Biomedical subjects

K Saunders

Publications and source records attributed to K Saunders.

At least 55 records · Page 3Linked to original sources

PubMed1995

Genome organization of ageratum yellow vein virus, a monopartite whitefly-transmitted geminivirus isolated from a common weed.

A full-length copy of a single genomic component of the whitefly-transmitted geminivirus ageratum yellow vein virus (AYVV) has been cloned from an extract of infected Ageratum conyzoides originating from Singapore. Sequence analysis shows that the genomic component encodes two virion-sense (V1 and V2) and four complementary-sense open reading frames (C1-C4), typical of DNA A of whitefly-transmitted geminiviruses from the Eastern hemisphere. A genomic component equivalent to DNA B was not detected in extracts of infected A. conyzoides. The cloned genomic component produced a systemic infection in Nicotiana benthamiana, Phaseolus vulgaris and Lycopersicon esculentum when introduced into plants by agroinoculation, and symptoms were identical to those produced by wild-type virus introduced into these hosts using viruliferous whiteflies. However, attempts to re-establish a systemic infection in A. conyzoides either by agroinoculation or by whitefly transmission of the cloned progeny were unsuccessful, suggesting that additional factors are required for infection of the natural host. The significance of A. conyzoides as a reservoir host for the economically important geminivirus diseases is discussed.

Animals↗

PubMed1995

Complementation of African cassava mosaic virus AC2 gene function in a mixed bipartite geminivirus infection.

We have previously demonstrated that African cassava mosaic virus (ACMV) DNAs A and B efficiently complement the systemic spread of tomato golden mosaic virus (TGMV) DNA A when co-agroinoculated onto Nicotiana benthamiana. Here, we show that a mixture of an ACMV DNA A AC2 mutant and DNA B that is normally unable to systemically infect N. benthamiana can do so at low frequency when co-agroinoculated with TGMV DNA A. Analysis of viral DNA showed that the AC2 mutation was retained during infection. The mixture of genomic components was sap transmissible, indicating that systemic infectivity is not specifically attributable to the use of agroinoculation. In the presence of TGMV DNA A, ACMV coat protein as well as the DNA B gene products BV1 and BC1 were detected in systemically infected tissues. The results demonstrate that dysfunctional AC2 can be complemented in planta by its TGMV homologue AL2.

Africa↗

PubMed1995

Late diagnosis of congenital sensorineural hearing impairment: why are detection methods failing?

This study was designed to look in detail at the paths to diagnosis for a group of 197 children with congenital sensorineural hearing impairment (SNHI), who were diagnosed between 1989 and 1991 in the state of Victoria, Australia. Despite the existence of universal infant screening at 7-9 months by distraction test or questionnaire, the median age at diagnosis for the study group was 18.0 months, with median age at aid fitting of 20.8 months, and median age at commencement of specialised intervention programmes of 22.3 months. Parent questionnaires completed for 143 (73%) of these children showed that 49% had known risk factors for hearing loss yet only 20% of them had been referred for audiological assessment before the 7-9 month screen. Only 63% of those eligible for the 7-9 month screen had received it. Of those children who were screened by distraction test 46% passed as did 57% of those screened by questionnaire. Twenty four parents (17%) described how they had initially 'denied' their own observations of their infants' abnormal hearing behaviour. When concerns were raised with professionals, 10% of parents were falsely reassured without audiological assessment. Detection methods are failing through a combination of poor screen test efficacy, incomplete population coverage, and parental and professional denial.

Age Factors↗

PubMed1992

RNA-primed complementary-sense DNA synthesis of the geminivirus African cassava mosaic virus.

The plant DNA virus African cassava mosaic virus (ACMV) is believed to replicate by a rolling circle mechanism. To investigate complementary-sense DNA (lagging strand) synthesis, we have analysed the heterogenous form of complementary-sense DNA (H3 DNA) from infected Nicotiana benthamiana by two-dimensional agarose gel electrophoresis and blot hybridisation. The presence of an RNA moeity is demonstrated by comparison of results for nucleic acids resolved on neutral/alkaline and neutral/formamide gels, suggesting that complementary-sense DNA synthesis on the virus-sense single-stranded DNA template is preceded by the synthesis of an RNA primer. Hybridisation with probes to specific parts of ACMV DNA A genome indicates that synthesis of the putative RNA primer initiates between nucleotides 2581-221, a region that includes intergenic sequences that have been implicated in geminivirus DNA replication and the control of gene expression.

