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Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 469 records · Page 26Linked to original sources

Metabolic acidosis does not contribute to chronic renal injury in the rat.

1. Metabolic acidosis invariably accompanies chronic renal failure, and short periods of metabolic acidosis cause renal growth and proteinuria in normal rats. Rates of ammoniagenesis are increased in chronic renal failure, and it has been suggested that this contributes to disease progression. This study assessed (i) whether prolonged acidosis causes chronic renal injury in the normal kidney and (ii) whether abrogation of acidosis slows disease progression in the remnant kidney. 2. Metabolic acidosis was induced in normal rats by dietary hydrochloric acid. Urinary excretion of total protein, lysozyme and albumin increased, peaking at week 8 but returning to baseline by week 14. At killing after 14 weeks, kidney weights, glomerular filtration rates and serum creatinine were the same in both groups, but kidney/body weight and kidney/heart weight ratios were greater in the acidotic group. All kidneys were normal by light microscopy. 3. Rats subjected to five-sixths nephrectomy were given sufficient dietary bicarbonate to abolish uraemic acidosis, and their outcome was compared with that of non-alkalinized remnants (controls). Proteinuria, glomerular filtration rates, blood pressure, histological injury and time to the development of terminal uraemia were no better in bicarbonate-supplemented animals than in controls. 4. These data demonstrate that metabolic acidosis neither causes nor exacerbates chronic renal injury. We conclude that the treatment of uraemic acidosis is unlikely to influence disease progression in patients with chronic renal failure.

Acidosis, Renal Tubular↗

Spermatology for understanding, managing and conserving rare species.

Most conventional spermatology research involves common mammalian species including livestock, laboratory animals and humans. Yet, there are more than 4500 mammalian species inhabiting the planet for which little is known about basic reproductive biology, including sperm characteristics and function. This information is important, not just as adjunct knowledge, but because the majority of these species are threatened with extinction, largely due to human-induced pressures. The field of conservation is changing rapidly, and global cooperation is emerging among a variety of wildlife enthusiasts, ranging from management authorities of nature reserves to curators of rare zoological collections. Conservation progress depends on systematic, multidisciplinary research first to answer basic questions, with new data then applied to endangered species management plans. The reproductive physiologist is a crucial component of this scheme. Reproduction is the essence of species survival, and enormous effort needs to be directed at these 'untraditional' research species, subspecies and populations. Spermatology research combined with simultaneous efforts in endocrinology, embryology and cryopreservation (among others) can lead to the successful application of assisted reproduction. Examples from this laboratory include an array of wild felid species and a rare cervid and mustelid. Obstacles to success are formidable, including unique species-specificities, diminished genetic diversity and a general lack of resources. Nonetheless, the field offers tremendous opportunities for generating unique knowledge of comparative interest and with conservation utility.

Animals↗

Identification of a novel gene, ETX1 from Xp21.1, a candidate gene for X-linked retintis pigmentosa (RP3).

A novel gene encoding a 2.2 kilobase transcript has been isolated from the Xp21.1 region of the human X chromosome by exon amplification. The gene, called EXT1, spans 80 kilobases and contains 12 exons, at least two of which are alternatively spliced and have predicted products of 464 and 471 amino acids respectively. Conceptual translation of the open reading frames shows one product with a 30 amino acid signal peptide, which is absent from the alternative transcript, followed by three complement control protein domains, a hydrophobic region with a possible role in membrane anchorage and short 17 amino acid putative cytoplasmic carboxyl terminus. An alternative first exon contains a 39 amino acid open reading frame which is rich in serine and threonine residues and contains a potential chondroitin/dermatan sulphate attachment site. Northern analysis showed ETX1 expression within the retina and heart with lower levels in several other tissues. Since ETX1 lies within the region thought to contain the x-linked retinitis pigmentosa (xIRP) gene, RP3, it was screened for mutation within a set of 45 xIRP patients using single strand conformation analysis and/or chemical cleavage of mismatch using reverse transcription/polymerase chain reaction amplification of polyA+RNA from blood cells. Three low frequently variants (17-23Ldel, P225S, S413F) were found in both patients and controls; one of which (P225S) was found in four of 45 unrelated patient chromosomes and one of 178 control chromosomes (p <0.001). The allelic association between P225S and xIRP alleles suggests a common ancestral chromosome bearing the P225S variant and an RP3 mutation at a neighbouring locus.

