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Biomedical subjects

L Johnson

Publications and source records attributed to L Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Tryptophan depletion in lithium-stabilized patients with affective disorder.

Central serotonergic function abnormalities are thought to be associated with the pathogenesis of affective disorder. Reduced serotonergic function, induced by tryptophan depletion, has in several studies transiently reversed the antidepressant effect of SSRIs in depressed patients in remission. Serotonergic pathways are suggested to be of importance in the mechanisms of the action of lithium. The purpose of this study was to investigate whether the stabilizing effect of lithium is dependent on short-term availability of serotonin. Tryptophan depletion was induced in thirty patients with affective disorder (20 bipolar and 10 unipolar), all stabilized on lithium treatment for at least one year. The study was performed using a randomized, double-blind, controlled design. Plasma tryptophan was reduced by 80% in the experimental group and 16% in the control group. However, no clinically relevant mood changes were observed. Transient reduction in serotonergic function does not seem to affect mood in affective-disorder patients stabilized on lithium treatment.

Adrenocorticotropic Hormone↗
PubMed2001

Wildtype Kras2 can inhibit lung carcinogenesis in mice.

Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.

Animals↗
PubMed2001

Gene delivery from the E3 region of replicating human adenovirus: evaluation of the 6.7 K/gp19 K region.

The use of genetically engineered, replication-selective viruses to treat cancer is being realized with viruses such as ONYX-015, a human adenovirus that selectively destroys p53 mutant cancer cells. To enhance further the clinical efficacy of ONYX-015 and viruses like it, we have developed a novel gene delivery system for replicating adenoviruses. This system has two unique features. First, it uses the endogenous adenoviral gene expression machinery (promoter, splicing, polyadenylation) to drive transgene expression. Second, a single region or gene in the multi-gene E3 transcription unit is selectively substituted for by the therapeutic transgene(s). Analyzing various transgene substitutions for the 6.7 K/gp19 K region of E3, we demonstrate the following: (1) transgene expression in this system is predictable and mimics the substituted endogenous gene expression pattern, (2) expression of surrounding E3 genes can be retained, (3) the insertion site choice can effect both the transgene expression level and the viral life cycle, and, (4) expression levels from this system are superior to those generated from a replication-defective virus using the HCMV enhancer-promoter and this is dependent on viral DNA replication. This unique methodology has broad application to the rapidly evolving field of replicating virus-based therapies.

Adenovirus E3 Proteins↗
PubMed2001

High resolution protein localization using soft X-ray microscopy.

Soft X-ray microscopes can be used to examine whole, hydrated cells up to 10 microm thick and produce images approaching 30 nm resolution. Since cells are imaged in the X-ray transmissive "water window", where organic material absorbs approximately an order of magnitude more strongly than water, chemical contrast enhancement agents are not required to view the distribution of cellular structures. Although living specimens cannot be examined, cells can be rapidly frozen at a precise moment in time and examined in a cryostage, revealing information that most closely approximates that in live cells. In this study, we used a transmission X-ray microscope at photon energies just below the oxygen edge (lambda = 2.4 nm) to examine rapidly frozen mouse 3T3 cells and obtained excellent cellular morphology at better than 50 nm lateral resolution. These specimens are extremely stable, enabling multiple exposures with virtually no detectable damage to cell structures. We also show that silver-enhanced, immunogold labelling can be used to localize both cytoplasmic and nuclear proteins in whole, hydrated mammary epithelial cells at better than 50 nm resolution. The future use of X-ray tomography, along with improved zone plate lenses, will enable collection of better resolution (approaching 30 nm), three-dimensional information on the distribution of proteins in cells.

3T3 Cells↗
PubMed2001

Participation in arranging continuing health care packages: experiences and aspirations of service users.

AIMS: This paper examines patients' and carers' experiences of receiving community health services, and considers the degree of patients' participation in the management of their continuing care. BACKGROUND: Care management, advocated for many years as a way of ensuring appropriate and coordinated care, emphasizes the involvement of patients and carers in care planning. Evidence suggests that such involvement is unusual. METHODS: Semi-structured interviews were carried out with 99 continuing health care patients and/or their carers. FINDINGS: A few informants had willingly chosen to be active in arranging and coordinating their care, and a few others, who did not take an active role, were very satisfied with the services which they received. The majority, however, were not satisfied, feeling unclear about how their needs had been assessed and how services had been arranged. They were mostly disappointed by the absence of information and by the lack of regular contact with NHS and/or Social Services personnel. Some had felt compelled to become proactive in order to ensure that the care provided was adequate. CONCLUSIONS: Community nurses are valued by patients, and are well placed to be care managers. However, less qualified staff are also able to offer the regular support and information which patients want and value.

