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M T Brown

Publications and source records attributed to M T Brown.

At least 37 records · Page 2Linked to original sources
PubMed1998

Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results.

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.

Adolescent↗
PubMed1998

Locally increased uptake of fluorine-18-fluorodeoxyglucose after intracavitary administration of iodine-131-labeled antibody for primary brain tumors.

UNLABELLED: After the intracavitary administration of 131I-labeled monoclonal antibody for treatment of primary brain tumors after surgical resection, a persistent rim of 18F-fluorodeoxyglucose (FDG) accumulation surrounding the cavity can be observed on PET. This rim, although it accumulates more FDG than adjacent normal brain tissue, is not necessarily associated with tumor. In our study, we examine the characteristics of the rim that indicate persistent tumor and tumor progression. METHODS: Sequential PET studies obtained after treatment in 10 patients were reviewed and the results correlated with dosimetry and post-treatment histologic diagnoses. RESULTS: The rim of FDG accumulation was seen on the first post-treatment scan obtained 1-3 mo after therapy and persisted unchanged over the 2-26 mo follow-up period. Pathologically, the nonmalignant rim was associated with marked increase of macrophage infiltrates. Nodularity of the rim was associated with tumor. CONCLUSION: Our study demonstrates that a rim of FDG accumulation is seen after intracavitary administration of 131I-labeled monoclonal antibody therapy independent of the presence of malignant disease. Malignant recurrence is suggested by the development of new nodularity in the rim of FDG accumulation.

Adolescent↗
PubMed1997

Overcoming the learning curve in microvascular head and neck reconstruction.

BACKGROUND: It is widely accepted that most microvascular reconstructive surgeons experience a learning curve. A compilation of 6 series of microvascular surgery reported in the literature revealed that the average rate of successful free flap transfer rose from 79% to 96% as the surgeons gained clinical experience. OBJECTIVE: To review the collective experience of 3 otolaryngologist-head and neck surgeons performing free flaps during their first year of clinical practice after completion of postgraduate training. DESIGN: A multi-institutional retrospective case series. SETTING: Three academic tertiary care otolaryngology-head and neck surgery programs. PATIENTS: Eighty-one microvascular free flaps were performed in patients undergoing surgical reconstruction of head and neck defects during a 1-year period. INTERVENTIONS: Free flap selection was based on specific defect characteristics. Radial forearm, fibula, and rectus abdominis flaps together accounted for 90% of the donor sites selected. MAIN OUTCOME MEASURE: Reported incidence of partial or complete free flap necrosis. RESULTS: There were 2 perioperative deaths. Among the surviving patients, there were 2 cases of complete flap failure, for an overall success rate of 97.5%. There were 2 additional cases of partial flap necrosis (2.5%) that were related to errors in flap insetting. CONCLUSION: The availability of high-quality postgraduate training combined with the judicious selection of free flaps that offer long vascular pedicles and large diameter vessels can allow junior microvascular head and neck surgeons to achieve free flap survival rates that are comparable with those reported by experienced microvascular surgeons.

Clinical Competence↗
PubMed1996

Different modes of inhibition of human adenovirus proteinase, probably a cysteine proteinase, by bovine pancreatic trypsin inhibitor.

The type of proteinase and the nature of the active site of the human adenovirus proteinase are unknown. For these reasons we produced an inhibitor profile of the enzyme. Enzyme activity in disrupted virions was inhibited by several serine-specific as well as cysteine-specific proteinase inhibitors. Of the inhibitors that worked, the most useful potentially in illuminating the nature of the active site was bovine pancreatic trypsin inhibitor (BPTI), and for this reason we extensively characterized the interaction with BPTI. In disrupted virions, the enzyme is irreversibly inhibited by BPTI with a Ki of 35 nM and a ki of 6.2 x 10(-4) s(-1). One reason enzyme activity is inhibited is that BPTI, a basic protein, precipitates the viral DNA, a cofactor of enzyme activity. In vitro with purified components, BPTI acts as a competitive inhibitor (Ki 2 microM) of the recombinant proteinase complexed with its 11-amino-acid cofactor pVIc. The recombinant endoproteinase is beat labile whereas its 11-amino-acid cofactor is heat stable. We estimate there are about 50 molecules of proteinase per virus particle.

