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Biomedical subjects

A J Garvin

Publications and source records attributed to A J Garvin.

At least 19 recordsLinked to original sources
PubMed1992

Expression of the 11p13 Wilms' tumor gene, WT1, correlates with histologic category of Wilms' tumor.

Homozygous inactivation of WT1, a Wilms' tumor gene located on chromosome 11 at p13, is believed to predispose to Wilms' tumor and therefore may be a common occurrence in this cancer. The expression of this gene in primary Wilms' tumors was examined by northern and quantitative RNA slot blot analysis and compared with clinical, histologic, and molecular features of each case. The characteristic 3.2 kb RNA was readily detected in most primary tumors although there was marked variation in the level of WT1-specific transcripts. No abnormal-sized RNA products were detected and expression of WT1 was not coordinated with that of several other oncofetal genes: N-myc, insulinlike growth factor 2 (IGF-2), and c-myc. The relative abundance of WT1-specific RNA did correlate with the histologic category of Wilms' tumor such that those tumors with heterologous differentiation have, in general, lower relative levels of WT1 transcripts than those tumors without heterologous differentiation. These results further establish the heterogeneity of Wilms' tumor with respect to the expression of tumor-associated oncofetal genes and suggest a relationship between WT1 expression and cellular differentiation.

Antigens, Neoplasm↗
PubMed1991

Characterization of a cell line derived from rhabdoid tumor of kidney.

Rhabdoid tumor of kidney (RTK) is a rare, highly malignant childhood neoplasm of uncertain histogenesis. Several recent studies have described considerable histochemical heterogeneity among cases of RTK, with confusing combinations of epithelial, mesenchymal, myogenous, and neuroepithelial markers in some tumors. The present study characterizes the histology, ultrastructure, histochemistry, cytogenetics, and oncogene expression in a cell line derived from RTK. The surgical specimen, nude mouse xenograft, and cell cultures demonstrated characteristic intermediate filament whorls by electron microscopy and expressed vimentin (diffusely) and cytokeratin (focally, in hyaline cytoplasmic inclusions) without detectable desmin, Thy-1, or epithelial membrane antigen. S-100 protein was absent in the surgical specimen and heterotransplant, and was seen very weakly and focally in the cell cultures. Light microscopic features of cultures were unchanged by several compounds (tissue plasminogen activator, nerve growth factor, cyclic adenosine monophosphate) which induce differentiation of some other pediatric neoplasms. The growth factor requirements of RTK cultures indicate a cell with mesenchymal features. Insulin-like growth factor-2 mRNA was detected in the RTK and in three Wilms' tumors also studied. Unlike most Wilms' tumors, RTK expresses the c-myc rather than the N-myc oncogene.

Desmin↗
PubMed1990

Growth factor binding and bioactivity in human kidney epithelial cell cultures.

Insulinlike growth factors (IGF) and epidermal growth factor (EGF) are produced in renal tissue, as are specific receptors for these hormones. To evaluate the significance of these observations to regulation of renal tubular cell proliferation, we have examined the interaction of IGF and EGF with cultured human proximal tubular epithelial cells (HPT). HPT cells showed specific binding of IGF-1, insulin, and EGF. IGF-1 binding was inhibited by antibody to the type 1 IGF receptor (alpha-IR3). Insulin receptors and type 1 IGF receptors were identified by bifunctional cross-linking. IGF-1, insulin, and EGF stimulated [3H]thymidine incorporation by 77, 73, and 87%, respectively. Half maximal stimulation by IGF-1, insulin, and EGF were produced with 4 X 10(-9) M, 2.5 X 10(-8) M, and 8 X 10(-10) M concentrations of these hormones. Alpha-IR3 inhibited stimulation of thymidine incorporation by IGF-1 and insulin but had no effect in EGF-stimulated thymidine incorporation. EGF and high concentrations of insulin both stimulated cell proliferation by 83 and 79%, respectively. These data are consistent with regulation of tubular epithelial proliferation by IGF-1, insulin, and EGF and suggest that the mitogenic activity of both insulin and IGF-1 is mediated by the type 1 IGF receptor.

Cells, Cultured↗
PubMed1990

Infantile fibrosarcoma--a misnomer?

Two cases of congenital or infantile fibrosarcoma are described that were incompletely excised at the time of primary excision and have not recurred or metastasized after 3 years. The tumors were composed of densely cellular spindle cells with a high mitotic index. Immunohistochemical stains were positive for vimentin but negative for desmin and S-100. The tumor cells were grown in vitro, and a karyotype was obtained. Both tumors had normal diploid modal karyotypes. In addition, fragments of the primary tumor from both cases were injected subcutaneously into nude mice; neither tumor could be heterotransplanted. The clinical course and biologic features of these two tumors suggest that congenital or infantile sarcoma does not have the properties of a malignant neoplasm, and thus the designation of these tumors as a sarcoma may be a misnomer.

Animals↗
PubMed1989

Heterotopic lingual brain in the newborn.