Adult↗
PubMed2001

Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans.

The pathogenic fungus Candida albicans is capable of responding to a wide variety of environmental cues with a morphological transition from a budding yeast to a polarized filamentous form. We demonstrate that the Ras homologue of C. albicans, CaRas1p, is required for this morphological transition and thereby contributes to the development of pathogenicity. However, CaRas1p is not required for cellular viability. Deletion of both alleles of the CaRAS1 gene caused in vitro defects in morphological transition that were reversed by either supplementing the growth media with cAMP or overexpressing components of the filament-inducing mitogen-activated protein (MAP) kinase cascade. The induction of filament-specific secreted aspartyl proteinases encoded by the SAP4-6 genes was blocked in the mutant cells. The defects in filament formation were also observed in situ after phagocytosis of C. albicans cells in a macrophage cell culture assay and, in vivo, after infection of kidneys in a mouse model for systemic candidiasis. In the macrophage assay, the mutant cells were less resistant to phagocytosis. Moreover, the defects in filament formation were associated with reduced virulence in the mouse model. These results indicate that, in response to environmental cues, CaRas1p is required for the regulation of both a MAP kinase signalling pathway and a cAMP signalling pathway. CaRas1p-dependent activation of these pathways contributes to the pathogenicity of C. albicans cells through the induction of polarized morphogenesis. These findings elucidate a new medically relevant role for Ras in cellular morphogenesis and virulence in an important human infectious disease.

Animals↗
PubMed2001

A consumer's perspective of a suicide intervention programme.

The objective of this study was to assess the impact of a suicide intervention program from a consumer perspective. Self-administered questionnaires were distributed to consumers who had been referred to a suicide intervention counsellor in the 2-year period of the programme in rural southwest Western Australia. Three-quarters of respondents were positive about their experience with the service, with half of the respondents no longer having thoughts of suicide and only 20% of all respondents reporting having attempted deliberate self-harm postcounselling. Reported suicidal ideation and attempted self-harm were much higher in the dissatisfied group. Dissatisfaction of respondents stemmed from the history of their treatment and 'the hassle created by the many systems for them to access care'. However, the overall outcome of this study is that, from the consumer's perspective, a high intensity approach to suicide intervention resolved or improved the presenting problem and their ability to deal with it.

Adaptation, Psychological↗
PubMed2001

Live human germ cells in the context of their spermatogenic stages.

BACKGROUND: Various types of live, dispersed, human testicular cells in vitro were previously compared with the morphologic characteristics of human spermatogenic germ cells in situ within seminiferous tubules. The current study extends those observations by placing live human germ cells in the context of their developmental steps and stages of the spermatogenic cycle. METHODS: Live human testicular tissue was obtained from an organ-donating, brain-dead person. A cell suspension was obtained by enzymatic digestion, and dispersed cells were observed live with Nomarski optics. Testes from 10 men were obtained at autopsy within ten hours of death, fixed in glutaraldehyde, further fixed in osmium, embedded in Epon, sectioned at 20 microm, and observed unstained by Nomarski optics. RESULTS: In both live and fixed preparations, Sertoli cells have oval to pear-shaped nuclei with indented nuclear envelopes and large nucleoli, which makes their appearance distinctly different from germ cells. For germ cells, size, shape, and chromatic pattern of nuclei, the presence of meiotic metaphase figures, acrosomic vesicles/structures, tails, and/or mitochondria in the middle piece are characteristically seen in live dispersed cells and those in the fixed seminiferous tubules. These lead to identification of live germ cells in man and placement of each in the context of their developmental steps of spermatogenesis at corresponding stages of the spermatogenic cycle. CONCLUSIONS: This comparative approach allows verification of the identity of individual germ cells seen in vitro and provides a checklist of distinguishing characteristics of live human germ cells to be used in clinical procedures or by scientists interested in studying live cells at known steps in spermatogenic development characteristic of germ cells in specific stages of the spermatogenic cycle.

Acrosome↗
PubMed2001

Are concerns over right laparoscopic donor nephrectomy unwarranted?

