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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals. North American Lamivudine HIV Working Group.

OBJECTIVES: To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit. METHODS: For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period. RESULTS: Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x 10(6)/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 10(6)/l CD4 cells (P < 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (CI), 1.44-6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20-8.59). The RH progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85). CONCLUSION: In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

Anti-HIV Agents↗
PubMed1997

Teaching pharmacology to advanced practice nursing students: issues and strategies.

A pharmacology course should prepare the advanced practice nursing student to understand the cellular mechanisms of drug action and physiologic outcomes (pharmacodynamics); mechanisms of absorption, distribution, metabolism, and excretion of drugs (pharmacokinetics); and the clinical use of drugs in the diagnosis, prevention, and treatment of disease (pharmacotherapeutics). The goal of a pharmacology course for advance nursing practice is to provide practitioners with knowledge that provides a rational basis for pharmacologic management of patients with complex health problems. A pharmacology course should teach the student the principles of pharmacology along with the process of pharmacologic reasoning.

Curriculum↗
PubMed1997

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

Amino Acid Sequence↗
PubMed1997

The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B.

The NIM1 (for noninducible immunity) gene product is involved in the signal transduction cascade leading to both systemic acquired resistance (SAR) and gene-for-gene disease resistance in Arabidopsis. We have isolated and characterized five new alleles of nim1 that show a range of phenotypes from weakly impaired in chemically induced pathogenesis-related protein-1 gene expression and fungal resistance to very strongly blocked. We have isolated the NIM1 gene by using a map-based cloning procedure. Interestingly, the NIM1 protein shows sequence homology to the mammalian signal transduction factor I kappa B subclass alpha. NF-kappa B/I kappa B signaling pathways are implicated in disease resistance responses in a range of organisms from Drosophila to mammals, suggesting that the SAR signaling pathway in plants is representative of an ancient and ubiquitous defense mechanism in higher organisms.

Amino Acid Sequence↗
PubMed1997

Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS.

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

In vitro inhibition of Cryptosporidium parvum infection by human monoclonal antibodies.

Cryptosporidium parvum infection of the small epithelial intestine causes unremitting diarrhea and malabsorption that can lead to chronic and sometimes fatal illness in patients with AIDS. The illness may be ameliorated by passive oral immunoglobulin therapy. The objective of this study was to produce anti-Cryptosporidium human monoclonal antibodies for evaluation as potential therapy. All human monoclonal cell lines that produced C. parvum antibodies were originally generated from the peripheral blood lymphocytes of a human immunodeficiency virus-seronegative woman. She had recovered from C. parvum infection and had a high specific antibody titer. Hybridization of these lymphocytes with a tumor cell line was accomplished by hypo-osmolar electrofusion. Twelve clones were identified by enzyme-linked immunosorbent assay (ELISA) as secreting anti-Cryptosporidium antibodies after the initial hybridization. From the 12 positive clones, two high antibody-secreting clones, 17A and 17B, were maintained in long-term culture. A second hybridization produced two other human monoclonal cell lines, EC5 and BB2. Human monoclonal antibody from the first two cell lines bound to C. parvum sporozoites and oocysts by immunofluorescence. The ability of human monoclonal antibodies to inhibit C. parvum infection in vitro was assessed by using a human enterocyte cell line, HT29.74. The antibodies of the four different human hybridomas inhibited infection by 35 to 68% (P < 0.05) compared to a control irrelevant human monoclonal antibody derived in a similar fashion. Human monoclonal antibodies are candidate molecules for immunotherapy of C. parvum infection.

Animals↗
PubMed1997

A hospital/school science fair mentoring program for middle school students.

The Massachusetts General Hospital (MGH) and the James P. Timilty Middle School established a partnership to enhance science education, promote faculty development, and improve the health status and academic performance of all Timilty students. This article describes one of the Partnership's Science Connection programs, the Science Fair Mentoring Program, designed to enhance middle school science education, inform urban early adolescents about professions in the health field, inspire them to pursue postsecondary study in the health sciences, and prepare them for rigorous academic work in high school. In this program, hospital-based clinical and research staff mentor young adolescent students. The authors describe the planning, implementation, and evaluation of the Science Fair Mentoring Program as an innovative learning experience.

