Pancreatitis and homocystinuria.
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Biomedical subjects
Publications and source records attributed to J E Collins.
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We examined expression and cytotoxic triggering capability of the three Fc receptors for IgG (Fc gamma R) on human monocytes, PMNs and myeloid cell lines after in vitro culture with various cytokines. Fc gamma R expression was evaluated using specific anti-Fc gamma R monoclonal antibodies (mAb). The cytotoxic capability of each Fc gamma R was examined after the effector cells were treated with the recombinant cytokines IFN-gamma. TNF alpha, GM-CSF, G-CSF, M-CSF, IL-1, IL-2, IL-3, IL-4, or IL-6. Hybridoma cell lines (HC) bearing antibody directed to Fc gamma RI (HC 32), Fc gamma RII (HC IV.3) or Fc gamma RIII (HC 3G8) were used as targets, as were chicken erythrocytes (CE) sensitized with heteroantibodies composed of anti-Fc gamma R mAbs (32, IV.3, 3G8) linked to anti-CE antibody. Only IFN-gamma treatment significantly increased Fc gamma R expression and then only Fc gamma RI. IFN-gamma dramatically up-regulated Fc gamma RI expression on all cells tested. However, ADCC was enhanced by treatment with a number of cytokines other than IFN-gamma. GM-CSF, TNF, and IFN-gamma treatment enhanced killing of HC 32 and HC IV.3 by in vitro cultured monocytes. G-CSF treatment enabled PMNs to kill HC through Fc gamma RII, whereas PMN killing of HC through Fc gamma RIII could not be induced by any of the cytokines studied. Although only IFN-gamma treatment increased ADCC of CE by monocytes, GM-CSF treatment as well as IFN-gamma treatment augmented ADCC of CE by PMNs. In addition to IFN-gamma treatment, IL-6 treatment enabled U937 cells to lyse CE. Whereas IFN-gamma-treated U937 cells killed CE through both Fc gamma RI and Fc gamma RII, IL-6-treated U937 cells killed CE only through Fc gamma RI. In addition to IFN-gamma treatment, G-CSF treatment enabled HL-60 cells to lyse CE through both Fc gamma RI and Fc gamma RII. These results demonstrate that although IFN-gamma appears unique in regulating Fc gamma R expression on myeloid cells, cytokines other than IFN-gamma affect ADCC by these cells in a receptor-specific manner.
Desmosomes are adhesive junctions of epithelial cells. Their expression may be altered or lost in carcinomas resulting in reduced cellular adhesiveness. The desmosomes of colorectal carcinomas have been studied by fluorescent antibody staining, immunoblotting and electromicroscopy. A series of 58 malignant specimens, comprised of primary tumours and metastases, were desmosome positive. There was no indication of a comparative reduction in desmosome expression that might give rise to reduced adhesiveness of tumour cells, although loss of polarised junctional distribution in poorly differentiated tumours might have such a consequence. Western blotting analysis of colorectal cancers and cultured carcinoma cells identified desmosomal polypeptides dp1 + 2, dg1 and dg2 + 3 with similar relative molecular weights to normal homologues. In addition, a polypeptide of 140,000 was recognised only in malignant epithelium by anti-dg2 + 3 antiserum. The significance of this polypeptide is not understood. Tumours and uninvolved epithelium were exposed to low extracellular [Ca2+] to test whether tumour desmosomes were of reduced stability. This caused much cellular degradation in tumours but some viable cell clumps possessed desmosomes resistant to disruption by low [Ca2+]. Desmosomes may thus have a positive role in metastasis by maintaining intercellular adhesion between metastasising cells.
A collection of Streptococcus suis strains from animal and human infections was examined for DNA-banding patterns after restriction endonuclease digestion and agarose gel electrophoresis. The endonuclease HaeIII produced the most discriminating restriction profiles among 23 serotypes studied. DNA from serotypes 9, 11, 12, and 16 was resistant to HaeIII cleavage. DNA from serotypes 9 through 16 was cleaved with HindIII and showed substantial genomic differences. We also examined 106 epidemiologically unrelated strains isolated from cases of pig meningitis or pneumonia and 5 strains isolated from cases of human meningitis in order to compare genomic fingerprinting and serotyping as epidemiological tools. Heterogeneity was found among fingerprints of serologically identical isolates, indicating genetic diversity within some serotypes. DNA fingerprints of some serotype 2 strains from different sources appeared identical, suggesting a clonal relationship among strains of this serotype. The data suggest that this technique represents an important tool for examining the natural history of disease caused by S. suis.