Amino Acid Sequence↗

Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype.

Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene. We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3' end of PAX6. In addition, the open reading frame of PAX6 is apparently free of mutations. We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a 'position effect' is the underlying mechanism of disease in these families.

Aniridia↗

Familial non-specific dementia maps to chromosome 3.

A significant minority of degenerative dementias lack distinctive inclusion bodies, plagues or tangles on pathological examination. Half of these cases have a positive family history of dementia. We have studied the largest published family with such a dementia and mapped the disease locus to a 12 cM region of chromosome 3 spanning the centromere. Haplotype analysis demonstrates a common region shared between all affected individuals between the markers D3S1284 and D3S1603. Like a number of other late onset neurodegenerative diseases, the disease presents at an earlier age when paternally inherited.

Chromosome Mapping↗

Prevalence of Bartonella henselae antibodies in pet cats throughout regions of North America.

Cat exposure has been directly associated with the development of human Bartonella henselae infections, resulting in cat-scratch disease, bacillary angiomatosis, or bacteremia. The prevalence of serum antibody titers to B. henselae was determined for selected pet cats from 33 geographic locations throughout the United States and several areas in western Canada. Seroprevalences paralleled increasing climatic warmth (P < .02) and annual precipitation (P < .03). These warm, humid areas with the highest seroprevalence would also have the highest number of potential arthropod vectors. The southeastern United States, Hawaii, coastal California, the Pacific Northwest, and the south central plains had the highest average prevalences (54.6%, 47.4%, 40.0%, 34.3%, and 36.7%, respectively). Alaska, the Rocky Mountain-Great Plains region, and the Midwest had low average prevalences (5.0%, 3.7%, and 6.7%, respectively). Overall, 27.9% (175/628) of the cats tested were seropositive. The seroprevalence of B. henselae in cats varies throughout the United States and appears to be influenced by climate.

Animals↗

Nosocomial transmission of hepatitis A in a pediatric hospital traced to an anti-hepatitis A virus-negative patient with immunodeficiency.

From July through October 1991, an outbreak of hepatitis A virus (HAV) infection involving 26 hospital staff, inpatients and household contacts occurred in a pediatric hospital. All ill staff members had cared for one inpatient who had profuse diarrhea with gross fecal contamination of the environment, negative HAV serology and idiopathic immunodeficiency. HAV infection in this patient was later confirmed by polymerase chain reaction. Among hospital staff HAV attack rates were highest in nursing personnel (15%). A retrospective cohort study of nurses found that the risk of infection was greatest in those who handled the source patient's soiled bed pad (relative risk, 6.7; 95% confidence intervals, 1.6, 27.8), diaper (relative risk, 5.4; 95% confidence intervals, 0.8, 39.2) or gown (relative risk, 2.9; 95% confidence intervals, 1.1, 7.8). Glove use during these activities was not associated with a lower risk of infection, possibly because of gross environmental contamination or less use than reported. This situation was unusual because the patient was HAV-infected but had negative serology, probably because of immunodeficiency. In situations of potentially extensive environmental contamination, such as with a diapered or incontinent patient with suspected or confirmed hepatitis A, careful attention to frequent handwashing is an essential protective measure; in addition strict glove use whenever entering the patient's room should be followed to provide additional protection.

Adult↗

Deaths from acute exposure to trichloroethylene.

Trichloroethylene (TCE) is a commonly used halogenated hydrocarbon in industry. We report on deaths attributed to TCE exposure that occurred between 1975 and 1992. In addition, we present a case report from the most recent death, including tissue concentration modeling. The deaths shared a number of features. All occurred in young men who were usually working in confined spaces without adequate ventilation. These preventable deaths suggest that safety precautions are not being observed by workers and employers. Employers should ensure that their employees are adequately trained in the dangers of working with TCE, that adequate ventilation of the working environment is provided, that the proper personal protective equipment (PPE) is available to their workers, and that workers should not work alone or unobserved when using TCE in confined spaces.