Heterotopic brain is a rare entity. Histologically, this lesion resembles mature brain and often contains specialized tissues similar to choroid plexus or glia. Specialized neural stains are necessary to differentiate this rare anomaly from other tumors or conditions found in the head and neck. The differential diagnosis includes squamous cell carcinoma, granular cell tumor, hemangioma, lymphangioma, thyroglossal duct cyst, dermoid cyst, hamartoma, rhabdomyosarcoma, and teratoma. We describe a newborn with heterotopic brain tissue occurring on the dorsum of the tongue. We found only one other description of this developmental aberration in the English literature. Our patient was successfully treated with carbon dioxide laser excision of the mass. There has been no evidence of complication or recurrence after one year of follow-up.

Brain↗
PubMed1989

Aggressive bladder carcinoma in an adolescent. Report of a case with immunohistochemical, cytogenetic, and flow cytometric characterization.

Malignant bladder neoplasms of urothelial origin are rare among children; fewer than 125 cases have been reported. Typically, these tumors are single papillary lesions of low grade and stage that have an excellent prognosis following surgical excision. A grade III transitional cell carcinoma of the bladder occurred in a 14-year-old boy who had no urinary tract malformation, carcinogenic exposure, or family history of cancer. Immunohistochemical stains of the tumor were positive for cytokeratin and high-molecular-weight keratin. The tumor tissue failed to stain with an antibody to the patient's blood group [anti-ABO(H)] but was positive for the Thomsen-Frieden-reich antigen. Flow cytometry of the tumor cells demonstrated a diploid or near-diploid DNA content. A karyo-type of the tumor showed a modal chromosome number of 46 with one reciprocal translocation between chromosomes 17 and 22 and a nonreciprocal translocation between chromosomes 18 and 22. The tumor was unique because of its highly aggressive nature and its diploid chromosome number. This case represents the first indepth characterization of a transitional cell carcinoma in a pediatric patient by flow cytometry and cytogenetics, as well as a variety of immunohistochemical studies including ABO(H) blood group and Thomsen-Freidenreich antigens.

Adolescent↗
PubMed1989

Immunohistochemical localization of transport mediators in Wilms' tumor: comparison with fetal and mature human kidney.

Immunostaining for Na+, K+-ATPase, carbonic anhydrase (CA) II, and band 3 anion channel glycoprotein was compared in developing and mature human kidneys and in Wilms' tumors. In fetal kidneys, ATPase first appeared in proximal and distal tubules. At birth an adult pattern was present with abundant enzyme in all segments of the distal tubule and lesser amounts in proximal and collecting tubules. CA II was detected in fetal kidneys first in proximal and then in distal tubules and eventually, as in the adult, throughout the nephron. Band 3 glycoprotein was not detected in fetal kidneys and only weak staining was present in the basolateral plasmalemma of intercalated cells in newborn and infant kidneys. The number of cells reactive for band 3 and the intensity of staining in a given cell increased to near adult levels at about 2 years. This finding may provide a partial explanation for the 'physiological acidosis' characterized by a low systemic pH in newborn and young infants. ATPase was present in basolateral membranes of most epithelial cells in nonanaplastic Wilms' tumors but was absent in the epithelial component of two anaplastic Wilms' tumors. CA II was detected only in a few epithelial cells in four tumors. Neoplastic epithelial cells reactive for CA II also stained for ATPase but not vice versa. Band 3 glycoprotein was not detected in any Wilms' tumor. These findings show that the immunohistochemical assessment of protein involved in electrolyte transport provides a further means for determining the relative level of differentiation of tumor cells of epithelial origin and suggest that these methods may be a valuable aid in determining the prognosis of some carcinomas.

Adolescent↗
PubMed1989

Antibody to type I insulinlike growth factor receptor inhibits growth of Wilms' tumor in culture and in athymic mice.

The role of the type I insulinlike growth factor (IGF) receptor in regulating growth of Wilms' tumor (WT) was evaluated by examining the effect of antibody-mediated inhibition of this receptor on tumor growth in cell cultures and as heterotransplants in athymic mice. An antibody to the human type I IGF receptor (alpha IR-3) inhibited 125I-IGF-1 binding and prevented stimulation of thymidine incorporation by IGF-1 in vitro. Intraperitoneal administration of alpha IR-3 to nude mice bearing WT heterotransplants prevented tumor growth for 4 weeks and resulted in partial regression of established tumors. These data indicate the importance of IGF action in control of WT growth in vivo, and suggest potential therapeutic application using antigrowth factor receptor antibodies to block growth factor action.

Animals↗
PubMed1989

Effect of fatty acids and their derivatives on mitochondrial structures.

