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Biomedical subjects

D A Watson

Publications and source records attributed to D A Watson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Identification, cloning, and sequencing of DNA essential for encapsulation of Streptococcus pneumoniae.

This paper reports the cloning and sequencing of a region of DNA from Streptococcus pneumoniae serotype 3 surrounding transposon Tn916, insertion of which was previously shown to result in lack of expression of the extracellular capsule. Sequence analysis revealed that the transposon inserted into a consensus insertion site 71 bp from the 5' end of the cloned fragment. Within the clone, 3' downstream regions from two different pneumococcal lytA genes were identified, as well as a putative 194 AA open reading frame (ORF1). Moreover, two copies of the repeat element BOX, oriented in opposite directions, were located immediately 3' of orf1. Within the region bounded by the first pair of internal sequencing primers, analysis revealed that the fragment amplified by PCR was always of the same size. Moreover, Southern blotting showed that for all serotypes examined to date, homology exists with the cloned fragment. These results indicate that this region of the chromosome is highly conserved and, taken together with other independently derived data, suggest that interruptions or deletions within this DNA lead to unencapsulation.

Bacterial Capsules↗
PubMed1995

Pneumococcal virulence factors and host immune responses to them.

The principal virulence determinant of most encapsulated bacterial pathogens is the possession of an extracellular capsule. This paper discusses biological aspects of the Streptococcus pneumoniae capsule, putative roles played by accessory virulence factors of this pathogen and prospects for improvement of the currently available pneumococcal vaccine. Even though the interruption of genes encoding selected proteins has been shown to attenuate virulence to some degree, the physical removal of the pneumococcal capsule or the interruption of encapsulation genes completely abolishes virulence in mice. The role of the capsule in pathogenesis is not completely clear, however, since it is not known whether this structure is important in colonization, the obligatory first step in the process. In addition, a number of proteins have been implicated as possible accessory virulence factors. These include pneumolysin, two distinct neuraminidases, an IgA1 protease and two surface proteins, pspA and psaA. While interruption of the expression of some of these proteins examined to date has been shown to attenuate virulence, so far it has not proven possible to completely abolish virulence in this fashion. Proteinaceous accessory virulence factors may prove important to the development of second-generation pneumococcal vaccines, however. Pneumococcal and other proteins conjugated to pneumococcal polysaccharides are currently being evaluated as carriers in attempts to improve the immunogenicity of polysaccharide vaccines, primarily in small children.

Animals↗
PubMed1995

Mitral valve replacement with the Carpentier-Edwards standard bioprosthesis: performance into the second decade.

From March 1978, 196 Carpentier-Edwards standard bioprostheses (stCE) were implanted in 194 patients. There were 154 isolated mitral valve replacements (MVR) and 42 aortic plus mitral valve replacements (AVR/MVR) with a mean follow-up of 7.05 (range 0-15.2) years and 7.15 (range 0-13.8) years, respectively. Freedom from structural valve failure at 10 years was 70.8% +/- 4.9% (MVR) and 59.6% +/- 11.1% (AVR/MVR). The incidence of structural valve failure increased sharply after 7 years. Freedom from thromboembolism was 83.0% +/- 3.8% (MVR) and 89.0 +/- 6.0% (AVR/MVR). Thromboembolic events were related to the presence of atrial fibrillation in patients not receiving anticoagulation. Anticoagulant-related haemorrhage was rare. Freedom from mitral valve prosthetic endocarditis at 10 years was 90.9% +/- 3.1% (MVR) and 86.1% +/- 8.4% (AVR/MVR). Prosthetic valve endocarditis was associated with more than 60% mortality. The probability of event-free survival at 10 years follow-up was 43.6% +/- 4.6% (MVR) and 33.3% +/- 8.6% (AVR/MVR). The performance of the stCE in the mitral position shows a low rate of thromboembolic events and anticoagulant-related haemorrhage, but the long-term performance of the prosthesis is unsatisfactory due to a high rate of structural valve failure. This confirms earlier reports.

Adult↗
PubMed1995

Molecular epidemiology of infections due to Enterobacter aerogenes: identification of hospital outbreak-associated strains by molecular techniques.

