Ratites (ostrich, emu) as potential heart donors for humans: immunologic considerations.
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Biomedical subjects
Publications and source records attributed to L Peters.
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The expression of a hybrid gene encoding an alpha-factor prepro leader peptide-miniproinsulin (MPI) fusion [MPI is the same as the LysArg human insulin precursor described by Thim et al. (1986)] was tested in a series of isogenic yeast strains to investigate the influence of some genetic and physiological factors on heterologous production in yeast. We found that: (i) an MF alpha 1 gene disruption in haploid cells, as well as MF alpha 1 gene product expression in diploid cells, do not affect the MPI secretion level; (ii) under conditions of exogenous leucine availability, MPI production is hindered by leucine auxotrophy (a leu2 mutation); (iii) rho- mutations increase the per-cell MPI yield approximately three-fold; (iv) the MPI yield is apparently dependent on the pH of the culture medium: the higher the external pH, the larger the per-cell MPI yield.
N,N-Dimethylaniline (DMA) N-oxidase activity indicative of flavin-containing monooxygenase (FMO) was examined in four tissues (liver, gill, muscle, and kidney) of the flounder (Platichthys flesus). Gill microsomes had the highest levels of activity (456 +/- 343 pmol/min/mg), while kidney (121 +/- 109) and liver (67 +/- 26) had levels just above detection. A single faint band of a 56 kD protein was observed in liver and gill microsomes following Western blot analyses with polyclonal antibodies to FMO 1. DMA N-oxidase activity in gill and liver directly correlated with the expression of the 56 kD protein recognized by polyclonal antibodies against FMO form 1. Likewise a mRNA band of approximately 2.5 kilobases was higher in gill than a 3.0 kb band in liver following hydridization with an FMO 1 cDNA probe. Gill and liver microsomal DMA N-oxidase from the euryhaline P. flesus was compared with that of the stenohaline turbot (Scophthalmus maximus). DMA oxidase activity, FMO protein and mRNA were significantly greater in the gill of P. flesus, while S. maximus had higher levels of enzyme activity in the liver, but also significant levels in gill. Comparison of the enzymatic properties of the P. flesus gill and S. maximus liver enzymes indicated dramatic differences in Km between gill and liver, but were both inhibited by equimolar concentrations of trimethylamine (TMA). Gill microsomal activity in each species was unaffected by the mammalian FMO 2 substrate (competitive inhibitor) n-octylamine. Differential expression of FMO in tissues from stenohaline and euryhaline fish suggests a functional relationship between FMO and osmoregulation.
The procedural validity of the computerized version of the Composite International Diagnostic Interview (CIDI-Auto) was examined against the consensus diagnoses of two clinicians for six anxiety disorders (agoraphobia, panic disorder (+/- agoraphobia), social phobia, simple phobia, obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD) and major depressive episode (MDE)). Clinicians had available to them all data obtained over a 2- to 10-month period. Subjects were 98 patients accepted for treatment at an Anxiety Disorders Clinic, thus, all subjects had at least one of the diagnoses being examined. While the CIDI-Auto detected 88.2% of the clinician diagnoses, it identified twice as many diagnoses as did the clinicians. The sensitivity of the CIDI-Auto was above 0.85 except for GAD, which had a sensitivity of 0.29. The specificity of the CIDI-Auto was lower (range: 0.47-0.99). The agreement between the CIDI-Auto and the clinician diagnoses, as measured by intraclass kappas, ranged from poor (kappa = 0.02; GAD) to excellent (kappa = 0.81; OCD), with a fair level of agreement overall (kappa = 0.40). Canonical correlation analysis suggested that the discrepancies between the CIDI-Auto and clinicians were not due to different diagnostic distinctions being made. It is suggested that the CIDI-Auto may have a lower threshold for diagnosing anxiety disorders than do experienced clinicians. It is concluded that, in a sample where all subjects have at least one anxiety disorder diagnosis, the CIDI-Auto has acceptable validity.
Surveying the literature on the assessment of quality of care from the patient's perspective, the concept has often been operationalized as patient satisfaction. Patient satisfaction has been a widely investigated subject in health care research, and dozens of measuring instruments were developed during the past decade. Quality of care from the patient's perspective, however, has been investigated only very recently, and only a few measuring instruments have explicitly been developed for the assessment of quality of care from the patient's perspective. The authors consider patient satisfaction as an indicator of quality of care from the patient's perspective. This review is concerned with the question of whether any reliable and valid instruments have been developed to measure quality of care from the patient's perspective.
