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Biomedical subjects

C W Patrick

Publications and source records attributed to C W Patrick.

32 records · Page 2Linked to original sources

Shear stress and cyclic strain modulation of gene expression in vascular endothelial cells.

Vascular endothelial cells are exposed to a complex humoral and hemodynamic environment. Investigations over the last two decades have demonstrated that hemodynamic forces cause alterations in endothelial cell function. More specifically, blood flow-induced wall shear stress and cyclic strain modulate gene expression of various bioactive molecules synthesized and secreted by endothelial cells. Although there currently is not a known unifying mechanism linking mechanical agonists to changes in gene expression, various second messengers, transcription factors, mechanically sensitive promoter elements, and cytoskeletal architecture have been proposed as mediators in the signal transduction pathway. Knowledge of the mechanisms by which hemodynamic forces modulate endothelial cell gene expression will lead to novel gene therapy applications and allow more effective management of cardiovascular diseases.

Animals↗

Correlation of circulating natural killer cell count with prognosis in large cell lymphoma.

A monoclonal antibody recognizing a natural killer (NK) cell-associated antigen was used to sequentially quantify numbers of peripheral blood NK cells in a small group of patients with large cell lymphoma. Patients with active disease had low numbers (less than 100/mm3) of NK cells. Patients in complete remission after therapy had normal numbers of NK cells, but those patients who relapsed had a fall of NK cell number to less than 100/mm3 preceding or concurrent with clinical relapse. A role for NK cells in the surveillance and control of abnormal lymphoproliferation is suggested, as is the possible prognostic utility of sequential peripheral blood NK cell quantification in patients with large cell lymphoma.

Antibodies, Monoclonal↗

Holding medium for cell surface phenotypic analysis.

Peripheral blood samples from 20 normal adults and 12 patients with diagnosed B cell lymphoproliferative disease were phenotyped with a panel of 20 monoclonal antibodies (Coulter) using a whole blood lysis technique at zero time and after storage in M199 containing insulin, transferrin and L-glutamine at 24, 48 or 72 h. The samples were analyzed using flow cytometry (EPICS V) to determine the percentage of positive events for each sample. A 2-way analysis of variance showed that there were no significant differences between the initial sample and those phenotyped after 24, 48 or 72 h. These data suggest that this medium can be utilized for the storage and transport of blood samples from patients and ensure satisfactory cell surface phenotypic analysis.

Adult↗

Immunoregulatory abnormalities in myelodysplastic disorders.

Immunoregulation was assessed in a group of patients with myelodysplasia (MDS) by flow cytometric analysis of peripheral blood lymphocyte subsets and in vitro studies of mitogen-stimulated T-lymphocyte blastogenesis. Mitogenesis was significantly depressed in MDS patients compared to controls (p less than .001) and a similar defect was found in a small group of patients with untreated acute nonlymphocytic leukemia (ANLL) (p less than .005). The impaired mitogenic response ability of T-cells in these patients did not appear to be the result of alteration in lymphocyte subpopulation ratios. The observed defect might result from defective cooperation between T-lymphocytes and abnormal myeloid elements. Alternatively, the lymphocytes themselves could be derived from the abnormal clone and thus be functionally abnormal.

Antigens, Surface↗

T-cell chronic lymphocytic leukemia with pure red cell aplasia: laboratory demonstration of persistent leukemia in spite of apparent complete clinical remission.

A 40-year-old woman presented with splenomegaly, macrocytic anemia, and red cell aplasia. Although lymphocytosis was absent in the peripheral blood, large atypical lymphoid aggregates were present in the bone marrow. Splenectomy resulted in partial remission of red cell aplasia, but a gradual increase in the number of peripheral blood lymphocytes followed during the next 36 months. Flow cytometric analysis demonstrated that the majority of these peripheral blood lymphocytes had suppressor, natural killer T-cell phenotype. No other treatment was given until red cell hypoplasia worsened 42 months after initial presentation. Repeat bone marrow evaluation again demonstrated severe erythroid hypoplasia and large abnormal lymphocytic infiltrates. Cyclophosphamide given for 8 months resulted in complete resolution of the red cell aplasia and complete clinical remission of CLL. However, flow cytometric analysis revealed persistent increase in bone marrow T-cells, and bone marrow co-culture studies demonstrated residual ability of peripheral blood mononuclear cells to inhibit erythropoiesis in vitro, suggesting that residual, clinically undetectable leukemia persists in spite of complete clinical remission.

Adult↗

Myeloid cell surface phenotype in myelodysplasia: evidence for abnormal persistence of an early myeloid differentiation antigen.

A panel of monoclonal antibodies recognizing myeloid cell surface differentiation-associated antigens was used to study the peripheral blood myeloid population of 23 patients with myelodysplastic syndromes (MDS) and 23 controls. A marker for immaturity, defined by the presence of the antigen recognized by the My9 antibody, was found to persist on the surface of mature neutrophils in a subgroup of MDS patients. Abnormal My9 positivity was concentrated primarily, but not exclusively, in previously described morphologically defined subgroups of MDS patients considered to be at highest risk for leukemic conversion. Longitudinal study of a larger number of patients will be required to test the hypothesis that abnormal persistence of My9 may have prognostic significance.