Molecular techniques were used to study the epidemiology of infections due to Enterobacter aerogenes in a tertiary-care hospital. Sixty-two clinical isolates were collected from 43 patients over 3 months. Restriction endonuclease analysis (REA) of chromosomal DNA and repetitive-element polymerase chain reaction (rep-PCR) with primers based on repetitive extragenic palindromic (REP) and enterobacterial repetitive intergenic consensus (ERIC) bacterial DNA sequences were used for genomic fingerprinting. REA with HindIII or EcoRI yielded complex banding patterns that differentiated community-acquired from some hospital-acquired organisms. Less complex fingerprints were obtained with rep-PCR, which also distinguished between epidemiologically unrelated strains. More discriminatory DNA fingerprints were provided by rep-PCR when REP primers rather than ERIC primers were used. Two clusters of genomically distinct isolates from patients with recent or current exposure to the hospital environment were identified by REA and rep-PCR. Most isolates within each cluster contained characteristic plasmids, and some isolates contained additional plasmids. These results suggest colonization and infection with genotypically related strains of E. aerogenes in a nosocomial setting. Although REA and plasmid profiling are useful techniques for the epidemiological typing of E. aerogenes, genomic fingerprinting with rep-PCR may offer the advantages of ease, speed, and broad species applicability over existing molecular-typing techniques.

Adult↗
PubMed1994

The Delta Valve: a physiologic shunt system.

PS Medical has advanced the state-of-the-art in hydrocephalus valve technology with the introduction of the Delta Valve. The Delta Valve is designed upon the premise that the shunted patient should have intracranial pressure (ICP) maintenance within a normal range regardless of cerebrospinal fluid (CSF) flow rate or body position. All previous valves have performance characteristics that are greatly influenced by the negative hydrostatic pressure caused by the gravitational effect on the vertical water column in the distal catheter. This negative pressure influence is non-physiologic and contributes directly to overdrainage that can cause slit ventricles, subdural hematoma, and proximal catheter occlusions. The Delta Valve is the only valve that maintains a near-constant pressure gradient regardless of flow rate or patient posture. It automatically adjusts for increasing negative pressures in the distal catheter by proportionally increasing its resistance to flow, thus nullifying the adverse effects of the hydrostatic force on intracranial pressures. The result is a shunt system that provides for CSF drainage while allowing the patient's normal physiologic conditions to control ICP. The early use of the Delta Valve in the treatment of hydrocephalus may reduce the incidence of the dramatic complications associated with overdrainage.

Cerebral Ventricles↗
PubMed1994

Molecular fingerprinting of Legionella species by repetitive element PCR.

Repetitive element PCR (rep-PCR) uses outward-facing primers to amplify multiple segments of DNA located between conserved repeated sequences interspersed along the bacterial chromosome. Polymorphisms of rep-PCR amplification products can serve as strain-specific molecular fingerprints. Primers directed at the repetitive extragenic palindromic element were used to characterize isolates of Legionella pneumophila and other Legionella species. Substantial variation was seen among the rep-PCR fingerprints of different Legionella species and serogroups. More limited, but distinct, polymorphisms of the rep-PCR fingerprint were evident among epidemiologically unrelated isolates of L. pneumophila serogroup 1. Previously characterized Legionella isolates from nosocomial outbreaks were correctly clustered by this method. These results suggest the presence of repetitive extragenic palindromic-like elements within the genomes of members of the family Legionellaceae that can be used to discriminate between strains within a serogroup of L. pneumophila and between different Legionella species. rep-PCR appears to be a useful technique for the molecular fingerprinting of Legionella species.

DNA Fingerprinting↗
PubMed1993

Antibody to capsular polysaccharides of Streptococcus pneumoniae: prevalence, persistence, and response to revaccination.

The prevalence of immunity to Streptococcus pneumoniae in the adult population of the United States is unknown. In the study described herein, military recruits had anticapsular IgG antibody to only 15% of common pneumococcal serotypes, whereas working men and elderly men had IgG antibody to 33% and 34% of the common serotypes, respectively (P < .001). Among eight elderly subjects, the prevalence of IgG antibody to capsular polysaccharides increased from 30% to 78% after pneumococcal vaccination; 6 years thereafter, the rate of positive reactions had declined to 58% and IgG levels had declined substantially. With revaccination, IgG levels returned to within (+/-) 40% of the original postvaccination levels. IgM and IgG antibody appeared or began to increase in titer 6 days after vaccination; the rate and degree of response were the same after the first and second exposures. Since most individuals rapidly develop IgG antibody after colonization by S. pneumoniae and since IgG confers immunity, these data suggest that pneumonia is infrequent among healthy adults not because preexisting immunity is widespread but because--with colonization--an immune response develops rapidly, preceding specific events that might lead to infection. Our findings support recommended vaccination procedures and suggest that wider application in subsets of healthy younger adults should be considered.