Adenoviruses, Human↗
PubMed1996

Regulation, substrates and functions of src.

Src is the best understood member of a family of 9 tyrosine kinases that regulates cellular responses to extracellular stimuli. Activated mutants of Src are oncogenic. Using Src as an example, and referring to other Src family members where appropriate, this review describes the structure of Src, the functions of the individual domains, the regulation of Src kinase activity in the cell, the selection of substrates, and the biological functions of Src. The review concentrates on developments in the last 6-7 years, and cites data resulting from the isolation and characterization of Src mutants, crystallographic studies of the structures of SH2, SH3 and tyrosine kinase domains, biochemical studies of Src kinase activity and binding properties, and the biology of transgenic and knockout mouse strains.

Amino Acid Sequence↗
PubMed1996

Characterization of human adenovirus proteinase activity in disrupted virus particles.

Virus-coded proteinases are attractive targets for antiviral therapy; however, lack of quick, sensitive, quantitative, and selective assays for enzyme activity makes it difficult to characterize these proteinases and to screen large numbers of potential inhibitors. Here we describe new substrates for the adenovirus proteinase, fluorogenic Rhodamine-based substrates containing tetrapeptides corresponding to sequences cleaved in adenovirus precursor proteins. Proteinase activity in as few as 10(9) disrupted virions could be quantitatively detected in a 30-min assay. With the substrate (Leu-Arg-Gly-Gly-NH)2-Rhodamine, the Km was 1.4 microM and the Vmax was 3.24 pmol substrate hydrolyzed/sec/pmol virus. Enzyme activity was stimulated by dithiothreitol and inhibited by several serine-specific as well as cysteine-specific proteinase inhibitors. In a thiol protection experiment, the virion enzyme was shown to have a cysteine residue with an unusually low pKa, a pKa similar to that of the active-site nucleophile of the cysteine proteinase papain. The curve of Vmax as a function of pH is unlike the curve from papain and implied that there are at least three ionizable groups whose protonation state can affect catalysis - one with a pKa of 6.2, another with a pKa of 7.2, and a third with a pKa of 8.3.

2,2'-Dipyridyl↗
PubMed1996

Characterization of three components of human adenovirus proteinase activity in vitro.

Human adenovirus contains a virion-associated proteinase activity essential for the development of infectious virus. Maximal proteinase activity in vitro had been shown to require three viral components: the L3 23-kDa protein, an 11-amino acid cofactor (pVIc), and the viral DNA. Here, we present a quantitative purification procedure for a recombinant L3 23-kDa protein (recombinant endoproteinase (rEP)) expressed in Escherichia coli and the procedure that led to the purification and identification of pVIc as a cofactor. The cofactors stimulate proteinase activity not by decreasing Km, which changes by no more than 2-fold, but by increasing kcat. rEP alone had a small amount of activity, the kcat of which increased 355-fold with pVIc and 6072-fold with adenovirus serotype 2 (Ad2) DNA as well. Curves of Vmax of rEP.pVIc complexes with the substrate (Leu-Arg-Gly-NH)2-rhodamine as a function of pH in the absence and presence of Ad2 DNA indicate that the pKa values of amino acids that affect catalysis are quite different from those that affect catalysis by the cysteine proteinase papain. The pKa values in the absence of Ad2 DNA are 5.2, 6.4, 6.9, 7.5, and 9.4, and those in its presence are 5.2, 6.5, 7.4, and 8.8.

Adenoviruses, Human↗
PubMed1996

Assessment of functional morbidity in the radial forearm free flap donor site.