Accidents, Occupational↗

Pilot trials of PDF symbology as a means of transfering data on blood units between transfusion centres.

PDF 417, a two-dimensional barcode, was used as a portable data file to transfer key information on blood units and delivery documentation between two Regional Blood Transfusion Centres. Multiple Codabar messages currently displayed on blood packs, as well as other useful information, i.e. microbiology conformance, were encoded in a 45-character single PDF barcode. The delivery note which accompanied each consignment of blood consisted of a series of PDF barcodes, each representing 20 blood units. Computer validation showed 100% reconciliation of PDF data with Codabar data. Readability of the code was excellent with a greater than 98% first-pass read rate. The delivery note PDF barcode identified eight operator errors which would have been undetected by the present manual system. We conclude that PDF 417 is an effective, secure and space efficient means of transferring data associated with the transfer of blood.

Blood Banks↗

The biochemistry and clinical application of urinary oestriol measurement during late pregnancy in the 1990's.

Part 1. The present disillusionment with oestriol measurement as a test of fetoplacental function could be explained by the use of poor methodology and inappropriate normal ranges rather than that the test has lost its usefulness. We have updated the Lever method for measuring oestriol in urine, and examined the automatic TDX system supplied by Abbott Laboratories. The precision of the methods and consistency of results between methods have been determined and normal ranges have been established for both methods. The overall accuracy of collection of 24-hour urine specimens in a routine laboratory setting has also been calculated. The normal ranges suggested as a guide for the TDX method by Abbott were based on those derived from the original method of Brown and were found to be too low and therefore unsuitable for clinical use. This study reports appropriate lower limits of normal for both the updated Lever and the TDX methods. Part 2. The results obtained using the updated Lever method since its introduction in 1991 have been compared with those obtained by the original Brown method during the years 1971-1989. The new, user-friendly Lever method of oestriol assay measurement used in 1991-1993 gave results of equivalent clinical value to the Brown method used in 1971-1989, although the perinatal mortality rates in the tested populations fell from 0.95% to 0.37%. During 1971-1989, low oestriol excretion on 1 or more occasions was associated with a 5.6-fold increase in the perinatal mortality rate (0.66% to 3.67%), whereas in 1991-1993, the factor was 4.4 (0.27% to 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Estriol↗

Viral tracer studies indicate contamination of marine waters by sewage disposal practices in key largo, Florida.

Domestic wastewater disposal practices in the Florida Keys are primarily limited to on-site disposal systems such as septic tanks, injection wells, and illegal cesspits. Poorly treated sewage is thus released into the highly porous subsurface Key Largo limestone matrix. To investigate the fate and transport of sewage in the subsurface environment and the potential for contamination of marine surface waters, we employed bacteriophages as tracers in a domestic septic system and a simulated injection well in Key Largo, Florida. Transport of bacteriophage (Phi)HSIC-1 from the septic tank to adjacent surface canal waters and outstanding marine waters occurred in as little as 11 and 23 h, respectively. Transport of the Salmonella phage PRD1 from the simulated injection well to a canal adjacent to the injection site occurred in 11.2 h. Estimated rates of migration of viral tracers ranged from 0.57 to 24.2 m/h, over 500-fold greater than flow rates measured previously by subsurface flow meters in similar environments. These results suggest that current on-site disposal practices can lead to contamination of the subsurface and surface marine waters in the Keys.

Journal Article↗

DNA amplification and restriction endonuclease analysis for differentiation of 12 species and taxa of Nocardia, including recognition of four new taxa within the Nocardia asteroides complex.

