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K Johnson

Publications and source records attributed to K Johnson.

At least 91 records · Page 5Linked to original sources
PubMed2000

IFNgamma secretion following stimulation with total tumor peptides from autologous human tumors.

Several issues remain to be resolved before the efficacy of various approaches to elicit anti-tumor immunity in patients can be evaluated. First, in vitro assays able to detect responses by T cells primed in vivo are needed. Second, a source of tumor antigen to stimulate patients' lymphocytes in vitro is required. The ELISPOT assay is attractive, because it can be performed with a small numbers of cells and requires only short-term culture in vitro. A source of tumor antigen is more problematic, since for most tumors, tumor-associated antigens (TAA) have not been identified and/or cloned. In this report we demonstrate that autologous antigen-presenting cells (APC) pulsed with total tumor peptides from autologous tumor tissue can stimulate IFNgamma release by patients' lymphocytes in the ELISPOT assay. Thus, this approach should be considered for monitoring immune responses in clinical immunotherapy trials.

Antigen Presentation↗
PubMed2000

Head injury and the risk of AD in the MIRAGE study.

OBJECTIVES: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-epsilon4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. SUBJECTS: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. METHODS: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. RESULTS: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking epsilon4 (OR = 3.3) than among epsilon4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). CONCLUSION: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE-epsilon4 compared with those having one or two epsilon4 alleles, suggesting that these risk factors may have a common biologic underpinning.

Aged↗
PubMed2000

Characterization of fungal spores by laser desorption/ionization time-of-flight mass spectrometry.

A considerable volume of research has now been completed on the application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to the analysis of bacteria; however, to date no definitive studies have been made using this technique on fungi. Preliminary studies on the application of the MALDI-MS methodology, previously developed for the analysis of bacteria, to the analysis of intact fungal spores are described here. MALDI-MS and electrospray mass spectrometry enable the high molecular weight analysis of proteins, glycoproteins, oligosaccharides and oligonucleotides. Using MALDI-MS with bacteria has demonstrated the ability to produce 'fingerprints' of the intact cells with the ions observed being associated with the proteinaceous components of the cell wall. This paper reports the adaptation of this technique to the direct analysis of fungal cells. The high percentage of carbohydrate in the fungal cell wall indicates that the ions observed in the mass spectrometric experiments may be of carbohydrate origin. Penicillium spp., Scytalidium dimidiatum and Trichophyton rubrum have been studied in this preliminary investigation and all show individually distinctive spectra which would appear to provide a profile of the cellular material with discrete peaks being observed over the mass range 2 to 13 kDa. The spectra obtained are reproducible within the method used but, as shown in our previous studies on bacteria, washing may selectively release components from the fungal cell wall.

Carbohydrates↗
PubMed2000

Extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 mitogen-activated protein kinase signaling and activation of activator protein 1 and nuclear factor kappaB transcription factors play central roles in interleukin-8 expression stimulated by monosodium urate monohydrate and calcium pyrophosphate crystals in monocytic cells.

OBJECTIVE: Monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals cause acute gout and pseudogout, respectively. Because acute gout and pseudogout appear to be dependent on interleukin-8 (IL-8)-induced neutrophil ingress, this study was undertaken to define and compare how MSU and CPPD crystals stimulate IL-8 messenger RNA (mRNA) expression in mononuclear phagocytes. METHODS: MSU and CPPD crystal-induced mitogen-activated protein kinase (MAPK) signal transduction and IL-8 transcriptional activation were studied in human monocytic cells, using the THP-1 cell line. RESULTS: MSU and CPPD crystals (0.5 mg/ml) induced activation of c-Jun N-terminal kinase, extracellular signal-regulated kinase 1 (ERK-1)/ERK-2, and p38 MAPK pathways in THP-1 cells. Activation of the ERK-1/ERK-2 pathway was essential for MSU and CPPD crystal-induced IL-8 mRNA expression, whereas the p38 pathway played a greater role in IL-8 mRNA expression in response to CPPD crystals in comparison with MSU crystals. Both crystals induced the binding of nuclear factor kappaB (NF-kappaB), including the NF-kappaB complex c-Rel/RelA, and activator protein 1 (AP-1, including N-terminal phosphorylated c-Jun) to the IL-8 promoter. Both crystals induced transcriptional activation of the IL-8 promoter, which was dependent on activation of c-Rel/RelA and AP-1. Activation of the NF-IL-6 transcription factor played a lesser role. Finally, crystal-induced IL-8 promoter activation was mediated by activation of the ERK-1/ERK-2 pathway, as demonstrated by transfection of dominant-negative raf-1. CONCLUSION: These results indicate that ERK-1/ ERK-2 signaling and transcriptional activation through AP-1 and NF-kappaB are essential for the induction of IL-8 expression in mononuclear phagocytes in response to CPPD and MSU crystals.

