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J M Brint

Publications and source records attributed to J M Brint.

7 recordsLinked to original sources
PubMed2001

Detection of simple mutations and polymorphisms in large genomic regions.

We have developed a novel technology that makes it possible to detect simple nucleotide polymorphisms directly within a sample of total genomic DNA. It allows, in a single Southern blot experiment, the determination of sequence identity of genomic regions with a combined length of hundreds of kilobases. This technology does not require PCR amplification of the target DNA regions, but exploits preparative size-fractionation of restriction-digested genomic DNA and a newly discovered property of the mismatch-specific endonuclease CEL I to cleave heteroduplex DNA with a very high specificity and sensitivity. We have used this technique to detect various simple mutations directly in the genomic DNA of isogenic pairs of recombinant Pseudomonas aeruginosa, Escherichia coli and Salmonella isolates. Also, by using a cosmid DNA library and genomic fractions as hybridization probes, we have compared total genomic DNA of two clinical P.aeruginosa clones isolated from the same patient, but exhibiting divergent phenotypes. The mutation scan correctly detected a GA insertion in the quorum-sensing regulator gene rhlR and, in addition, identified a novel intragenomic polymorphism in rrn operons, indicating very high stability of the bacterial genomes under natural non-mutator conditions.

Bacterial Proteins↗
PubMed1998

Geriatric evaluation is a useful adjunct to traditional medical care of the frail older patient.

GEMU evaluation is most helpful in complicated cases where frail elderly patients appear likely to require custodial nursing home care in the near future. The best results and most significant reductions in subsequent mortality have occurred in less ill or more recently debilitated elders with a reasonable chance of returning to modified self-care in the home or in assisted living situations. Adapting these principles in an effective, cost-efficient manner for outpatient care is the focus of the majority of current investigations of CGA/GEM. Unfortunately, this option will not be universally available even after the proper parameters for its use are determined. Furthermore, better geriatric assessment and earlier intervention could logically prevent or forestall the patient's functional decline, dependency, and the need for placement. Toward that goal, the reader is referred to a practical guide to efficient outpatient geriatric assessment for general internists and other primary care providers, published by Dr. D.B. Reuben in 1996. A number of questionnaires and rapid screening techniques are included, which make these assessments less cumbersome and thus feasible in this era of austere Medicare reimbursement. However, when managing the care of outpatients with multiple impediments to independent living or hospitalized patients who are partially dependent upon others and are likely to require nursing home placement at (or shortly after) discharge, careful consideration should be given to referral for formal GEM, even if travel to a metropolitan area is required.

Activities of Daily Living↗
PubMed1995

Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the autoinducer-responsive LuxR-LuxI family.

Mutants of Pseudomonas aeruginosa PAO1 that were deficient in the ability to produce proteases that degrade casein were detected among the survivors of chemical mutagenesis. One such mutant (PDO31) showed reduced production of elastolytic activity, beta-hemolytic activity, and pyocyanin. A 4.3-kb EcoRI fragment from a gene bank of PAO1 that complemented defects in PDO31 was found. Transposon mutagenesis and deletion derivatives of the clone were used in conjunction with complementation tests to determine the physical location of the gene of interest. Nucleotide sequence analysis revealed an open reading frame (rhlR) encoding a putative 27.6-kDa protein (RhlR) with homology to autoinducer-responsive regulators of quorum sensing systems such as LuxR of Vibrio fischeri and LasR of P. aeruginosa. Further sequence analysis downstream of rhlR revealed an independently transcribed gene (rhlI) that encodes a putative 22.2-kDa protein with homology to members of the family of autoinducer synthetases, such as LuxI of V. fischeri and LasI of P. aeruginosa. The rhlRI sequences were also recently reported by others (U.A. Ochsner and J. Reiser, Proc. Natl. Acad. Sci. USA 92: 6424-6428, 1995) as an autoinducer-mediated regulation mechanism for rhamnolipid biosurfactant synthesis in P. aeruginosa PG201. Mutants with defects in rhlR or rhlI were constructed in PAO1 by gene replacement, using clones modified by Tn501 insertion. Compared with the wild type, the rhlR and rhlI mutants both showed defects in the production of elastase, LasA protease, rhamnolipid, and pyocyanin. Transcription from the gene for elastase, as measured with a lasB-cat fusion, demonstrated that production of elastase was subject to cell density-dependent gene activation in PAO1. However, transcription of lasB-cat in the rhlI mutant, which had lost the presumptive autoinducer synthetase (predicted to activate RhlR), showed low basal activity and had lost all cell density-dependent transcription of lasB. Thus, RhlR-RhlI represent the second autoinducer-responsive regulatory mechanism found in P. aeruginosa that controls expression of multiple virulence factor exoproducts, including elastase.

