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Biomedical subjects

A E Kalderon

Publications and source records attributed to A E Kalderon.

At least 19 recordsLinked to original sources

The potential oncogenic activity of influenza A virus in lungs of mice.

Adult male CD1 mice were inoculated with chicken egg-propagated influenza type A/PR8/34 virus. Fully developed pulmonary pneumonia was found 7 d after the infection. In addition to the pneumatic condition, pronounced thickening of the bronchiolar epithelium denoting hyperplastic and dysplastic transformation of the epithelial cells were also observed. By 11 d of the experiment, extensive papillomatous proliferation of the bronchiolar epithelial cells could be demonstrated. Furthermore, invasive growth of these epithelial cells through the basement membrane and muscularis layer into the alveolar tissues were evident. Such invasive transgression of transformed epithelial cells strongly suggested malignant growth of these cells. Detailed histopathological survey of all the virus-infected lungs revealed tumorous nodule formations in over 80% of the specimens examined. Our present investigation not only confirmed previous claims that cellular transformations (hyperplasia, metaplasia, dysplasia) can be induced with influenza type A virus but also for the first time successfully demonstrated invasive growth and tumorous formation in lungs of infected animals. Our study further reaffirms the oncogenic potential of influenza type A virus.

Animals↗

Synovial immunofluorescence in patients with slipped capital femoral epiphysis.

To evaluate if the immune system is active in slipped capital femoral epiphysis (SCFE) or chondrolysis, 16 patients with SCFE were studied by evaluation of their serum immunoglobulins, histology of their synovium, and immunofluorescent staining of their synovium. Patients with Perthes' disease, chondromalacia patellae, septic arthritis, sickle cell disease, and torn meniscus were controls. Serum immunoglobulins were normal in all patients. The histology demonstrated synovitis in all patients except in one normal knee. Plasma cells were a prominent feature of the synovitis in the patients with SCFE. Three patients had positive synovial immunofluorescence for IgG and C3. Two of these patients subsequently developed chondrolysis and one did not. One additional patient who had negative synovial immunofluorescence developed chondrolysis. It is postulated that the immune system is active in some patients with SCFE, but what, if any, role it plays in the disease or its complications remains to be shown.

Adolescent↗

Localization of 3',5'-cyclic adenosine monophosphate phosphodiesterase (cAMP-PDEase) activity in isolated bovine thyroid plasma membranes.

Isolated bovine thyroid plasma membrane preparations were obtained by isopycnic density gradient centrifugation. Cyclic AMP-PDEase (EC 3.1.4.c) activity has been demonstrated by electron microscopic histochemistry on the unit membrane of isolated bovine thyroid cells. 3-isobutyl-1-methyl-xanthine (IBMX) produced partial inhibition, while omission of the substrate revealed no reaction product deposition. These observations correlated well with biochemical studies that showed 0.4% of the total cAMP-PDEase activity to be present in the plasma membrane preparations. Kinetic analysis of cAMP hydrolysis yielded two apparent Michaelis constants for the homogenate and the plasma membrane-rich fraction. Dose-response curves for IBMX inhbition showed cAMP-PDEase of the homogenate to be more sensitive to inhibition than that of the plasma membrane-bound enzyme. Furthermore, wash experiments indicate that the plasma membrane-associated enzyme is tightly bound. This investigation strengthens our previous study and suggests that bovine thyroid cell plasma membranes contain a cAMP-PDEase that may be involved in interactions between the cell and the external environment in a manner yet to be determined.

3',5'-Cyclic-AMP Phosphodiesterases↗

Successful therapy of crystalcryoglobulinemia: a case report.

Successful therapy for a case of multiple myeloma with a spontaneously crystallizing cryoglobulin of the IgG2-kappa light chain variety was achieved, using both continuous-flow cell centrifugation plasmapheresis to rapidly lower the M component and combination chemotherapy with phenylalanine mustard, prednisone, procarbazine, and vincristine to control the myeloma process. This resulted in resolution of incapacitating large and small necrotic cutaneous ulcerations of the extremities. Physicochemical studies of the crystalcryoprotein demonstrated that cryoprecipitation was rapid and accompanied by the formation of needle-shaped crystals, yet was completely reversible at 37 degrees C. Cryocrit determinations varied depending upon relative centrifugal forces and temperature and did not always relate linearly to the amount of abnormal protein, thus making these alone unreliable in assessing response to therapy.

Antineoplastic Agents↗

Secretion and adenylate cyclase in thyroid nodules.

Thyrotropin (TSH)- and sodium fluoride (NaF)-sensitive adenylate cyclase (AC) activity was measured in ten cases of "cold" thyroid nodules and compared with perinodular tissue. Findings were correlated with the ultrastructure of the nodular and perinodular tissue. Comparisons of the results of assay studies revealed an increase of basal and NaF- and TSH-stimulated AC activity in cold lesions. There was no dissociation of NaF- and TSH-sensitive AC. Ultrastructural findings disclosed a lack of correlation between elevated AC activity and the expected organelle profile indicative of stimulation. Since organelle modulations that are associated with increased protein synthesis were not observed in the face of increased AC activity, an unknown intracellular defect may exist in the expression of the AC-cyclic AMP (adenosine 3':5'-cyclic phosphate) system in cold thyroid nodules.