Calcium Pyrophosphate↗
PubMed2000

Mitochondrial oxidative phosphorylation is a downstream regulator of nitric oxide effects on chondrocyte matrix synthesis and mineralization.

OBJECTIVE: Increased chondrocyte nitric oxide (NO) and peroxynitrite production appears to modulate decreased matrix synthesis and increased mineralization in osteoarthritis (OA). Because NO inhibits mitochondrial respiration, this study was undertaken to directly assess the potential role of chondrocyte mitochondrial oxidative phosphorylation (OXPHOS) in matrix synthesis and mineralization. METHODS: We studied cultured human articular chondrocytes and immortalized costal chondrocytes (TC28 cells). We also assessed the effects of antimycin A and oligomycin (inhibitors of mitochondrial complexes III and V, respectively) on chondrocyte mitochondrial respiration, ATP synthesis, and inorganic pyrophosphate (PPi) generation, and the mineralizing potential of released matrix vesicles (MV). RESULTS: Articular chondrocytes and TC28 cells respired at comparable rates. Peroxynitrite and NO donors markedly suppressed respiration and ATP generation in chondrocytes. Because NO exerts multiple effects on chondrocytes, we investigated the primary functions of mitochondrial respiration and OXPHOS. To do so, we identified minimally cytotoxic doses of antimycin and oligomycin, which both induced intracellular ATP depletion (by 50-80%), attenuated collagen and proteoglycan synthesis, and blocked transforming growth factor beta from increasing intracellular ATP and elaboration of PPi, a critical inhibitor of hydroxyapatite deposition. Antimycin and oligomycin also abrogated the ability of the ATP-hydrolyzing enzyme plasma cell membrane glycoprotein 1 (PC-1) to increase chondrocyte PPi generation. Finally, MV from cells treated with antimycin or oligomycin contained less PPi and precipitated >50% more 45Ca. CONCLUSION: Chondrocyte mitochondrial reserve, as NO-sensitive mitochondrial respiration-mediated ATP production, appears to support matrix synthesis and PPi elaboration and to regulate MV composition and mineralizing activity. NO-induced depression of chondrocyte respiration could modulate matrix loss and secondary cartilage mineralization in OA.

Adenosine Triphosphate↗
PubMed2000

A feline model of experimentally induced islet amyloidosis.

The study of the pathogenesis of islet amyloidosis and its relationship to the development and progression of type 2 diabetes mellitus has been hampered by the lack of an experimentally inducible animal model. The domestic cat, by virtue of the fact that it is one of the few species that spontaneously develop a form of diabetes mellitus that closely resembles human type 2 diabetes, including the formation of amyloid deposits derived from islet amyloid polypeptide (IAPP), was considered to be an excellent candidate species in which to attempt to develop a nontransgenic animal model for this disease process. To develop the model, 8 healthy domestic cats were given a 50% pancreatectomy, which was followed by treatment with growth hormone and dexamethasone. Once a stable diabetic state was established, cats were randomly assigned to groups treated with either glipizide or insulin at doses appropriate to control hyperglycemia. Cats were maintained on this treatment regimen for 18 months and then euthanized. Based on light microscopic examination of Congo red-stained sections of pancreas, all cats were negative for the presence of islet amyloid at the time of pancreatectomy. At the end of the study all 4 glipizide-treated cats had islet amyloid deposits, whereas only 1 of 4 insulin-treated cats had detectable amyloid. In addition, the glipizide treated cats had threefold higher basal and fivefold higher glucose-stimulated plasma IAPP concentrations than insulin-treated cats, suggesting an association between elevated IAPP secretion and islet amyloidosis. Blood-glycosylated hemoglobin concentrations were not significantly different between the two treatment groups. This study documents for the first time an inducible model of islet amyloidosis in a nontransgenic animal.