OBJECTIVE: To examine the ability of several large, experienced transplantation centers to perform right-sided laparoscopic donor nephrectomy safely with equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early reports noted a higher incidence of renal vein thrombosis and eventual graft loss. However, exclusion of right-sided donors would deprive a significant proportion of donors a laparoscopically harvested graft. METHODS: A retrospective review was performed among 97 patients from seven centers performing right-sided laparoscopic donor nephrectomy. Surgical and postoperative demographic factors were evaluated. Complications were identified and long-term renal allograft function was compared with historical left-sided laparoscopic donor nephrectomy cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying reasons, including multiple left renal arteries or veins, smaller right kidney, or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients secondary to bleeding or anatomical anomalies. Mean warm ischemic time was limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5 +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost during the early experience of these centers to renal vein thrombosis. Both surgical and postoperative complications were limited, with few long-term adverse effects. Mean serum creatinine levels were higher than open and left laparoscopic donor nephrectomy on postoperative day 1, but at all remaining intervals the right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These results confirm that right laparoscopic donor nephrectomy provides similar patient benefits, including early return to diet and discharge. Long-term creatinine values were no higher than in traditional open donor or left laparoscopic donor cohorts. These results establish that early concerns about high thrombosis rates are not supported by a multiinstitutional review of laparoscopic right donor nephrectomies.

Adolescent↗
PubMed2001

Inosine-5'-monophosphate dehydrogenase is required for mitogenic competence of transformed pancreatic beta cells.

The relation of inosine-5'-monophosphate dehydrogenase (IMPDH; the rate-limiting enzyme in GTP synthesis) to mitogenesis was studied by enzymatic assay, immunoblots, and RT-PCR in several dissimilar transformed pancreatic ss-cell lines, using intact cells. Both of the two isoforms of IMPDH (constitutive type 1 and inducible type 2) were identified using RT-PCR in transformed beta cells or in intact islets. IMPDH 2 messenger RNA (mRNA) and IMPDH protein were both regulated reciprocally by changes in levels of their end-products. Flux through IMPDH was greatest in rapidly growing cells, due mostly to increased uptake of precursor. Glucose (but not 3-0-methylglucose, L-glucose, or fructose) further augmented substrate uptake and also increased IMPDH enzymatic activity after either 4 or 21 h of stimulation. Serum or ketoisocaproate also increased IMPDH activity (but not uptake). Two selective IMPDH inhibitors (mycophenolic acid and mizoribine) reduced IMPDH activity in all cell lines, and, with virtually identical concentration-response curves, inhibited DNA synthesis (assessed as bromodeoxyuridine incorporation) in response to glucose, serum, or ketoisocaproate. Inhibition of DNA synthesis was reversible, completely prevented by repletion of cellular guanine (but not adenine) nucleotides, and could not be attributed to toxic effects. Despite the fact that modulation of IMPDH expression by guanine nucleotides was readily detectable, glucose and/or serum failed to alter IMPDH mRNA or protein, indicating that their effects on IMPDH activity were largely at the enzyme level. Precursors of guanine nucleotides failed, by themselves, to induce mitogenesis. Thus, adequate IMPDH activity (and thereby, availability of GTP) is a critical requirement for beta-cell proliferation. Although it is unlikely that further increases in GTP can, by themselves, initiate DNA synthesis, such increments may be needed to sustain mitogenesis.

3-O-Methylglucose↗
PubMed2001

Management of hepatic cysts by percutaneous drainage and instillation of tetracycline hydrochloride.

This paper reports two cases of benign hepatic cysts successfully treated by the instillation of tetracycline hydrochloride. The patients presented with solitary large symptomatic hepatic cysts and underwent ultrasound guided needle aspiration followed by the instillation of tetracycline hydrochloride. The cyst size diminished without complication and the patients have remained symptom free. We review the treatment of this uncommon entity and propose that injection of tetracycline hydrochloride is an effective nonoperative treatment of symptomatic solitary hepatic cysts.

Adolescent↗
PubMed2001

Developing a protocol for an educational software competition.

This project developed a protocol for the inaugural Instructional Software Competition of the American Dental Education Association (ADEA). The evaluation instrument was derived from the Guidelines for the Design of Educational Software developed by the ANSI-accredited Standards Committee for Dental Informatics. Eleven judges were calibrated in a conference call and rated a total of 30 submissions using a 66-question instrument. The maximum score was 204 points. The mean score of WWW-based programs was 106.7 points, and of CD-ROM-based programs 109.5 points. The summative review of the judging process identified several potential improvements, such as distinguishing between standalone programs and educational support material; increasing the number of answer choices on rating scales; differential weighting of criteria; and a more discriminative approach to judging formative and summative evaluations. We plan to improve the protocol by supporting the process through a Web-based application; calibrating judges with an online handbook; improving and adapting the rating instrument itself; using at least three judges for each program; and conducting a measurement study.

American Dental Association↗
PubMed2001

Quality of care in family planning clinics in Jamaica. Do clients and providers agree?

