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Biomedical subjects

C D Bedetti

Publications and source records attributed to C D Bedetti.

At least 19 recordsLinked to original sources

Pulmonary arterial histology and morphometry in systemic sclerosis: a case-control autopsy study.

Morphometric measurements were performed on pulmonary arteries in 58 patients with systemic sclerosis (20 limited cutaneous and 38 diffuse cutaneous involvement [21 with and 17 without renal crisis]) and age, race, and sex matched autopsy controls. Matched pairs analysis was employed. For arteries of all sizes, the area of the intima and percent luminal occlusion were greater in the limited and diffuse (no renal crisis) groups than in controls, and these differences were statistically significant for large and medium sized vessels. The greatest luminal occlusion was found in limited cutaneous patients, and especially those with clinical evidence of pulmonary arterial hypertension, providing a rationale for the poor response to vasodilator therapy in these patients.

Constriction, Pathologic

Renal vascular histology and morphometry in systemic sclerosis. A case-control autopsy study.

An autopsy case-control study of renal vascular histology and morphometry in systemic sclerosis (scleroderma) was performed. Thirty-five of 70 systemic sclerosis cases had renal tissue available for study: 26 had diffuse cutaneous involvement (9 with "renal crisis" and 17 without) and 9 had limited cutaneous disease (CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias]). Age-matched (within 10 years) and sex-matched controls with renal specimens were obtained. New sections were cut from tissue blocks, and morphometry was completed using a Zeiss Image Analyzer. Using analysis of variance, the intimal area (Ai) was significantly increased (intimal thickening) in small and medium-sized arteries of patients with diffuse scleroderma and in small arteries of CREST patients, compared with those in controls, while a decreased medial area (Am) was seen consistently in all groups. The proportion of the vessel wall occupied by intima (Ai:[Ai + Am]) was significantly greater in all vessel size groups in patients with diffuse scleroderma compared with that in controls. The percentage of luminal occlusion was greatest in patients with diffuse disease with renal crisis. These same patients had severe edematous and mucinous intimal thickening in small and medium vessels, often in association with fibrinoid necrosis. We conclude that renal vascular structural changes are an integral part of systemic sclerosis. However, the significant differences between diffuse scleroderma patients and CREST syndrome patients, for both intimal thickening and percentage of luminal occlusion, suggest that the arterial disease in these 2 patient subsets is distinctive.

Calcinosis

Hypophysectomy and adrenalectomy decrease Ca2+-induced swelling of rat liver mitochondria.

Hypophysectomized rats showed significant modifications in Ca2+-induced swelling and MgATP-induced contraction of liver mitochondria. Two-three months after operation, maximal swelling (MS), rate of swelling (VS), maximal contraction (MC) and rate of contraction (VC) were decreased by 77 (MS), 83 (VS), 79 (MC) and 62 (VC) % (in all cases P less than 0.05 as compared with normal rat mitochondria). Treatment of hypophysectomized rats with bovine pituitary extract, for two weeks, counteracted the effect of hypophysectomy, whereas treatment with bovine growth hormone was ineffective. Adrenalectomy produced similar though less extensive modification of Ca2+-induced swelling but failed to affect the MgATP-dependent mitochondrial contraction. Substrate oxidation by hypophysectomized or adrenalectomized rat mitochondria showed no modification of the energy-yielding mechanisms, capable of explaining the observed changes in mitochondrial swelling.

Adrenal Glands

Calcium transport and energy coupling in diabetic rat liver mitochondria.

Liver mitochondria from chronic diabetic rats took up Ca ions at a significantly slower rate than their normal counterparts. The same mitochondria, inhibited with ruthenium red, released Ca ions at a faster rate than normal mitochondria. In good agreement with the decrease of Ca ions uptake, measurement of the inner membrane potential by the safranine method yielded a significantly lower value with diabetic than with normal mitochondria. Respiratory control and P/O ratios were also decreased in diabetic mitochondria.

Animals

Skeletal myxoid chondrosarcoma with microtubular aggregates within rough endoplasmic reticulum.

A skeletal myxoid chondrosarcoma of the femur was examined by light and electron microscopy. Light microscopic features were characteristic for myxoid chondrosarcoma or "chordoid sarcoma." Electron microscopy disclosed crystalline arrays of microtubules within dilated rough endoplasmic reticulum, a feature previously described in extraskeletal myxoid chondrosarcomas. Tumors with the histologic characteristics of extraskeletal myxoid chondrosarcoma ("chordoid sarcoma") occurring in bone have been rarely reported. We describe herein such a tumor and document the existence of distinct microtubules within the endoplasmic reticulum.

Bone Neoplasms

Malignant epithelioid hemangioendothelioma of the colon. Report of a case.