Adenoma↗

Ultrastructure of myeloma cells in a case with crystalcryoglobulinemia.

The bone marrow of a patient with multiple myeloma of the IgG2 Kappa type with spontaneously crystallizing cryoglobulin was studied by electron microscopy. The ultrastructure of the myeloma cells disclosed the presence of a crystalline material in the cytoplasm within the rough endoplasmic reticulum (RER) as well as in extracisternal sites. The crystalline material was also seen extracellulary with a distinctly unique subunit structure. The tubular units measured 200 +/- A (SEM) externally with an internal diameter of 100 +/- A (SEM). The intracellular distribution did not indicate a characteristic organelle association usually observed in protein synthesizing cells. It is suggested, based on the present observations and the findings of others, that the crystalline material may represent polymerized protein synthesized by free ribosomes mostly in extracisternal locations, a pattern often seen in neoplastic plasma cells. Diffusion to extracisternal sites of precrystalline material through the membranes of the RER is a possible alternative mechanism.

Bone Marrow↗

Immune complex deposits in Graves' disease and Hashimoto's thyroiditis.

The thyroid glands of four patients with Graves' disease and five patients with Hashimoto's thyroiditis were investigated to demonstrate in vivo immune complex deposition. By electron microscopy, electron-dense deposits were observed in the follicular basal lamina--basement membrane--(FBL) often associated with lymphocytic and plasma cell infiltration. A positive correlation was obtained with all cases by immunofluorescent studies using anti-IgG, IgA, IgM, C3 and antithyroglobulin conjugated serums. The staining was of a granular pattern and coincided to the FBL region. No discrepancies were noted in electron microscopic and immunofluorescent observations between patients with Graves' disease and Hashimoto's thyroiditis, and the occasional observation of immune complexes in areas devoid of infiltrate in some patients with Graves' disease. Morphologically, the deposits were found to be similar to those described in the Obese Strain chickens with spontaneous autoimmune thyroiditis.

Antigen-Antibody Complex↗

Electron-dense deposits in the follicular basal lamina of obese strain chickens with spontaneous hereditary autoimmune thyroiditis. An electron microscopic study.

Thyroid glands of 36 chickens of the obese strain with hereditary spontaneous autoimmune thyroiditis were examined by electron microscopy at 1, 3, 5, 7, 10, and 14 weeks of age with particular emphasis on basal lamina changes. All chickens were of the B1B1 genotype. The electron microscopic results were compared with six normal White Leghorn chickens of the same age. The major abnormality observed in obese strain chickens was the persistent presence of electron-dense deposits along the follicular basal lamina in the thyroid beginning with 7-week-old chickens. The deposits morphologically comparable to immune complexes were noted either between the basal plasma membrane and the follicular basal lamina or below the follicular basal lamina. In 14-week-old chickens, the electron-dense deposits were observed within abnormally thickened basal lamina. The deposits were not present in the vascular basal lamina adjacent to the thyroid follicles and were not observed in the thyroids of 1- to 5-week old chickens and were also not encountered in normal White Leghorn chickens. Indirect morphologic evidence suggests that these may be antigen-antibody complexes, but characterization of these deposits and their role remain to be determined.

Animals↗

Mixed gonadal dysgenesis.

Mixed gonadal dysgenesis (MCG) is a rare intersexual disorder, characterized in most cases by the presence of a testis and a contralateral streak gonad; in some cases the contralateral gonad may be rudimentary not having differentiated into an ovary or into a testis and in other cases it may be absent. A personal case was recently studied by the authors in some detail: A 51-year-old individual reared as a female with primary amenorrhea, short stature, subnormal intelligence, male type habitus, hirsutism, moderate breast development, ambiguous external genitalia with a 5 x 2 cm phallus, labia majora with scrotal type skin, and a urogenital sinus. Internal genitalia consisted of a hypoplastic vagina and uterus, a streak gonad on the right and intraabdominal testis, fallopian tube, and epididymis on the left side. The dysgenetic testis contained a gonadoblastoma and the streak a gonadoblastoma and dysgerminoma. A buccal smear was chromatin negative and karyotype analysis revealed XO/XY mosaicism. Thyroid and adrenocortical function was normal. A plasma testosterone level of 0.15 mu-g% rose to 0.45 mu-g% with 3 days of HCG administration. With bilateral gonadectomy the plasma testosterone level fell to 0.06 mu-g% and there was no response following HCG administration. 109 cases of MGD and 2 cases of unilateral gonadal dysgenesis reported in the world literature between 1937 and 1973 were reviewed. On the basis of their clinical and pathological features, the latter two patients were excluded from the category of MGD. In 15 of the 109 cases of MGD, a gonadoblastoma obscuring the gonad of origin was opposed by a dysgenetic gonad with or without a gonadoblastoma or no gonad. In these cases the presence of a testis was not proven histologically and their clinical-pathological features were similar to those found in pure gonadal dysgenesis. Of the remaining 94 cases of MGD, 72 had testicular tissue on one side and a streak or embryonic gonad on the other while 22 had a testis and no contralateral gonad...

Amenorrhea↗