Adolescent↗
PubMed1997

Brain stem auditory-evoked response in relation to neonatal glucose metabolism.

Imprecise control of glucose homeostasis is a hallmark of neonatal glucose metabolism. A relatively wide range of glucose concentrations is considered 'euglycemic' (2.22-6.94 mmol/l, 40-125 mg/dl) in the neonatal period. We investigated the effects of a wide range of glucose concentrations on brain stem conduction time (BCT) I-V interpeak latency or prolonged wave V latency. Neonates were assessed by brain stem auditory-evoked response followed immediately by heelstick sampling to determine the blood glucose concentration. Twenty-seven appropriate for gestational age (AGA) term neonates (birth weight 3,245 +/- 766 g, mean +/- SD; gestational age 39 +/- 2 weeks) were studied 3.1 +/- 3.7 days after birth. Twenty-three AGA preterm neonates (birth weight 2,175 +/- 477 g; gestational age 35 +/- 1 weeks) were studied 6.0 +/- 7.2 days after birth. Brain stem conduction time wave I-V interpeak latency and wave V latency were determined in two trials using a Grason-Stadler ABR screener at a 60-decibel stimulation level in the right ear. Neonates were studied between 33 and 40 weeks gestational age. Although the blood glucose concentration ranged from 1.38 to 6.83 mmol/1 (25-123 mg/dl), there was no correlation between either brain stem conduction time wave I-V interpeak latency or wave V latency and blood glucose concentration. We conclude that alterations in glucose concentration within the generally accepted neonatal euglycemic range do not effect the functional status of the brain stem auditory pathway. We suggest that the data can be interpreted to affirm that tighter clinical control of glucose homeostasis is probably not required in the neonatal period.

Birth Weight↗
PubMed1997

Comparison of train-of-four and best clinical assessment during continuous paralysis.

Train-of-four (TOF) monitoring is recommended in published guidelines during use of continuous-infusion neuromuscular blocking agents (NMB) in the intensive care unit (ICU). To test that recommendation, dual protocols were established in a medical ICU after intensive nursing education. Paralyzed patients received either TOF monitoring with a goal of three twitches or best clinical assessment while receiving atracurium by continuous infusion. Demographics and mean duration of paralysis of 20 patients in the TOF group were no different than that of the 16 patients in the best clinical assessment group. Although most patients demonstrated atracurium tolerance over time, there was no difference between groups in total mg (+/- SEM) infused (10,460 +/- 2,409 versus 9,201 +/- 3,237) or mean microgram/kg/min (15.2 +/- 1.5 versus 12.0 +/- 1.1). The time to clinical recovery was no different between groups (50 +/- 10 versus 45 +/- 12 min). Two complications occurred in the TOF group, with pulmonary emboli despite prophylaxis and an unrecognized cerebrovascular accident in one patient each. We conclude that careful titration of NMB using clinical bedside markers should remain the standard of care with these drugs.

Adult↗
PubMed1997

Fingertip temperature during cardiopulmonary bypass.

Temperature changes in the nasopharynx, fingertip, forearm and extracorporeal circuit were continuously monitored, starting 10 min before and up to 16 min into the rewarming period of hypothermic (32 degrees C) cardiopulmonary bypass in 14 patients operated on for coronary artery revascularization. Arterial blood temperature was the first to increase after starting rewarming, followed by the nasopharynx and the fingertip temperatures. Fingertip temperature started to increase abruptly 6.2 (2.02 SD) min after rewarming started. At this point, nasopharyngeal temperature was 34.2 degrees C (1.42 SD) and took a further 8.3 min to reach 37 degrees C. Assuming that increasing fingertip temperature indicates a central thermoregulatory response to warming, we suggest that nasopharyngeal temperature is a poor monitor of brain temperature. We also suggest that fingertip temperature may be used to monitor the point at which cerebral temperature reaches 'normothermia'. Further body warming, using arterial temperatures > or = 39 degrees C, should be avoided because of the danger of brain hyperthermia.

Aged↗
PubMed1997

Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA125.

