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Biomedical subjects

G Fine

Publications and source records attributed to G Fine.

At least 19 recordsLinked to original sources
PubMed2000

Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.

OBJECTIVE: The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells. MATERIALS AND METHODS: The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design. RESULTS: Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil count >0.5 x 10(9)/L day 10; platelet count >50 x 10(9)/L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34+ selected or unselected autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction >3.12. CONCLUSIONS: CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses >0.8 x 10(6) CD34+Thy1+ HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

Adult↗
PubMed2000

Employee competence and performance-based assessment: A college of American pathologists Q-probes study of larboratory personnel in 522 institutions.

OBJECTIVE: To survey employee competence assessment practices in departments of pathology and laboratory medicine and provide suggestions for improvement. DESIGN: A 3-part study consisting of a questionnaire about current competence assessment practices, an evaluation of compliance with stated competence assessment practices using personnel records of 30 employees, and a written appraisal of competence of 5 specimen-processing staff members per institution. SETTING: A total of 522 institutions participating in the College of American Pathologists 1996 Q-Probes program. MAIN OUTCOME MEASURES: Institutional competence assessment practices, compliance of each institution with their own practices, and determination of competence of specimen-processing personnel. RESULTS: Of the participating institutions, 89.8% had a written competence plan and 98.1% reported reviewing employee competence at least yearly. General competence was reviewed by direct observations (87.5%), review of test or quality control results (77.4%), review of instrument preventive maintenance (60.0%), written testing (52.2%), and/or other methods (20.8%). In 8.6% of institutions, employees who failed competence assessment were not allowed to continue their usual work. On review of records of 14 029 employees for adherence to the laboratory's general competence plan, adherence was 89.7% for direct observations, 85.8% for review of quality control and test results, 78.0% for review of instrument records, and 74.0% for written testing. Employee failure rate ranged from 0.9% to 6.4%, depending on the competence evaluated. Adherence to an institution's plan was 90.4% for new employees, 93.1% for computer skills, 95.8% for laboratory safety, and 92.1% for continuing education. When a written competence assessment was given to 2853 specimen-processing staff members, 90.0% responded satisfactorily. CONCLUSIONS: Opportunities for improvement in employee competence assessment are numerous, and we provide several specific suggestions.

Educational Measurement↗
PubMed1996

IL-16 inhibition of CD3-dependent lymphocyte activation and proliferation.

We have recently described the cDNA and predicted protein structure of a natural soluble CD4 ligand, IL-16. IL-16 is chemotactic for CD4+ T cells and induces functional IL-2 receptors in CD4+ T cells. The binding of IL-16 to CD4 results in activation of p56(lck), whose adaptor function is essential for the chemotactic response. Subsequently, increases in intracellular Ca2+ and phosphatidylinositol 1,4,5-trisphosphate occur, as does translocation of protein kinase C from cytosol to membrane. Because of the similarities between these signals and functions and those noted for the CD4 ligand HIV-1 gp120, we investigated the potential regulatory effects of IL-16 on CD3/TCR-mediated lymphocyte activation. Preincubation of human T cells with IL-16 up to 24 h before activation with plate-bound anti-CD3 Abs reduced T cell activation by 80%, as monitored by IL-2R expression and [3H]thymidine uptake. If IL-16 was added following anti-CD3 activation, no suppression was noted. The suppressive effects of preincubation with IL-16 were not rescued by the addition of rIL-2 and were not the result of priming for anti-CD3-induced apoptosis. In addition, IL-16 had no effect on surface expression of CD3 or CD4. However, IL-16 did reduce the magnitude of the anti-CD3-induced intracellular Ca2+ increase. These studies indicate that while the interaction of CD4 with its natural ligand, IL-16, results in Ag-independent chemotaxis and IL-2R expression, this pro-inflammatory state is associated with subsequent transient inhibition of responsiveness via the CD3/TCR complex.

Apoptosis↗
PubMed1996

CD4 ligand IL-16 inhibits the mixed lymphocyte reaction.