OBJECTIVE: To quantitate the functional morbidity to the hand and wrist due to the harvest of a radial forearm free fasciocutaneous flap. DESIGN: Case-control study with age-matched control groups. SETTING: Tertiary care hospital. PATIENTS: A consecutive sample of 21 patients who underwent a radial forearm free flap reconstruction of the head and neck from June 1993 to February 1995 constitute the experimental group. Thirteen of those eligible patients participated in the study. Two control groups were identified. One cohort included 13 patients with head and neck cancer who underwent free tissue transfer other than the radial forearm flap. The other cohort consisted of 16 subjects who were healthy volunteers, patients without cancer, or patients who were considered to be cured of cancer. OUTCOME-MEASURES: Wrist range of motion, grip strength, and sensation in the radial, ulnar, and median nerve distributions on the hands, bilaterally. RESULTS: No significant differences (P > .05) were detected between the groups for the modalities that were tested. CONCLUSION: There is minimal functional morbidity associated with the harvest of the radial forearm free fasciocutaneous flap.

Adult↗
PubMed1996

The dilemma of factitious demographic distinctions in psychological research.

Terms such as race, sex and age are assumed to reflect biological characteristics and distinctions. In psychological research, these terms are often treated as if they were a reflection of a meaningful set of psychological constructs. A review of articles in 3 prominent journals over a 30-year period reveals that these supposed biological identifiers are not used consistently and lack empirical and conceptual validity. An analysis of those articles shows that, over time, the term race has given way to the use of the more general and psychologically relevant term ethnicity, sex and gender have been used interchangeably, and the psychological constructs underlying or supposedly reflected in age are seldom discussed. It is proposed that psychosocial researchers and editors adopt a consistent definition of these terms and that research include an effort to identify the underlying concepts that the investigators assume to be reflected in these distinctions whenever these labels are used to report research findings.

Clinical Trials as Topic↗
PubMed1996

Microbiology of tracheal granulation tissue associated with silicone airway prostheses.

Granulation tissue formation and contraction is inevitable during the healing of open wounds. The presence of infection and a foreign body, such as a silicone airway prosthesis or other tracheotomy tube, magnifies this response. In airway reconstruction, wound contraction secondary to chronic inflammation is a liability. Cultures of granulation tissue were taken from 12 patients with silicone cannulas of T-Tubes. Polymicrobial colonization predominated, with variable combinations of gram-positive, gram-negative, and anaerobic organisms being present. On the basis of sensitivity data, amoxicillin-clavulanate potassium and ciprofloxacin hydrochloride were chosen as empirical antimicrobials. Anecdotally, impressive decreases in the quantity of granulation tissue were seen. We recommend a prospective trial to more accurately define the role of antibiotics in this setting.

Adult↗
PubMed1996

The use of the temporoparietal fascial flap in temporal bone reconstruction.

After routine canal wall down mastoidectomy, local muscle flaps with and without bone paté, cartilage and fascia are the standard techniques available to otologists wishing to obliterate the mastoid and reconstruct the external auditory canal. Reconstructive options for temporal bone defects after extirpative surgery for cancer, osteoradionecrosis, and revision surgery for chronic granulomatous otitis media, however, are few. Although the neighboring temporoparietal fascia flap (TPFF), based on the superficial temporal vessels, has been frequently employed for auricular reconstruction, its versatility in temporal bone reconstruction has not been widely explored. The TPFF has recently been employed at our institution in 11 patients who presented with a variety of reconstructive problems, including defects after temporal bone resection, surgery for malignant otitis externa, and revision mastoid surgery. Follow-up in these patients ranged from 1 to 43 months (average 18.4 months) and surgical objectives of achieving a dry mastoid bowl, fully epithelialized canal, and/or reduction of mastoid cavity volume was attained in 100% of cases. The TPFF offers many advantages to the otologic surgeon when faced with reconstruction dilemmas that center around a poorly vascularized mastoid cavity and temporal bone. The TPFF is a reliable source of local well-vascularized tissue that is extremely pliable and facilitates both hearing and nonhearing preservation temporal bone reconstruction.

Adult↗
PubMed1996

Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results.