DNA, Viral↗

PubMed1992

A chronic disease score from automated pharmacy data.

Using population-based automated pharmacy data, patterns of use of selected prescription medications during a 1 year time period identified by a consensus judgement process were used to construct a measure of chronic disease status (Chronic Disease Score). This score was evaluated in terms of its stability over time and its association with other health status measures. In a pilot test sample of high utilizers of ambulatory health care well known to their physicians (n = 219), Chronic Disease Score (CDS) was correlated with physician ratings of physical disease severity (r = 0.57). In a second random sample of patients (n = 722), its correlation with physician-rated disease severity was 0.46. In a total population analysis (n = 122,911), it was found to predict hospitalization and mortality in the following year after controlling for age, gender and health care visits. In a population sample (n = 790), CDS showed high year to year stability (r = 0.74). Based on health survey data, CDS showed a moderate association with self rated health status and self reported disability. Unlike self-rated health status and health care utilization, CDS was not associated with depression or anxiety. We conclude that scoring automated pharmacy data can provide a stable measure of chronic disease status that, after controlling for health care utilization, is associated with physician-rated disease severity, patient-rated health status, and predicts subsequent mortality and hospitalization rates. Specific methods of scoring automated pharmacy data to measure global chronic disease status may require adaptation to local prescribing practices. Scoring might be improved by empirical estimation of weighting factors to optimize prediction of mortality and other health status measures.

Adolescent↗

PubMed1992

Problems measuring contrast sensitivity in children.

A preliminary study measured the contrast sensitivity function (CSF) in 30 children (aged 3 months-5 years). Preferential looking techniques were used to assess CSF to sine wave gratings displayed on one of two screens. To find a meaningful contrast sensitivity procedure we compared the results with a shorter procedure using an edge stimulus. The following problems were encountered: measuring the contrasts required to detect four or five different spatial frequencies took time, resulting in boredom and loss of attention in our subjects; there was poor correlation between CSF and edge detection; an interesting artefact resulted in a plateau rather than a low frequency fall-off in the CSF of five of the children greater than 30 months old. This artefact may have resulted from peripheral rather than central retinal responses and/or motion artefacts in the stimulus onset. A follow up study with 41 additional children aged 3-36 months limited the contrast testing to that of the spatial frequency corresponding to the peak of the CSF. The shortened procedure, plus a lot of encouragement, resulted in higher contrast sensitivities in all but the oldest age group and successful monocular contrast measurements. In order to avoid artefacts arising from peripheral vision, children were encouraged to look at each screen before responding.

Child, Preschool↗

PubMed1991

DNA forms of the geminivirus African cassava mosaic virus consistent with a rolling circle mechanism of replication.

We have analysed DNA from African cassava mosaic virus (ACMV)-infected Nicotiana benthamiana by two-dimensional agarose gel electrophoresis and detected ACMV-specific DNAs by blot-hybridisation. ACMV DNA forms including the previously characterised single-stranded, open-circular, linear and supercoiled DNAs along with five previously uncharacterised heterogeneous DNAs (H1-H5) were resolved. The heterogeneous DNAs were characterised by their chromatographic properties on BND-cellulose and their ability to hybridise to strand-specific and double-stranded probes. The data suggest a rolling circle mechanism of DNA replication, based on the sizes and strand specificity of the heterogeneous single-stranded DNA forms and their electrophoretic properties in relation to genome length single-stranded DNAs. Second-strand synthesis on a single-stranded virus-sense template is evident from the position of heterogeneous subgenomic complementary-sense DNA (H3) associated with genome-length virus-sense template (VT) DNA. The position of heterogeneous virus-sense DNA (H5), ranging in size from one to two genome lengths, is consistent with its association with genome-length complementary-sense template (CT) DNA, reflecting virus-sense strand displacement during replication from a double-stranded intermediate. The absence of subgenomic complementary-sense DNA associated with the displaced virus-sense strand suggests that replication proceeds via an obligate single-stranded intermediate. The other species of heterogeneous DNAs comprised concatemeric single-stranded virus-sense DNA (H4), and double-stranded or partially single-stranded DNA (H1 and H2).