Adolescent↗
PubMed1993

A brief history of the pneumococcus in biomedical research: a panoply of scientific discovery.

Because of its prominence as a cause of disease in humans, Streptococcus pneumoniae has been the subject of intensive investigation at both the clinical level and the basic scientific level during the past century. In a number of instances, these studies have resulted in important progress toward the comprehension of basic biological principles. The areas advanced by studies of the pneumococcus include an understanding of the concept of pathogenesis of infectious disease; the development of Gram's stain for identification of bacteria in specimens from patients; the elucidation of the role of the bacterial capsule in resistance to phagocytosis by cells of the host's immune system; the demonstration that molecules other than proteins are capable of eliciting the host's humoral immune responses and later, by extension, that isolated bacterial exopolysaccharides can be used safely and effectively as vaccines in humans; the documentation of the efficacy of penicillin; the collection of conclusive evidence that DNA encodes genetic information; and the investigation of putative proteinaceous virulence factors.

Animals↗
PubMed1993

Liposome-encapsulated gentamicin treatment of Mycobacterium avium-Mycobacterium intracellulare complex bacteremia in AIDS patients.

TLC G-65, a liposome-encapsulated gentamicin, was given intravenously twice weekly for 4 weeks to AIDS patients with Mycobacterium avium-M. intracellulare complex (MAC) bacteremia at 1.7 mg of gentamicin per kg of body weight per infusion (4 patients), 3.4 mg/kg (10 patients), and 5.1 mg/kg (7 patients). MAC colony counts in blood fell by 75% or more in all three groups (P < 0.005). Drug resistance did not emerge during the study period. Transient renal insufficiency developed in one patient; no other adverse effects were detected. Liposome-encapsulated gentamicin is a potential therapy for MAC infections in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

IgG antibody reactive with five serotypes of Streptococcus pneumoniae in commercial intravenous immunoglobulin preparations.

Intravenous immunoglobulin replacement is recommended for immunoglobulin deficiency, but comparison of the efficacy of intravenous immunoglobulin preparations (IVIGs) has been hindered by the lack of standardized assays to measure immunoglobulin levels against important bacterial pathogens. IgG reactive with five commonly isolated serotypes of Streptococcus pneumoniae in four commercially available IVIGs was measured by ELISA. Specific antibody to capsular polysaccharide was quantitated before and after adsorption with cell wall polysaccharide (CWPS). All IVIGs contained measurable levels of antibody to the five pneumococcal serotypes, although the levels against an individual serotype varied by as much as sevenfold from one preparation to another. Each IVIG also contained substantial concentrations of IgG reactive with CWPS. The amount of each IVIG that protected mice was nearly identical after the doses were adjusted on the basis of specific IgG measured by ELISA, thereby providing proof in vivo of the validity of this in vitro assay system.

Animals↗
PubMed1992

Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients.

OBJECTIVE: To investigate the efficacy of fluconazole prophylaxis against systemic fungal infections in HIV-positive patients. DESIGN: Open label treatment compared with historical controls. SETTING: Patients were seen at the Parkland Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28 February 1991. PATIENTS, PARTICIPANTS: Three hundred and thirty-seven historical controls were followed for 157 patient-years, and 329 fluconazole-treated patients for 145 patient-years. INTERVENTIONS: Fluconazole (100 mg daily) was administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l seen at our HIV clinic after 1 March 1990. MAIN OUTCOME MEASURES: Lysis-centrifugation blood cultures were recorded monthly for all patients during both study periods. RESULTS: Twenty infections (16 cryptococcosis, four histoplasmosis) occurred in 337 historical reference control patients (product-limit 1-year incidence, 7.5 +/- 2.0/year). Four infections (one cryptococcosis, three histoplasmosis) occurred in the treated patient group (product-limit 1-year incidence, 1.8 +/- 0.9/year). CONCLUSIONS: Fluconazole warrants further evaluation for prophylaxis against systemic fungal infections in HIV-positive patients.

Adult↗
PubMed1991

Pig-bel but no pig: enteritis necroticans acquired in Australia.

