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Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 217 records · Page 12Linked to original sources

Correlation of serum tumor markers in advanced germ cell tumors with responses to chemotherapy and surgery.

Remission rates induced by chemotherapy alone or by combined chemotherapy and surgery were analyzed in relation to specific serum tumor marker abnormalities immediately before treatment in 103 patients with Stage III or bulky Stage II nonseminomatous germ cell tumors. Complete remission occurred in 92% (12 of 13) of patients with normal levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), in 26% (6/23) with elevated AFP only, in 46% (13/28) with elevated HCG only, and in 39% (13/36) with abnormalities of both AFP and HCG. Patients with elevated AFP less frequently had a complete remission (CR) to chemotherapy (CR, 34% versus 61% with normal AFP), but benefitted from adjunct surgery (CR, up to 59%). Patients with very high (greater than 1000 ng/ml) serum AFP or HCG responded poorly to chemotherapy (CR, 17%) but especially large tumor burdens may have contributed to these unfavorable responses. Patients with both minimal and advanced metastatic disease had higher CR rates if they had serum tumor marker levels below rather than above 1000 ng/ml. Adjunct surgery eliminated the correlation between the "poor prognostic factors" associated with specific marker abnormality and an incomplete response to chemotherapy by rendering a significant number of such patients free of disease through resection of residual metastatic deposits.

Antineoplastic Combined Chemotherapy Protocols↗

Cultured mouse marrow cell lines: interactions between fibroblastoid cells and monocytes.

Continuous cell lines were derived from primary cultures of adherent bone marrow cells from SJL/J, BALB/c, C3H/eb, RF, and nude-ICR mice. All these lines readily assumed a pure fibroblastoid appearance with the exception of the BALB/c line (MBA-14), which retained both fibroblastoid and monocytoid cells. This particular line could promote the proliferation of myeloid progenitors (CFU-C) in short-term bone-marrow cultures. The two cell types that composed the MBA-14 cell line were successfully isolated and grown separately; the monocytes as the 14M and 14M1 cell lines and the fibroblastoid cells as the 14F clones. The latter were found to be preadipocytes and accumulated fat in the absence of added hydrocortisone, in medium supplemented with fetal calf serum. Growth of the monocyte lines (14M and 14M1) was dependent upon the mononuclear phagocyte stimulator CSF-1. In the parent MBA-14 cell line the growth of monocytes seemed to depend upon stimulating factor(s) produced by the fibroblastoid cells. The 14M1 monocytes were able to process and degrade antigen as efficiently as primary macrophages. Furthermore, processed antigen produced by 14M1 cells evoked proliferative response by antigen-primed lymph-node cells. In addition to these immunological functions the 14M1 cells were capable of modulating the colony-stimulating activity and degree of adipogenesis exhibited by the fibroblastoid cells. These interactions between monocytes and fibroblastoid cells may constitute part of the mechanism controlling the activity of the hematopoietic microenvironment.

Adipose Tissue↗

Demonstration and characterization of virus released by murine B cell leukemia cells (BCL1).

LPS-stimulated leukemia cells derived from BALB/c mice bearing transplantable B-lymphocytic leukemia (BCL1) which arose spontaneously in a female BALB/c mouse, contained viral particles as suggested by electron microscopy as well as by tissue cultures using the XC assay. Some cell free extracts prepared from BCL1 cells were capable of transforming normal B-lymphocytes when inoculated into untreated syngeneic recipients. Cytogenetic analysis of spleen cells obtained from a splenomegalic male mouse neonatally inoculated with cell-free extract indicated that the tumor cells had a male karyotype with 42 chromosomes as compared to 37 chromosomes and a female karyotype in original BCL1 cells, thus excluding the possibility of tumor propagation by transplantation of intact BCL1 cells. These findings suggest viral involvement in the etiology of BCL1.

Animals↗

Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome.