Reye's Syndrome (RS) is characterized by encephalopathy, fatty degeneration of viscera and high levels of free fatty acids which are implicated in cellular toxicity. We have examined the effects of octanoic acid (C8:0), palmitic acid (C16:0) and oleic acid (C18:1) on rat liver mitochondrial swelling by spectroscopic and microscopic techniques. Of the fatty acids tested oleic acid had a greater effect than palmitic acid while octanoic acid had no effect. Acyl-CoA derivatives produced greater mitochondrial swelling than either acyl-carnitine or free fatty acids. However, identical amounts of palmitoyl-CoA and oleoyl-CoA were required to produce the same degree of swelling. Addition of carnitine (2mM) to oleoyl-CoA reduced the mitochondrial swelling significantly thus suggesting that the toxicity of the fatty acids may be reduced by conversion to their carnitine derivatives. Twice the concentration of oleoyl-carnitine was required to produce half the maximum swelling as compared to oleoyl-CoA. Ultrastructural profiles of mitochondria treated with oleic acid, oleoyl-CoA and oleoyl-carnitine demonstrated greater swelling with oleoyl-CoA than with oleic acid or oleoyl-carnitine. These results suggest that carnitine may protect the mitochondria from damage by the fatty acids and their acyl-CoA derivatives in Reye's Syndrome.

Acyl Coenzyme A↗
PubMed1988

Mesenchymal hamartoma of the liver: report of a case in a 28-year-old.

A 28-year-old black woman presented with increasing abdominal girth and gross hepatomegaly. Preoperative investigations demonstrated an enlarging vascular tumor involving the right lobe of the liver. A right hepatic trisegmentectomy was performed, and histologic examination of the tissue revealed a mesenchymal hamartoma, a tumor usually presenting in early childhood. This case is unique because the patient is 22 years beyond the average presenting age, and is the oldest patient reported.

Adult↗
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↗
PubMed1988

Growth characteristics of human Wilms' tumor in nude mice.

Ten Wilms' tumors (WT) were heterotransplated into athymic (nude) mice. Eight of the tumors (80%) grew and were serially passaged as many as 20 times. The histology of the primary heterotransplants resembled that of the surgically excised tumors (seven classical and one anaplastic). Histological examination of serial passages of the classical WT demonstrated the tendency of the stromal and tubular components to disappear. The anaplastic tumor, however, maintained histological features identical to the primary tumor through all passages examined. One WT cell line that exhibited a prominent skeletal muscle component failed to grow beyond the third passage. Spontaneous glomerular differentiation was noted in several heterotransplants. The site of transplantation (subcutaneous, peritoneal, or renal capsule) had no effect on the differentiation of the tumors, and attempts to produce intravenous metastases were unsuccessful. Unilateral nephrectomy of WT-bearing mice gave a transient increase in pulse labeling of the tumors with bromodeoxyuridine, a thymidine analogue, compared with sham-operated controls or mice bearing Ewings' sarcoma heterotransplants. The increased labeling of tumor nuclei reached a maximum at 48 h. Similar increased labeling was observed in the remaining kidney following unilateral nephrectomy. These data show that although WT is a malignant neoplasm, its cells retain the capacity to respond to physiological signals resulting from nephrectomy and that differentiation cannot be modulated by the site of heterotransplantation or serial passage in athymic mice.

Animals↗
PubMed1988

Detection of type 1 insulinlike growth factor (IGF) receptors in Wilms' tumors.

Insulinlike growth factors (IGFs) are peptide hormones that regulate proliferation and differentiation of several types of normal and neoplastic cells. Recent studies of Wilms' tumor, a childhood kidney neoplasm, have detected increased expression of IGF-2 mRNA and protein. The present report describes detection of Type 1 IGF receptors in specimens of Wilms' tumor and adjacent nonneoplastic kidney tissue. These receptors recognize both IGF-1 and IGF-2, and binding of either peptide activates endogenous tyrosine kinase activity of the Type 1 IGF receptor beta subunit. These data indicate that Wilms' tumors contain receptors that recognize and respond to exogenous IGF in vitro, and that autocrine IGF production might contribute to the increased proliferation and abnormal differentiation of these cells in vivo.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

Distribution of fucosubstance in kidney and related neoplasms. Absence of lectin-reactive alpha-fucose from the vasculature of bilateral Wilm's tumors.

Two alpha-fucose-binding lectins, Ulex europaeus agglutinin I (UEA I) and Lotus tetragonolobus agglutinin, were employed to compare and contrast the distribution of fucosubstance in normal human kidneys and a variety of renal tumors. The study employed a total of 31 kidneys surgically removed for the presence of a variety of tumors, including 11 unilateral Wilms' tumors, two cases of bilateral Wilms' tumors, 13 renal cell carcinomas, two congenital mesoblastic nephromas, one renal oncocytoma, one neuroblastoma metastatic to the kidney, and one clear cell sarcoma of the kidney. The results show that UEA I-reactive fucosubstance is detected in vascular endothelium of all kidneys and tumors, except bilateral Wilms' tumors. The presence of UEA I-reactive alpha-fucose in the vasculature of unilateral but not bilateral Wilms' tumors defines a unique histochemical distinction between the two groups of tumors. Conceivably, this property might be exploited as a screening procedure for the more aggressive bilateral neoplasms. Other findings detail histochemical differences between UEA I and L tetragonolobus agglutinin, as evidenced by the ability of one lectin to stain a particular cell type that is not reactive with the other lectin.

Blood Vessels↗