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Biomedical subjects

P Bitterman

Publications and source records attributed to P Bitterman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mesenchymal cells isolated after acute lung injury manifest an enhanced proliferative phenotype.

After acute lung injury, mesenchymal cells migrate into the alveolar airspace where they proliferate and deposit connective tissue macromolecules. Early in the disease process, inflammatory cell-derived trophic factors modulate these mesenchymal cell functions. However, in those patients who die, even as the inflammatory response abates, the fibroproliferative response continues, resulting in extensive intraalveolar fibrosis. We therefore hypothesized that lung mesenchymal cells obtained from individuals dying with acute alveolar fibrosis would manifest an enhanced proliferative capacity that was independent of persistent exogenous signals. To examine this hypothesis, the in vitro growth properties of mesenchymal cells prepared from patients dying with acute lung injury (n = 3) were analyzed in defined medium and compared with those of mesenchymal cells similarly prepared from patients dying with histologically normal lungs (n = 3). Isolates were characterized as mesenchymal cells by using morphological and immunohistochemical criteria. In accord with the hypothesis, mesenchymal cells isolated from lung-injured patients doubled within 3 d in the complete absence of exogenous peptide growth factors, reaching a saturation density of approximately 15 x 10(3) cells/cm2. As expected, lung mesenchymal cells from normal individuals failed to significantly increase in number. Consistent with this proliferative phenotype, the immediate early cell division cycle genes c-fos and c-jun were constitutively expressed in each cell strain prepared from injured lungs, but not in those from control lungs. The observed proliferative phenotype was stable through the fifth subcultivation of the cells. Despite these proliferative properties, three separate criteria indicated the mesenchymal cells from injured lungs were not transformed: normal karyotype; finite lifespan in vitro (9-10 subcultivations); and inability to disseminate in mice with severe combined immunodeficiency. These data support the hypothesis that mesenchymal cells manifest an enhanced proliferative state after acute lung injury.

Acute Disease↗
PubMed1992

Primary osteosarcoma of the uterus: report of a case with immunohistochemical study.

A 63-yr-old female presented with uncontrollable uterine bleeding. Pathological evaluation revealed a uterine mesenchymal neoplasm which histologically represented a primary osteosarcoma. Immunohistochemistry was utilized to help support the diagnosis. The English literature regarding this rare uterine neoplasm is briefly reviewed.

Biomarkers, Tumor↗
PubMed1991

Müllerian adenosarcoma of the uterus with pure angiosarcoma: case report.

We report a case of müllerian adenosarcoma of the uterus with benign endometrioid epithelial component and histologically pure angiosarcoma. This seemingly unique sarcomatous ingredient, among uterine and extrauterine adenosarcomas reported in the English literature, is considered to be a homologous component of the tumor. The patient, a 71-year-old woman with a several-month history of intermittent vaginal bleeding, was found at abdominal hysterectomy to have a large polypoid intrauterine tumor with superficial extension into the myometrium. The patient was treated with 6,000 rad of adjuvant radiation but died a few months after of what clinically appeared to be massive abdominal bleeding. The literature regarding uterine tumors classified as angiosarcoma or malignant hemangioendothelioma is briefly reviewed.

Aged↗
PubMed1991

In situ amplification of visna virus DNA in tissue sections reveals a reservoir of latently infected cells.

Maedi and visna are, respectively, the pulmonary and neurological manifestations of slowly progressive infections of sheep caused by retroviruses of the lentivirus subfamily. Lentivirus infections are also persistent infections in which host defenses are generally not successful in eliminating the infectious agent because of restricted viral gene expression in many infected cells. In this report, we describe a method for amplifying and detecting viral DNA in tissue sections which has made it possible to verify experimentally the postulated existence of this reservoir of latently infected cells, as well as to estimate the actual number of cells which harbor viral genomes in infected tissues. In the discussion, we present a simple mathematical model that relates this number to the rate at which inflammatory lesions develop. This model can account for both the slow progression of natural infections and for the rapid accumulation of inflammatory foci in the high dosage experimental system analysed in our studies.

Animals↗
PubMed1991

Toxicities in rats with free versus liposomal encapsulated cisplatin.

Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1 or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution intraperitoneally biweekly for 15 injections. Rats in the free drug group showed significantly less weight gain; two rats died during the study. At necropsy, the free cisplatin--treated rats showed gross and microscopic evidence of peritoneal fibrosis that was not detected in any of the remaining groups. The free cisplatin--treated rats showed serum and histologic evidence of renal damage; all five rats had moderate or severe acute tubular necrosis. No renal abnormalities were detected in rats that received 1 mg/kg, and only focal or mild changes were found in rats that received 2 mg/kg of the liposomal preparation. Neurotoxicity, as determined by nerve conduction and inclined plane studies, developed in rats treated with free and liposomal cisplatin. These results are encouraging and warrant further investigation.

Animals↗
PubMed1991

Primary leiomyosarcoma of adrenal gland. Case report with immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the right adrenal gland is reported in a 49-year-old male who presented with progressive flank pain. This is the second case in the English language literature and the first to have documentation of malignant behavior. The tumor measured 11 cm in diameter and showed marked necrosis with prominent mitotic activity (average 15 per 10 high-power fields). Smooth muscle differentiation was apparent ultrastructurally and confirmed by positive immunostaining for muscle-specific and alpha-smooth muscle actin. Bony metastases developed; following palliative treatment with radiation and chemotherapy, the patient is alive with tumor 9 months later. Origin from smooth muscle associated with the central adrenal vein or its tributaries is proposed.

Adrenal Gland Neoplasms↗
PubMed1991

Morphine-augmented cholescintigraphy in acute cholecystitis. A satisfactory alternative to delayed imaging.

The utility of morphine-augmented cholescintigraphy was reviewed in 32 patients with suspected acute cholecystitis. All patients were administered 2 mg morphine sulfate intravenously when the gallbladder failed to visualize 30 minutes into the study, and imaging continued for up to 60 minutes. Sensitivity for detection of acute cholecystitis was 93% (13 out of 14). Specificity was 78% (14 out of 18). Three of four false-positives occurred in the setting of prolonged fasting and chronic cholecystitis. Cumulative experience suggests that the technique is diagnostically equivalent to imaging for up to 4 hours and that specificity remains incomplete in the setting of prolonged fasting, chronic cholecystitis and other conditions known to affect conventional cholescintigraphy.

Acute Disease↗
PubMed1991

Identification and partial characterization of angiogenesis bioactivity in the lower respiratory tract after acute lung injury.

Survival after acute lung injury (ALI) depends on prompt alveolar repair, a process frequently subverted by the development of granulation tissue within the alveolar airspace. Immunohistochemical examination of the intraalveolar granulation tissue confirmed that capillaries as well as myofibroblasts were the principal cellular constituents. We therefore hypothesized that angiogenesis factors would be present on the air-lung interface after ALI. To evaluate this hypothesis, bronchoalveolar lavage fluid from patients with ALI (n = 25) and patient controls (n = 8) was examined for angiogenesis bioactivity by its ability of induce endothelial cell migration. While lavage fluid from controls had no bioactivity, lavage fluid from 72% of patients with ALI promoted endothelial cell migration. Heparin affinity, ion exchange, and gel filtration chromatography resolved the bioactivity into at least two moieties. One appeared identical to the well characterized endothelial cell growth factor, basic fibroblast growth factor. The other was a 150-kD non-heparin binding protein that mediated endothelial cell migration and attachment in vitro, and the growth of new vessels in vivo. These data are consistent with the hypothesis that the growth of capillaries into the alveolar airspace results from angiogenesis factors present on the alveolar surface of the lung after ALI.

Acute Disease↗
PubMed1990

The significance of epithelial differentiation in mixed mesodermal tumors of the uterus. A clinicopathologic and immunohistochemical study.