The effectiveness of bovine superoxide dismutase (SOD) in the prevention of bronchopulmonary dysplasia was evaluated in a prospective double-blind controlled study in 45 neonates (mean gestational age 28.7 weeks, mean weight 1154 gm) with severe respiratory distress syndrome. All were ventilator dependent with FiO2 greater than or equal to 0.7 at 24 hours of age. Either bovine SOD (0.25 mg/kg) or saline solution was administered subcutaneously every 12 hours according to random selection until patients could be maintained in room air without ventilatory or continuous positive airway pressure (CPAP) support. SOD levels were detected in all patients given treatment. Mean peak values at 4 hours after dose ranged from 0.15 micrograms/ml (dose 1) to 0.45 micrograms/ml (dose 10). The drug was well tolerated, and no side effects were detected. Among the 31 survivors (SOD 14, placebo 17) radiologic evidence of BPD was significantly less in patients given SOD (3/14 vs 12/17, P = 0.008). Clinical signs of bronchopulmonary dysplasia (wheezing, pneumonia) were less in patients given SOD (3/14 vs 11/17, P = 0.019). Patients given SOD required fewer days of CPAP (P less than 0.003). There were no differences in days of O2 therapy, intermittent positive pressure breathing, or incidence and severity of patent ductus arteriosus or intraventricular hemorrhage. This preliminary study suggests that SOD may be helpful in reducing the severity of bronchopulmonary dysplasia in infants with respiratory distress syndrome.

Animals↗

Role of computed tomography in the radiological evaluation of painful radiculopathy after negative myelography: foraminal neural entrapment.

Thirty-five patients with an unremarkable or a negative water-soluble contrast myelogram and a diagnosis of foraminal neural entrapment made or more firmly established by computed tomography (CT) were detected in evaluating 950 patients presenting for myelography. The CT criterion of foraminal neural entrapment was the presence of a mass displacing epidural fat and encroaching on the neural intervertebral foramen or lateral recess so as to compromise an emerging nerve root. The entrapment (confirmed operatively) was due to a laterally prolapsed disc (16 cases), superior articular hypertrophy (4 cases), lateral recess stenosis (3 cases), posterolateral vertebral bone lipping (2 cases), tumors (6 cases), postoperative scarring (2 cases), spondylolisthesis (1 case), and synovial cysts that encroached on the neural foramina (1 case). CT is an important additional investigation in patients with a painful radiculopathy and a negative or equivocal water-soluble contrast myelogram.

Adult↗

Molecular events in the processing of avidin by antigen-presenting cells (APC). I. The immune response of T lymphocytes to avidin is regulated by H-2-linked Ir genes.

The immune response of T lymphocytes to avidin was measured by proliferative assays, antibody production and delayed-type hypersensitivity. Mice of H-2k haplotypes were found to be low responders, whereas mice of other haplotypes, and particularly of H-2s, were high responders. Ir genes controlling this response were mapped to the I subregion of H-2. Helper T cells were found to be responsible for the Ir phenotype of antibody production. These results indicate the feasibility of using the avidin-biotin complex as a tool for studying molecular mechanisms by which antigens under Ir gene control are processed and presented to T lymphocytes.

Animals↗

Molecular events in the processing of avidin by antigen-presenting cells (APC). II. Identical processing by APC of H-2 high- and low-responder mouse strains.

The differences between the immune response (Ir) phenotypes of H-2 gene-controlled high- and low-responder mice have been attributed to events occurring at the interaction between antigen-presenting cells (APC) and lymphocytes. To investigate this interaction we undertook a study of molecular events in the processing of avidin, a molecule whose uniquely strong affinity for binding to biotin renders it traceable at very low concentrations, and a molecule to which the T-lymphocyte immune response is controlled by Ir genes. In this paper we describe the generation of processed avidin by APC and characterize it biochemically and immunologically. We found that APC of H-2 genetically high- and low-responder mice were indistinguishable in their capacity to generate immunogenic processed avidin (PA). Immunogenic PA differed from native avidin in size and carbohydrate moieties, but preserved its capacity to bind biotin, and was 1000-fold more efficient than NA as an immunogen for primed T lymphocytes. Primed T lymphocytes appeared to recognize PA that was conformationally intact. Highly immunogenic PA was not H-2 restricted. Thus, differences in the Ir phenotype of the response to avidin could not be attributed to determinant selection by APC.

Animals↗

Molecular events in the processing of avidin by antigen-presenting cells (APC). III. Activation of T-lymphocyte lines and H-2 restriction are mediated by processed avidin associated with I-region gene products.

