Search PubMed⌕ Search

Biomedical subjects

M T Brown

Publications and source records attributed to M T Brown.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: short-duration response and multifocal intracerebral recurrence preceding radiotherapy.

The activity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of primary central nervous system lymphoma (PCNSL) prior to radiotherapy was studied in six patients. Primary lesions were reduced by 80% or more on contrast-enhancing cross-sectional area in four patients and to a lesser extent in two others after two cycles of chemotherapy. The primary lesion sites demonstrated no contrast enhancement in the three patients who completed four cycles of therapy. However, concurrent with response at the primary disease sites, multiple lesions occurred at distant, noncontiguous CNS parenchymal sites in five patients after two to four cycles of chemotherapy. Median survival was 8.5 months for the six enrolled patients and 16.5 months for the four patients completing craniospinal radiotherapy. PCNSL is highly responsive to standard systemic non-Hodgkin's lymphoma chemotherapy regimens, but the pattern and rapidity of relapse suggest mechanisms of failure including inherent or rapidly evolving antineoplastic drug resistance and perhaps limited drug delivery to occult sites of disease in the brain.

Aged↗
PubMed1993

Chemotherapy for pilocytic astrocytomas.

BACKGROUND: Although pilocytic astrocytomas (PA) generally are considered benign, a subset of patients with PA have disease progression despite standard treatment with surgery and radiation therapy. The authors report their experience with chemotherapy in this patient group. METHODS: The authors treated 11 patients (4 males and 7 females; median age at diagnosis, 8 years) with pathologically confirmed PA with chemotherapy. In eight patients, tumor progression or recurrence despite prior surgery and radiation therapy led to chemotherapy treatment. In three children younger than 5 years, chemotherapy was given in lieu of radiation therapy immediately after diagnosis (in one patient) or at the time of disease progression after surgery (in two patients). The authors used ten different chemotherapy regimens to treat the 11 patients. RESULTS: Chemotherapy produced clinical and radiographic improvement (R/R) in four (36%) patients, clinical stabilization and radiographic improvement (SD/R) in 1 (9%), clinical and radiographic stabilization (SD/SD) in 3 (27%), and was associated with clinical and radiographic progression (PD/PD) in 3 (27%). Three of the five patients with radiographic improvement had a greater than 75% reduction of maximal cross-sectional tumor area. Hematologic toxicity resulted in dose reductions in 43 of 110 (39%) total courses of chemotherapy. There were three hospitals admissions for fever and neutropenia and one chemotherapy-related death. CONCLUSIONS: The authors conclude that chemotherapy may benefit those with progressive inoperable PA. Chemotherapy may delay the need for radiation therapy in young patients with unresectable PA requiring treatment. PA may be a chemosensitive primary brain tumor.

Adolescent↗
PubMed1993

Progressive sensorineural hearing loss in association with distal renal tubular acidosis.

The autosomal recessive inherited syndrome of distal renal tubular acidosis and sensorineural hearing loss may present in one of two distinct fashions. The rare adolescent form is characterized by mild renal tubular acidosis, mild to moderate sensorineural hearing loss, and otherwise normal growth and development. The more common infantile type typically presents in the first year of life with failure to thrive, acidosis, and a more severe sensorineural hearing loss. In this report, progression of sensorineural hearing loss is documented for the first time in two siblings with the infantile variant. This association suggests that all children with distal renal tubular acidosis should undergo sequential audiologic evaluations with the institution of appropriate amplification and educational intervention as needed.

Acidosis, Renal Tubular↗
PubMed1993

MIF2 is required for mitotic spindle integrity during anaphase spindle elongation in Saccharomyces cerevisiae.

The function of the essential MIF2 gene in the Saccharomyces cerevisiae cell cycle was examined by overepressing or creating a deficit of MIF2 gene product. When MIF2 was overexpressed, chromosomes missegregated during mitosis and cells accumulated in the G2 and M phases of the cell cycle. Temperature sensitive mutants isolated by in vitro mutagenesis delayed cell cycle progression when grown at the restrictive temperature, accumulated as large budded cells that had completed DNA replication but not chromosome segregation, and lost viability as they passed through mitosis. Mutant cells also showed increased levels of mitotic chromosome loss, supersensitivity to the microtubule destabilizing drug MBC, and morphologically aberrant spindles. mif2 mutant spindles arrested development immediately before anaphase spindle elongation, and then frequently broke apart into two disconnected short half spindles with misoriented spindle pole bodies. These findings indicate that MIF2 is required for structural integrity of the spindle during anaphase spindle elongation. The deduced Mif2 protein sequence shared no extensive homologies with previously identified proteins but did contain a short region of homology to a motif involved in binding AT rich DNA by the Drosophila D1 and mammalian HMGI chromosomal proteins.

Alleles↗
PubMed1993

Pilocytic astrocytoma: correlation between the initial imaging features and clinical aggressiveness.