CD4 participation in TCR/CD3-associated activation through interaction with the MHC class II Ags results in formation of a CD4-TCR/CD3 complex capable of maximal signal transduction. When CD4 binds to alternative ligands such as HIV-1 gp120 or anti-CD4 Abs, Ag stimulation of TCR/CD3 is markedly inhibited, and an unresponsive state develops. To determine if the natural CD4 ligand interleukin-16 also induces unresponsiveness, we tested the effects of rIL-16 on T cell proliferation in mixed lymphocyte reactions. rIL-16 suppressed T cell proliferation in a dose-dependent manner at concentrations of 10(-11) to 10(-7) M. Inhibition of proliferation was present on days 5 to 9 of the mixed lymphocyte reaction. rIL-16 did not modulate membrane CD4, significantly change basal [3H]thymidine incorporation in resting T lymphocytes, or alter viability. The suppressive effect was specifically blocked by preincubation with neutralizing anti-rIL-16 mAb or with recombinant soluble CD4. While the expression of IL-2R on responder cells was unaffected by rIL-16, the addition of exogenous rIL-2 did not restore T cell responsiveness. The unresponsiveness induced by rIL-16 is distinct from that of other CD4 ligands in that CD4 and IL-2R expression are unaffected. The failure of rIL-2 to restore proliferation suggests that the decrease in T cell responsiveness induced by rIL-16 may result from an interruption in the IL-2R-signaling mechanism. These results may help explain how CD4 delivers both activating and inhibitory signals and provides a rationale for the role of IL-16 in the regulation of immune responses.

CD4 Antigens↗
PubMed1991

Adenoma of type 2 pneumocytes with oncocytic features.

An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly.

Adenoma↗
PubMed1990

Effect of exercise level on ventilatory adaptation to respirator use.

The effect of exercise on the adaptation to an air-purifying respirator type load (dead space + inspiratory resistance) was studied in a group of 13 volunteers with a rapidly incremental exercise protocol. The difference between loaded and unloaded breathing at each exercise level was determined for each subject for a series of parameters describing the ventilatory work to overcome the respirator load pattern of breathing and metabolic work. Linear regression and t tests determined the average effect of the respirator load and the extent to which this effect was affected by the level of exercise. The inspiratory time and duty cycle were increased by the load, and exercise did not significantly affect the magnitude of this adaptation. High exercise did, however, increase the magnitude of the effect of the respiratory load on ventilatory work. These findings suggest that constraints to respiratory pattern adjustment, which may decrease respirator tolerance, occur at high exercise levels.

Adaptation, Physiological↗
PubMed1989

Effects of respirator dead space, inspiratory resistance, and expiratory resistance ventilatory loads.

The effects of respiratorlike inspiratory resistance (IR), expiratory resistance (ER), and dead space (DS) were assessed in a group of 11 normal volunteers during moderate steady-state (SS) and rapidly incremented (RI) exercise. The physiologic effects of IR were predominant, increasing inspiratory time, duty cycle, and several measures of ventilatory work. Effects of DS appear related to increased minute ventilation and include increasing flow rates and duty cycle and requiring greater ventilatory work; during RI exercise, the DS effect became relatively smaller at higher exercise levels. ER compressed expiratory time. These results characterize the response to IR, ER, and DS loads and suggest that DS may be relatively less physiologically significant than IR.

Airway Resistance↗
PubMed1989

Primary papillary serous neoplasia of the peritoneum: a clinicopathologic and ultrastructural study of eight cases.

The well-documented but rare primary papillary serous peritoneal tumors are difficult problems for the pathologist and the clinician. Because of their unusual location, these tumors are often classified as mesothelioma or advanced ovarian carcinoma. In this study, we report the clinicopathologic features of eight primary peritoneal serous papillary tumors and compare their histologic and ultrastructural features to 12 serous ovarian tumors and 16 epithelial mesotheliomas (two peritoneal and 14 pleural). The eight peritoneal serous papillary tumors occurred in women aged 19 to 75 years; two were serous tumors of low malignant potential (borderline) and six were serous carcinomas. The tumors were located in the mesosalpinx, left pelvis, omentum, and/or surface of the ovary. The two patients with borderline neoplasms had long disease-free survival (11 years and 20 years), while three of the four patients with carcinoma with more than 1 year of follow-up died of disease. The peritoneal serous papillary tumors were morphologically identical to serous ovarian tumors of equivalent grade. Well-differentiated papillary structures with distinct fibrovascular cores and one or several layers of columnar, crowded cells, dense overlapping nuclei with a long axis perpendicular to the surface of the papillary cores, and numerous psammoma bodies were features of the peritoneal and ovarian serous tumors. In contrast, the tubulo-alveolar, solid, or poorly defined papillary structures lined by well-spaced polygonal to cuboidal cells with abundant cytoplasm, absence of nuclear polarity, and infrequent psammoma bodies characterized the mesotheliomas. Epithelial mucin and carcinoembryonic antigen (CEA) immunoreactivity, when present, supported a diagnosis of serous tumor in these generally mucin-poor and CEA-negative neoplasms. Ultrastructurally, the cells of serous tumors had slender, straight microvilli of variable length interspersed with or without cilia, while the nonciliated cells of mesothelioma had long, exuberant, wavy microvilli. The morphologic and clinical features of the peritoneal papillary serous tumors are distinctive enough to warrant their separation from mesotheliomas.

