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Biomedical subjects

J S Johnson

Publications and source records attributed to J S Johnson.

At least 37 records · Page 2Linked to original sources

Resistance against the membrane attack complex of complement induced in porcine endothelial cells with a Gal alpha(1-3)Gal binding lectin: up-regulation of CD59 expression.

Endothelial cells (EC) play central roles in vascular physiology and pathophysiology. EC activation results in proinflammatory activities with production of cytokines and expression of adhesion molecules. However, we have shown before in a model of xenotransplantation that prolonged stimulation of porcine EC with human anti-porcine IgM natural Abs can activate the cells to become resistant against cytotoxicity by the membrane attack complex of complement (MAC). Now we report the major characteristics of induction and maintenance of resistance elicited in porcine EC with Bandeiraea simplicifolia lectin that binds terminal gal alpha(1-3)gal. Lectin-treated cells underwent little or no cytotoxicity and PGI2 release when exposed to MAC. Induction of resistance required incubation of the EC with lectin for 4 h but was not fully manifested until 16 h later. Most of the initially bound lectin remained on the cell surface for >60 h. EC-bound lectin did not inhibit binding of IgM natural Abs or activation and binding of C components, including C9, but a C-induced permeability channel of reduced size was present. Induction of resistance required protein synthesis, developed slowly, and was associated with up-regulation of expression of mRNA for the MAC inhibitor CD59 and membrane-associated CD59 protein. Resistance lasted at least 3 days, and the cells regained normal morphology and were metabolically active. This induced resistance may have a physiologic counterpart that might be amenable to pharmacologic manipulation in vascular endothelium pathophysiology.

Animals↗

Chiral bis(oxazoline) copper(II) complexes: versatile catalysts for enantioselective cycloaddition, Aldol, Michael, and carbonyl ene reactions.

A bis(oxazoline) (box) copper(II) complex and its hydrated counterpart (1 and 2) function as enantioselective Lewis acid catalysts for carbocyclic and hetero Diels-Alder, aldol, Michael, ene, and amination reactions with substrates capable of chelation through six- and five-membered rings. X-ray crystallography of the chiral complexes reveals a propensity for the formation of distorted square planar or square pyramidal geometries. The sense of asymmetric induction is identical for all the processes catalyzed by [Cu((S,S)-t-Bu-box)](X)(2) complexes 1 and 2 (X = OTf and SbF) resulting from the intervention of a distorted square planar catalyst-substrate binary complex. These catalyzed processes exhibit excellent temperature-selectivity profiles. Reactions catalyzed by [Cu(S,S-Ph-pybox)](SbF(6))(2) and their derived chelation complexes are also discussed.

Biological Factors↗

A 12,000 rad whole genome radiation hybrid panel for high resolution mapping in cattle: characterization of the centromeric end of chromosome 1.

We have constructed a 12,000 rad bovine whole-genome radiation hybrid panel (BovR12) to complement the 5000 rad panel (BovR5) currently available to the bovine genomics research community. Initial characterization with markers from chromosome 1 reveals a higher frequency of breakage between adjacent markers and subsequently a larger number of 'linkage' groups on this chromosome. For this set of markers, the retention frequency is also higher than in BovR5.

Animals↗

Small intestinal infarction: a fatal complication of systemic oxalosis.

Primary hyperoxaluria is a rare genetic disorder characterised by calcium oxalate nephrolithiasis and nephrocalcinosis leading to renal failure, often with extra-renal oxalate deposition (systemic oxalosis). Although ischaemic complications of crystal deposition in vessel walls are well recognised clinically, these usually take the form of peripheral limb or cutaneous ischaemia. This paper documents the first reported case of fatal intestinal infarction in a 49 year old woman with systemic oxalosis and advocates its consideration in the differential diagnosis of an acute abdomen in such patients.

Abdomen, Acute↗

Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats.

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734-1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873-881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.

Animals↗

Mail surveys among college students: do initial responders score differently from nonresponders on the 16PF?

A single experiment is reported which investigated possible personality differences between college students who responded to a mail survey and those who did not. 208 college students completed the 16PF as part of a class assignment. Then each student was mailed a survey dealing with either a national or local issue (environmental, media, or sports). Multivariate analysis of the 16 subscales of the 16PF yielded a significant interaction between sex and response type. Subsequent protected univariate analyses identified significant sex x response type interactions on scales Q2 (Self-reliance), F (Liveliness), and O (Apprehension). Mean differences on the Self-reliance and Apprehension were sex differences rather than personality differences between responders and nonresponders. The only mean difference for response type was on Liveliness and applied only to men; responders scored lower than nonresponders. Multivariate analysis of the global scales of the 16PF yielded a significant interaction between sex and response type. Protected univariate analyses indicated a significant interaction between sex and response type on the Extraversion scale and a sex difference; female nonresponders scored higher than male nonresponders. No other comparisons were significant.