PURPOSE: A phase II study was performed of oral altretamine in 71 patients with ovarian carcinoma who entered clinical complete remission with CA125 levels less than 35 U/mL after initial or second-line chemotherapy, and relapsed more than 6 months later. Response was compared between standard and CA125-based criteria. PATIENTS AND METHODS: Altretamine 260 mg/m2 was given in divided doses daily for 14 days per month. Response was evaluated according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 45 of 66 eligible patients. Response was assessed according to precise CA125 criteria in 51 patients based on either a confirmed > or = 50% or > or = 75% decrease in CA125 levels. RESULTS: A combination of domperidone, dexamethasona, and chlorpromazine at night controlled toxicity in most patients, which was mainly nausea (National Cancer Institute criteria grade 2 or 3 in 27), vomiting (grade 2 or 3 in 19, grade 4 in one), and tiredness (grade 2 or 3 in 15). Responses (complete plus partial) were seen in 18 (40%; 95% confidence interval [CI], 25.4% to 54.6%) of those evaluated according to EORTC criteria and in 20 (39%; 95% CI, 25.5% to 52.9%) of those evaluated according to CA125 level. The overall response rate was 26 of 57 (45.6%) and was related to treatment-free interval: 6 to 12 months, 35%; 12 to 24 months, 52%; and greater than 24 months, 67%. The medium duration of response was 8 months. CONCLUSION: Oral altretamine is a useful agent in patients-who relapse after previously responsive ovarian cancer. Response evaluation by a strict CA125 definition gave a similar estimate of the efficacy of altretamine as EORTC criteria.

Administration, Oral↗
PubMed1997

Skeletal alteration to improve beef longissimus muscle tenderness.

A prerigor cut was made through the 12th thoracic vertebra of one side of the beef carcasses (Tendercut) studied (five unbranded), and the other sides served as the controls (C). After 48 h postmortem, the longissimus from each side was removed starting from the junction between the 5th and 6th lumbar vertebrae to the point between the 5th and 6th thoracic vertebrae. The longissimus muscle was cut into four equal boneless sections to determine the effectiveness of this treatment on improving tenderness at different locations along this muscle. The effects of Tendercut upon yield grade, sensory attributes, and tenderness of longissimus steaks were determined. This treatment did not affect (P > .05) yield grade, CIE L* a* b* values, chemical states of myoglobin, purge and cooking losses, and total collagen. Steaks located closer to the treatment site were more juicy than controls. Peak force values were not significantly different. Sarcomere length was longer (P < .05) and sensory panel ratings for myofibrillar tenderness, connective tissue, and overall tenderness were higher (P < .05), indicating that this skeletal alteration technique increased tenderness. Sensory data revealed that skeletal and connective tissue cuts at a single site (12th thoracic vertebrae) on the beef rib improved the tenderness along the entire length of the longissimus muscle. This study demonstrated that Tendercut, a simple process that does not require any new equipment or alterations to existing facilities to implement, is a viable tenderness enhancement technique.

Animals↗
PubMed1997

Clinical course of human immunodeficiency virus type 1 associated pulmonary tuberculosis during short-course antituberculosis therapy.

To describe the clinical response to antituberculosis therapy in HIV-1 disease, 49 HIV-1 positive Ugandan adults (mean age 29.4 years; 68% men) with active pulmonary tuberculosis (PTB) were studied in a trial of rifampicin containing short-course antituberculosisis regimens. At presentation, 18 patients were PPD non-reactors (PPD skin test induration < 2mm), ten patients (20%) had non-cavitary lung disease. The mean CD4 lymphocyte count at presentation was 339/microliters (+/- SD 275). Among patients with abnormal baseline clinical values, the median time to resolution of fever, weight gain of 10%, increase of haemoglobin to 10g/dl and of Karnofsky performance score (KPS) to 80 occurred before sputum smear and culture conversion. Short-term survival was associated with: baseline lymphocytes < 1200/microliters, (Odds ratio (OR) 17.5), CD4+ lymphocytes < 200/microliters (OR 9.8), cavitary lung disease, (OR 0.6), atypical chest radiograph, (OR 6.7), and PPD non-reactivity, (OR 13.5), PPD non-reactivity and non-cavitary disease were associated with significantly lower CD4 lymphocyte counts. Affordable serial measurements parallel the response to therapy and predict survival in HIV-associated PTB.

AIDS-Related Opportunistic Infections↗
PubMed1996

Characterization of human DSPG3, a small dermatan sulfate proteoglycan.