We investigated the interaction between processed avidin (PA) and avidin-specific lines of T lymphocytes free of resident antigen-presenting cells (APC). We found that PA was able to replace the requirement for APC in the T-lymphocyte proliferative assay, only if the PA was associated with an Ia-positive moiety (IPM) supplied by the APC. In addition to supplying a necessary signal for a proliferative response to PA, IPM imposed H-2 restriction on the PA molecule. The association between PA and IPM was reversible and the two moieties could be physically separated and recombined. The results support a conclusion that major histocompatibility restriction of the interaction between T lymphocytes and APC is due to the association between processed antigen and an APC element containing I-region products.

Animals↗

Prospective trial of warfarin and dipyridamole in patients with membranoproliferative glomerulonephritis.

A prospective trial of warfarin and dipyridamole was performed in patients with membranoproliferative glomerulonephritis. Eighteen completed either a control or treatment year, and 13 completed both a control and treatment year. To obviate the bias of excluding control patients who had renal failure after one year, both an unpaired and a paired analysis were performed. The unpaired analysis compared 10 patients followed for an initial control year with eight patients receiving treatment first. Renal function remained stable over the year in the treated group, but worsened in the control group. Slopes of regression lines for reciprocal serum creatinine values were significantly different between groups (p less than 0.025). Urine protein excretion also decreased in the treated group. Four of 10 control patients had a two-fold increase in serum creatinine levels, but no treatment patient did. In the paired crossover analysis, significant differences in renal function were detected between control and treatment years in six patients whose renal function significantly changed over one of the years. In every instance, there was better preservation of renal function in the treatment year. Urinary protein also decreased significantly over the treatment year compared with the control year. Bleeding was the most frequent complication. These data suggest that warfarin and dipyridamole have a beneficial effect on renal function in membranoproliferative glomerulonephritis.

Adult↗

Experience using two CT-guided stereotactic biopsy methods.

15 patients had intracranial CT-guided stereotactic biopsies. Biopsies were performed either with a Riechert-Mundinger stereotactic frame modified for use in the CT or by using the CT scan to establish the relationship of the intracranial lesion to identifiable bony landmarks, and subsequently performing the biopsy in a standard stereotactic frame. Both systems provided safe and accurate methods for obtaining intracranial tissue.

Adolescent↗

Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10M protocols.

Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.

Adolescent↗

Fibrosarcoma of the heart metastatic to the brain.

A right parietal lobe metastasis of a fibrosarcoma originating in the left atrium of the heart was resected twice in a 33-year-old man. Light microscopy showed lightly packed, pleomorphic spindle cells with abundant collagen production and an alcian blue-positive matrix. Electron microscopy confirmed the fibroblastic character of these cells. Review of the literature reveals one other cardiac fibrosarcoma metastatic to the brain. The case presented is the first reported example of successful surgical resection of this unusual metastatic sarcoma. Although he succumbed to metastatic disease, the patient remained neurologically intact until the time of death.

Adult↗

T lymphocyte line specific for thyroglobulin produces or vaccinates against autoimmune thyroiditis in mice.

We investigated Ly-1+ T lymphocyte line cells specifically reactive to thyroglobulin (Tg) that were isolated from mice primed with mouse Tg in adjuvant. Intravenous inoculation of as few as 10(5) line cells was sufficient to cause severe and prolonged thyroiditis in recipient mice that were intact, irradiated, or athymic nudes. Disease was independent of circulating Tg antibodies, suggesting that anti-Tg T lymphocytes could cause thyroiditis unaided by antibodies. Thyroiditogenic T lymphocytes could be isolated as cell lines from apparently healthy mice that had been immunized with non-thyroiditogenic bovine Tg in adjuvant, which indicates that autoimmune effector T lymphocytes may develop covertly in the course of immunization with foreign antigens. Finally, a single i.v. inoculation of anti-Tg T lymphocyte line cells attenuated by irradiation vaccinated mice completely against subsequent development of autoimmune thyroiditis produced either by active immunization to Tg or by passive transfer of intact line cells. Vaccinated mice that were protected from inflammatory lesions of thyroiditis still produced high titers of Tg antibodies in response to active immunization. Thus, vaccination specifically inhibited thyroiditogenic T lymphocytes but not helper T lymphocytes required for the production of Tg autoantibodies.

Animals↗