Mixed mesodermal tumors and carcinosarcomas of the uterus are classified as sarcomas. However, in other sites, malignant biphasic tumors may be classified as carcinomas, mesotheliomas, or sarcomas. In order to clarify their behavior and patterns of differentiation, we performed a clinicopathologic and immunohistochemical study of 22 cases aimed at analyzing the pattern of spread and histologic appearance of the metastasis, as well as the distribution of intermediate filaments in the primary tumor and the metastasis. Four monoclonal antibodies (Mabs) were used to detect epithelial lineage, three that recognize keratin (AE1/AE3, CAM5.2, MAK6) and one that recognizes epithelial membrane antigen (EMA). A Mab against vimentin was also used. Metastases involved the omentum, pelvic peritoneum, ovaries, fallopian tubes, pelvic or para-aortic lymph nodes, liver parenchyma, and tonsil. These metastases were composed of carcinoma only. Lymphatic/vascular invasion was identified in 11 cases; it consisted exclusively of carcinoma. In all 12 cases evaluated immunohistochemically, keratin and EMA were identified in the majority of the cells in the epithelial component and in a more focal distribution in the spindle cell component in 11 (92%). Vimentin was detected in the majority of spindle cells in nine cases (75%) and in a more focal distribution in the epithelial component in six cases (50%). In the spindle cell component, keratin and EMA were present in widely scattered individual spindle-shaped and rounded cells, within solid clusters of rounded cells, and in nests of cells with small lumens. The distribution of keratin, EMA, and vimentin in the metastases (carcinoma in all instances) was similar to the epithelial component in the primary tumor. Our findings indicate that the epithelial component of these tumors invades lymphatic/vascular spaces and metastasizes, whereas the spindle cell component has limited metastatic potential, if any. Since the behavior of these neoplasms is dictated by the epithelial element, we believe that mixed mesodermal tumors of the uterus should be classified as carcinomas rather than sarcomas.

Aged↗
PubMed1989

Sertoli-Leydig cell tumor associated with a mature cystic teratoma in a single ovary.

Sertoli-Leydig cell tumors of the ovary are rare neoplasms of young women and are best known for their frequent virilizing effects. They have very rarely been reported in association with other ovarian neoplasms. We report such a tumor associated with a mature cystic teratoma in the same ovary. The wide variety of histologic patterns seen in many Sertoli-Leydig cell tumors including the present case, often causing difficulty in diagnosis, is reviewed.

Adult↗
PubMed1988

Fecapentaenes and their precursors throughout the bowel--results of an autopsy study.

The fecapentaenes are potent mutagens found in the stool of some humans and pigs. These compounds are produced by Bacteroides species in the gut from an uncharacterized family of precursor compounds, and have been postulated to pose a risk of human colorectal cancer. To better understand fecapentaene production in vivo, and to determine if excreted levels measured in epidemiologic studies are representative of the entire colon, fecapentaenes were assayed from multiple sites in the bowel in an autopsy study of 16 humans and 2 pigs. An indirect measurement of fecapentaene precursors was also made. Colonic concentrations of fecapentaenes and precursors varied widely between individuals, but were consistent for each individual throughout the colon. In addition, the measurements of rectal contents, assumed to approximate values in excreted stool, were equivalent to measurements from the colon.

Adult↗
PubMed1987

Melanoma antigens as modified normal gene sequences.

Melanomas are highly aggressive tumors with a well-documented antigenic nature. Several melanoma antigens have been reported, four of which, p97, Ia-like antigen, B700, and A have been implicated as having regions in common with normally occurring proteins. P97 has partial sequence homology with transferrin and lactotransferrin, Ia-like antigen is immunologically cross-reactive with alpha and beta chains of Ia-like proteins, A is a variant of alpha actin, and B700 resembles a normal melanosomal membrane protein. In addition, B700 has partial sequence homology to serum albumins. These observations suggest that melanoma tumors can produce antigenic proteins by modification of normally occurring proteins. The possible mechanisms are discussed.

Actins↗
PubMed1980

Delayed hemolytic transfusion reaction presenting as sickle-cell crisis.

Eighteen patients with sickle-cell disease underwent partial exchange transfusion. Three developed delayed hemolytic reactions, with selective disappearance of transfused cells. All reactions occurred within 6 days of transfusion, and patients presented with the clinical features of painful crises. The two most severe reactions were associated with antibodies to Jka. These patients developed fever, arthritis, and a clinical course suggesting serum sickness. In both patients, other alloantibodies had previously been seen. A fourth patient developed multiple alloantibodies, accelerated destruction of tranfused cells, but milder illness. Such reactions may be commoner than in appreciated and should be suspected when patients have recurrent or severe sickle crises after transfusion. Blood that is nonimmunogenic in antigen systems frequently associated with delayed hemolytic reactions (Rh, Kell, Duffy, and Kidd) is preferred for sickle-cell patients who lack these antigens, especially if these patients have previously demonstrated capability to form erythrocyte alloantibodies.

Adolescent↗