Adult↗

Effects of prosodic stress and serial position on syllable omission in first words.

The authors documented syllable omission in one child's multisyllabic vocabulary from 10 to 20 months of age to evaluate L. Gerken's (1991, 1994a, 1994b) proposal that children organize their productions according to a trochaic metrical (strong-weak) template and omit syllables from target utterances that do not conform to this pattern. The trochaic template hypothesis was not supported by these early productions. Results indicated that the likelihood of producing a target syllable was influenced primarily by the strength of the prosodic stress placed on it and secondarily by its serial order within a word. Over time, the child demonstrated an increasing ability to include syllables with weaker prosodic stress in multisyllabic productions. Omissions became much less common with the onset of 2-word speech.

Humans↗

Dimorphic immunohistochemical staining in ocular sebaceous neoplasms: a useful diagnostic aid.

PURPOSE: We studied whether patterns of immunostaining in formalin-fixed, paraffin-embedded tissue could help to distinguish between sebaceous neoplasms of the eyelid and other eyelid neoplasms. METHODS: We applied antibodies to human milk fat globule-1 (HMFG1), cytokeratins (PKK1 and MNF116), epithelial membrane antigen (EMA) and carcino-embryonic antigen (CEA) to normal eyelid tissue and to a range of sebaceous lesions of the eyelid; these included sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma, in addition to well to poorly differentiated sebaceous carcinoma. RESULTS: The central and peripheral cellular components of normal sebaceous glands and neoplastic sebaceous lesions showed a distinctive dimorphic staining pattern with the antibody panel used. The central foamy 'sebaceous' cells expressed HMFG1 and EMA, but not PKK1 or MNF116, whereas the smaller, peripheral basal and ductal cells expressed PKK1 or MNF116 but not HMFG1 or EMA. CEA expression in sebaceous cells was unhelpful diagnostically. CONCLUSION: Normal sebaceous glands and all sebaceous neoplasms show a dimorphic cell population that can be identified using a small panel of antibodies on formalin-fixed, paraffin-embedded tissue. This distinctive staining pattern can be assessed retrospectively, even in small biopsies, and largely removes the need for fat stains on frozen sections to differentiate sebaceous lesions from other ocular neoplasms. The results also support the suggestion that ocular sebaceous neoplasms arise from a common stem cell, rather than from either sebaceous or basal/ductal cells.

Adenocarcinoma, Sebaceous↗

Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation.

We recently demonstrated that systemic hypoxia during reduced inspired PO(2) produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the ROS signal changes when PO(2) levels return to normal after a period of systemic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia.

Animals↗

Update on the treatment of Wegener's granulomatosis.

Mortality due to WG has been significantly decreased by cytotoxic therapy with cyclophosphamide and glucocorticoids. Several studies have addressed different treatment regimens, particularly different maintenance regimens, in order to reduce the potential for cyclophosphamide-induced toxicity. Relapse may be precipitated by the chronic carrier-state of S aureus in the nasopharynx, and is sometimes heralded by rising c-ANCA titers. The treatment of the relapse is determined by the severity of its manifestations. Options for maintenance therapy include methotrexate and azathioprine. The value of therapy with TMSx for maintenance of remission still is uncertain, although its use 3 times a week is recommended for Pneumocystis prophylaxis. The ACR guidelines for monitoring drug toxicity should be followed when treating WG.

Anti-Inflammatory Agents↗

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online.

Gaucher disease results from mutations in the glucocerebrosidase gene located on human chromosome 1q21. Three clinical forms of Gaucher disease have been described: type 1, nonneuropathic; type 2, acute neuropathic; and type 3, subacute neuropathic. We have identified a novel mutation in a German-British patient with type 1 Gaucher disease which results in V191G of the glucocerebrosidase polypeptide. Because the mutation abolishes a HphI cleavage site, its presence was confirmed by HphI RFLP analysis of PCR-amplified genomic DNA. In the second allele of the patient, the mutation identified was g.5841A G(N370S). Sequence analysis of the remainder of the coding region of the gene as well as the exon-intron boundaries showed identity to normal controls. Because mutation N370S has so far been found only in type 1 Gaucher disease and postulated to result in mild clinical presentation, and since the clinical course of this patient has been relatively mild with minimal skeletal involvement, we speculate that the V191G/N370S genotype may also result in good prognosis.

