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Biomedical subjects

R A Lewis

Publications and source records attributed to R A Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1997

Studies of the repressor (BlaI) of beta-lactamase synthesis in Staphylococcus aureus.

Purified BlaI, the putative repressor of the beta-lactamase operon in Staphylococcus aureus, binds specifically to two regions of dyad symmetry (operators) located in the blaZ-blaR1 intergenic region. BlaI binds with similar affinity to the two regions and to the related sequence upstream of the mec gene found in methicillin-resistant strains of S. aureus, providing physical evidence for the cross-talk previously observed between these systems. A change from a lysine in the N-terminus of BlaI to an alanine or deletion of the C-terminal 23 amino acids severely reduces its DNA-binding ability, demonstrating the functional importance of both the N- and C-termini. An operator DNA-protein complex observed with crude cell lysates from repressed cells, indistinguishable from that observed with purified BlaI, was eliminated by induction of the beta-lactamase operon. Furthermore, BlaI is proteolytically cleaved in response to the addition of inducer in a blaR1-dependent manner, providing primary evidence for the molecular basis of induction. Thus, BlaI is shown to be the repressor of the beta-lactamase system.

Bacterial Proteins↗
PubMed1997

Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, mental retardation, and renal Fanconi syndrome. The OCRL1 gene, which, when mutated, is responsible for OCRL, encodes a 105-kD Golgi protein with phosphatidylinositol (4,5)bisphosphate (PtdIn[4,5]P2) 5-phosphatase activity. We have examined the OCRL1 gene in 12 independent patients with OCRL and have found 11 different mutations. Six were nonsense mutations, and one a deletion of one or two nucleotides that leads to frameshift and premature termination. In one, a 1.2-kb genomic deletion of exon 14 was identified. In four others, missense mutations or the deletion of a single codon were found to involve amino acid residues known to be highly conserved among proteins with PtdIns(4,5)P2 5-phosphatase activity. All patients had markedly reduced PtdIns(4,5)P2 5-phosphatase activity in their fibroblasts, whereas the ocrl1 protein was detectable by immunoblotting in some patients with either missense mutations or a codon deletion but was not detectable in those with premature termination mutations. These results confirm and extend our previous observation that the OCRL phenotype results from loss of function of the ocrl1 protein and that mutations are generally heterogeneous. Missense mutations that abolish enzyme activity but not expression of the protein will be useful for studying structure-function relationships in PtdIns(4,5)P2 5-phosphatases.

Amino Acid Sequence↗
PubMed1997

Is asthma treatment affordable in developing countries?

BACKGROUND: A study was undertaken to assess whether the therapeutic aspects of published international asthma management guidelines are practically applicable in developing countries. METHODS: Questionnaires were sent to expatriate doctors working in developing countries. RESULTS: Forty one replies were received from 24 countries in Africa and Asia. Oral salbutamol was prescribed "usually" or "often" by 35 of the 41 respondents, theophyllines by 30, inhaled bronchodilators by 12, inhaled steroids by two, and cromoglycate by two. Theophyllines were locally available in all 41 cases, oral salbutamol in 40, inhaled bronchodilators in 34, and inhaled steroids (usually beclomethasone 50 micrograms) in only 15. Where they were available, the median (range) coat of a beclomethasone 50 micrograms inhaler was 20% (6.8-100%) of average local monthly income, salbutamol inhaler 13% (3.3-250%), 90 salbutamol 4 mg tablets 3.8% (0.8-75%), and 90 aminophylline 100 mg tablets 4.5% (0.5-70%). If they were available locally at a cheaper price, 34 (83%) respondents would prescribe more inhaled steroids and 37 (90%) would prescribe more inhaled bronchodilators. CONCLUSIONS: Many asthma patients in developing countries are not receiving adequate treatment because the required drugs are not available in their area or are prohibitively expensive.

Africa↗
PubMed1997

Ritual handwashing.

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Hand Disinfection↗
PubMed1997

Ocular and orbital complications of intraarterial cisplatin. A case report.

Despite advances in neurosurgery, radiation oncology, and chemotherapy, the prognosis for glioblastoma multiforme remains poor, with a median survival time of 11-12 months. Cisplatin (cis-diamminedichlorideplatinum II) is one treatment for glioblastoma multiforme. Higher response rates have been achieved by intraarterial (i.a.) infusion than by systemic infusion of this agent. Cisplatin therapy may cause neurologic complications, and i.a. delivery has been reported to cause ocular toxicity. We report a patient who experienced intraorbital and intraocular toxicity following supraophthalmic i.a. injection of cisplatin.

Adult↗
PubMed1996

Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic, neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter.