OBJECTIVE: To report a case of enteritis necroticans acquired in Australia, and to review the history, epidemiology, pathogenesis, clinical features, management and prevention of this disease. CLINICAL FEATURES: A 44-year-old diabetic and alcoholic restaurateur of Chinese-Malay origin, who had been living in Australia for over 20 years, was admitted to hospital with bloody diarrhoea which progressed to fulminant toxaemia and circulatory collapse, and ultimately required laparotomy. Typical pathological features and the isolation of Clostridium perfringens type C from faeces confirmed the diagnosis of enteritis necroticans. INTERVENTION AND OUTCOME: He was treated initially with ampicillin, gentamicin, metronidazole and chloramphenicol, and later with penicillin and metronidazole, and he required large volumes of intravenously administered fluid and blood for his toxaemic, hypotensive state. Laparotomy was performed as a life-saving procedure. Despite a lengthy convalescence, the patient recovered. CONCLUSIONS: Enteritis necroticans is a rare disease in developed countries, however it is likely to be underdiagnosed. Clinicians are encouraged to be on the alert for signs of severity that may indicate the need for laparotomy in a predisposed individual with features of this condition.

Adult↗
PubMed1990

Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide.

Available pneumococcal vaccines provide only limited protection for certain at-risk populations. Fifteen healthy young adults and 11 older chronic bronchitics received 23-valent pneumococcal vaccine. ELISA showed that IgG reactive with capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 8, 14, and 19F increased after vaccination. Bronchitics exhibited lesser responses for four of these serotypes, although differences between the groups were significant only for serotype 3. Adsorption of postvaccination sera with pneumococcal cell wall polysaccharide significantly reduced mean antibody levels in both groups and lowered the proportion of sera that demonstrated type-specific antibody responses. Reactive IgG was largely restricted to the IgG2 subclass. Pneumococcal vaccine may provide suboptimal protection of older adults because antibody responses to some capsular polysaccharides are lower in elderly bronchitics than in healthy young adults. A substantial proportion of measured antibody reflects IgG reactive with cell wall polysaccharides rather than with type-specific, capsular constituents, suggesting that antibody responses in subjects of all ages deserve reappraisal.

Adsorption↗
PubMed1990

Does naturally acquired IgG antibody to cell wall polysaccharide protect human subjects against pneumococcal infection?

Antibody to the non-serotype-specific cell wall polysaccharide (CWPS) of Streptococcus pneumoniae has been said to confer a degree of non-serotype-specific protection against pneumococcal infection. The hypothesis underlying the present study was that if this antibody is protective, relatively higher levels are likely to be detected in patients who are colonized by pneumococci but do not have infection, those who have febrile bronchitis but do not have pneumonia, and those who have pneumococcal pneumonia but are not bacteremic. Mean IgG reactive with CWPS by ELISA in 15 healthy young adults was 43.9 micrograms/ml and in 126 randomly selected hospital patients of all ages was 41.9 micrograms/ml. In subjects with chronic bronchitis with or without known pneumococcal carriage, mean anti-CWPS IgG was 87.7 micrograms/ml. In three groups of patients (3 with acute purulent tracheobronchitis, 13 with nonbacteremic pneumococcal pneumonia, and 14 with S. pneumoniae bacteremia) at the time of admission, mean antibody levels were essentially identical, 104.9-110.1 micrograms/ml. The data suggest that naturally present anti-CWPS IgG does not protect against the evolution of acute pneumococcal infection from colonization to acute purulent bronchitis, from bronchitis to pneumonia, or from pneumonia to bacteremia.

Adsorption↗
PubMed1990

The effect of HIV infection on phagocytosis and killing of Staphylococcus aureus by human pulmonary alveolar macrophages.

Pulmonary alveolar macrophages (PAM) play a central role in host defense against pulmonary infection. The authors studied the number, viability, and ultrastructure of PAM recovered by bronchoalveolar lavage from normal and HIV-infected subjects, and their ability to phagocytose and kill Staphylococcus aureus. PAM from HIV-infected subjects who did not have pneumonia were present in greater numbers and phagocytosed significantly more opsonized Staphylococcus aureus (32.5% and 27.3% for nonsmokers and smokers, respectively) than did PAM from healthy controls (19.5% and 18.2%). In 15 patients with AIDS and pneumonia (due to Pneumocystis carinii in 13/15), viability of PAM and their phagocytic capacity were significantly reduced; in smokers with AIDS and pneumonia, the PAM yield was also dramatically decreased. Killing of S. aureus was similar by PAM from all patient groups. HIV infection was associated with the electron microscopic finding in PAM of extensively ruffled PAM cell-surfaces and ingestion of lymphocytes. Thus, HIV infection stimulates the phagocytic capacity and produces morphologic changes consistent with the possibility that PAM are activated by this retroviral infection. In patients with AIDS who develop pneumonia, especially in smokers, the number, viability and phagocytic capacity of PAM are significantly decreased; our study could not determine whether this diminished activity reflects evolution of the HIV infection or a secondary effect of the pneumonia.

Adult↗