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Biomedical subjects

D R Johnson

Publications and source records attributed to D R Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Unexplained reduced microbiological efficacy of intramuscular benzathine penicillin G and of oral penicillin V in eradication of group a streptococci from children with acute pharyngitis.

OBJECTIVE: To evaluate the efficacy of oral penicillin V and intramuscular benzathine penicillin G (BPG) in eradicating group A streptococci from the upper respiratory tract. METHODOLOGY: Two randomized, single-blind, multicenter antibiotic efficacy trials in children using recommended doses of either oral penicillin V or intramuscular BPG for treatment of acute-onset pharyngitis associated with isolation of group A streptococci were conducted. Throat examinations and cultures were obtained at enrollment and on days 5 to 8, 10 to 14, and 29 to 31. RESULTS: Thirty-five percent of 284 evaluable patients treated with oral penicillin V and 37% of BPG-treated patients were microbiologic treatment failures at either 10 to 14 or 29 to 31 days. CONCLUSIONS: Although these findings do not provide sufficient evidence to change current treatment recommendations or public health policy, important questions are raised about currently recommended penicillin doses, about the role of the carrier state, and possibly about adequate bioavailability of intramuscular BPG. These findings require confirmation.

Acute Disease↗
PubMed2001

Genetic characteristics of double hypoglossal canal as a nonmetric trait.

The hypothesis that the hypoglossal canal bridging or double (HGCD), a nonmetric cranial trait, is a powerful discriminator between populations (Dodo, 1980, 1987) is still controversial. To examine this issue, the incidences of HGCD were investigated in six inbred mice strains (CBA, C57BL, BALB/c, Strong A, NZB, and DAB) and one group of wild mice, six matings of CBA and C57BL, and four experimental diet groups. The above hypothesis was supported by some results such as no effects of diet on the incidences of HGCD and significant differences among the incidences of HGCD in some inbred strains. However, significant differences were also detected in the incidences of HGCD among groups within an inbred strain. Therefore, we think that further conservative and experimental assessments should be performed to determine the usefulness of incidences of HGCD as a powerful discriminator in skeletal studies on populations and family history.

Animals↗
PubMed2000

Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study.

PURPOSE: To study the impact of preoperative radiation dose escalation and postoperative adjuvant chemotherapy on the outcome of tethered and fixed rectal carcinoma. METHODS AND MATERIALS: We have treated 156 patients with 3 consecutive preoperative chemoradiation protocols with escalating treatment intensity. Schedule 1 consisted of 40 Gy radiation with concurrent 5-fluorouracil (5-FU) infusion and mitomycin C. Schedule 2 used a sandwich design with preoperative (40 Gy) and postoperative (18 Gy) radiation with concomitant 5-FU infusion, leucovorin, and mitomycin C. In schedule 3, the preoperative radiation dose was increased to 50 Gy and adjuvant 5-FU/leucovorin chemotherapy was added following surgery. There were 54, 27, and 75 patients treated in schedules 1, 2, and 3, respectively. RESULTS: The resectability was 91% for schedule 1 and 100% for both schedules 2 and 3. A dose-response relationship was observed between the radiation dose and the tumor downstaging and local control. The pathological complete response (T0N0M0) rates for schedules 1, 2, and 3 were 4%, 15%, and 25%, respectively. The respective rates of tumor downstaging were 41%, 33%, and 68%, respectively. The 5-year local relapse-free rates were 67% for schedule 1 (40 Gy), 96% for schedule 2 (58 Gy), and 92% for schedule 3 (50 Gy) (p = 0.0011). The addition of postoperative chemotherapy appeared to improve both the survival and the relapse-free survival. The 5-year survival was increased from 52% to 84% (p = 0.0004) and the 5-year progression-free survival was improved from 48% to 74% (p = 0.0008). CONCLUSION: Preoperative 5-FU infusion, leucovorin, mitomycin C, and 50-Gy pelvic radiation, followed by postoperative bolus 5-FU/leucovorin chemotherapy, appeared to be an effective treatment for tethered/fixed rectal cancers. However, its therapeutic efficacy could only be validated in randomized studies.

