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Biomedical subjects

J Merritt

Publications and source records attributed to J Merritt.

At least 19 recordsLinked to original sources
PubMed2000

Development and scale-up of a fed-batch process for the production of capsular polysaccharide from Haemophilus influenzae.

The production of the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus influenzae type b is important for the production of effective conjugate vaccines. Factors limiting the production of this polysaccharide from H. influenzae type b in liquid culture were investigated. A fed-batch fermentation was developed that increased cell density and PRP titer approximately four fold when compared to the batch fermentation. This fed-batch process was successfully scaled from the 1.5 l development scale to the 500 l manufacturing scale. The maximum cell density in the 500 l fermentation was 6 g dry cell weight per liter and the PRP concentration was 1.3 g l(-1).

Bacterial Capsules↗
PubMed2000

Gene replacement strategies for treating non-small cell lung cancer.

Fewer than 15% of the 170,000 patients who develop lung cancer each year will survive their disease, which shows the need for novel, more specific, and less toxic therapeutic strategies. Recent advances in molecular biology have made it possible to ascertain which genetic alterations contribute to the etiology of cancer. For example, the tumor-suppressor gene, p53, responsible for directing repair of damaged DNA or committing a cell to apoptosis, is mutated or otherwise altered in more than 50% of cancers, including 40% to 70% of non-small cell lung cancers. Many p53-deficient tumors have proven remarkably resistant to radiotherapy and chemotherapy. The preclinical and clinical studies of gene therapy reviewed in this article show (1) successful transfer and expression of a potentially therapeutic p53 gene construct in tumor cells, (2) observation of antitumor effects in vitro and in vivo, and (3) most critically, a lack of significant toxicity. The results of these studies indicate that gene replacement therapy is a feasible alternative therapy for cancer. In addition, these studies show that transfer of the p53 gene can induce radiation sensitization in previously radiation-resistant tumors, leading to the possibility of new therapeutic protocols combining gene replacement with radiation therapy.

Apoptosis↗
PubMed2000

Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Adenoviruses, Human↗
PubMed2000

Adenoviral-mediated p53 gene transfer to non-small cell lung cancer through endobronchial injection.

OBJECTIVE: The objective was to determine the degree of toxicity and antitumor activity following bronchoscopic injection of an adenoviral-mediated p53 gene (Adp53) into tumors causing airway obstruction. DOSING: This was a subset analysis of a phase I dose escalation trial. SETTING: Patients were treated in the outpatient clinics at the University of Texas (MD Anderson Cancer Center, Houston, TX) and at Medical City Dallas Hospital (US Oncology, Dallas, TX). PATIENTS: Twelve patients (median age, 60 years) with advanced endobronchial non-small cell lung cancer (NSCLC) (squamous cell carcinoma, six patients; adenocarcinoma, six patients) were entered into trial. The median tumor area was 5 x 3.2 cm. All patient tumors contained a p53 gene mutation. INTERVENTIONS: Adp53 (dose range, 1 x 10(6) to 1 x 10(11) plaque-forming units) was administered by bronchoscopic intratumoral injection once every 28 days. MEASUREMENTS AND RESULTS: Toxicity attributed to the Adp53 vector was minimal. Six of the 12 patients had significant improvement in airway obstruction, and 3 patients met the criteria for partial response. CONCLUSIONS: Direct bronchoscopic injection of Adp53 into endobronchial NSCLC is safe, with acceptable levels of toxicity. The initial clinical results demonstrating relief of airway obstruction warrant further clinical investigation.

Adenoviruses, Human↗
PubMed1999

Culture-positive Bartonella quintana endocarditis.

A 50-year-old alcoholic man with a 1-year history of pyrexia of unknown origin was admitted with symptoms of endocarditis. Large vegetations on his mitral and aortic valve were found on echocardiography. Using the Bactec 9240 system. Bartonella quintana could be grown from two culture sets of blood collected before the start of antimicrobial therapy. This is the first case report of culture-proven bartonella infection in the UK. and is noteworthy because Bartonella quintana was detected in conventional blood culture systems after prolonged incubation.

Bacteremia↗
PubMed1999

Cell phones and cancer: what is the evidence for a connection?

There have been allegations in the media and in the courts that cell phones and other types of hand-held transceivers are a cause of cancer. There have also been numerous public objections to the siting of TV, radio and cell phone transmission facilities because of a fear of cancer induction. A recent publication in Radiation Research by Repacholi et al. (147, 631-640, 1997) which suggests that exposure to radiofrequency (RF) radiation may increase lymphoma incidence in mice has contributed to this controversy. The goal of this review is to provide biomedical researchers a brief overview of the existing RF radiation-cancer studies. This article begins with a brief review of the physics and technology of cell phones. It then reviews the existing epidemiological studies of RF radiation, identifying gaps in our knowledge. Finally, the review discusses the cytogenetics literature on RF radiation and the whole-animal RF-radiation carcinogenesis studies. The epidemiological evidence for an association between RF radiation and cancer is found to be weak and inconsistent, the laboratory studies generally do not suggest that cell phone RF radiation has genotoxic or epigenetic activity, and a cell phone RF radiation-cancer connection is found to be physically implausible. Overall, the existing evidence for a causal relationship between RF radiation from cell phones and cancer is found to be weak to nonexistent.