The relationship between and the inter-rater reliability of the Composite International Diagnostic Interview (CIDI) and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) for anxiety and depressive disorders were explored. The CIDI and the SCAN were administered by trained interviewers in counterbalanced order. A subsample of interviews was observed to determine the inter-rater reliability of the instruments. Subjects were 101 patients accepted for treatment at an Anxiety Disorders Clinic; 29 of the 101 patients participated in the inter-rater reliability study. Concordance between the instruments as measured by canonical correlation analysis was moderate for current (r = 0.69, p = 0.05) and for lifetime (r = 0.66, p = 0.05) diagnoses. Inter-rater reliability of the CIDI was perfect (overall intraclass kappa = 1.00), and of the SCAN was good (overall intraclass kappa = 0.67). It is concluded that although the two instruments made similar diagnostic distinctions, the clinical judgment involved in administering the SCAN resulted in the more moderate levels of agreement between the interviewer and observer than those found for the CIDI.
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Patients who experience local failure following radiation treatment of epithelial malignancies exhibit a substantially higher rate of distant metastasis than those patients who achieve permanent local control. This fact has raised concern that the local failure to control the primary/regional tumor may serve as a marker of a particularly malignant neoplasm, i.e., high metastatic activity and radiation resistance. If this were true, there would be no gains in survival by increasing the efficacy of treating the primary/regional disease because the new local controls would develop distant metastasis. To investigate this concept, the relationship between distant metastasis probability and tumor cell radiation resistance has been studied by examining laboratory and clinical data (in vitro and in vivo assays) from six collaborating centers. TCD50s (radiation dose which inactivates half of the irradiated tumors) and incidence of distant metastasis in mice with local control have been evaluated for 24 murine tumor systems. SF2s (surviving fraction after 2 Gy) were determined in vitro for cell lines from 8 human, 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activity assessed after injection of the cells into syngeneic murine hosts and xenogenic hosts for the human tumors. SF2s of cells from carcinomas of the head/neck, cervix, and endometrium which were controlled locally by radiation +/- surgery from four centers were compared for those which did and those which did not metastasize. The total number of patients studied was 222. The cumulative distributions of SF2s of locally controlled tumors which did and did not metastasize were not different in each of the data sets. Similarly, there was no demonstrable relationship between TCD50s and metastatic frequency in local control mice. Furthermore, the SF2s of murine and human tumor cell lines did not track with metastatic activity. Radiation sensitivity of clinical and laboratory tumors did not correlate with metastatic activity in studies of data from six centers.
Experiments were performed to establish the extent and kinetics of tumor cell repopulation in a murine sarcoma, designated SA-NH, treated with cyclophosphamide (CY). Mice bearing 8-mm leg tumors were treated with 200 mg/kg CY which caused a transient tumor regression. Changes in the absolute clonogen content of tumors was determined by the change in TCD50 values (50% tumor control) obtained under hypoxic conditions of local tumor irradiation at different times after CY treatment until tumors regrew to the pretreatment size. For comparison, hypoxic TCD50 values were determined during the growth of tumors not treated with CY. CY greatly depleted tumors of clonogenic cells as manifested by the reduction in the control TCD50 value of 64.5 Gy to 32.8 Gy 1 day after CY treatment. The reduced TCD50 value remained unchanged for 2 weeks after treatment with CY, at which time the TCD50 began to rapidly increase, continuing until the end of the observation period of 21 days when tumors reached the pretreatment size. In contrast, there was a constant but slower increase in TCD50 values during the growth of tumors not treated with CY. The daily increase in TCD50 was more than twice as high in CY-treated than in CY-untreated tumors: 4.5 Gy/day versus 2.1 Gy/day. This implies that the rate of clonogen production in CY-treated tumors was twice as high as that of unperturbed tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
This article addresses the issue of stigmatization and discrimination towards people with AIDS (PWAs) using Weiner's attributional theory of motivation and emotion. In a field experiment, subjects responded to vignettes describing patients with AIDS, syphilis, lung cancer or tuberculosis. In these vignettes, the onset of the diseases was either described as personally controllable or as uncontrollable. Results show that although attributional variables do account for a significant amount of variance in helping behavior and emotions towards PWAs, other variables such as the incurability of the disease, the risk of infection and associations with (homo)sexuality, may be more useful in explaining reactions to PWAs. Implications for education tailored at the prevention of the stigmatization of PWAs are discussed.
A 10-month inhalation study using newborn female mice was performed to determine pulmonary tumorigenicity of polycyclic aromatic hydrocarbon (PAH)-enriched exhausts. At two exhaust doses containing 50 micrograms/m3 (group II) and 90 micrograms/m3 benzo(a)pyrene (BaP) (group III) a significant increase of lung tumors was observed and the incidence of malignant lung tumors was dose-dependent. Bronchiolo-alveolar adenomas were observed in all mice of groups II and III (40/40 each) as compared to 5/40 in the control (group I). Bronchiolo-alveolar adenocarcinomas developed in 10/40 and in 33/40 mice of groups II and III, respectively, but were absent in group I. Single or multiple squamous cell carcinomas, which showed variable degrees of differentiation were observed exclusively in 6 mice of group III. One adenosquamous carcinoma was seen in an further animal of this group.