Chromosomes, Human, Pair 1↗

Evaluation of a statistically derived decision tree for the cytodiagnosis of fine needle aspirates of the breast (FNAB).

A decision tree for the diagnosis of FNAB was derived from defined human observations using a rule induction method, C4.5 (a derivative of the ID3 algorithm). This algorithm is an implementation of the top-down induction method where the tree is determined iteratively by adding those nodes and branches which maximize the information gain at each step. The tree was derived from a training set of 200 FNAB with known outcome using 10 defined features (from one observer) and patient age. The tree contained a total of seven nodes (six observable features and patient age) with eight endpoints (four benign, four malignant). The tree was applied to a test set of 400 further FNAB with observations from the training observer and produced a sensitivity of 95%, specificity of 93% and a positive predictive value (PPV) of a malignant result of 89%. Four trainee pathologists were given a training session on the observable features and then used the tree to determine outcome in a further 50 FNAB. The observers were blind to clinical details apart from age and the endpoints were coded with letters and not labelled benign or malignant. The results from these observers produced ranges of sensitivity 80-96%, specificity 64-92%, PPV 73-92% and kappa statistics (with known outcome) 0.6-0.8. Reported difficulties in using the tree included estimation of nuclear size. These results were worse than the performance of the observers on a further 50 cases without using the decision tree (sensitivity 80-100%, specificity 72-100%, PPV 78-100%, kappa 0.72-0.92). The original 50 case test set was rerandomized and the four trainee observers made all 10 defined observations on each specimen without using the decision tree; these observations were then used to derive decisions from the tree. The performance from this method was similar to that using selected features from the tree, suggesting that observation of all features together does not improve the reliability of each specific observation. The poor performance of this tree suggests that this methodology may be unsuitable for producing decision support aids for diagnostic or training purposes in this domain.

Biopsy, Needle↗

Fatal Serratia marcescens meningitis and myocarditis in a patient with an indwelling urinary catheter.

Serratia marcescens is commonly isolated from the urine of patients with an indwelling urinary catheter and in the absence of symptoms is often regarded as a contaminant. A case of fatal Serratia marcescens septicaemia with meningitis, brain abscesses, and myocarditis discovered at necropsy is described. The patient was an 83 year old man with an indwelling urinary catheter who suffered from several chronic medical conditions and from whose urine Serratia marcescens was isolated at the time of catheterisation. Serratia marcescens can be a virulent pathogen in particular groups of patients and when assessing its significance in catheter urine specimens, consideration should be given to recognised risk factors such as old age, previous antibiotic treatment, and underlying chronic or debilitating disease, even in the absence of clinical symptoms.

Aged↗

Effects of sampling interval on peak oxygen consumption in patients evaluated for heart transplantation.

BACKGROUND AND METHODS: Peak oxygen consumption is a commonly accepted criterion in patient selection for cardiac transplantation. To determine the effect of various gas exchange sampling intervals on the variability of peak oxygen consumption, 15 consecutive patients evaluated for cardiac transplantation performed maximal treadmill testing using a ramped protocol. Oxygen consumption was measured via breath-by-breath analysis of expired air. Peak oxygen consumption was determined for each test using the following sampling intervals: 60-, 30-, and 15-s averages, eight breath rolling average, and true breath by breath. Variability of the mean peak oxygen consumption for each sample average was compared using analysis of variance on repeated measures. RESULTS AND CONCLUSIONS: Measures of peak oxygen consumption differed significantly (p<0.001) between sampling averages. A maximum variability of 20% was noted between the largest and smallest averages (13.8+/-4.2 mL/kg/min for 60 s vs 17.3+/-4.2 mL/kg/min for breath by breath). No significant difference was found between the 30-s, 15-s, and eight breath rolling averages (14.2+/-3.7 vs 14.5+/-3.9 vs 14.7+/-4.3 mL/kg/min), respectively. Results of the study suggest (1) the sampling average can have a significant effect on peak oxygen consumption influencing patient selection for transplantation, and (2) sample averages larger than breath by breath but smaller than 60 s be used for determination of peak oxygen consumption.

