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Biomedical subjects

U Raju

Publications and source records attributed to U Raju.

At least 55 records · Page 3Linked to original sources

An unusual embryonal tumor of the nasal cavity in a neonate--a nasal blastoma? A clinical, histologic, and ultrastructural study.

We report the clinicopathological and ultrastructural features of a primitive embryonal tumor which occurred as a polypoid mass in the nasal cavity of a newborn infant. Its primitive-appearing, glycogen-rich, small round cells exhibited epithelial characteristics histologically, immunohistochemically, and ultrastructurally. The tumor was initially diagnosed as embryonal carcinoma because of evidence for endodermal differentiation and lack of specific features of other types of small round cell tumors of childhood. However, it did not have the characteristic features of endodermal sinus tumor nor the anaplasia of the adult type of embryonal carcinoma. It had some resemblance to embryonic somatic tissues and the blastemal component of some of the primitive tumors of childhood. Because of its unique morphological appearance, which has never been reported, and its relatively indolent behavior after chemotherapy and radiotherapy, we believe that this is a distinctive primitive teratoid tumor which may be classified as nasal blastoma.

Humans↗

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↗

Neurofibromatosis, factor IX deficiency, and rhabdomyosarcoma.

A paratesticular rhabdomyosarcoma occurred in a child with factor IX deficiency and neurofibromatosis, illustrating the need to consider carefully the various etiologic possibilities of a soft-tissue mass in a child with neurofibromatosis and/or a bleeding disorder.

Diseases in Twins↗

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↗

Opsomyoclonus and neuroblastoma.

Three cases of neuroblastoma with opsomyoclonus are reported, reconfirming favorable prognostic significance of the association. In one case, computed tomography of the abdomen was the only confirmatory diagnostic study. Two of the cases also were unusual in that the patients had a concomitantly inherited genetic disorder not known to be associated with childhood cancer.

Abdominal Neoplasms↗

Neurofibromatosis and malignancy.

Neural crest and nonneural crest tumors occur frequently in neurofibromatosis (NF). We report one case of NF and recurrent malignant fibrous histiocytoma, a tumor that is uncommon in childhood, and another case of the concomitant occurrence of NF, hemophilia B, and a paratesticular rhabdomyosarcoma.

Adolescent↗

Androsterone long chain fatty acid esters in human breast cyst fluid.

We reported previously that incubation of [3H] androsterone in homogenates of human breast tumor resulted in production of long chain fatty acid esters of androsterone (A-LCFE). To identify the individual A-LCFE, breast tumor homogenates were incubated with androsterone, then submitted to solvent extraction, Celite chromatography, high pressure liquid chromatography and OH- negative chemical ionization mass spectrometry. The (M-1)-ions of the oleate, linoleate, palmitoleate, palmitate, arachidonate, and stearate esters of androsterone were produced. The first 3 cited unsaturated esters accounted for over 90% of the total. Since fibrocystic disease of the breast is a reported risk factor for the development of breast cancer, breast cyst fluids were analyzed for A-LCFE as part of an overall program to relate endocrine profiles in cyst fluid to the incidence of cancer. Breast cyst fluids were analyzed for total A-LCFE by a method involving solvent extraction, saponification, purification of the liberated androsterone, and then quantification of the steroid by RIA. The 10 fluids analyzed contained 0.52-3.79 ng/ml fatty acid esters, measured as androsterone. In 4 of these samples, the individual A-LCFE were analyzed by mass spectrometry. As in the incubation study, the unsaturated fatty acid esters predominated. In 3 samples, palmitoleate and in 1 sample, oleate predominated. The palmitate varied from undetectable to 25% of the total. The divergent total concentrations and profiles of A-LCFE indicate potential parameters for correlations with the subsequent course of fibrocystic disease of the breast.

Androsterone↗

Estriol in human breast cyst fluid.

Although cystic lesions of the breast are not precancerous per se, statistical studies have indicated that this condition predisposes a 2- to 4-fold greater risk for breast cancer. Seeking a hormonal etiology to this correlation, investigators have analyzed breast cyst fluid ( BCF ) for steroids and have compared the levels to those in the blood. The 17-ketosteroids-androsterone, dehydroisoandrosterone and their sulfates are elevated in BCF . The same is true for estrone sulfate and estradiol-3-sulfate. We have found the most dramatic differences with estriol-3-sulfate (E3-3S), the concentration of which ranged from 187-6134 pg/ml in over 40 specimens analyzed, whereas in 12 serum specimens from normal women, E3-3S was barely detectable. The origin of E3-3S is not known. [3H]E3-3S is not concentrated in BCF following its injection into an arm vein. The blood half-life of [3H]E3-3S is much lower than that of estrone sulfate. Samples of breast nipple aspirates from normal women were also analyzed for E3-3S. None could be detected. The best explanation of the data accumulated thus far is that E3-3S is synthesized at the epithelial lining of the cyst and released into the BCF , from which its efflux is inefficient.