Amyloid↗
PubMed2000

Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity.

Medullary carcinomas of the pancreas are a recently described, histologically distinct subset of poorly differentiated adenocarcinomas that may have a unique pathogenesis and clinical course. To further evaluate these neoplasms, we studied genetic, pathological, and clinical features of 13 newly identified medullary carcinomas of the pancreas. Nine (69%) of these had wild-type K-ras genes, and one had microsatellite instability (MSI). This MSI medullary carcinoma, along with three previously reported MSI medullary carcinomas, were examined immunohistochemically for Mlh1 and Msh2 expression, and all four expressed Msh2 but did not express Mlh1. In contrast, all of the medullary carcinomas without MSI expressed both Msh2 and Mlh1. Remarkably, the MSI medullary carcinoma of the pancreas in the present series arose in a patient with a synchronous but histologically distinct cecal carcinoma that also had MSI and did not express Mlh1. The synchronous occurrence of two MSI carcinomas suggests an inherited basis for the development of these carcinomas. Indeed, the medullary phenotype, irrespective of MSI, was highly associated with a family history of cancer in first-degree relatives (P < 0.001). Finally, one medullary carcinoma with lymphoepithelioma-like features contained Epstein-Barr virus-encoded RNA-1 by in situ hybridization. Therefore, because of medullary carcinoma's special genetic, immunohistochemical, and clinical features, recognition of the medullary variant of pancreatic adenocarcinoma is important. Only by classifying medullary carcinoma as special subset of adenocarcinoma can we hope to further elucidate its unique pathogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Feasibility and safety of AS-3 red blood cells for neonatal transfusions.

OBJECTIVES: Most extremely low birth weight (<1 kg) infants receive red blood cell (RBC) transfusions. RBCs stored up to 42 days can be transfused safely in small volumes to preterm infants; however, because the formulation of RBC anticoagulant/preservative solutions differs, clinical studies are required to document the safety of each solution before widespread use. Our goal was to study the feasibility and safety of AS-3 anticoagulant/preservative solution to preterm infants. STUDY DESIGN: Two clinical studies were conducted in sequence: (1) a randomized trial to compare RBC transfusions given as stored (< or =42 days) AS-3 RBCs (11 infants) versus fresh (< or = 7 days) citrate, phosphate, dextrose, and adenine RBCs (10 infants) and (2) a subsequent evaluation of the safety of stored AS-3 RBCs in 33 additional preterm infants given 120 AS-3 RBC transfusions. RESULTS: Results of both the randomized study and the subsequent evaluation documented that AS-3 RBCs stored < or =42 days and transfused in small volumes (15 mL/kg) were safe for RBC transfusions of preterm infants. Donor exposure was significantly reduced, clinical transfusion reactions were rare, and post-transfusion blood hematocrit, pH, and plasma Na, K, Ca, lactate, and glucose measurements were similar when AS-3 and citrate, phosphate, dextrose, and adenine RBC transfusions were compared. CONCLUSIONS: AS-3 RBCs can be used safely for small-volume RBC transfusions for preterm infants.

Adenine↗
PubMed2000

Randomized trial assessing the feasibility and safety of biologic parents as RBC donors for their preterm infants.