Exercise Test↗

Improvement of expression and secretion of a fungal xylanase in the rumen bacterium Butyrivibrio fibrisolvens OB156 by manipulation of promoter and signal sequences.

Promoters and signal sequences for expression and secretion of a fungal xylanase encoded by a modified Neocallimastix patriciarum xynA cDNA in the rumen bacterium, Butyrivibrio fibrisolvens OB156, were investigated. Successful expression of the fungal xylanase in OB156 was obtained using the putative xylanase promoter from B. fibrisolvens strain 49. Replacing the putative -35 region sequence (TTGCAC) of the xylanase promoter with the sequence TTGACA by mutagenesis reduced the fungal xylanase expression level 4-fold in OB156, indicating that this B. fibrisolvens strain did not efficiently recognise the E. coli consensus -35 sequence. Reduction of the spacer length between the -35 and -10 regions of the xylanase promoter from 18 to 17 base-pairs (bp) considerably increased the expression levels of the fungal enzyme in both E. coli and OB156. Insertion of a pUB110 mob promoter upstream of the xylanase promoter also significantly improved the fungal xylanase expression. Secretion of the fungal xylanase mediated by the alpha-amylase signal peptide from B. fibrisolvens strain H17c was efficient in E. coli, but very poor in OB156. An increase in the hydrophobicity of the signal sequence resulted in a 4-fold increase in the extracellular portion of the fungal xylanase in OB156, indicating marked improvement in xylanase secretion efficiency. The recombinant plasmids and xylanase expression/secretion cassettes were found to be stable in OB156 after prolonged cultivation (100 generations) in the absence of antibiotic selection. These results suggest that the rumen bacterium B. fibrisolvens can be manipulated to produce and secrete a eukaryotic extracellular protein with stable maintenance of the expression cassette in plasmid form.

Amino Acid Sequence↗

A production limitation in syllable number: a longitudinal study of one child's early vocabulary.

The present paper reports on the phonological form of one child's productive vocabulary from age 0;10 to 1;8 with primary focus on his production of multisyllabic targets. A large percentage of his multisyllabic vocabulary was produced as one syllable until the age of 1;6. This limitation was not due to a tendency to extract only single syllables from the speech stream, but rather due primarily to a limitation on production. While some portion of his one-syllable productions could be interpreted as the result of single syllable extraction, a sizeable portion affirmed that he extracted the target size correctly by his inclusion of first and final target phonemes in his productions (e.g. [po] for piano and [kiz] for candies). The resolution of this limitation coincides with his move toward two-word speech. We conclude that there is a developmental and perhaps maturational limitation in the capacity to carry out the processes underlying word and sentence production.

Child Language↗

Experimental evaluation of rodent exclusion methods to reduce hantavirus transmission to humans in rural housing.

An experimental assessment of methods to reduce rodent infestations in rural housing was conducted in Yosemite National Park, California, Sequoia/Kings Canyon National Parks, California, and Shenandoah National Park, Virginia. During pretreatment surveys, nearly all (63 of 68) selected units had past or ongoing rodent activity inside. Active infestations were found in 58.8% of the units. Peromyscus spp. represented 91.2% of all animals caught inside housing units. Despite little harborage, rodent activity was common near housing (290 animals/2,254 trap nights). The most common species present was Peromyscus maniculatus (43-50% of all captures). This species was especially frequent (49-87% of Peromyscus captures) around the foundations of housing units. Habitat had little effect on captures. There were 1.8 Peromyscus caught per unit along the foundations of housing in modified rural settings with grass lawns compared with 1.2 Peromyscus caught per unit in sites located in mature woodlands. During autumn of 1994, randomly selected housing units were rodent proofed by sealing openings associated with chases, roof eaves, and attics with insulation and wire mesh. Housing was examined and the fauna was resampled in the spring-summer of 1995. Rodent-proofed houses were infested significantly less often (3 of 28) than control houses (13 of 36) (P = 0.02) and the intensity of infestation was lower in experimental houses (6 versus 23 mice/treatment). More than 25% of the mice trapped inside the houses had been marked outside the houses during the three-day surveys, demonstrating movement of mice adjacent to the buildings into not rodent-proofed housing. As in the previous autumn, most of the animals captured in (98.9%) and along the foundations of the houses (77.5%) were Peromyscus spp. These results demonstrate that Peromyscus frequently invade rural housing but rodent-proofing effectively eliminates or substantially reduces rodent activity.

Animals↗