This paper uses data from 199 providers and 20 simulated clients collected at 50 public sector and Non Governmental Organization (NGO) health facilities islandwide in 1995 to compare the two groups' views on quality of care of family planning services. Each of the five components of quality of care studied can be improved in Jamaica. Nearly two-thirds of the simulated clients felt able to freely choose a contraceptive method; however, more adequate and appropriate information needs to be imparted to clients through improved counselling, including promotion of dual method use (against STD/HIV/AIDS and conception). The requirement that a woman must be menstruating to receive services has inadvertently resulted in many clients going away empty-handed (without counselling or condoms) when they visit family planning clinics. While providers generally treat clients well, training and service delivery practices need to be revised to improve the technical competence of providers. All of the providers would recommend these clinics to others, compared to a little over half of the simulated clients. Both the providers and simulated clients said that privacy should be strengthened, particularly in small facilities in rural areas. Many of these aspects of quality of care are being improved in Jamaica's public sector health facilities. Managers can learn more about quality of care by seeking the knowledge, opinions and experiences of both providers and clients.

Adult↗
PubMed2000

The modified rivermead mobility index: validity and reliability.

PURPOSE: This paper presents the evaluation of the following psychometric properties of the Modified Rivermead Mobility Index (MRMI): face/content validity, responsiveness, test-retest reliability, inter-rater reliability and internal consistency. This mobility scale represents a further development of the Rivermead Mobility Index (RMI). In its new form the scoring was adapted from a two-point to a six-point scale. The number of test items was reduced from fifteen to eight items in order to measure mobility-related items that physiotherapists consider being essential for demonstrating treatment effects in patients following a stroke. METHOD: A consensus exercise with forty-two physiotherapists attending a stroke care conference established face/content validity. Inter-rater and test-retest reliability were examined by assessing thirty patients by two independent raters selected from a pool of eight physiotherapists in two different settings, an elderly care unit and a stroke rehabilitation unit. All patients were hospitalised and had experienced a stroke within the past six weeks. Responsiveness was examined by calculating the effect size statistic on the admission and discharge score of sixteen acute patients following stroke. RESULTS: The results showed that the modified RMI was: responsive to change (effect size = 1.15), stable when tested on two occasions (paired t-test = 0.732; p = 0.47), highly reliable between raters (ICC = 0.98; p < 0.001) with high internal consistency (Cronbach's alpha = 0.93). CONCLUSIONS: These results suggest that when using the Modified RMI to assess patients in the early stages following stroke, similar results can be obtained by different raters, regardless of experience. However there needs to be a difference of more than 4.5 points (degree of measurement error at 95% confidence level) in the overall score to detect true changes in the patient's level of mobility.

Aged↗
PubMed2000

Correlates of enrollment in methadone maintenance treatment programs differ by HIV-serostatus.

OBJECTIVES: To identify correlates of enrollment in methadone maintenance treatment programs (MMTP) among a prospective cohort of injection drug users (IDUs) in Baltimore, Maryland. METHODS: A total of 1480 IDUs undergoing semi-annual HIV tests and interviews were studied between 1994 and 1998, during which time a needle exchange program was introduced. Longitudinal analysis using generalized estimating equations was used to identify correlates of MMTP participation over time. RESULTS: Although similar proportions of HIV-seropositive and -seronegative IDUs enrolled in MMTP during follow-up (26 versus 22%, respectively), correlates of enrollment differed by HIV-serostatus. Among HIV-seropositive participants, older age [adjusted odds ratio (AOR, 1.37)] was associated with enrollment in MMTP. Among HIV-seronegative IDUs, factors associated with not enrolling in MMTP were being African American (AOR, 0.22) and having been recently incarcerated (AOR, 0.62) or homeless (AOR, 0.72). In both groups, females were twice as likely to be enrolled in MMTP, and those with Medicaid were 1.5 times more likely to be enrolled. When behavioral factors were lagged one visit, needle exchange program attendance was positively associated with MMTP enrollment among HIV-negative IDUs (AOR, 2.10); however, this association diminished significantly over time as dedicated treatment slots for needle exchange program participants became saturated. CONCLUSIONS: These findings underscore the need to improve access to MMTP, especially to certain subgroups such as African-Americans, the homeless, incarcerated and uninsured. Our data suggest that health care providers and needle exchange programs can facilitate enrollment into MMTP provided that adequate treatment slots are consistently available to this particularly vulnerable population.

Adult↗
PubMed2000

The natural history of hepatitis C virus infection: host, viral, and environmental factors.

CONTEXT: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. OBJECTIVE: To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. DESIGN AND SETTING: Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. SUBJECTS: A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up. MAIN OUTCOME MEASURES: Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. RESULTS: Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. CONCLUSIONS: Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456

Adult↗