Adult↗

Glucosiduronidation of androsterone by human breast tumors in vitro in relation to the progesterone receptor content.

Homogenates of human breast tumors were incubated with 3H-androsterone and the percentage conversions to androsterone glucosiduronate were determined. In addition, separate portions of the tumors were analyzed for estrogen receptor (ER) and progesterone receptor (PR) to see whether conjugation and receptor content could be correlated. Sixteen of thirty-two tumor homogenates formed androsterone glucosiduronate (0.03-5.9%) from androsterone. There was no correlation between ER content and glucuronyltransferase activity. Considering the twenty-six malignant mammary tumors, of the fifteen PR positive types, five (one-third) formed the conjugate. In contrast, almost two-thirds (seven of eleven) of the PR negative tumors formed androsterone glucosiduronate. These correlations indicate a trend, but not of statistical significance.

Androsterone↗

Diffuse nonsecretory osteosclerotic myeloma with extensive erythrophagocytosis.

A 51-year-old, black man presented with severe anemia and weakness. X-ray studies showed diffuse osteosclerosis involving most of his skeleton. He was documented to have similar bone changes on x-ray 5 years previously. Peripheral blood findings were suggestive of a myelophthisic anemia. Open biopsy of the iliac bone showed osteosclerotic myeloma. Secretion of abnormal protein could not be demonstrated through many examination of serum or urine. A unique finding at the autopsy was the presence of extensive erythrophagocytosis by the neoplastic plasma cells and macrophages.

Erythrocytes↗

Glucosiduronidation and esterification of androsterone by human breast tumors in vitro.

The metabolism of 3H-androsterone was studied in homogenates (fortified with uridine 5'-diphosphoglucuronic acid and adenosine 3'-phosphate 5'-phosphosulfate) of eighteen breast tumors, one muscle underlying the primary breast carcinoma and metastatic axillary lymph nodes from a patient with suspected primary breast cancer. The major metabolites identified were less polar than androsterone. On saponification these lipoidal derivatives afforded androsterone as the only product (3 to 48%). Unmetabolized androsterone and lesser quantities of epiandrosterone, 5 alpha-androstane- alpha, 17 beta-diol and 5 alpha-androstane-3,17-dione comprised the free steroid fraction. Androsterone glucosiduronate was isolated (0.17-4.1%) from weight breast tumor homogenates and from the node tissue incubation (17%). There was no apparent correlation between glucuronyltransferase activity and histopathology or estrogen receptor content.

Adenofibroma↗

On the occurrence and transport of estriol-3-sulfate in human breast cyst fluid: the metabolic disposition of blood estriol-3-sulfate in normal women.

The high concentration of estriol-3-sulfate (E3-3S) in human breast cyst fluid has been confirmed in 14 women with multiple cysts. The concentrations of E3-3S found in individual cysts drained within a short time span from the same patient were variable, the ratios ranging from unity to 40. After the iv administration of [14C]estriol or [3H]E3-3S, only minor accumulation of either isotope was detected in the cyst fluids aspirated 6.5-30 h later. Since surprisingly small amounts of isotopes were found in blood, the metabolism of [3H]E3-3S was studied in 2 normal women. The test compound was injected iv, and blood samples were taken at intervals up to 7.5 h. In addition, total urine was collected for 3 days. The blood clearance of [3H]E3-3S was rapid, with the half-life ranging from 15-30 min. However, E3-3S was only a minor component of the urine, indicating rapid tissue extraction and metabolism rather than renal excretion for the compound. The studies indicate that E3-3S of human breast cyst fluid does not equilibrate rapidly with other body pools and that its uptake, if any, from the blood would be against a gradient.

Adult↗

Primary tracheal neurilemoma: report of a case with ultrastructural examination.

A case of tracheal neurilemoma that was removed by segmental tracheal resection was studied. Only seven other cases of benign neurogenic tracheal tumor (three neurofibromas and four neurilemomas) were found in the literature. Failure to consider this rare tracheal tumor as a cause of respiratory distress has frequently resulted in delay of its recognition.

Adult↗

Conjugation of androgens and estrogens by human breast tumors in vitro.