Adult↗
PubMed2000

Dependence of elevated human leukocyte antigen class I molecule expression on increased heavy chain, light chain (beta 2-microglobulin), transporter associated with antigen processing, tapasin, and peptide.

Human leukocyte antigen (HLA) class I molecule expression was investigated by DNA-mediated gene transfer. Cell surface expression was increased up to 75% by transfection of HLA-A2 or HLA-B8 heavy chain genes but not genes encoding light chains (beta(2)-microglobulin (beta(2)m)), transporter associated with antigen processing (TAP), or tapasin. Interferon (IFN) treatment further increased expression of transfected heavy chains, suggesting that IFN inducible molecules support heavy chain expression. IFN induces beta(2)m, TAP, and tapasin mRNAs. Transfected heavy chain expression increased upon cotransfection with genes encoding TAP1 and TAP2 but not individual TAP subunits, beta(2)m, or tapasin. Tetracycline inducible heavy chain gene expression was also increased by IFN treatment or TAP cotransfection, suggesting that IFN-induced TAP supports heavy chain maturation. Expression of a mutant that does not interact strongly with TAP, HLA-A2-T134K, was also increased by IFN. Inhibition of TAP-dependent peptide transport by ICP47 reduced heavy chain expression. Expression of HLA-A2, but not HLA-B8, was restored in ICP47 cells by HLA-A2-binding (IP-30) signal peptides. However, these peptides did not further increase transfected HLA-A2 expression, suggesting that peptide availability does not limit heavy chain expression in the absence of ICP47. These results suggest that cytokine-induced TAP supports maturation of HLA class I molecules through combined chaperone and peptide supply functions.

Antiporters↗
PubMed2000

Rapid cloning of HLA class I cDNAs by locus specific PCR.

The human major histocompatibility complex (MHC) class I loci, human leukocyte antigen (HLA)-A, -B, -C, encode highly polymorphic molecules that mediate immune recognition of infectious pathogens and can initiate the rapid rejection of transplanted tissue. Cloning of HLA class I alleles is complicated by polymorphism as well as interlocus homology. Here, HLA class I cDNAs are amplified by PCR using one common primer with one of three locus specific primers whose 3' ends map to conserved, locus specific nucleotides. Using these primers, HLA-A, -B, and -C alleles were cloned from a number of cell lines and two different HLA-B alleles were cloned from a single, heterozygous cell line. The amplified products encode the entire extracellular portion of the class I molecules. An amplified HLA-A allele was cloned into an expression vector and the protein product was detected on the surface of a transfected cell. A premature termination codon was engineered into the HLA-A allele by site directed mutagenesis and the soluble protein product was detected in the culture medium of transfected cells. Therefore, these primers can be used to rapidly clone, alter, and express HLA class I molecules. This method may expedite the generation of reagents for testing the antigen specificity of antibodies, natural killer cells, or T cells.

Alleles↗
PubMed2000

The effects of St. John's Wort (Hypericum perforatum) on NK cell activity in vitro.

St. John's Wort (Hypericum perforatum; H. perforatum) is a popular herbal supplement used to treat mild to moderate depression. H. perforatum possesses serotonergic properties such as inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake. Serotonergic pharmacotherapy is associated with amelioration of depression as well as increases in natural killer (NK) cell activity (NKCA). Also, 5-HT and 5-HT analogs augment NKCA in vitro. Considering the serotonergic properties of H. perforatum, the effects of H. perforatum on NKCA were assessed in vitro. Mononuclear cells (MNCs) from normal donors were exposed in vitro to an extract of H. perforatum (LI160s) or established 5-HT stimulators of NKCA. After an overnight incubation, cells were washed and a standard 51Cr-release cytotoxicity assay performed to assess NKCA. LI160s at all concentrations failed to augment NKCA. However, in corroboration of previous studies, 5-HT, the selective serotonin reuptake inhibitors (SSRIs), paroxetine and norfluoxetine, and alpha-interferon augmented NKCA above control levels. Though an efficacious treatment for mild to moderate depression, H. perforatum differs from commonly prescribed serotonergic antidepressants insofar as H. perforatum fails to enhance NKCA in vitro. Therefore, the present results are consistent with pharmacologic studies indicating that H. perforatum possesses, at best, weak serotonergic activity.