Angiosarcoma of the colon with epithelioid and histiocytoid features, a malignant counterpart of epithelioid hemangioendothelioma, was observed in a 72-year-old man. The disease first manifested as a right cervical mass, with the histologic appearance of malignant, undifferentiated, large-cell epithelioid neoplasm. Light microscopy of the colonic tumor disclosed angiosarcoma, with active erythrophagocytosis and positive immunoperoxidase reactions to lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. Ultrastructural features of the tumor cells were those of intermediate between endothelial and histiocytic cells. The disease took a rapid fatal course with recurrence, peritoneal dissemination, and massive peritoneal hemorrhage. The cause remains unknown.

Aged

Ultrastructural localization of rat Clara cell 10 KD secretory protein by the immunogold technique using polyclonal and monoclonal antibodies.

Using a monoclonal antibody and affinity-purified polyclonal antiserum against a 10 KD protein isolated from rat pulmonary lavage, we have localized the protein within Clara cells by a post-embedment protein A-gold technique. The gold particles were localized over the secretory granules of rat Clara cells. Ultrastructural immunolocalization was abolished when the primary antibodies were previously absorbed with purified 10 KD protein. Other pulmonary cells, including type II pneumocytes and ciliated cells, were negative with this technique. These results demonstrate the presence of the 10 KD protein in the secretory granules of the Clara cell and support the concept that this protein constitutes a specific and unique secretory product of Clara cells.

Animals

Effect of diabetes, adrenalectomy and hypophysectomy on D-3-hydroxybutyrate dehydrogenase activity and substrate oxidation by rat mitochondria.

In good agreement with previous observations, D-3-hydroxybutyrate dehydrogenase (OHBD) activity in disrupted liver mitochondria decreased significantly in chronic diabetic rats, whereas insulin treatment prevented this decrease. Similar effects were observed with kidney mitochondria. Adrenalectomy increased OHBD activity in liver and brain mitochondria from normal rats and in liver mitochondria from diabetic rats. Corticosterone depressed OHBD activity in liver mitochondria of normal rats and restored the normal level of OHBD in adrenalectomized rats. Hypophysectomy increased OHBD activity in normal rats, this effect being further increased by growth hormone administration. D-3-hydroxybutyrate (OHB) oxidation by liver mitochondria from diabetic, adrenalectomized or hypophysectomized rats varied as expected from OHBD activity in disrupted mitochondria, but to a relatively lesser degree. Submitochondrial particles from diabetic rats showed significant diminution in OHB-, succinate- and NADH-oxidase activities, whereas mitochondria from diabetic rats oxidized succinate and L-malate + L-glutamate at a slower rate than the corresponding controls.

3-Hydroxybutyric Acid

Cyclosporin A-induced cholestasis. The mechanism in a rat model.

Cyclosporin A (CyA) causes cholestasis in a significant proportion of transplant patients. Doses of 5, 10, and 15 mg CyA/kg body wt or the Miglyol 812 vehicle were administered intraperitoneally for 1, 2, and 3 wk to separate groups of rats to investigate the mechanism of this cholestasis. At 1 wk a dose-response relationship between serum CyA levels and increasing CyA doses was noted. A maximum CyA blood level was achieved by 2 wk with the 10- and 15-mg/kg doses. Subsequent studies were performed using the smaller (10 mg/kg) dose administered for 3 wk. This dose resulted in a marked increase in serum bile acid levels compared with vehicle-treated controls (24.6 +/- 4.0 vs. 4.3 +/- 1.2 mumol/L, p less than 0.001) without inducing significant changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, bilirubin, alkaline phosphatase, and albumin levels or hepatic architectural alterations. With CyA treatment, baseline bile flow decreased by 35% and bile salt secretion decreased by 25% compared with vehicle-treated animals. Cyclosporin A and vehicle-treated rats were infused intravenously with taurocholate (4 mumol/min X kg) for 2 h and then depleted of bile salts over the next 24 h. Bile samples collected over this period were graphed as bile salt secretion versus bile flow. The mean slope of the linear regression for the CyA-treated rats was 62% of the control, demonstrating a decrease in bile salt-dependent flow. Extrapolation of the linear regression to the ordinate demonstrated a 22% decrease in bile-independent flow with CyA treatment. Therefore, in our experimental model of CyA-induced cholestasis, the decrease in flow observed was the result of a decrease in both bile salt-dependent and bile salt-independent flows and occurred in the absence of significant biochemical or histologically evident hepatotoxicity.

Animals

Primary adenocarcinoma arising at an ileostomy site. An unusual complication after colectomy for ulcerative colitis.