The metabolism of 3H-androstenedione (delta 4-A) and 3H-estriol (E3) was studied in 12 human breast tumors. Part of each tumor was analyzed for estrogen receptor content. Aliquots of tumor homogenates were incubated for 2 hr separately with 3H-delta 4-A and 3H-E3 in the presence of appropriate cofactors. No distinct differences emerged in the profiles of the unconjugated metabolites of 3H-delta 4-A, the major compounds in the approximate order of descendence being androsterone, androstanedione, testosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, epiandrosterone, and dihydrotestosterone. One tumor homogenate from an infiltrating lobular carcinoma converted 3H-delta 4-A to glucosiduronate metabolites (11%), of which androsterone, 6.4%; testosterone, 1.6%; and androstanediol, 0.6% predominated. The homogenate of this tumor and two other tumors converted 3H-E3 to 3H-E3-3S. Conversions of E3 to E3-3S in the other tumor homogenates were less than 0.6%. No correlation between receptor content and the capability of the tumor to conjugate delta 4-A or E3 evolved. However, correlations between steroid hormone metabolism and tumor histopathology may exist.

Adult↗

Steroid metabolism in human breast cancer cell lines.

The metabolism of 1,2-3H-androstenedione was studied in 2 cell lines, MCF-7 (estrogen responsive) and BT-20 (estrogen nonresponsive) over 48 hrs. Water soluble and unconjugated metabolites were separated by solvent partition and the former was submitted to chromatography on Sephadex LH-20 and enzyme hydrolysis. The resulting unconjugated steroids were separated by paper chromatography and identities were established by reverse isotope dilution. The unconjugated steroids initially obtained were separated by chromatography and identified by reverse isotope dilution. About 70% of the androstenedione was metabolized by both cell lines. However, the respective conversions to conjugates by MCF-7 and BT-20 were 31% and 0.32%. In the former, glucosiduronates predominated (94%) and consisted of androsterone (55%), etiocholanolone (9.4%) and androstanediol (5alpha-androstane-3alpha,17beta-diol) (9.3%). Androsterone comprised most of the unconjugated metabolites in both cell lines. Androstanediol was found in both cell lines, 2% in MCF-7 and 12% in BT-20. Testosterone, 5alpha-androstane-3,17-dione and 3beta-hydroxy-5alpha-androstan-17-one were isolated only from MCF-7. The metabolism of 3H-estriol was studied in a similar way. Both cell lines produced about equal amounts of estriol-3-sulfate (9%) and a compound with properties of estriol-3-glucosiduronate (0.15--0.5%). The results worthy of emphasis are: 1. The far greater conjugation of androgens exhibited by the MCF-7 cell lines as compared to the BT-20 cell lines; 2. In MCF-7, the high conversion of androstenedione to etiocholanolone (glucosiduronate form), a metabolite reported to form only in liver and sebaceous cysts; 3. The possible formation in both cell lines of estriol-3-glucosiduronate, normally a metabolite of the intestine.

Androstenedione↗

Serum unconjugated estriol in the menstrual cycle and early pregnancy.

A radioimmunoassay for serum unconjugated estriol in the menstrual cycle with a sensitivity of about 5 pg/ml is described. 8 cycles were studied. In 2 cycles, single spikes of 22 and 30 pg/ml were obtained. In 3 cycles, concentrations of 4-5 pg/ml were found whereas in the other 3 studies, no estriol was detected. In general, peaks of estriol corresponded to peaks in estradiol plus estrone. Patients in 4-12 weeks of gestation were also studied. Concentrations as high as 262 pg/ml were found but in isolated instances, no estriol was detected. The results support the view that in contrast to the pregnant state, in the normal menstrual cycle, the bulk of the estriol produced is conjugated before release into the blood.

Estriol↗

Correlation of concentrations of estriol-3-sulfate with those of potassium and sodium in human breast cyst fluid.

Estriol-3-sulfate (E3-3S) was assayed in 92 specimens of human breast cyst fluid (BCF) obtained by needle aspiration from women with fibrocystic disease. The concentrations of K+ and Na+ were determined in the same samples. The median concentration of E3-3S in the fluids from premenopausal women under 51 years of age (69 cases) was 4.4 ng/mL. Based on the K+ levels the samples were divided into two groups, above 50 mM (Type I) and below 50 mM (Type II). Correlations were made between the concentrations of the estrogen conjugate and the univalent ions. In the premenopausal women, Type I cysts were associated with above median E3-3S and Type II cysts with below median E3-3S (P less than 0.01). A K+/Na+ ratio of more than one was also related to elevated E3-3S (P less than 0.025). The BCF obtained from postmenopausal women and women older than 50 years tended to be low in E3-3S (median 1.64 ng/mL) and high in K+ but there were too few cases to permit statistical comparisons to be made. Since fibrocystic disease constitutes a risk factor for the development of breast cancer, it will be of interest to determine retrospectively whether any of the above subsets of BCF may be useful in identifying a patient at such risk.

Adult↗