Chromatography↗

PubMed1991

Bile duct carcinoma in the elderly. A rationale for surgical management.

Recent studies have advocated the nonoperative treatment of elderly patients with bile duct cancer using biliary endoprostheses. In addition to a 30-day mortality rate of 9%, disadvantages with this approach include lack of a definitive diagnosis and the inability to assess resectability. For comparison, we reviewed 42 consecutive cases of bile duct cancer managed surgically at UCLA (from 1954 to 1988) among patients age 70 years or older. Histologic confirmation of bile duct cancer was obtained for 40 surgical patients (95%) in the series. The 30-day mortality rate was 10%. There was a trend to more aggressive surgical management during the study, with a concomitant doubling in survival rates (from 21% among patients treated between 1954 and 1978 to 53% among patients treated between 1979 and 1988 at 1 year after surgery.) We conclude that elderly patients should not be denied surgical evaluation of malignant neoplasms of the bile duct simply on the basis of age.

Adenocarcinoma↗

PubMed1991

Mutational analysis of complementary-sense genes of African cassava mosaic virus DNA A.

We have investigated the ability of African cassava mosaic virus DNA A mutants, containing disrupted complementary-sense genes, to infect Nicotiana benthamiana and to replicate in Nicotiana tabacum protoplasts. Three overlapping open reading frames (ORFs) with the capacity to encode proteins with an Mr greater than 10K (AC1, AC2 and AC3) are highly conserved between geminiviruses that infect dicotyledonous plants and one (AC4) is less well conserved. Of these, only AC1 is a prerequisite for DNA replication; disruption of this ORF rendered the DNA noninfectious in plants and prevented DNA replication in protoplasts. Disruption of ORF AC2 prevented plant infection but mutants were capable of autonomous replication and replicated DNA B in trans in protoplasts to produce DNA forms that comigrated with wild-type virus DNAs. The AC2 mutant phenotype suggests that the product of this ORF is involved in virus spread within the plant. Mutants in which ORF AC3 had been disrupted retained the ability to replicate and to infect plants systemically although symptom development was delayed and attenuated, and mutant DNA accumulated to much lower levels (10 to 20%) in comparison with wild-type infection. Typical geminate virus particles were observed in extracts of plants infected with ORF AC3 mutants indicating that this gene is not essential for coat protein synthesis or virus assembly but possibly acts by modulating virus levels in infected tissues. Disruption of ORF AC4 had no effect on infectivity or symptom development suggesting that this ORF is maintained only because it overlaps the highly conserved ORF AC1.

DNA Mutational Analysis↗

PubMed1991

Diffuse bile duct tumors: guidelines for management.

The majority of patients with bile duct cancer have small focal adenocarcinomas localized to the upper, middle, or lower third of the bile duct. In contrast, a small subgroup of patients have been identified with bile duct tumors that are diffuse, involving multiple segments of the extrahepatic biliary tract. Among 186 patients with documented bile duct cancer treated at the UCLA Medical Center between 1954 and 1988, 13 patients (7%) had diffuse lesions. Patients with diffuse tumors had markedly poorer survival rates than did those with focal lesions. As diffuse tumors are not amenable to resection, surgical management consists primarily of establishing suitable biliary drainage. All patients with bile duct cancer should undergo careful intraoperative evaluation to exclude a diffuse lesion before tumor resection.

Adult↗

PubMed1991

Activation of mouse peritoneal macrophages by maintenance in serum-free medium.

Normal mouse peritoneal macrophages maintained in a serum-free medium for 48-72 h and then stimulated with phorbol myristate acetate, zymosan or bacteria, released large amounts of hydrogen peroxide. Opsonized zymosan and bacteria stimulated greater release than their unopsonized counterparts. Enhanced peroxide production was not a consequence of increased uptake of particles. Addition of serum to the serum-free medium abolished activation. The addition of interferon-gamma to the serum-free medium enhanced the effect of the serum-free treatment of macrophages from C3H/HeJ mice but abolished the effect of serum free treatment of macrophages from CFLP mice. The results are discussed in terms of negative regulation of receptor-oxidase linkage by serum.