Bacterial Proteins↗
PubMed1994

Appropriate and inappropriate prescribing of narcotics for ambulatory HIV-positive patients.

OBJECTIVE: To assess the appropriateness of narcotic-prescribing practices in an ambulatory clinic for patients infected with HIV. DESIGN, SETTING, AND PATIENTS: The medical records of 220 (190 HIV-positive) patients, seen in a clinic primarily designed for the long-term follow-up of ambulatory HIV-infected patients and located in an inner-city, public teaching hospital, were retrospectively reviewed to determine the prevalence and appropriateness of prescribing Drug Enforcement Administration schedule 2 narcotics. Appropriateness was based on published guidelines for the use of narcotics in the treatment of cancer patients. MEASUREMENTS AND MAIN RESULTS: The prevalence of narcotic use among the HIV-positive patients was 15%. Narcotics were prescribed for 38% of the patients who died, 33% of those with AIDS [Centers for Disease Control and Prevention (CDC) clinical class C], 4% of those with AIDS-related complex (ARC) (CDC clinical class B), and 5% of asymptomatic HIV-positive patients (CDC clinical class A). None of the HIV-negative patients seen in the clinic received narcotics. Narcotics were more likely to be prescribed for patients with AIDS than for patients with ARC (p < 0.001) or for HIV-positive patients (p < 0.001). For the three CDC clinical classes, there was no significant difference among the proportions of patients receiving narcotics inappropriately (p = 0.108). Among the risk groups, intravenous drug abusers were more likely to be prescribed narcotics inappropriately than were men who were homosexual (p < 0.001) or individuals who were heterosexual (p = 0.013); transfusion recipients were also more likely to be prescribed narcotics inappropriately than were homosexual men (p = 0.026) or heterosexual men or women (p = 0.032). Narcotics were more likely to be prescribed for patients with disseminated histoplasmosis (p = 0.022), Pneumocystis carinii pneumonia (p = 0.001), candidal esophagitis (p = 0.020), Kaposi's sarcoma (p < 0.001), or wasted appearance (p = 0.043). Inappropriate prescriptions were more likely to be given to patients with dementia (p = 0.005) or wasted appearance (p = 0.019). CONCLUSIONS: Physicians tend to prescribe narcotics inappropriately to patients known to have previously abused drugs and to those who appear wasted or have dementia. Physicians have a duty to prescribe narcotics appropriately as guided by recognized medical indications and the patients' views concerning their current medical needs.

AIDS-Related Complex↗
PubMed1992

Blastomycotic cranial osteomyelitis.

This is the second case report of a temporal bone osteomyelitis caused by Blastomyces dermatitidis, which presented as a chronic serous otitis media. The presenting serous otitis media was refractory to conventional medical and surgical management and progressed to a temporal bone osteomyelitis prior to diagnosis. B. dermatitidis is a rare fungal pathogen that causes a systemic pyogranulomatous disease that primarily manifests itself in the skin, bones, pulmonary, and genitourinary systems. If left untreated it is associated with a high rate of mortality. The otologic presentation of this rare disease is emphasized, while the clinical and therapeutic features are reviewed.

Adult↗