Fifty consecutive patients undergoing resection of colorectal cancer were randomized to either receive cimetidine at a dose of 400 mg bd for a minimum of 5 pre-operative days, then intravenously for 2 postoperative days, or to act as controls. Baseline immune function was determined in all patients by in vitro testing of lymphocyte proliferation (LP) in response to mitogen, skin testing for cell mediated immunity (CMI) and measurement of lymphocyte subsets. Immune function was retested in both groups on the second postoperative day. In control patients the mean postoperative LP value was 41% of pre-operative levels (P < 0.0001) and the mean CMI reduced to 29% (P < 0.0001). Patients treated with cimetidine had no significant fall in these parameters. Numbers of T and natural killer (NK) cells fell after surgery in both groups, and B cell numbers were maintained in the cimetidine group. It is concluded that cimetidine reduces the immunosuppression that follows colonic resection.
1. D-Penicillamine (125 mg) was administered orally to control (healthy volunteers), Parkinson's and Motor Neurone Disease patients following an overnight fast. 2. Blood was collected at 08:00 h for the preparation of red blood cell membranes used in the in vitro S-methylation studies. Urine was collected from 08:00 to 16:00 h and analysed for D-penicillamine and its metabolites. 3. Metabolism occurred via S-methylation, N-acetylation and disulphide formation. Both the Parkinson's and Motor Neurone Disease patients excreted significantly higher median levels of S-methyl-D-penicillamine in the urine than the controls (177 and 209% more for the Parkinson's and Motor Neurone Disease patients respectively). 4. The in vitro and in vivo production of S-methyl-D-pencillamine was highly correlated in the control (rs = 0.936), Parkinson's (0.986) and Motor Neurone Disease (0.752) populations.
In previous studies we have shown that levels of IgM-rheumatoid factor (RF) in plasma and peripheral blood mononuclear cell supernatants are correlated with disease activity and response to second-line therapy in patients with rheumatoid arthritis (RA). The present studies were designed to examine whether IgA-RF levels are also correlated with clinical features of this disease. Two groups of RA patients were studied. Group I consisted of 87 patients in whom extensive clinical data had been collected. Group II included nine patients beginning treatment with gold or methotrexate who were studied during the first year of therapy. Measurement of IgM, IgA, IgM-RF and IgA-RF in culture supernatants and plasma was done by an ELISA method. These data were examined for correlations with clinical and laboratory features. Levels of IgA-RF in supernatants and plasma were found not to be correlated with disease features in the cross-sectional analysis of Group I patients, while IgM-RF and total IgA levels did show significant clinical correlation. Treatment of Group II patients with gold or methotrexate was associated with significant decreases in plasma levels of total IgA and IgM-RF as well as a small but statistically significant decrease in plasma IgA-RF. Plasma levels of total IgM were not altered during therapy. These findings suggest that production of IgA but not IgA-RF is correlated with disease status in patients with RA.
A new technique for the treatment of certain types of cardiac arrhythmias was used in a 3-year-old dog that was evaluated for incessant supraventricular tachycardia (220 to 280 beats/min), which had been refractory to several treatment regimens. The mechanism of supraventricular tachycardia was atrioventricular (AV) reentry, using a dorsoseptal accessory pathway (AP) for retrograde ventriculoatrial conduction (concealed AP). With the dog under general anesthesia and with fluoroscopic monitoring, electrode catheters were introduced into the heart via peripheral vessels. Electrical recordings allowed localization of the accessory AV pathway. Programmed electrical stimulation was used to verify the function of the abnormal AV connection. At the atrial insertion site of the AP, 2 applications of radiofrequency current (45 V, 21.6 W) were delivered to the dorsoseptal right atrium (near the coronary sinus ostium), which eliminated AP conduction and AV reentrant tachycardia. The dog has remained free of tachycardia and has not required medication during more than 1 year of follow-up.
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A chloramphenicol-resistance gene (cml) was introduced into the Lactobacillus plantarum gene encoding conjugated bile acid hydrolase (cbh) on a ColE1 replicon. This plasmid which is nonreplicative in Lactobacillus was used to transform L. plantarum strain 80. A homologous double cross-over recombination event resulted in replacement of the chromosomal cbh gene by the cml-containing cbh gene. The transformants obtained were unable to synthesize active conjugated bile acid hydrolase (Cbh). The Cbh- CmlR phenotype was stably maintained for more than 100 generations under nonselective conditions.