Adult↗
PubMed2000

Differential expression of human major histocompatibility class I loci: HLA-A, -B, and -C.

Expression of the human class I MHC loci, HLA-A, -B, and -C, was examined by reverse transcription and competitive PCR with locus-specific primers. This approach allows unambiguous identification of target sequences by analysis of the amplified products. JY and Pala lymphoblastoid B cells express more HLA-A than HLA-B mRNAs and little HLA-C mRNA. Raji Burkitt lymphoma and HeLa carcinoma cells express approximately equal amounts of HLA-A and HLA-C mRNAs but less HLA-B mRNA. Jar trophoblast cells express no HLA class I mRNAs. Surprisingly, K562 leukemia cells express significant amounts of HLA-C mRNA. However, K562 cells contain no detectable HLA-A or -B mRNAs, suggesting that these loci are regulated independently. Furthermore, cultured endothelial cells and smooth muscle cells express low, approximately equal amounts of HLA-A, -B, and -C mRNAs, whereas donor-matched, EBV transformed B cells express much more HLA-B mRNA, suggesting that cell type dependent regulation underlies differential locus expression. Finally, expression of HLA class I molecules on the cell surface correlates with total HLA mRNAs but not with mRNAs encoded by any one locus. Differential expression of these HLA class I loci may contribute to cell-type dependent immune reactions by preferentially presenting distinct peptides to T cells.

Binding, Competitive↗
PubMed2000

The death domain of tumor necrosis factor receptor 1 is necessary but not sufficient for Golgi retention of the receptor and mediates receptor desensitization.

TNF signals are mediated through two different receptors, TNFR1 and TNFR2. In endothelial cells, TNFR1 is predominantly localized in the Golgi apparatus and TNFR2 on the plasma membrane. To investigate structural features responsible for the disparate localization, endothelial cells were transfected with epitope-tagged or green fluorescent protein-fused wild type and mutant receptor molecules. Wild type receptors recapitulated the distribution of endogenous receptors. Deletions of the entire TNFR1 intracellular domain or of the C-terminal death domain (TNFR1(-DD)) allowed expression of the receptor on the plasma membrane. However, addition of the death domain to the C-terminus of TNFR2 (TNFR2(+DD)) did not lead to Golgi-retention of this chimeric receptor. Overexpressed TNFR1, TNFR2, and TNFR2(+DD) increased basal expression of a cotransfected NF-kappaB-dependent promotor-reporter gene. Overexpressed TNFR1(-DD) did not activate NF-kappaB but acted as a ligand-specific dominant negative inhibitor of TNF actions. Unexpectedly, TNF responses were also inhibited by overexpressed TNFR1 and TNFR2(+DD), but not TNFR2. We conclude that the death domain of TNFR1 is required for retention of TNFR1 in the Golgi apparatus but is not sufficient to direct Golgi retention of a TNFR2(+DD) chimera, and that overexpressed receptors that contain the death domain (TNFR1 and TNFR2(+DD)) spontaneously activate NF-kappaB while inhibiting TNF responses.

Animals↗
PubMed2000

Interactive psychoeducational group therapy in the treatment of authority problems in combat-related posttraumatic stress disorder.

The use of Interactive Psychoeducational Group Therapy to ameliorate authority problems of veterans with combat-related posttraumatic stress disorder is described. Despite the common occurrence of authority problems in this population, and the degree of damage they have caused in family, work, and legal domains, they are rarely specifically targeted by treatment interventions. A conceptual framework linking psychological trauma with distortions in authority relations is presented, followed by the format, procedures, and case examples of this form of group therapy. By uncovering the distorted beliefs associated with traumatic schemas as they emerge in the group interaction, the group therapist can first help the clients question their assumptions about authority, and then explore more adaptive behaviors. The need to examine in greater detail the causes and impact of authority problems among clients with posttraumatic stress disorder is emphasized.