BACKGROUND: Most very low birth weight (<1.0 kg) infants receive RBC transfusions. Several reports have demonstrated that RBCs stored up to 42 days can be transfused safely in small volumes to preterm infants to decrease donor exposure without consequent hyperkalemia, acidosis, or other adverse effects. Although biologic parents are likely candidates as donors of blood for their neonates, it has been suggested that their blood may be serologically incompatible with that of their infants. STUDY DESIGN AND METHODS: A two-arm randomized study was conducted to compare the feasibility and immediate safety of two single-donor programs for providing small-volume RBC transfusions to preterm infants: in one arm, infants received RBCs collected from unrelated donors and stored up to 42 days, and in the other arm, RBCs were collected from one of the biologic parents and stored identically. All infants received compatible RBCs that were WBC reduced before storage, stored in AS-3, and gamma-radiated. All transfusions were given uniformly as 15 mL per kg of RBCs transfused over 5 hours, during which time the infants were closely observed for clinical reactions. In addition, laboratory studies were performed shortly before and after each transfusion. RESULTS: A total of 40 preterm infants received 120 RBC transfusions. Biologic parents experienced several donor eligibility problems. However, once enrolled as donors, they were able to supply all RBCs needed by their infants. Significant differences in rates of clinical transfusion reactions and laboratory abnormalities were rare and had no apparent clinical importance, regardless of whether RBCs were donated by biologic parents or unrelated donors. CONCLUSION: A single-donor system, in which AS-3 RBCs were collected either from unrelated blood donors or from biologic parents and then stored up to 42 days, was able to supply small-volume RBC transfusions needed by individual preterm infants without immediate, adverse effects. Because the risk of infectious disease transmission is likely reduced by limiting donor exposure, it is logical to conclude that single-donor programs should increase transfusion safety and that biologic parents should be considered as blood donors for their infants.

Blood Donors↗
PubMed2000

Alloimmunization in preterm infants after repeated transfusions of WBC-reduced RBCs from the same donor.

BACKGROUND: Preterm infants are among the most heavily transfused of patient groups, yet multiply transfused infants only rarely produce alloantibodies against RBC or WBC antigens. It is not known whether rates of alloimmunization might be increased by repeated exposure to RBCs and WBCs from the same donor, as in limited-donor-exposure programs, or whether infants might benefit from WBC-reduced RBC components as a means of diminishing the risk of possible alloimmunization. STUDY DESIGN AND METHODS: Preterm infants (birth weight 0.6-1.3 kg) received prestorage WBC-reduced RBCs from dedicated donors, collected in AS-3 as a means of limiting donor exposures. Blood samples were collected serially from infants shortly after birth until either discharge or age 6 months and were studied for RBC and WBC antibodies-the latter with reactivity against either HLA class I or neutrophil-specific antigens. RESULTS: Thirty preterm infants received 139 transfusions (mean, 4.6; median, 4 transfusions per infant), with 81 percent of transfusions obtained from one donor per infant. Eighty-four blood samples (mean, 2.7/infant) were studied, and no infant produced RBC antibodies. Twenty-seven percent of infants exhibited WBC antibodies, but only 13 percent actually produced WBC antibodies (passive maternal antibody excluded). Of the WBC antibodies produced by infants, three were against HLA class I and one was against neutrophil-specific antigens; none were linked to adverse effects. CONCLUSIONS: Because infants only rarely produce RBC antibodies, no changes in blood banking practices are necessary for limited-donor-exposure programs. Although the production of WBC antibodies by infants occurs, it seems to be uncommon; thus, the possible benefits, if any, of WBC reduction are uncertain, and further study is required before changes in practice can be justified.

Blood Donors↗
PubMed2000

Ventilation and perfusion scanning in children.

Ventilation and perfusion scintigraphy (VQ scans) provide a relatively non-invasive evaluation of lung function. They indicate the relative blood flow to each lung and allow a quantitative assessment of the perfusion of each lung segment. They can detect areas of abnormal aeration and demonstrate air trapping. However, VQ scanning gives relatively poor anatomical detail of the lungs and so is commonly used in conjunction with other radiological modalities, most notably the chest X-ray. VQ scans have been utilized for a large range of pathological conditions including congenital cardiac and lung abnormalities, suspected pulmonary emboli, the assessment of childhood diseases, including cystic fibrosis, bronchopulmonary dysplasia and asthma.

Child↗
PubMed2000

Use of telephone follow-up for post-cardiac surgery patients.

Telephone follow-up has been used in a variety of settings as a means of supporting patients post-discharge. This paper describes the implementation of a telephone follow-up service for cardiac surgical patients, both to monitor their progress and to bridge the gap between home and hospital. Surgical unit nurses called 1594 patients between May 1995 and October 1997. These calls were made a month after each patient had been discharged and a specially designed form was used as a guideline for the calls. This covered three main aspects of their recovery: discharge monitoring; medical problems; and convalescence problems. As well as providing a framework for the calls, the forms were then used for data collection. The forms were audited on a monthly basis with the results being communicated to the ward staff. Data gathered from the calls have highlighted areas where patient education needs to be improved, e.g. pain control, and this has been addressed. In October 1996, an evaluation of the service was performed. One hundred patients were sent a postal questionnaire asking for their views on the telephone service. Eighty-two of these were returned and the results of this survey are also contained in this report. Over time, the number of patients called each month has increased; information regarding support post-discharge has improved and the form used for calls has been revised to make the questions more appropriate.

