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Biomedical subjects

K McDaniel

Publications and source records attributed to K McDaniel.

7 recordsLinked to original sources

Investigation into the mechanism of the loss of laminin 5 (alpha3beta3gamma2) expression in prostate cancer.

Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability, migration, and anchoring filament formation. Protein and gene expression of the alpha3, beta3, and gamma2 chains of laminin 5 were investigated in normal and invasive prostate carcinoma using immunohistochemistry, Northern analysis, and in situ hybridization. Laser capture microdissection of normal and carcinomatous glands, in conjunction with RNA amplification and reverse Northern analysis, were used to confirm the gene expression data. Protein and mRNA expression of all three laminin 5 chains were detected in the basal cells of normal glands. In contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein expression with variable expression of alpha3 chains. Despite the loss of protein expression, there was retention of beta3 and gamma2 mRNA expression as detected by in situ hybridization, Northern and reverse Northern analysis. Our findings imply that an altered mechanism of translation of beta3 or gamma2 mRNAs into functional proteins contributes to failure of anchoring filaments and hemidesmosomal formation. The resultant hemidesmosome instability or loss would suggest a less stable epithelial-stromal junction, increased invasion and migration of malignant cells, and disruption of normal integrin signaling pathways.

Carcinoma↗

Matrilysin expression in human prostate carcinoma.

The metalloproteinases, a multigene family of metal-requiring enzymes, have been suggested to play a role in tumor invasion and metastasis. Previously, we demonstrated that human primary prostate tumors express higher levels of matrilysin and gelatinase A mRNA than normal prostate does. In the study presented here, we used in situ hybridization and immunohistochemical staining of serial sections of paraffin-embedded primary prostate tumors to compare the sites of matrilysin and gelatinase A expression and protein localization. These results confirmed the epithelial nature of matrilysin expression and protein localization. In contrast, gelatinase A mRNA was localized to the interstitial stroma, whereas the protein was associated with the epithelial tumor cells. In situ hybridization was also used to demonstrate that gelatinase B expression was restricted to macrophages infiltrating the tumors. Proteins isolated from an additional set of frozen tumor specimens were analyzed by western blotting to determine the relative amounts of matrilysin in the active and proenzyme forms. The western analyses demonstrated that in all cases in which matrilysin was detected, at least some of the enzyme was in the active form. These results are discussed with respect to the possible role these enzymes may play in prostate tumor progression.

Amino Acid Sequence↗

Comparison of propofol with thiopentone for treatment of bupivacaine-induced seizures in rats.

Thirty Sprague-Dawley rats were paralysed with pancuronium and their lungs ventilated mechanically with 70% nitrous oxide and 0.5% halothane in oxygen. Bupivacaine 2 mg kg-1 min-1 was infused continuously i.v. until the animals died. At the onset of seizures, animals were given an i.v. bolus of propofol 1 mg kg-1 (n = 10), thiopentone 2 mg kg-1 (n = 10) or lipid vehicle (n = 10). Administration of propofol or thiopentone was repeated each time seizures restarted and lipid vehicle administrations were repeated at 2-min intervals until the electroencephalogram became isoelectric. All animals developed seizures, arrhythmias, isoelectric EEG and asystole. Administration of lipid vehicle induced no obvious changes in ongoing epileptiform activity. The initial doses of thiopentone and of propofol stopped epileptiform activity in all animals, usually within 6 s after administration. The seizure-free period after the initial administration of thiopentone and of propofol lasted, on average, 0.98 min and 1.72 min, respectively. We conclude that propofol may have value in treating seizures induced by bupivacaine.

Animals↗

Primary malignant small round cell tumor of the abdomen: CT findings in five cases.

Malignant small round cell tumor of the abdomen is a newly described clinicopathologic entity. The features of this entity include a predilection for young men, predominant abdominopelvic location, and aggressive behavior. Pathologic analysis demonstrates a small-cell tumor unusually coexpressing desmin and keratin. This study describes CT characteristics in five patients with malignant small round cell tumor of the abdomen. All patients were young white men, 20-36 years old (mean, 28 years). In all five cases, CT scans revealed lobulated masses appearing to arise primarily from peritoneal surfaces and predominantly involving the peritoneal cavity of the abdomen (two cases) and pelvis (two cases); diffuse abdominopelvic involvement was noted in one case. The masses were centrally necrotic and enhanced inhomogeneously after administration of iodinated contrast material. Additional CT features included ascites (one case), calcifications in the dominant mass (one case), omental implants (two cases), hydronephrosis (four cases), anterior diaphragmatic lymphadenopathy (two cases), liver metastases (two cases), and retroperitoneal lymphadenopathy (two cases). CT findings of abdominal malignant small round cell tumor are nonspecific and mimic findings noted in other conditions, such as peritoneal carcinomatosis and leiomyosarcomatosis.

Abdominal Neoplasms↗

Characterization of brain samples in studies of aging, Alzheimer's, and other neurodegenerative diseases.

We review current understanding of the clinical and pathologic information needed for the determination of optimal brain tissue samples for the conduct of studies of Alzheimer's disease (AD). Characteristics that may distinguish AD from other dementing disorders are discussed. Selected considerations in the conduct of basic neurobiological studies are also outlined. Although the 28 NIA-funded Alzheimer's Centers can provide excellent clinical and neuropathological data, studies conducted outside these centers should also strive to gather the information suggested here. Clinical and neuropathological data should be used not only to classify subjects as control or AD, but also as variables that may significantly contribute to the analysis of neurobiological data obtained in the laboratory.

Aging↗

Embryonic ethanol exposure impairs detour learning in chicks.

Six groups of 30 fertile eggs each were injected with 200 microliters of either sterile water or a 37.5% (v/v) ethanol solution immediately before incubation or on days 7 or 14 of incubation. Regardless of day of injection, the ethanol groups had a lower proportion of chicks who completed pipping and hatching. Of the chicks surviving to pip and hatch, the group injected with ethanol immediately before incubation was delayed significantly in pipping compared to the other ethanol-injected groups and to the group injected with water immediately before incubation (p less than 0.05 in all cases). Also, compared to the chicks injected with water, the chicks in all ethanol groups required more trials to attain criterion on a detour learning task when tested 7-10 days after hatching (p less than 0.05).

Animals↗