Nineteen reference and 156 clinical strains of the genus Nocardia belonging to 12 taxonomic groups were studied for restriction fragment length polymorphism (RFLP) by using an amplified 439-bp segment of the 65-kDa heat shock protein gene. Of 30 restriction endonucleases, digestion with MspI and then digestion with BsaHI produced RFLP band patterns which separated all 12 groups except N. asteroides type IV from 6 of 12 N. transvalensis isolates and N. carnea from the N. asteroides type VI isolates. Commonly encountered species such as N. nova, N. farcinica, N. brasiliensis sensu stricto, and N. otitidiscaviarum were easily separated. Each taxon resulted in a single RFLP band pattern that included > or = 96% of all biochemically grouped isolates for 9 of 12 taxa with MspI and for 8 of 12 taxa with BsaHI. With the use of both patterns, only 6 of 175 (3.4%) isolates failed to fit the biochemically defined group patterns. These studies provide the first evidence for the separate identities of four antibiogram-defined (but currently unnamed) groups within the N. asteroides complex (types I, II, IV, and VI) and the presence of two subgroups within N. transvalensis. They also provide genotypic evidence for the separate identities of N. nova and N. farcinica. The lack of BstEII recognition sites in amplicons obtained from nocardiae provides a simple and rapid method for the differentiation of nocardiae from mycobacteria. DNA amplification with RFLP analysis is the first rapid method that distinguishes all clinically significant taxa and recognized species within the genus Nocardia.

Bacterial Typing Techniques↗

Mammography screening: an incremental cost effectiveness analysis of two view versus one view procedures in London.

STUDY OBJECTIVE: To compare the costs and effects of routine mammography screening by a single mediolateral-oblique view and two views (mediolateral-oblique plus craniocaudal) of each breast. DESIGN: A cost effectiveness analysis of a prospective non-randomised trial comparing one and two view mammography screening was carried out at St Margaret's Hospital, Epping. All women in the study had two view mammography. The mediolateral-oblique view was always the first image read by the radiologist. After reading the films for a clinic session, the same radiologist then went back and read both the mediolateral-oblique and craniocaudal views together. Each set of films was read by two radiologists. The main outcome measures were recall rates, number of cancers detected, screening and assessment costs, and cost effectiveness ratios. SUBJECTS: A total of 26,430 women who attended for breast screening using both one and two view mammography participated. A sample of 132 women attending for assessment provided data on the private costs incurred in attending for assessment. RESULTS: There was a reduction in the recall rate from 9.1% (2404 of 26,430) after one view screening to 6.7% (1760 of 26,430) after two view screening. The results also suggest that for every 10,000 women screened an additional five cancers would be detected earlier with two view screening. The additional health service screening cost associated with two view screening was estimated to be 3.63 pounds: the costs associated with one and two view screening policies were estimated to be 41.49 pounds and 32.99 pounds respectively. Private costs incurred were estimated to be 0.35 pounds per woman screened and 32.75 pounds per woman assessed. Two cost effectiveness ratios were calculated: an incremental health service cost per additional cancer detected of 4129 pounds and an incremental health service plus private cost per additional cancer detected of 2742 pounds. The sensitivity analysis suggested that the results were sensitive to relatively large changes in a number of parameters. These included screening costs, assessment costs, equipment life, and recall rates. CONCLUSIONS: Use of two view screening increased early cancer detection and also costs. The reduction in the recall rate with two views was not sufficiently large to make the cost of two view screening neutral. While these results are not completely generalisable, a framework is provided to allow other centres to estimate the cost effectiveness of two view screening in their locality.

Breast Neoplasms↗

Natriuretic peptide receptors in the fetal rat.

In vitro autoradiography of rat fetuses from embryonic days 12-19 (E12-E19) showed widespread high-affinity specific binding sites for natriuretic peptides. The sites on E16 somites avidly bound C-type natriuretic peptide [CNP-(1-22)] as well as C-ANP, a synthetic ligand that selects the C-type natriuretic peptide receptor (NPR-C). Most somitic binding sites had high affinity for atrial natriuretic peptide [ANP-(1-28)], confirming their resemblance to NPR-C. A few had a lower apparent affinity for ANP-(1-28), suggesting that they might be NPR-B. CNP-(1-22) was more powerful than ANP-(1-28) as an agonist of guanosine 3',5'-cyclic monophosphate production in somites, and ATP augmented the action of CNP-(1-22). These observations further suggest the presence of NPR-B. However, with cross-linking of 3-[125I]iodo-0-tyrosyl rat CNP-(1-22) to somitic membranes followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, only a single 64-kDa binding protein was detected under reducing conditions. This is not consistent with intact approximately 120-kDa NPR-B. In vitro autoradiography of the binding of natriuretic peptides to E16 liver implied the presence of NPR-A and NPR-C-like receptors. Hepatic guanosine 3',5'-cyclic monophosphate production was most powerfully stimulated by ANP-(1-28), as expected for NPR-A. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also identified NPR-A and NPR-C-like proteins in E16 hepatic membranes. Thus different NPRs are expressed by specific fetal tissues. This may be developmentally significant.