A case is reported of a 45-year-old man who developed a primary adenocarcinoma at the ileostomy site 23 years after proctocolectomy for ulcerative colitis. The patient underwent wide local excision of the tumor and died 13 months later with disseminated adenocarcinoma. Including the present case, a total of seven patients with ileostomy adenocarcinoma have been reported in the literature. Six patients were treated surgically for ulcerative colitis, and the other one for adenomatous polyposis coli. The diagnosis of stomal malignancy was made three to 23 years after the ileostomy (mean interval, 13 years). Of the four patients available for clinical follow-up, two died of disseminated adenocarcinoma ten and 13 months after diagnosis. Awareness of this unusual but important complication of ileostomy should lead to earlier diagnosis and treatment with improvement in prognosis.

Adenocarcinoma

Extracapsular spread of carcinoma in cervical lymph nodes. Impact upon survival in patients with carcinoma of the supraglottic larynx.

The treatment results and histologic findings in the cervical lymphatics of 96 patients with squamous cell carcinoma of the supraglottic larynx were studied retrospectively. The clinical assessment of the extent of disease in the cervical lymphatics correlated poorly with histologic findings. Forty-one percent of patients judged to have no evidence of cervical metastases were found to have carcinoma in the cervical lymphatics. Twenty percent of patients judged clinically NO were found to have extracapsular spread of tumor. Patients were subdivided according to the histologic findings in the cervical lymphatics. Three-year no-evidence-of-disease (NED) follow-up was available on all patients. Patients with no tumor in cervical lymphatics had a 71% 3-year NED. By comparison, patients with cervical metastases confined to the lymph node were 79% NED. Patients with histologic evidence of extracapsular spread of tumor were 45% NED (P less than 0.05). The use of histologic findings in predicting prognosis and treatment planning is discussed.

Carcinoma, Squamous Cell

Cervical lymph node metastases. Incidence and implications of extracapsular carcinoma.

The incidence and prognostic significance of extracapsular spread (ECS) of tumor in cervical lymphatics was investigated. The surgical specimens from 349 patients treated for squamous cell carcinoma by radical neck dissection between 1978 and 1982 have been examined retrospectively. Follow-up data were available relative to recurrence rate, site of recurrence, and disease-free intervals. Fifty-nine percent of the patients with N1 cervical metastases had ECS. Patients were classified according to the histopathologic findings in the radical neck dissection specimens. The three groups identified were patients with normal nodes, patients with no ECS, and patients with ECS. The histopathologic evidence of ECS was associated with a statistically significant reduction in survival when compared with patients without ECS. The disease-free interval between treatment and the development of recurrent disease was shorter for patients with ECS than for patients with no ECS.

Carcinoma, Squamous Cell

Immunocytochemical demonstration of cytochrome c oxidase with an immunoperoxidase method: a specific stain for mitochondria in formalin-fixed and paraffin-embedded human tissues.

Cytochrome c oxidase (CO) is the terminal electron carrier of the respiratory chain and is localized exclusively in the inner membrane of the mitochondria. Using a specific rabbit antiserum against bovine heart CO, mitochondria were specifically stained in sections of formalin-fixed paraffin-embedded human tissues by an immunoperoxidase method. The intensity of the immunostaining in different human tissues correlated mainly with the number of mitochondria and abundance of mitochondrial cristae, i.e., surface area of the inner mitochondrial membrane. Mitochondrion-rich cells, such as myocardial and gastric parietal cells, had very strong cytoplasmic staining. This technique was especially useful for the specific identification of oncocytes in normal tissues and in lesions composed of oncocytes. In addition, the immunoperoxidase method for CO makes possible retrospective investigations of lesions composed of oncocytes, since routine paraffin blocks of formalin-fixed tissue are quite suitable for such studies.

Cell Transformation, Neoplastic

Teflon felt embolism of coronary arteries after cardiac surgery: a case report.

A case is presented of fatal coronary embolism of Teflon felt used to buttress sutures in the placement of a Björk-Shiley aortic valve prosthesis. The embolism occurred on the tenth postoperative day, lodging in the left anterior descending branch of the left coronary artery 5.5 cm. from the ostium, causing a large anterior myocardial infarct. The patient died in less than 24 hours following the infarct. A review of the literature indicates that this is the first reported case of clinically significant embolism of Teflon felt used in the placement of a Björk-Shiley aortic valve.

Coronary Disease

Influence of the hypophysis on mitochondrial protein synthesis.

Hypophysectomy significantly decreased the capacity to synthesize protein by isolated liver and skeletal muscle mitochondria. Total hypophyseal extract, growth hormone or thyroxine administered to the whole animal in adequate doses prior to sacrifice enhanced protein synthesis to values similar or higher to those of the control, especially in the case of thyroxine.

Animals