Abnormalities, Multiple↗
PubMed1996

Detection of altered membrane phospholipid asymmetry in subpopulations of human red blood cells using fluorescently labeled annexin V.

The phospholipids of the human red cell are distributed asymmetrically in the bilayer of the red cell membrane. In certain pathologic states, such as sickle cell anemia, phospholipid asymmetry is altered. Although several methods can be used to measure phospholipid organization, small organizational changes have been very difficult to assess. Moreover, these methods fail to identify subpopulations of cells that have lost their normal phospholipid asymmetry. Using fluorescently labeled annexin V in flow cytometry and fluorescent microscopy, we were able to identify and quantify red cells that had lost their phospholipid asymmetry in populations as small as 1 million cells. Moreover, loss of phospholipid organization in subpopulations as small as 0.1% of the total population could be identified, and individual cells could be studied by fluorescent microscopy. An excellent correlation was found between fluorescence-activated cell sorter (FACS) analysis results using annexin V to detect red cells with phosphatidylserine (PS) on their surface and a PS-requiring prothrombinase assay using similar red cells. Cells that bound fluorescein isothiocyanate (FITC)-labeled annexin V could be isolated from the population using magnetic beads covered with an anti-FITC antibody. Evaluation of blood samples from patients with sickle cell anemia under oxygenated conditions demonstrated the presence of subpopulations of cells that had lost phospholipid asymmetry. While only a few red cells were labeled in normal control samples (0.21% +/- 0.12%, n = 8), significantly increased (P < .001) annexin V labeling was observed in samples from patients with sickle cell anemia (2.18% +/- 1.21%, n = 13). We conclude that loss of phospholipid asymmetry may occur in small subpopulations of red cells and that fluorescently labeled annexin V can be used to quantify and isolate these cells.

Anemia, Sickle Cell↗
PubMed1996

Anion-selectivity of the swelling-activated osmolyte channel in eel erythrocytes.

Osmotic swelling of fish erythrocytes activates a broad-specificity permeation pathway that mediates the volume-regulatory efflux of taurine and other intracellular osmolytes. This pathway is blocked by inhibitors of the erythrocyte band 3 anion exchanger, raising the possibility that band 3 is involved in the volume-regulatory response. In this study of eel erythrocytes, a quantitative comparison of the pharmacology of swelling-activated taurine transport with that of band 3-mediated SO4(2-) transport showed there to be significant differences between them. N-ethylmaleimide and quinine were effective inhibitors of swelling-activated taurine transport but caused little, if any, inhibition of band 3. Conversely, DIDS was a more potent inhibitor of band 3-mediated SO4(2-) flux than of swelling-activated taurine transport. In cells in isotonic medium, pretreated then co-incubated with 0.1 mM DIDS, the band 3-mediated transport of SO4(2-) and Cl- was reduced to a low level. Exposure of these cells to a hypotonic medium containing 0.1 mM DIDS was followed by the activation of a Cl- permeation pathway showing the same inhibitor sensitivity as swelling-activated taurine transport. The data are consistent with swelling-activated transport of taurine and Cl- being via a common pathway. A comparison of the swelling-activated transport rates for taurine and Cl- with those for several other solutes was consistent with the hypothesis that this pathway is an anion-selective channel, similar to those that mediate the volume-regulatory efflux of Cl- and organic osmolytes from mammalian cells.

Animals↗
PubMed1996

Ophthalmic manifestations of Smith-Magenis syndrome.

PURPOSE: The Smith-Magenis syndrome (SMS) is a multiple-anomaly, mental retardation syndrome associated with deletions of a contiguous region of chromosome 17p11.2. Prior reports have described ophthalmic anomalies with SMS, including telecanthus, ptosis, strabismus, myopia, iris anomalies, cataracts, optic nerve hypoplasia, and retinal detachment. This report defines the ophthalmic spectrum in 28 individuals with SMS subjected to a multidisciplinary clinical and molecular survey. METHODS: Individuals with deletion of chromosome 17p11.2 detected by high-resolution cytogenetic analysis underwent complete ophthalmologic evaluation comprised of ophthalmic history, visual acuity, cycloplegic refraction, motility, and biomicroscopic and ophthalmoscopic examination. RESULTS: Among the 28 subjects, ranging in age from 0.8 to 29.3 years, the most frequent ocular findings were iris anomalies (68%), microcornea (50%), myopia (42%), and strabismus (32%). Bilateral microphthalmos with uveal and retinal coloboma was observed in one individual. No subject had cataract or retinal detachment. CONCLUSIONS: This is the largest single-center series of subjects with SMS that includes ophthalmic evaluation. As in prior reports, iris anomalies and strabismus were observed, but microcornea had not been noted previously. The absolute refractive error was hypermetropic in half of these subjects. Cataract, ptosis, and retinal pathology, including detachment, were not observed in any subject. All individuals with SMS should be evaluated by an ophthalmologist, with special attention to strabismus, microcornea, iris anomalies, and refractive errors.