Antibodies, Monoclonal↗

Prolonged survival in Richter syndrome with subsequent reemergence of CLL: a case report including serial cell-surface phenotypic analysis.

The development of a large cell lymphoma in a patient with chronic lymphocytic leukemia (Richter syndrome) is associated with a poor prognosis. There is dispute regarding the clonal origin of the large cell component. We described a patient in whom prolonged remission of the large cell component was achieved with combination chemotherapy, followed by subsequent reemergence of the less aggressive CLL clone. Serial cell surface phenotypic data are presented suggesting origin of both histologies from a common B-cell clone.

B-Lymphocytes↗

Flow cytochemical analysis of atopic reactions.

The technicon H-6000 has the unique ability among automated hematology systems to discriminate basophils from other hematopoietic cells on the basis of astra blue positivity of heparin-containing granules. We therefore examined the ability of this flow cytochemistry system to predict allergic diathesis in vitro by examining the number of basophils detected before and after incubation with a variety of allergens. One hundred subjects with documented atopic reactions to known allergens were examined and compared to 13 patients who had undergone successful desensitization and 12 normal subjects who had no history of atopy. One subject who had a previous anaphylactic response to penicillin but was skin-test negative to the major antigenic determinant demonstrated 55% degranulation after incubation with penicillin G. Finally, the basophil degranulation as assessed by the Technicon H-6000 was compared to a histamine release assay to determine the sensitivity of the automated system. The results suggest that flow cytochemistry may prove a valuable tool in predicting the success of desensitization therapy for common allergens and may have the potential to screen atopic reaction in the routine hematology laboratory.

Allergens↗

A simple device for the collection of cells sorted by flow cytometry.

A simple device for the collection of cells sorted by flow cytometry under sterile and nonsterile conditions is described. Cells collected in this manner reflect a high recovery rate with superior preservation of viability and cytomorphology. Key terms: Cell sorting, cytomorphology, testing collection device.

Flow Cytometry↗

Fc gamma bearing T cells in non-Hodgkin lymphoma.

T-cell subpopulations have been implicated in the regulation of normal human B-cell reactivity. As the non-Hodgkin lymphomas (NHL) represent predominantly clonal B-cell malignancies, we examined the relationship of total T-cell [Sheep Red Blood Cell (SRBC) binding] and Fc gamma bearing T-cell populations in these disorders. Peripheral blood from seven low-grade (Rai stage 0), six high-grade (Rai stage 3 or 4) CLL patients, lymph node specimens from five patients with WDLL, seven patients with PDLL-D, three patients with MC-D, and eight patients with DHL were studied. All values were compared to normal controls. The percentage of total T cells in each disease category was decreased compared to controls. In addition, there was a reproducible correlation between the percentage of Fc gamma bearing T cells and the histopathologic diagnosis. The percentage of Fc gamma bearing T cells was highest in low-grade CLL and decreased incremently from high-grade CLL and WDLL, to MC-D, and PDLL-D. In DHL, we found no Fc gamma bearing T cells. Finally, the percentage of Fc gamma bearing T cells in each disease category was decreased compared to controls. These findings suggest a correlation between Fc gamma bearing T cells and the clinical aggressiveness of disease in NHL. In addition, they may raise important questions about therapy. Finally, they may offer a useful clinical test as an adjunct to histopathology although this will need to be confirmed in larger series.

Humans↗

Adipose tissue engineering: the future of breast and soft tissue reconstruction following tumor resection.

Reconstructive surgeons have always been at the forefront of medical technology. The history of reconstructive surgery began with ablative surgery, which was followed by tissue and organ transplantation, leading to contemporary tissue reconstruction. The field of reconstructive surgery is poised at the next stage of its evolution, namely tissue regeneration. The field of tissue engineering has largely defined this evolutionary leap. One active area of investigation is the development of tissue engineering strategies for adipose tissue. Bioengineers, life scientists, and reconstructive surgeons are synergistically coupling expertise in areas such as cell culture technology, tissue transfer, cell differentiation, angiogenesis, computer modeling, and polymer chemistry to regenerate adipose tissue de novo for breast replacement and soft-tissue augmentation following tumor resection. This work presents the current state of the art in adipose tissue engineering, as well the clinically translatable strategies currently under development. Semin. Surg. Oncol. 19:302-311, 2000.

Adipose Tissue↗

Pore morphology effects on the fibrovascular tissue growth in porous polymer substrates.

The feasibility of developing biodegradable polymer scaffolds to engineer tissues was investigated by studying the effects of pore size on the dynamics of fibrovascular tissue ingrowth. Tissue advanced into amorphous poly(L-lactic acid) porous substrates faster as the pore diameter increased. Porous cylindrical devices of 13.5 mm diameter, 5 mm thickness, and approximately 500 microns pore size were filled completely by tissue 5 days postimplantation. Although prevascularized devices possessed minimal void volume for cell seeding to regenerate metabolic organs, they hold promise in the regeneration of tubular tissues by relying on the epithelization of prevascularized grafts.

Alginates↗