Adult↗
PubMed1989

Predictors of falls among elderly people. Results of two population-based studies.

A study was performed to identify and rank risk factors for falling among populations of institutionalized (fallers, N = 79, nonfallers, N = 70) and noninstitutionalized (fallers, N = 34, nonfallers, N = 34) elderly persons. Fallers were matched by age, sex, and living location to nonfaller control subjects. A nurse practitioner performed a comprehensive physical assessment in all subjects using a standardized protocol and physician consultation. Fallers in both populations were significantly more physically and functionally impaired than control subjects. Logistic regression identified hip weakness, poor balance, and number of prescribed medications as factors most strongly associated with falling among institutionalized subjects. A fall prediction model was developed from these findings yielding 76% overall predictive accuracy (89% sensitivity, 60% specificity). Using the model, the predicted 1-year risk of falling ranged from 12% for persons with none of the three risk factors to 100% for persons with all three risk factors. Findings among noninstitutionalized subjects were similar. These data support the concept of performing focused fall risk assessments to identify elderly patients at high risk for falling.

Accidental Falls↗
PubMed1988

Determinants of pattern of breathing during respirator use.

The relationship between the pattern of breathing in response to respirator-type loads and an individual's psychophysiologic sensitivity to loads (load scaling sensitivity, LSS) was investigated in the study of 11 normal volunteers. LSS was measured by having the subjects numerically rate a series of resistors; Steven's Psychophysical Law was used to evaluate sensitivity as the slope relating log (sensation) to log (stimulus). Peak pressure and actual added resistance were the stimuli. Inspiratory time, peak pressure, duty cycle, and tidal volume were inversely related to independently measured LSS during exercise and with a respiratory-type dead space and inspiratory resistance load. Because the need for changes in respiratory timing is a major adaptation in respirator use, it suggests that workers who are very sensitive to loads may have limited ability to adapt to respirator use.

Adult↗
PubMed1987

Congenital polycystic tumor of the atrioventricular node (endodermal heterotopia, mesothelioma): a histogenetic appraisal with evidence for its endodermal origin.

The small, variously designated, primary atrioventricular node tumor has been considered to be of endothelial, endodermal, or mesothelial origin. To identify its derivation, we studied seven tumors using silver staining and immunocytochemical labeling with a variety of antibodies. Cytoplasmic argyrophil granules but not argentaffin granules were found in isolated cells among the more numerous tubule-lining cells in four tumors. Serotonin and calcitonin were demonstrable in seven and six tumors, respectively, in a similar distribution to that of the argyrophil cells. A positive reaction of different distribution from that of the argyrophil cells was noted in a varying number of tubule-lining cells for carcinoembryonic antigen, epithelial membrane antigen, and blood group antigen in seven, four, and seven tumors, respectively. No activity was noted in the tumor cells for factor VIII-related antigen or a number of peptides. An endodermal rather than mesothelial or epithelial origin for the tumor is substantiated by the presence of neuroendocrine cells in the midst of the more numerous carcinoembryonic-antigen-positive lining cells of the tumor tubules.

Atrioventricular Node↗
PubMed1987

Predictors of recurrence and survival of patients with breast cancer.