We aimed to determine the maximum tolerated dose (MTD) of 131I-labeled 81C6 in patients with leptomeningeal neoplasms or brain tumor resection cavities with subarachnoid communication and to identify any objective responses. 81C6 is a murine IgG monoclonal antibody that reacts with tenascin in gliomas/carcinomas but does not react with normal adult brain. 131I-labeled 81C6 delivers intrathecal (IT) radiation to these neoplasms. This study was a Phase I trial in which patients were treated with a single IT dose of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating doses of 131I (starting dose, 40 mCi; 20 mCi escalations) on 10 mg 81C6. MTD is defined as the highest dose resulting in serious toxicity in no more than two of six patients. Serious toxicity is defined as grade III/IV nonhematological toxicity or major hematological toxicity. We treated 31 patients (8 pediatric and 23 adult). Eighteen had glioblastoma multiforme. Patients were treated with 131I doses from 40 to 100 mCi. Hematological toxicity was dose limiting and correlated with the administered 131I dose. No grade III/IV nonhematological toxicities were encountered. A partial response occurred in 1 patient and disease stabilization occurred in 13 (42%) of 31 patients. Twelve patients are alive (median follow-up, > 320 days); five are progression free >409 days median posttreatment. The MTD of a single IT administration of 131I-labeled 81C6 in adults is 80 mCi 131I-labeled 81C6. The MTD in pediatric patients was not reached at 131I doses up to 40 mCi normalized for body surface area.

Adolescent↗
PubMed1995

Sequence similarities between the yeast chromosome segregation protein Mif2 and the mammalian centromere protein CENP-C.

A short stretch of strong homology between the Saccharomyces cerevisiae chromosome segregation protein Mif2 and the DNA-binding motifs of the Drosophila D1 and mammalian HMGI(Y) chromosomal proteins suggested that Mif2 may act directly on chromosomes. Because this conserved motif is involved in binding A.T DNA, it was proposed that Mif2 may interact with chromosomes at the highly A + T-rich DNA element found in yeast centromeres. Comparison of the Mif2 amino-acid sequence with sequence databases showed that Mif2 shares at least two regions of similarity with the mammalian centromere protein CENP-C, suggesting an evolutionary conservation of centromere protein function from yeast to mammals. The order, spacing and location of these regions are also similar in the two proteins. Sequence analysis of several conditional lethal alleles of MIF2 generated by random mutagenesis revealed mutations in regions homologous to CENP-C, as well as in the highly conserved A.T DNA-binding motif. A potential phosphorylation site for p34cdc2 kinase located adjacent to the A.T DNA-binding motif was also found to be mutated in one of the mutants, suggesting that phosphorylation at this site may be important for Mif2 function and possibly for DNA binding.

Amino Acid Sequence↗
PubMed1995

Primary central nervous system lymphoma with systemic metastasis: case report and review.

Primary central nervous system lymphoma (PCNSL) almost always remains confined to the nervous system. We report a patient with well documented PCNSL who responded to treatment, but subsequently developed pathologically confirmed systemic metastases without repeated local failure 35 months after initial diagnosis. In a review of the world's literature we identified 5 other cases of PCNSL with histologically confirmed antemortem systemic metastases and a total of 62 cases of central nervous system (CNS) lymphoma in some way associated with extraneural lymphoma. These cases are classified and discussed. Clinicians caring for PCNSL patients must remain alert to the possibility of systemic metastasis, especially as local control of PCNSL improves.

Aged↗
PubMed1994

Prognostic profile in rectal cancer.

PURPOSE: The purpose of this article was to review the prognostic factors of significance in rectal cancer. METHODS: This is a retrospective review of various reports and an examination of our data. RESULTS: Current imaging techniques with endorectal ultrasound, magnetic resonance imaging with a rectal probe, and possibly tagged monoclonal antibodies allow for presurgical assessment of the invasion of the rectal wall and detection of lymph node involvement. CONCLUSIONS: Tumor penetration of the rectal wall and lymph node metastases are the most important prognostic indicators in rectal cancer and predict local and distant recurrences. When lymph node metastases occur, they are more common in small lymph nodes (< 5 mm). Patients with lymph node metastases always need to be considered for multimodality therapy. Tumors larger than or equal to T3 or with associated lymph node metastases should not be treated with sphincter-saving surgical procedures alone.

Biomarkers, Tumor↗