Animals↗

PubMed1991

Gastrointestinal complications after cardiac transplantation: a spectrum of diseases.

Cardiac transplantation has become an accepted treatment modality for end-stage cardiac failure. The gastrointestinal (GI) tract represents a potential source of posttransplant morbidity and mortality. To define the scope of this problem, records of all patients undergoing cardiac transplantation at UCLA between January 1984 and July 1989 were reviewed. In all, there were 120 patients (90 males and 30 females) with a mean age of 45.4 yr. Among them, there were 61 patients (51%) who developed a total of 112 posttransplant GI complications. Of the entire 120 patients, 41 (34%) developed minor complications and 20 (17%) sustained major GI morbidity. Eighteen patients (15%) underwent either endoscopy or surgical intervention. These data suggest that most cardiac transplant recipients will experience some form of GI complication, although most are minor and can be managed conservatively. However, when major, life-threatening complications occur, evaluation and intervention should proceed expeditiously. The gastroenterologist and GI surgeon should play complimentary roles in the care of these complicated patients.

Adolescent↗

PubMed1990

Early effects of colectomy and endorectal pullthrough operation on biliary lipid composition.

In order to determine the effects of total colectomy and endorectal pullthrough with ileal reservoir (ERP) on biliary lipid composition in the early postoperative period, gallbladder bile of dogs was examined after biliary cannulation alone (control); biliary cannulation and colectomy with ileorectal anastomosis (IRA); and biliary cannulation, colectomy with mucosal proctectomy, and ERP. Bile collected from 3 to 6 weeks postoperation was analyzed for total bile acids, cholesterol, phospholipids, bilirubin, and calcium concentrations. Cholesterol saturation was calculated. Serum collected over the same period was analyzed for electrolytes and liver function tests. There was no evidence of sludge or gallstones post-operatively in any animal. Significant decreases in total bile acids, phospholipids, and calcium concentrations were noted in the bile of the IRA group when compared to the bile of the controls (P less than 0.05) and in total bile acids, cholesterol, phospholipids, and calcium in ERP vs controls (P less than 0.05). Moreover, all three biliary lipids and calcium were significantly decreased in ERP animals compared to those in the IRA group (P less than 0.05). No change in cholesterol saturation was noted between any of the three groups. Other than an increase in alkaline phosphatase concentrations compared to preoperative levels (P less than 0.05) which was noted in all groups, no significant changes were noted in serum parameters. We conclude that during the early postoperative period, ERP causes a significant decrease in gallbladder bile concentrations of total bile acids, cholesterol, phospholipids, and calcium which cannot be explained by colectomy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal Canal↗

PubMed1990

Host regulation of the cauliflower mosaic virus multiplication cycle.

The DNA genome of cauliflower mosaic virus (CaMV) replicates in the cytoplasm of infected plant cells by reverse transcription of an RNA template. Viral RNA is generated in the nucleus by transcription of an episomal minichromosome containing supercoiled DNA. We have assessed the relative activities of the nuclear and cytoplasmic phases of the CaMV multiplication cycle by monitoring unencapsidated viral DNA forms and polyadenylylated RNAs in different organs of one host plant and in different host species. Systemically infected leaves of a highly susceptible host, turnip (Brassica rapa), contained abundant 35S RNA and 19S RNA transcripts and unencapsidated reverse transcription products but relatively little supercoiled DNA. In contrast, supercoiled DNA accumulated in roots and other tissues of turnip plants but without significant amounts of steady-state viral RNA. Infected but asymptomatic leaves of a less susceptible CaMV host, kohlrabi (Brassica oleracea), contained supercoiled DNA almost exclusively but negligible viral RNA and DNA products of reverse transcription. An allotetraploid species, rape (Brassica napus), exhibited infection characteristics and minichromosome expression levels intermediate between the other two species from which it was derived. We conclude that expression of the CaMV minichromosome is a key phase of the virus multiplication cycle, which is regulated differentially in organs of a highly susceptible host species. Furthermore, this regulation exhibits genetic variation among different Brassica species and controls host susceptibility to CaMV infection.

Blotting, Northern↗

PubMed1990

Susceptibility of Brassica species to cauliflower mosaic virus infection is related to a specific stage in the virus multiplication cycle.