Abnormalities, Multiple↗
PubMed1996

Smoking and preference for brand of cigarette among adolescents.

This study examined the association between having a preferred brand of cigarette and smoking in African American, Mexican American, and White 5th, 7th, 9th and 11th graders. The prevalence of having a preferred brand of cigarette increased with grade level, with over 20% of 11th graders reporting having a preference. Brand preference was related to cigarette use in a dose-response fashion for all subgroups, with preference highest among African American students who smoked at least half a pack of cigarettes on a daily basis. There was a strong association between having a brand preference and current daily cigarette use, whereas preference also was related to intention to smoke cigarettes when older. These findings suggest that brand preference may play an important role in cigarette use acquisition and maintenance among adolescents.

Adolescent↗
PubMed1996

Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti type 2.

Incontinentia Pigmenti 2 (IP2) is an X-linked dominant disorder with male lethality. Affected females display a characteristic skin eruption that evolves through four classic stages, frequently accompanied by dental and retinal abnormalities. Non-random (skewed) X-inactivation in peripheral blood leukocytes and in fibroblasts has been observed in females with IP2; however, sample sizes have been small and methods of analysis varied. We have examined X-inactivation in a large group of multigenerational IP2 families, in smaller families, and in isolated cases. Ninety-eight percent of affected females in multigenerational IP2 pedigrees show completely skewed patterns of X-inactivation, while only approximately 10% of a normal control population is skewed. Results both in small families and in new mutation cases with subsequent segregation consistent with Xq28 linkage are similar. Isolated cases show a lower percentage (85%) of skewed affected individuals; this difference may be due to inaccurate clinical ascertainment. The parent of origin of new mutations could be determined in 15 families; paternal new mutations were twice as common as maternal. Fibroblast subclones from a biopsy at the boundary of a skin lesion in a newborn IP2 patient were isolated, and clones with either one or the other X active were identified, demonstrating that cells with the active disease-bearing X chromosome are still present in stage I skin lesions.

Adult↗
PubMed1996

Schmidt's syndrome associated with sarcoidosis.

We present a case of Schmidt's syndrome (autoimmune Addison's disease and hypothyroidism) associated with sarcoidosis. There have been only four previous reports of Schmidt's syndrome with sarcoidosis, and a possible fifth with negative autoantibodies. We have been able to find only four other reports of adrenal failure (without hypothyroidism) in sarcoidosis. It is important to be aware of the potential for masking the diagnosis of Addison's disease by steroid treatment.

Addison Disease↗
PubMed1996

The relationship between asthma admission rates, routes of admission, and socioeconomic deprivation.

This study aimed to explore the relationship between hospital admissions for asthma and socioeconomic deprivation. A retrospective study examined one year of hospital admissions for asthma in the West Midlands region of England (n = 10,044), and in one of the region's wealthier districts, Worcester (n = 251). Age standardized admission ratios (SARs) for asthma, and the routes of hospital admission, were compared with the Towns- end Deprivation Index for the place of residence. Asthma SAR was strongly associated with deprivation as measured by the Towns end Index for the district of residence (Spearman rank correlation coefficient rho = 0.65; p = 0.004). Asthma admission rates for all age groups, except those aged over 65 yrs, were higher in poorer districts. A significantly greater proportion of emergency admissions in poorer districts came via Accident and Emergency departments, rather than general practitioner referrals (rho = 0.76; p < 0.001). Within Worcester District, SAR was associated with Townsend Index for the ward of residence (rho = 0.39; p < 0.001). This remained significant after excluding repeat admissions (rho = 0.45; p < 0.001). We conclude that asthma admissions are strongly associated with deprivation in the community. Differences in the health care received during acute exacerbations by asthma patients from different economic backgrounds is likely to be an important factor in this relationship.

Adolescent↗
PubMed1996

Neurologic presentation of Wilson disease without Kayser-Fleischer rings.

A 41-year-old woman presented with a 6-month history of gradually progressive postural instability and dysarthria associated with cerebellar and extrapyramidal signs. No Kayser-Fleischer (K-F) rings were observed on biomicroscopic examination of each cornea. The only evidence of hepatic dysfunction was a modest elevation of alanine-aminotransferase. The diagnosis of Wilson disease (WD) was based on low serum ceruloplasmin, abnormal serum copper and urinary copper excretion, and DNA marker segregation analysis. WD should be considered in the presence of characteristic neurologic and laboratory features, regardless of age at onset, evidence of hepatic dysfunction, or absence of K-F rings.

Adult↗