In this study, the characteristics of 646 patient's primary breast carcinomas, including histologic grade (HG), nuclear grade (NG), mitotic grade (MG), final grade (FG), estrogen receptor (E2R) status, and patient's lymph node status (LN) at the time of surgery were correlated with recurrence-free interval and patient survival in order to determine whether any one parameter or group of parameters serve as adequate predictors of tumor behavior and, therefore, patient's prognosis. The authors' results showed that LN, tumor size, and tumor grade were themselves significant predictors of early recurrence and breast cancer death. Each unit increase in LN or MG increased the risk of death by a factor of 1.5 and 2.0, respectively. However, prediction of time to recurrence or death was considerably more accurate when those parameters were used in conjunction, rather than individually. E2R was also significant in predicting death. MG separated patients within a single LN group or E2R group into two subsets having clinically and statistically different prognoses. It was found that patients who had negative lymph nodes and whose tumors were MG1 had a better prognosis than those with MG2,3 tumors; in these latter patients recurrence and death patterns were similar to those of patients with MG1 tumors having one to three positive lymph nodes. Similarly, whereas patients with four or more positive lymph nodes had bad prognoses, those bearing MG1 tumors tended to behave more like those with MG2,3 tumors and having only one to three positive lymph nodes.

Actuarial Analysis↗
PubMed1987

Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.

Adolescent↗
PubMed1986

Congenital testicular juvenile granulosa cell tumor in a neonate with X/XY mosaicism.

A congenital sex cord-stromal tumor of the testis with morphologic features of juvenile granulosa cell tumor is reported. The tumor occurred in an abdominal testis of a newborn infant with an X/XY karyotype and ambiguous genitalia and presented as a partially cystic mass associated with ascites. Histologically the tumor was comprised of an admixture of solid, cellular, poorly differentiated lobules mimicking graafian follicles. Residual hypoplastic testicular tissue was present at the periphery. This is the 19th reported case of testicular juvenile granulosa cell tumor and the fourth with an underlying sex chromosome anomaly, further emphasizing the relationship of this uncommon neoplasm to abnormal sexual or gonadal development.

Adolescent↗
PubMed1986

Breast lesions: differential diagnosis using digital subtraction angiography.

To evaluate its potential for differentiating benign from malignant breast lesions, digital subtraction angiography of the breast (DSAB) was performed in 23 women with mammographic evidence of disease, and the results were compared with surgical biopsy findings. The DSAB technique employed breast immobilization with modest compression and bolus injection; following the injection of contrast material, 30-40 sequential subtraction images were obtained over a 5-minute interval. The average technical settings were 50 k Vp and 10 mAs, resulting in an estimated radiation dose to the breast of 0.05 mrad (0.5 mu Gy) per exposure. DSAB consistently demonstrated retention of contrast material and abnormal vasculature in malignant lesions but not in benign lesions. In the 22 breast lesions for which there was histopathologic correlation, DSAB correctly categorized eight of nine malignant and 11 of 13 benign lesions. Although this series is small, the initial results of DSAB suggest its potential for differentiating benign from malignant lesions.

Adenocarcinoma↗
PubMed1985

Differentiation between benign and malignant disease of the breast using digital subtraction angiography of the breast.

The authors have investigated digital subtraction angiography (DSA) for the differential diagnosis of breast lesions detected initially by mammography. Eighteen patients scheduled for biopsy first underwent digital subtraction angiography of the breast (DSAB). Criteria for malignancy included the presence of abnormal vessels and a "blush" in the area of the lesion. A total of 17 lesions are currently available for histopathologic correlation. Although this is a small series, the initial results of DSAB suggest its potential utility for differentiating between benign and malignant lesions.

Angiography↗
PubMed1985

Idiopathic degeneration of the aortic valve: a common cause of isolated aortic regurgitation.

To establish the etiology of isolated aortic valvular regurgitation, histologic examination was carried out on 27 consecutive surgically removed aortic valves from patients with aortic regurgitation. In 12 patients, the regurgitation was due to rheumatic or syphilitic valvular disease or a congenital bicuspid aortic valve. In the remaining 15, no etiology was apparent. In the latter group, seven aortic valves were identified by the surgeon as redundant and eight as thickened and retracted. Despite these gross differences, the histologic features of the 15 valves were similar and consisted of increased and disorganized elastic and collagen fibers, with variable quantities of acid mucopolysaccharide and calcium. Although small foci of myxomatous stroma were present, they did not differ substantially from those observed in age-matched competent aortic valves removed at necropsy, nor were they as extensive as described in reports of floppy aortic valves. Idiopathic degeneration was the most common cause of aortic regurgitation, occurring in more than half of the surgically treated patients. An underlying defect in the synthesis of collagen or elastic fibers, similar to that described in mitral valve prolapse, may be an important feature in aortic valve degeneration.

Adult↗