Adult↗
PubMed1999

TNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the principal subcellular location of TNF-R1.

The subcellular localization of TNF-R1 to the Golgi apparatus, initially observed in endothelial cells, has been confirmed using transfection of bovine aortic endothelial cells with a human TNF-R1 expression plasmid. The subcellular interactions of TNF-R1 and the TRADD (TNFR-associated death domain protein) adaptor protein have been analyzed in the human monocyte cell line U937 and the human endothelial cell line ECV304 by confocal immunofluorescence microscopy and by Western blot analysis of fractionated cell extracts. In untreated cells, in which TNF-R1 is found on the cell surface but principally localizes to the trans-Golgi network, TRADD is concentrated in the cis- or medial-Golgi region, but separates from the Golgi during cell fractionation. Coimmunoprecipitation studies have shown that TRADD binds to TNF-R1 within 1 min of TNF treatment in a cell fraction-containing plasma membrane. This association is followed by a gradual dissociation, which is prevented if receptor-mediated endocytosis is inhibited by hypertonic medium. In contrast, no association is detected between TRADD and TNF-R1 in the Golgi in response to exogenous TNF at any time examined. These results suggest that although TNF-R1 is predominantly a Golgi-associated protein and TRADD also localizes to the Golgi region, exogenous TNF causes TRADD to bind to TNF-R1 only at the plasma membrane.

Animals↗
PubMed1999

A new approach to teaching prehospital trauma care to paramedic students.

STUDY OBJECTIVE: A modification of the standard Department of Transportation student paramedic curriculum encouraging individualized patient assessment decreases inappropriate on-scene procedures (OSPs) and scene time, measured on simulated patients. METHODS: Scenario-based testing from 1991 through 1993 was videotaped for all students. A new trauma curriculum was introduced in 1992, individualizing patient assessment and prioritization of OSPs. Recorded OSPs included spinal immobilization, application of military antishock trousers, endotracheal intubation, cricothyrotomy, intravenous catheter insertion, and needle thoracostomy. Twenty videotaped random student performances of the 1991 class was compared with a similar sample of 20 from the 1993 class; scene times and the OSP numbers were measured. Two board-certified independent emergency physicians unfamiliar with the students or the new curriculum reviewed all 40 tests on a master videotape. Patient assessment appropriateness, scene time, OSPs, scenario difficulty, and number of inappropriate OSPs were evaluated using a linear analog scale. Data are presented as means with confidence intervals (CIs), analyzed by Student's t test and the Mann-Whitney 2-sample test. RESULTS: Scene time from 1991 to 1993 decreased overall with a mean of 4.3 minutes (95% CI 2.8 to 5.8 minutes), as did the number of OSPs: 3.1 versus 1.7 (mean difference, 1.45 OSPs per scenario; 95% CI.91 to 1.99). Physician reviewers noted improvements in the appropriateness of patient assessment, scene time, and OSPs from 1991 to 1993. There was no significant difference in scenario difficulty for 1991 compared with 1993. Inappropriate OSPs done on scene declined. Physician 1 indicated a mean of inappropriate procedures of 1.6 in 1991 versus.5 in 1993. Physician 2 indicated a mean of 1.4 in 1991 versus.3 in 1993. CONCLUSION: This new paramedic curriculum decreased on-scene time and inappropriate use of procedures in stabilizing the condition of patients with simulated critical trauma.

Curriculum↗
PubMed1999

Testosterone and men's health.

Medical and behavioral research depicts the influence of testosterone on health in opposite ways, the former finding beneficial effects and the latter potentially detrimental ones. We investigate the relationship between testosterone and health risk behavior, indicators of disease, and overall health in a sample of 4393 men who were interviewed and medically examined. Analysis revealed that having a high level of testosterone, compared to a low level, increased the odds of health risk behavior. With respect to disease, high testosterone increased the odds of some health problems but decreased the chances of others. At very high levels testosterone loses many of its beneficial effects. Overall, men with high testosterone would be healthier if they did not engage in health risk behavior.

