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Biomedical subjects

M E Healy

Publications and source records attributed to M E Healy.

14 recordsLinked to original sources
PubMed2000

Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571.

Small cell lung cancer (SCLC) is an aggressive cancer characterized by several autocrine growth mechanisms including stem cell factor and its receptor c-Kit. In order to arrive at potentially new and novel therapy for SCLC, we have investigated the effects of the tyrosine kinase inhibitor, STI 571, on SCLC cell lines. It has been previously reported that STI 571 does not only inhibit cellular Abl tyrosine kinase activity but also the PDGF receptor and c-Kit tyrosine kinases at similar concentrations (approximately 0.1 microM). There is no expression of the PDGF-receptor, and the Abl kinase is not activated by SCLC, but over 70% of SCLC contain the c-Kit receptor. Utilizing this preliminary data, we have determined that three (NCI-H69, NCI-H146 and NCI-H209) of five (including NCI-H82 and NCI-H249) SCLC cell lines had detectable c-Kit receptors and were inhibited in growth and viability at concentrations 1 - 5 microM of STI 571 after 48 h of treatment. The SCLC cell lines, NCI-H69, NCI-H146 and NCI-H209, showed a dose-response (tested between 0.1 - 10 microM) inhibition of tyrosine phosphorylation of c-Kit as well as in vitro kinase activity (at 5 microM) of c-Kit in response to STI 571. STI 571 inhibited cell motility, as assessed by time-lapsed video microscopy, within 6 h of STI 571 treatment (5 microM). STI 571 also decreased intracellular levels of reactive oxygen species (ROS) by at least 60%, at a concentration (5 microM) that also inhibited cell growth. Cell cycle analysis of STI 571 responsive cells showed that cells were generally slowed in G2/M phase, but there was no arrest at G1/S. A downstream phosphorylation target of c-Kit, Akt, was not phosphorylated in response to stem cell factor in the presence of STI 571. These data imply that STI 571 inhibits growth of SCLC cells through a mechanism that involves inactivation of the tyrosine kinase c-Kit. The effectiveness of STI 571 in this study suggests this drug may be useful in a clinical trial, for patients with SCLC. Oncogene (2000) 19, 3521 - 3528

Animals↗
PubMed1988

MR imaging of brain contusions: a comparative study with CT.

Ninety-eight brain contusions in 17 patients served as a data base for a comparative study of MR and CT for defining brain contusions. MR was the more sensitive technique, detecting 98% of the brain contusions compared with only 56% by CT. CT was slightly better for showing hemorrhagic components, documenting 77% of hemorrhages compared with 71% for MR. The appearance of the contusions on MR was variable, depending on the T1- and T2-weighting of the images and the constituents of the contusions, such as edema, hemorrhage, and encephalomalacia. On MR, hemorrhagic components appeared as high signal on T1-weighted images and as either low or high signal on T2-weighted images, depending on the age of the hemorrhage. The approximate ages of hemorrhagic contusions were often suggested by their appearance on T1- and T2-weighted images. CT is very effective for evaluating acute head trauma, but MR is recommended for documenting brain contusions during the subacute and chronic stages of head injuries.

Adolescent↗
PubMed1987

Increased detection of intracranial metastases with intravenous Gd-DTPA.

Three patients with intracranial metastases were studied with magnetic resonance imaging at 1.5 T before and after intravenous administration of 0.1 mmol/kg gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). Axial pre- and postcontrast images demonstrated a total of six and 38 metastases, respectively. Of the 35 lesions detected only after administration of contrast material, all were less than 10 mm, and none had evidence of surrounding edema. Lesion conspicuity was comparable on postcontrast mixed (T1, proton density, and T2) images and T1-weighted images, indicating the feasibility of effectively screening for metastases with a single postcontrast spin-echo sequence providing mixed and T2-weighted images. Sagittal and coronal images depicted temporal lobe lesions not seen on axial images. No discomfort, side effects, or complications resulted from the contrast medium. The detection of additional lesions with Gd-DTPA increased the radiologic suspicion of metastatic disease, revealed locations more favorable for biopsy, prompted the search for a primary tumor, and modified therapeutic objectives and methods.

Adult↗
PubMed1987

Demonstration by magnetic resonance of symptomatic spinal epidural lipomatosis.

In patients with Cushing's syndrome or morbid obesity, excessive accumulation of fat in the hips, upper back, abdomen, and mediastinum is well known (1, 3, 7). Excessive deposition of fat in the epidural space is less common, but must be recognized as a potential cause of neurological deficit (1-8). We report a patient with iatrogenic Cushing's syndrome, in whom magnetic resonance imaging (MRI) established the specific diagnosis of spinal cord compression secondary to excess epidural fat.

Adult↗
PubMed1986

Magnetic resonance imaging of hemorrhagic cerebral infarction.

A comparative study between magnetic resonance (MR) and computed tomography (CT) showed MR to be more sensitive than CT for detecting subacute and chronic hemorrhage into cerebral infarction. The hemorrhage appeared as either high signal on T1 weighted images or low signal on T2 weighted images, depending on the age of the hemorrhage. Cortical hemorrhagic infarction showed a characteristic gyral pattern. Methemoglobin and hemosiderin served as markers of previous hemorrhage into cerebral infarcts.

Adolescent↗
PubMed1986

Paramagnetic enhancement of cerebral lesions with gadolinium-DTPA.