Animals↗

Natriuretic peptide receptors are expressed during cerebral growth in the fetal rat.

Autoradiography of frozen sections of fetal rat brain shows that receptor-like binding sites for atrial and C-type natriuretic peptides (ANP and CNP) occur in the generative juxtaventricular zone of the telencephalon after the 12th embryonic day (E12). These sites avidly bind both ANP and CNP. They thus resemble the cloned NPR-C type of natriuretic peptide receptor. Covalent cross-linking of 3-[125I]iodo-O-tyrosyl CNP-(1-22) and 3-[125I]iodo-28-tyrosyl rat ANP-(1-28) to membrane proteins from E16 telencephala labels a single protein band on reducing sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The protein has high affinities for ANP and CNP and a molecular mass of 60-70 kDa under reducing conditions, consistent with reduced NPR-C. However, because the telencephalic protein has unusual physicochemical properties in SDS under nonreducing conditions it was not possible to assess whether this protein can form disulfide-bridged dimers like NPR-C. CNP-(1-22) was a full agonist and ANP-(1-28) was a partial agonist of guanosine 3',5'-cyclic monophosphate (cGMP) production by E16 telencephalon. C-ANP, a synthetic ligand of NPR-C, antagonized CNP-(1-22)-mediated cGMP production. The results imply that either the NPR-C-like telencephalic receptor modulates the level of cGMP or a guanylate cyclase-coupled receptor, such as the 120-kDa B-type NPR, for which CNP-(1-22) is a full agonist, is present at levels insufficient to be detected by autoradiography or protein labeling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of sucrose-containing chewing-gum use on in situ enamel lesion remineralization.

Two independent cross-over studies have now been carried out to evaluate the effect of a regime of chewing sucrose-containing gum on enamel lesion remineralization. The first study has been reported in detail elsewhere. This further study aimed to increase the data set with an additional 13 volunteers. Similar protocols were followed in both studies. Weighted averages from the two studies showed delta z values corresponding to 16.8% remineralization for the gum versus 11.6% remineralization for the control (p = 0.046, two-sided). A significant difference between test and control was evident for lesion body (p = 0.0004, two-sided) but not for surface zone (p = 0.32, two-sided).

Adult↗

Regional expression of natriuretic peptide receptors during the formation of arterial neointima in the rabbit.

In vitro evidence suggests that natriuretic peptide receptors (NPR)-B and NPR-C inhibit vascular smooth muscle (VSM) proliferation. NPR-B is guanylate cyclase-coupled and selectively activated by C-type natriuretic peptide (CNP)-(1-22). NPR-C is not guanylate cyclase-coupled and, unlike NPR-B, avidly binds atrial natriuretic peptide (ANP)-(1-28) as well as CNP-(1-22). Here, we investigate these receptors during the VSM proliferation and neointimal formation found 5, 7, and 20 days after compressing the central ear artery of the rabbit. Receptors were mapped autoradiographically using [125I-Tyr0]CNP-(1-22), which binds NPR-B and NPR-C, and 125I-ANP-(1-28), which binds NPR-C and NPR-A, another guanylate cyclase-coupled receptor. Normal tunica media had NPR-B-like binding sites, and the level of these did not change significantly after compression. Consistent with this, CNP-(1-22) stimulated cGMP production equally with membranes from normal or damaged arteries and was more effective than ANP-(1-28). Neointima, which became evident 5 to 7 days after arterial damage, expressed NPR-C-like sites and no detectable NPR-B-like binding. NPR-C-like sites also appeared on the media for the first time between 5 and 7 days after compression. Immunohistochemistry for proliferating cell nuclear antigen revealed widespread mitosis in VSM at 5 days after compression, but mitosis was virtually restricted to the neointima at and beyond 7 days after compression. Thus, whereas levels of NPR-B did not change significantly after arterial injury and NPR-A was not detected, NPR-C-like receptors were upregulated as mitosis declined in the media and as a prominent neointima formed.

Animals↗