PG-Lb is a small dermatan sulfate proteoglycan that has been previously characterized in chicken. In the developing limb, chick PG-Lb appears to be exclusively expressed in the zone of flattened chondrocytes. We have cloned and sequenced the human homolog to chick PG-Lb from two human chondrocyte cDNA libraries and a human chondrocyte RNA sample. The human homolog has been named DSPG3, as it is the third member of the small dermatan sulfate proteoglycan family to be identified and characterized along with biglycan (PG-I) and decorin (PG-II). DSPG3 maps to chromosome 12q21 and is composed of 1515 nucleotides of cDNA that code for a 322-amino-acid protein. The protein contains three potential glycosaminoglycan attachment sites, two N-glycosylation sites, a poly- glutamic acid stretch, and six cysteines. By Northern analysis, we have demonstrated that DSPG3 is expressed in cartilage, as well as ligament and placental tissues.

Amino Acid Sequence↗
PubMed1996

Multiple gamma-Aminobutyric acid plasma membrane transporters (GAT-1, GAT-2, GAT-3) in the rat retina.

gamma-Aminobutyric acid (GABA) plasma membrane transporters (GATs) influence synaptic neurotransmission by high-affinity uptake and release of GABA. The distribution and cellular localization of GAT-1, GAT-2, and GAT-3 in the rat retina have been evaluated by using affinity-purified polyclonal antibodies directed to the C terminus of each of these GAT subtypes. Small GAT-1-immunoreactive cell bodies were located in the proximal inner nuclear layer (INL) and ganglion cell layer (GCL), and processes were distributed to all laminae of the interplexiform layer (IPL). Varicose processes were in the optic fiber layer (OFL) and the outer plexiform layer (OPL). Weak GAT-1 immunostaining surrounded cells in the INL and GCL, and it was found in the OFL and OPL and in numerous processes in the outer nuclear layer (ONL) that ended at the outer limiting membrane. GAT-1 is therefore strongly expressed by amacrine, displaced amacrine, and interplexiform cells and weakly expressed by Müller cells. GAT-2 immunostaining was observed in the retina pigment epithelium and the nonpigmented ciliary epithelium. GAT-3 immunoreactivity was distributed to the OFL, to all laminae of the IPL, GCL and INL, and to processes in the ONL that ended at the outer limiting membrane. Small GAT-3-immunoreactive cell bodies were in the proximal INL and GCL. GAT-3 is therefore strongly expressed by Müller cells, and by some amacrine and displaced amacrine cells. Together, these observations demonstrate a heterologous distribution of GATs in the retina. These transporters are likely to take up GABA from, and perhaps release GABA into, the synaptic cleft and extracellular space. This suggests that GATs regulate GABA levels in these areas and thus influence synaptic neurotransmission.

Amino Acid Sequence↗
PubMed1996

Regulation of in vitro gene expression using antisense oligonucleotides or antisense expression plasmids transfected using starburst PAMAM dendrimers.

Starburst polyamidoamine (PAMAM) dendrimers are a new type of synthetic polymer characterized by a branched spherical shape and a high density surface charge. We have investigated the ability of these dendrimers to function as an effective delivery system for antisense oligonucleotides and 'antisense expression plasmids' for the targeted modulation of gene expression. Dendrimers bind to various forms of nucleic acids on the basis of electrostatic interactions, and the ability of DNA-dendrimer complexes to transfer oligonucleotides and plasmid DNA to mediate antisense inhibition was assessed in an in vitro cell culture system. Cell lines that permanently express luciferase gene were developed using dendrimer mediated transfection. Transfections of antisense oligonucleotides or antisense cDNA plasmids into these cell lines using dendrimers resulted in a specific and dose dependent inhibition of luciferase expression. This inhibition caused approximately 25-50% reduction of baseline luciferase activity. Binding of the phosphodiester oligonucleotides to dendrimers also extended their intracellular survival. While dendrimers were not cytotoxic at the concentrations effective for DNA transfer, some non-specific suppression of luciferase expression was observed. Our results indicate that Starburst dendrimers can be effective carriers for the introduction of regulatory nucleic acids and facilitate the suppression of the specific gene expression.

Animals↗