Aftercare↗
PubMed2000

Expression of a homeobox gene (SIX5) in borderline ovarian tumours.

AIMS: To assess the expression of SIX5 (a homeobox gene) mRNA in surface coelomic epithelium, endocervical epithelium, Fallopian tube epithelium, and benign, borderline, and malignant epithelial ovarian tumours. METHODS: 10 normal premenopausal ovaries, 10 normal Fallopian tubes, 10 normal cervices, 10 normal postmenopausal ovaries, 10 benign epithelial ovarian tumours, 10 malignant epithelial ovarian tumours, and 40 borderline epithelial ovarian tumours were studied retrospectively. The tissues had been fixed in formalin and embedded in paraffin wax. The tumours had previously been typed into mucinous, serous, or mixed tumours and assigned to the borderline category according to the FIGO/WHO criteria. Expression was assessed by in situ binding of SIX5 specific sense and antisense riboprobes. Hybridization of the riboprobes was detected using a standard immunohistochemical technique and the results correlated with expression in the normal epithelium of the endocervix, Fallopian tube, surface coelomic epithelium, and ovarian tumours. RESULTS: Expression of SIX5 mRNA was demonstrated in normal Fallopian tube epithelium and normal endocervical epithelium. SIX5 mRNA was not detected in normal ovarian epithelial tissue at any of the times studied during the menstrual cycle. Expression of SIX5 was not shown in benign epithelial ovarian tumours or in any of the malignant epithelial ovarian tumours. In 31 of 37 borderline epithelial ovarian tumours (84%), SIX5 expression was found in the epithelial cells. CONCLUSIONS: SIX5 expression is present in the normal epithelium throughout most of the female reproductive tract, suggesting it may have a role in maintaining epithelial differentiation in these tissues. SIX5 expression appears to be restricted to borderline epithelial ovarian tumours and may be a marker of epithelial differentiation in these tumours; thus borderline ovarian tumours may not be part of a continuum of disease between benign and malignant epithelial ovarian tumours. Further investigation of expression of SIX5 may clarify the molecular processes that promote differentiation of the ovarian surface epithelium.

Cystadenoma, Mucinous↗
PubMed2000

Improving public awareness of organ transplantation in Japan.

The goals of the Japanese chapter of the Transplant Recipients International Organization are to act as a mediator in the provision of mutual aid to transplant recipients, candidates, and their families and to provide education in both the public and professional arenas to promote organ transplantation in Japan. Since 1991, members of the Japanese chapter of the Transplant Recipients International Organization have acted as volunteer facilitators for more than 150 transplant candidates and recipients. The organization's activities have included fund-raising to cover the costs of transplantation, preparing an original donor card for distribution, and petitioning members of the Diet (the Japanese legislative body) 14 times, including speaking at public hearings twice and submitting a petition requesting early passage of the organ transplant bill. The Japanese Diet finally passed an organ transplant bill in June 1997. The activities of the Japanese chapter of the Transplant Recipients International Organization have contributed to the promotion of organ transplantation in Japan and to understanding and support for transplantation within the Japanese community as a whole.

Attitude to Health↗
PubMed2000

Japanese organ transplant law: a historical perspective.

Although organ transplantation following brain death has progressed in the West, it has lagged far behind in Japan, following the first such case in 1968. As effective immunosuppressants made transplantation a better option, Japanese patients increasingly sought treatment overseas. Japanese physician groups studied issues related to transplantation but did not succeed in making brain-dead donor transplants available to patients, and the matter was referred to the government. However, transplant medicine was still marked by controversy, and as political pressure was applied the controversy deepened, splintering public opinion. At the same time, transplant groups continued working to establish structures to allow transplantation to proceed. Public awareness and knowledge of brain death grew, and acceptance widened. Eventually, legislation was passed in June 1997 that allowed organ donations from some brain-dead donors. The law is restrictive, and such organ transplants in Japan are still limited.

Attitude to Health↗