OBJECTIVE: Astrocytomas are classified as either fibrillary or pilocytic on the basis of their histologic appearance. The imaging features of the fibrillary astrocytoma correlate closely with the tumor's clinical aggressiveness and are, therefore, useful in predicting prognosis. Correlation between the imaging features and the clinical aggressiveness of the pilocytic astrocytoma, however, is not well established. Accordingly, we compared the initial MR and CT appearances of the lesion with tumor aggressiveness as seen clinically to determine if a correlation exists. MATERIALS AND METHODS: We retrospectively evaluated the initial MR images or CT scans of 32 consecutive patients who had a histologic diagnosis of pilocytic astrocytoma. The lesions were evaluated with regard to location, size, calcification, morphology, and degree of contrast enhancement. These initial imaging features were correlated with the aggressiveness of the tumor as seen clinically. Tumors were classified as aggressive or nonaggressive on the basis of their clinical manifestations. Patients with clinically aggressive lesions had progressive symptoms and radiologic evidence of tumor progression or recurrence within an unusually short period. Patients with clinically nonaggressive lesions had a more indolent course, either improving or remaining stable, on both clinical and radiologic evaluations. In 12 patients, the tumor was classified as aggressive clinically, either progressing or recurring within a median time of 7.5 months (range, 2.5-118 months) from the initial diagnosis. The remaining 20 patients had a clinically nonaggressive course. RESULTS: In our series of patients, lesion size and location were not significantly different between the nonaggressive and aggressive tumors, as noted clinically. Furthermore, the aggressive and nonaggressive tumors were similar with regard to the presence or absence of calcium. Most tumors in both groups showed either moderate or marked enhancement and were multilobular. CONCLUSION: The initial CT and MR features of pilocytic astrocytoma are unreliable for predicting which lesions will behave in a more aggressive manner clinically and have a poor prognosis.

Adolescent↗
PubMed1987

Ultrasound findings in children with cystic fibrosis.

The results of a prospective study using ultrasound to assess abdominal complications in 76 children with proven cystic fibrosis are reported. Fifty-six patients (74%) had normal liver ultrasound scans. The most striking abnormality was an irregular, inferior edge to the liver occurring in 85% of abnormal liver scans and in 70% there was corresponding clinical and biochemical evidence of abnormal liver function. This finding has been only briefly mentioned before. Increased reflectivity in abnormalities of the pancreas and gallbladder is also described.

Adolescent↗
PubMed1986

Platelets contain a peptide inhibitor of endothelial cell replication and growth.

Platelets release specific growth factors that stimulate division of aortic endothelial cells. Acidification or heating to 56 degrees C of platelet extracts is required to detect these factors. Nonheated platelet extracts inhibit endothelial growth. To determine if this inhibitory effect is due to a discrete chemical substance, a crude extract obtained by freezing and thawing human platelets was incubated with an endothelial cell mitogen and found to inhibit the endothelial cell incorporation of [3H]thymidine by greater than 95%. The inhibitor was partially purified by ion-exchange and gel-filtration chromatography. The partially purified material inhibited endothelial cell division as well as DNA synthesis. Inhibition caused by the partially purified material was concentration dependent, reversible, and not due to cytotoxicity. Further purification by heparin-Sepharose chromatography resulted in removal of greater than 95% of the contaminating substances without a loss of inhibitory activity. Physical characterization revealed that heparin-Sepharose-purified factor was heat labile, had a molecular size estimated at 35-40 kDa, and was stable between pH 4.5 and 9.0. Treatment with proteolytic enzymes destroyed all biologic activity, suggesting a peptide composition. These data support the conclusion that platelets contain a potent inhibitor of endothelial replication and growth. Since platelet deposition and release occur after endothelial denudation, release of this platelet-derived growth inhibitor may be an important regulator of reendothelialization that occurs after vessel injury.

Animals↗
PubMed1983

Dialyzable factor in human serum of platelet origin stimulates endothelial cell replication and growth.

Porcine aortic endothelial cells were isolated and maintained in Dulbecco's modified Eagle's medium (DME medium)/10% citrate-treated human plasma. They were stimulated by DME medium/10% human serum to grow from a density of 10,100 +/- 500 per well to a final density of 83,000 +/- 1,800 per well over a 9-day period. On the other hand these cells grew poorly (11% increase) in DME medium/10% human platelet-poor plasma prepared without chelating agents and containing platelet factor 4 at 18 ng/ml by radioimmunoassay. Dialysis of the human serum (M(r) cutoff, 3,500) eliminated all the stimulatory activity. The activity recovered from the dialysate stimulated growth when added to endothelial cultures in conjunction with either dialyzed serum or platelet-poor plasma alone. The dialyzable factor could be obtained directly from platelets; both acetic acid extracts and boiled NaCl extracts stimulated porcine aortic endothelial cell replication. Gel filtration chromatography on Sephadex G-15 showed that the endothelial growth factor had a molecular weight of 700. Partially purified material induced a concentration-dependent stimulation of porcine aortic endothelial cell replication in the presence of DME medium alone; however, simultaneous incubation with platelet-poor plasma resulted in a much greater response. Fibroblast growth factor isolated from bovine brain was found to be mitogenic only in the presence of nondialyzed serum or of the dialyzable factor together with plasma. In the absence of this serum factor, fibroblast growth factor had no effect. We conclude that human serum contains a potent endothelial cell mitogen of platelet origin. Human plasma that is devoid of platelet content does not stimulate endothelial cell growth. This growth factor may be an important stimulant of the endothelial cell response to vascular wall injury.

Blood Platelets↗