Acute and chronic graft-versus-host disease appeared to occur with similar frequencies in all groups, except for a slightly higher incidence among Blacks with acute non-lymphocytic leukaemia. Larger numbers of patients need to be examined before firm conclusions can be drawn.

Actuarial Analysis↗
PubMed1986

Decreased incidence of marrow graft rejection in patients with severe aplastic anemia: changing impact of risk factors.

Patients with severe aplastic anemia were conditioned with cyclophosphamide (200 mg/kg) and given marrow grafts from HLA-identical family members. Among 233 patients transplanted, 225 survived greater than or equal to 14 days and could be evaluated for engraftment. Forty-four of the 225 rejected their graft; 33 of these died and 11 survive. One hundred eighty-one patients had sustained engraftment; of these, 46 died and 135 survived. Binary logistic regression analyses revealed five risk factors for graft rejection: year of transplant, a large number of platelet transfusions, a positive relative response in mixed leukocyte culture, a low marrow cell dose, and omission of donor buffy coat cell infusion for transfused patients. These data show that patients transplanted recently had a lower likelihood of graft rejection than did patients transplanted in earlier years. Conceivably, this was related to changes in transfusion practices, but other factors as yet unidentified are likely to be involved. The data confirm that the largest possible number of marrow cells should be transplanted. Although the difference in the incidence of graft rejection between untransfused and transfused patients was not significant, it should be noted that transfused patients were given buffy coat cells. Because the addition of buffy coat cells results in a higher incidence of chronic graft-v-host disease (GVHD), it is still desirable to transplant patients with marrow alone early in their course before they have been transfused.

Anemia, Aplastic↗
PubMed1985

Marrow transplant studies in dogs with malignant lymphoma.

Ninety-five dogs with spontaneous malignant lymphoma in chemotherapy-induced remission were treated with total-body irradiation (TBI) and bone marrow transplantation. Among 38 dogs treated with 8.4 Gy delivered at 4 cGy/min, 9 (24%) became long-term disease-free survivors. Ten of the 38 (26%) died of transplant-related complications and the actuarial relapse rate was approximately 65%. Forty animals were treated with higher-dose TBI (13.5 Gy). The higher-dose TBI led to an increased incidence of transplant-related deaths (55% vs. 26%) and did not reduce the actuarial relapse rate. Eight animals were treated with 8.4 Gy at 4 cGy/min, allogeneic marrow from unrelated donors, and posttransplant immunosuppression with methotrexate and cyclosporine. Of 8 animals, 6 died within 2 weeks of transplant of infection and 2 died later of graft-versus-host disease. Finally, 9 dogs were treated with 8.4 Gy at 4 cGy/min, autologous marrow, and posttransplant methotrexate and cyclosporine. Six of these animals died within 2 weeks of transplant. These studies thus demonstrated that dogs with malignant lymphoma in remission can be cured with high-dose TBI and autologous marrow transplantation, that increasing the total dose of TBI led to increased toxicity without a decrease in the relapse rate, and that post-transplant therapy with methotrexate and cyclosporine was poorly tolerated in these animals.

Animals↗
PubMed1984

The mediating role of the parathyroid gland in the effect of low calcium intake on blood pressure in the rat.

Recent reports suggest an inverse relationship between calcium intake and blood pressure. This effect could be mediated by parathormone (PTH), since a low calcium intake leads to an increase in PTH and this hormone produces an increase in intracellular calcium, raising the excitability of the muscle arteriolar cells. Wistar female rats, 56 days old, were submitted to a parathyroidectomy or to a sham operation. After that, they were placed on a normal or on a calcium-free diet during 10 weeks. Four groups of nine rats were studied: parathyroidectomized animals on a normal calcium diet, parathyroidectomized ones on a calcium-free diet, controls (sham operation) on a normal calcium diet, and controls (sham operation) on a calcium-free diet. The control calcium-free diet showed a significant increase in blood pressure values over the treatment period. The parathyroidectomized calcium-free diet group did not show any increase. The difference between these two groups regarding change in blood pressure was statistically significant. The parathyroidectomized-calcium-free group showed no weight increase during the study, while rats in the other three groups significantly increased their weight. PTH could be the mediator of the blood pressure rise observed in the calcium-deprived rats in spite of the possible confounding effect of the poor weight increase detected in the parathyroidectomized-calcium deprived animals. These results warrant future studies since the role of PTH in the regulation of blood pressure needs to be confirmed. This possibility, therefore, opens a new area of research in the study of the pathophysiology of hypertension.

Animals↗
PubMedDate not supplied

Immunity during pregnancy: lymphocyte subpopulations and mitogen responsiveness.

Many hypotheses have been proposed to explain the alteration of maternal immune status that allows the fetus to escape rejection. Published data using monoclonal antibodies have stated that there are small variable reductions in circulating T-lymphocytes and little or no change in helper-to-suppressor ratios. Specific decreased levels of helper T-cells have been claimed by other workers. Our laboratory has previously reported alterations in tritiated thymidine uptake (3H-TdR) and HLA antibodies during pregnancy. The present study evaluates total T-cells, lymphocyte T-cell subsets, helper-to-suppressor ratios of T-cells, B-cells, and lymphocyte blast transformation (LBT) throughout pregnancy. These lymphocyte measurements were compared to hormonal changes occurring during pregnancy to determine whether or not hormonal levels have a significant correlation on the maternal immune response during gestation. Data from 100 women revealed no significant alteration of total T-cells or T-cell subsets during pregnancy or after parturition, as measured by monoclonal antibodies. Helper-to-suppressor ratios were within normal limits. B-cells showed a significant decrease (P less than 0.001) during the postpartum period. There was decreased lymphocyte responsiveness to mitogenic stimulation by phytohemagglutinin-P (PHA-P), concanavalin-A (CON-A), and pokeweed mitogen (PWM) in the first, second and third trimesters (P less than 0.01). The mechanisms of fetal protection from maternal immune recognition remain obscure.

Adolescent↗
PubMedDate not supplied

Lymphomas: membrane markers and cell flow cytometric diagnosis.

Lymphocytes are characterized by membrane markers which, in part, reflect biological and functional activity. This is particularly true for T lymphocyte subsets identified by monoclonal antibodies. The B lymphocytes can be identified but in a more general manner. It has been proposed that the use of these markers will aid in the differential diagnosis of a variety of lymphomas. The objective of this work was to evaluate the use of monoclonal antibodies (MAb-s) and surface immunoglobulin (sIg) analysis in a cell flow cytometer (CFC) as methods to identify and classify lymphomas. The cell flow cytometric findings were then evaluated in light of the histopathologic diagnosis (HPD). Fifty-eight (58) patients with a variety of lymphomas and benign lymph node disorders were studied. Lymph node tissue samples were obtained after surgical removal and appropriately prepared for evaluation in a CFC. Results showed that the variety of hyperplasias and reactive follicular lymphadenopathies could not be characterized by the technique or application of CFC alone. Both B cell and T cell lymphomas could be recognized and differentiated by MAb-s and/or light chain monotypism using sIg's in a CFC, but morphologic and clinical information were required for diagnostic confirmation. Hodgkin's disease could not be identified by CFC because of the lack of a specific identifiable marker. Cell flow cytometry provides an easy and rapid adjunct to the diagnosis of a variety of lymphomas. At the present time, membrane markers in cell suspensions from tissues (lymph nodes) identified by MAb-s and sIg's in a CFC cannot be used to provide definitive diagnoses for reactive lymphadenopathies, Hodgkin's disease or some classes of lymphomas.

Antibodies, Monoclonal↗