Animals↗
PubMed1998

Sialomucin complex at the rat ocular surface: a new model for ocular surface protection.

The ocular surface, which is among the most accessible and vulnerable tissues in mammals, is protected by a complex tear film composed of lipid, aqueous and mucin layers. In spite of its importance, the molecular nature of the mucin contribution remains uncertain. Since membrane mucins have been implicated in the protection of other epithelia, we have analysed rat corneal and conjunctival tissues for sialomucin complex (SMC), a membrane mucin found at the apical epithelial cell surfaces in the airway and uterus. Using Northern and Western blot analyses, SMC expression was found in both ocular tissues, being particularly abundant in the cornea. In contrast with the other known membrane mucin, MUC1, SMC was localized more heavily towards the apical surface of the epithelial cells. SMC in ocular surface epithelia was produced in both soluble and membrane forms, the latter being found predominantly in the most superficial cells and at apical surfaces. The soluble form was found loosely adsorbed to apical cell surfaces, particularly of the cornea, as indicated by a mild rinsing protocol. Finally, the tear fluid contained substantial amounts of SMC. From these results, we propose a new model for tear mucin components in which SMC is expressed at the apical ocular surface in both membrane-bound and adsorbed soluble forms to provide a direct protective barrier. SMC secreted into the tear fluid may also participate in maintaining the stability of the preocular tear film by acting with other secreted mucins to determine the physical properties and protective behaviour of the tear film.

Amino Acid Sequence↗
PubMed1997

Validating the packaging process using factorial designs.

The development of an effective process requires a comprehensive understanding of two factors: the variables that can affect the process and the ability of the process to control those variables. This article examines the application of factorial designs in the qualification and validation of packaging systems. Using a case study to illustrate the concept, it describes a three-step approach that allows a reduction in the quantity of sampling compared with other experimental methods.

Equipment and Supplies↗
PubMed1996

Comparison between serum-free and fibroblast-cocultured single-cell clonal culture systems: evidence showing that epithelial anti-apoptotic activity is present in 3T3 fibroblast-conditioned media.

PURPOSE: To compare the supporting mechanism between the serum-free and the fibroblast-cocultured single-cell clonal culture systems. METHODS: Clonal growth, measured by colony forming efficiency (CFE) and size, was compared between rabbit corneal and limbal epithelial cells in a previously-established serum-free MCDB medium supplemented with growth factors, and in a coculture system with a feeder layer of mitomycin C-treated mouse 3T3 fibroblasts grown in the MCDB or DMEM medium plus 20% fetal bovine serum (FBS). RESULTS: Limbal epithelial cells in the serum-free MCDB medium had a significantly lower CFE than corneal epithelial cells (p < 0.001), suggesting that this system promoted more clonal growth of corneal progenitor cells. In contrast, with cocultured 3T3 fibroblasts limbal CFE was significantly increased (p < 0.001), while corneal CFE was not changed, indicating that the 3T3 system promoted more clonal growth of limbal progenitor cells. Addition of 20% FBS in the MCDB medium cocultured with 3T3 fibroblasts significantly promoted both limbal and corneal CFEs (p < 0.001). For both cultures, switching the serum-containing MCDB medium to the serum-containing DMEM medium produced clonal growth only with cocultured fibroblasts. This epithelial growth-promoting activity was not present on the cell surface or in the extracellular matrix, but present in pre-centrifuged and prefiltered 3T3 fibroblast-conditioned media. Both growth-promoting and anti-apoptotic activities were present in fibroblast-derived serum-free conditioned media. In the presence of this anti-apoptotic activity, serum addition promoted clonal growth, and the expression of cornea-type K3 keratin in limbal colonies was negative using AE-5 monoclonal antibody. CONCLUSIONS: Further purification and characterization of this fibroblast-derived anti-apoptotic survival factor will facilitate understanding of the mechanism by which epithelial stem cells are regulated via epithelial-mesenchymal interactions.

3T3 Cells↗
PubMed1996

Physician glut. Physicians--the next victims of "downsizing?".

Should physicians really be polishing up their CVs or preparing to enter another line of work? In a word: No. What a recent survey makes clear is that, while managed care is driving physicians from some markets, jobs are still available in other markets traditionally underserved by physicians. This is not to suggest that the physician employment market has gone unchanged. Many physicians, particularly specialists, have taken income hits, and some specialists truly are in need of work. Primary care physicians, however, have seen their stars rise and are now in a position to work wherever they want. Physicians may no longer be able to practice within 50 miles of where they were raised or where they were trained, as has been their wont. Instead, they will have to do what other professionals have long done--go where job opportunities take them. In short, they will have to add a career strategy to their scientific mindset, and that means an aggressive job search, coupled with a strong consumer orientation.

Consumer Behavior↗