Adult↗
PubMed1999

Altruism and the Vietnam War veteran: the relationship of helping to symptomatology.

This study examines the relationships among demographic factors, combat experiences, personality characteristics, altruism, and posttraumatic stress disorder (PTSD) symptomatology. Participants were Vietnam War veterans currently undergoing treatment for PTSD. The developmental level of internalized schemas of interpersonal relations (object relatedness) and the altruistic intent to help were significant predictors of PTSD symptomatology, with lower levels of symptomatology associated with higher levels of altruism. Results indicated that predispositional variables and altruistic intentions may be important factors to consider in designing and implementing treatment programs for chronically impaired veterans with PTSD.

Altruism↗
PubMed1999

Shape differences in the cervical and upper thoracic vertebrae in rats (Rattus norvegicus) and bats (Pteropus poiocephalus): can we see shape patterns derived from position in column and species membership?

The shapes of cervical (C1-C7) and upper thoracic (T1, T2) vertebrae from the rat and the grey-headed flying fox have been analysed by Fourier analysis to investigate the types of variation present and to try to isolate bones according to position along the vertebral column and species. It was found that the T2 vertebrae of the rat are very different from all others in the study, that C2 and C6 vertebrae are very similar and that the remaining vertebrae split according to species.

Animals↗
PubMed1999

The impact of mammalian reproduction on cancellous bone architecture.

Pregnancy and lactation make demands on maternal calcium homeostasis which may affect bone strength. Recently, changes in cancellous architecture have been described in iliac crest bone biopsies from normal pregnant women but the rarity of such human material means an animal model is essential. The microanatomy of cancellous bone was compared in uniparous and multiparous rats using undecalcified histological sections of lumbar and caudal vertebrae and also proximal femora. An automated trabecular analysis system (TAS) measured a comprehensive range of structural variables including the trabecular number, connectivity and width. In the first pregnancy cycle an early stimulation of bone formation (which quadrupled at some sites) was indicated by an increase in the skeletal uptake and spacing of double calcein labels and the immediate generation of thicker more numerous and interconnected trabeculae. A 40% increase in cancellous bone volume was observed in the lumbar spine in comparison with age-matched virgin controls. In contrast, a rapid succession of 3 pregnancy cycles (including lactation) culminated in cancellous atrophy of 15% at the same site, with a loss in trabecular number ranging from 20% (caudal vertebra) to 30% (lumbar vertebrae). In comparison, the proximal femur lost 40% of its struts but, nevertheless, uniquely sustained its cancellous bone volume. When lactation was excluded the number of struts lost was halved although trabecular thinning then took place which was sufficient to maintain the previous 15% deficit in bone volume. It was concluded that a single pregnancy strengthens the cancellous component of the maternal skeleton while a quick succession of pregnancies weakens it. Lactation influences the pattern of bone loss but not its amount.

Animals↗
PubMed1999

Variable susceptibility to opsonophagocytosis of group A streptococcus M-1 strains by human immune sera.

Immunity to group A streptococci (GAS) is thought to be related to the acquisition of type-specific antibody directed against the M protein. However, recent work suggests that immunity may only be strain and not M-type specific. Therefore, susceptibility of 70 different GAS M-1 strains to opsonization and killing by convalescent sera was compared by using a highly sensitive chemiluminescence assay and by standard bactericidal assay. Sequencing of the emm1 gene in 10 strains with variable susceptibility to opsonization revealed 100% homology in 9 strains. Several substitutions in the N-terminal and 2 in the A3 repeat regions of strain CS-190 were associated with profound resistance to opsonization. Thus amino acid substitutions within different regions of the M-1 protein molecule may adversely affect opsonization by immune sera. In addition, non-M protein factors from identical M types influence susceptibility to phagocytosis. These findings may in part explain the persistently high prevalence of M-1 strains worldwide over the last 15 years.

Amino Acid Sequence↗