Magnetic resonance imaging (MRI) was performed on 30 patients with cerebral symptoms before and after intravenous gadolinium-DTPA (Gd-DTPA) administration. T1 and T2 weighted images were obtained in all patients. Fifty abnormalities were found in 27 patients. The post-contrast images revealed lesions not seen on pre-contrast scans in 6 patients. Also, the post-contrast images showed a change in morphology of the lesions in 15 that provided additional information for assessing the abnormality. The Gd-DTPA did not obscure any of the lesions seen on pre-contrast scans. Gd-DTPA improves conspicuity, helps characterize and delineate the extent of lesions and increases the sensitivity for detection of cerebral abnormalities.

Adult↗
PubMed1984

Uriniferous pseudocyst: computed tomographic findings.

The computed tomographic (CT) scans of nine consecutive patients with proved uriniferous pseudocyst (UP) were analyzed retrospectively. Analysis disclosed perirenal space tumefaction in seven patients, tumefaction outside the perirenal space in two patients, cystlike uniformity of attenuation (with specific exceptions) in all nine patients, contrast medium-opacified urine extravasating into the UP in three patients, contrast material within the dependent portion of the UP in one patient, anterior and superior displacement of the kidney in seven patients, hydronephrosis in all nine patients, and associated findings suggesting the underlying cause of UP in five patients. Although these CT findings appear to be quite specific, consideration of this uncommon entity in the CT differential diagnosis requires knowledge of its reported causes, the patient's medical history, and the clinical presentation.

Aged↗
PubMed1977

Diagnostic medium containing inositol, urea, and caffeic acid for selective growth of Cryptococcus neoformans.

An agar medium containing inositol and urea as sole carbon and nitrogen sources, caffeic acid and ferric citrate as agents for the selective pigmentation of Cryptococcus neoformans, gentamicin as a broad-spectrum bacterial antibiotic, and yeast nitrogen base without amino acids and ammonium sulfate (Difco) was tested against 137 clinical isolates, 4 survey specimens, and 11 ATCC yeast and yeast-like strains. All 28 strains of C. neoformans showed heavy growth and dark brown pigmentation after 36 h. All other tested species of Cryptococcus showed heavy growth after 36 h but only light brown pigmentation after 48 h. No growth was observed in any tested strains of Geotrichum, Pityrosporum, Rhodotorula, Saccharomyces, and Torulopsis. Only the Cryptococcus-like Candida humicola grew of the 8 species and 62 strains of Candida tested. Six of 15 strains of Trichosporon cutaneum and 1 of 2 strains of Trichosporon pullulans showed moderate growth after 48 h. Very different colonial and microscopic morphology and/or the absence of brown pigmentation easily differentiated these strains of T. cutaneum, T. pullulans, and C. humicola from C. neoformans. The growth- and pigmentation-providing characteristics of the medium were unaffected by 2 h of exposure to 254 nm of ultraviolet light.

Agar↗
PubMedDate not supplied

Benefits of Gd-DTPA for MR imaging of intracranial abnormalities.

Forty patients with symptoms of intracranial disease were studied with magnetic resonance before and after intravenous injection of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). The T1- and T2-weighted images were obtained in all patients. Ninety brain lesions were found in 36 patients, including primary (20 patients) and metastatic (six) tumors, hemorrhage (one), progressive multifocal leukoencephalopathy (one), cysticercosis (one), infarction (four), and postoperative changes (four). Postcontrast images revealed lesions not seen on precontrast scans in eight (20%) patients. Also, the postcontrast images showed a change in appearance of the lesions in 20 (50%) that provided helpful information for assessing the abnormality in 20 cases (50%). Gadolinium-DTPA did not obscure any of the lesions seen on precontrast scans. It improved conspicuity, helped characterize and delineate the extent of lesions, and increased the sensitivity for detection of cerebral abnormalities.

Adult↗
PubMedDate not supplied

MR demonstration of reversible brain abnormalities in eclampsia.

A 24-year-old woman with eclamptic convulsions during her 25th week of gestation is presented. Magnetic resonance imaging revealed multiple hyperintense foci within the cerebral cortex, most likely related to cerebral ischemia and edema. The MR abnormalities resolved completely within 1 week.

Adult↗
PubMedDate not supplied

Brain magnetic resonance imaging in the evaluation of lacunar stroke.

Thirty-one patients with presumed lacunar stroke, recent (18 patients) or remote (13 patients), were evaluated with brain magnetic resonance imaging (MRI). MRI detected small, deep lesions appropriate to symptoms in 23 of the patients (74%) and was diagnostically superior to brain computed tomography (CT) in those cases where both studies were obtained acutely. MRI also appeared useful in distinguishing between acute and chronic ischemic lesions. Especially in the setting of suspected acute lacunar infarction, MRI, when available, should replace CT as the diagnostic imaging procedure of choice.

Aged↗
PubMedDate not supplied

Primary intracranial CNS lymphoma: MR manifestations.

We reviewed MR scans of 10 patients with biopsy-proved primary CNS lymphoma. Twenty-five lesions were identified in 10 patients (four with AIDS and six without AIDS). In general, the typical lesion of CNS lymphoma was found to have the following MR characteristics: they were slightly hypointense on T1-weighted images and slightly hyperintense on proton density and T2-weighted images relative to gray matter; they induced mild edema and mild to moderate mass effect. In AIDS patients, 82% of the lesions were smaller than 2 cm in diameter, and were frequently located in the temporal lobes and basal ganglia; they were often multiple. In non-AIDS patients, 75% of the lesions were larger than 2 cm in diameter and were primarily found in the deep parietal lobe; most were solitary.

Acquired Immunodeficiency Syndrome↗