The relative susceptibilities and symptom responses of different Brassica species to infection by cauliflower mosaic virus (CaMV) have been compared and related to molecular events of the virus multiplication cycle. Variants of B. rapa (genome descriptor aa) were highly susceptible to infection by CaMV strain Cabb B-JI and contained relatively large amounts of virus; B. oleracea (cc) variants showed low susceptibility and contained small amounts of virus. B. nigra (bb) and allotetraploid species. B. juncea (aabb), B. napus (aacc) and B. carinata (bbcc), showed moderate responses to CaMV. CaMV unencapsidated DNA forms were isolated from different Brassica plants and examined by two-dimensional gel electrophoresis and blot hybridization. Viral RNA was estimated by dot blot analysis. These analyses showed differences in accumulation of key viral replication cycle intermediates within the broad range of host plants studied. The most susceptible species contained relatively small amounts of supercoiled (SC) DNA, a component of the CaMV mini-chromosome, but abundant viral transcripts and reverse transcription replication products. Tolerant plant hosts contained high levels of SC DNA but low levels of viral transcripts and reverse transcription DNA products. Allotetraploids contained SC DNA, RNA transcripts and replication product levels which were generally intermediate between those of their respective progenitor species. Evidence is presented that accumulation of CaMV SC DNA in the less susceptible host species is probably not due to autonomous DNA replication or tissue-specific expression. We conclude that a major component of the susceptibility of Brassica plants (and probably all CaMV host species) to CaMV infection is the level of viral minichromosome expression, influenced directly by the host genotype.

Brassica↗

PubMed1990

Changing patterns in diagnosis and management of bile duct cancer.

An analysis of 186 patients treated for bile duct cancer at UCLA Medical Center from November 1954 to December 1988 demonstrated improvements in several areas of diagnosis and management. Comparison of 96 patients treated between 1954 and 1978 (group 1) with 90 patients treated between 1978 and 1988 (group 2) showed earlier diagnosis and treatment in group 2 (2.1 months from onset of symptoms) than in group 1 (4.9 months; p less than 0.05) and this was correlated with increased use of ultrasonography, computed tomographic (CT) scans, transhepatic cholangiography, and endoscopic retrograde cholangiopancreatography. Operative mortality rates were lower in group 2 (4%) than in group 1 (12%) and the difference was most marked in patients with upper-third lesions, where resections in group 1 had a 23% operative mortality rate but group 2 resected patients had zero mortality (p less than 0.001). A program of operative staging and selection of patients for resection or palliative procedures has resulted in better operative risks with no deterioration in survival.

Adenoma, Bile Duct↗

PubMed1989

Characterization of a loss-of-function mutation in the isopenicillin N synthetase gene of Acremonium chrysogenum.

The N-2 strain of Acremonium chrysogenum accumulates the beta-lactam precursor tripeptide delta-(L-alpha-amino-adipoyl)-L-cysteinyl-D-valine and has no discernible activity for three of the cephalosporin C (Ce) biosynthetic enzymes. This phenotype is consistent with a mutation either within pcbC [the isopenicillin N synthetase (IPNS)-encoding gene] or in a pathway-regulator gene. To distinguish these possibilities we have cloned and sequenced pcbC from strain N-2. There is a single C----T mutation at nt 854 within the coding sequence, changing aa 285 from proline to leucine. An IPNS-specific monoclonal antibody recognises a catalytically inactive IPNS protein in extracts of N-2 cells. These findings suggest that strain N-2 carries a simple IPNS mutation and that IPNS or its biosynthetic product isopenicillin N is involved in regulation of the later stages of the Ce biosynthetic pathway.

Acremonium↗

PubMed1989

Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro.

A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing and epithelial disruption. Electron microscopy showed a toxic effect of pneumolysin on epithelial cells: cytoplasmic blebs, mitochondrial swelling, cellular extrusion, and cell death, but no change in ciliary ultrastructure. Recombinant pneumolysin (10 micrograms/ml) caused ciliary slowing in the absence of changes in cell ultrastructure. Release of pneumolysin in the respiratory tract during infection may perturb host defenses, allowing bacterial proliferation and spread.

Autolysis↗