Enterotoxigenic Bacteroides fragilis elicited fluid accumulation in the intestinal tract and exfoliation of epithelial cells in the proximal colon of the 2-week-old rabbit. The rabbit model was employed to screen isolates of B. fragilis for enterovirulence and to study the pathogenesis of disease caused by enterotoxigenic B. fragilis.
Blood glucose concentrations were measured prospectively in 27 small for dates infants in the first 48 hours after birth: 10 infants became hypoglycaemic. Of these, five had inappropriately raised plasma insulin concentrations. Plasma free fatty acids were lower and carbohydrate intake higher in these five infants, further supporting the diagnosis of hyperinsulinism. The hypoglycaemia recurred in four of the five hyperinsulinaemic infants, but in none of those who were not hyperinsulinaemic. Hyperinsulinism is common in small for dates babies. It is important to recognise this because hypoglycaemia is likely to recur and appropriate treatment is needed to prevent long term sequelae.
The N-terminal sequence of a mixture of desmosomal glycoproteins 2 and 3 (dg2/3, desmocollins) from bovine nasal epidermis, prepared by electro-elution from polyacrylamide gels, was determined by solid-phase Edman degradation. A sequence of 23 amino acids was obtained. This showed 43% identity with that of the N terminus of the calcium-dependent cell adhesion molecule, N-cadherin. A lesser degree of identity with other members of the cadherin-uvomorulin-L-CAM family was also found. In order to confirm that the sequence was derived from the dg2/3 molecules a rabbit antiserum was raised against a synthetic peptide corresponding to the sequence, conjugated to keyhole limpet haemocyanin (KLH). The antiserum obtained showed high (titre) activity against both the peptide and KLH in ELISA. Each activity could be specifically adsorbed with the appropriate ligand. The antiserum reacted specifically with both dg2 and dg3 of bovine nasal epidermis on immunoblots, this binding was blocked by the N-terminal peptide but was unaffected by KLH. The identity of dg2 and -3 in these preparations was confirmed by immunoblotting with two monoclonal antibodies and one polyclonal antiserum raised against the whole molecules. The N-terminal peptide antiserum was shown to bind to the intercellular space of desmosome profiles by immunoelectron microscopy on ultra-thin frozen sections. One of the two monoclonal antibodies (07-4D) also reacted with the desmosomal intercellular space. dg2 and -3 were shown by Staphylococcus aureus V8 protease digestion to have identical one-dimensional peptide maps. Both the N-terminal antiserum and 07-4D reacted with a V8 fragment of 19,000 Mr derived from dg2 and dg3.(ABSTRACT TRUNCATED AT 250 WORDS)
Ripened nightshade berries (Solanum dulcamara) are among the most commonly reported plant ingestions in Minnesota. Because of the lack of adequate information regarding the toxic qualities of S. dulcamara berries, the ingestion of even small quantities by children is usually treated conservatively with syrup of ipecac. The toxicity of S. dulcamara berries was studied by gavaging mice with a preparation of lyophilized berries, ripened and unripened, collected at various times of the year. Mice receiving unripened fruit from early in the season had gastrointestinal tissue changes consistent with solanine toxicity. Animals dosed with unripened fruit from the latter part of the year showed behavioral signs suggestive of solanine toxicity, however gastrointestinal lesions were not observed. In no case did the ripened fruit produce behavioral or histologic toxicity. Aggressive treatment of children ingesting limited amounts of ripened S. dulcamara berries appears to be unnecessary.
Glucose production was measured using stable isotopic techniques in two patients with phosphorylase b kinase deficiency before and after oral ethanol (0.75 g/kg). Glucose production was normal before the ethanol. In one patient, who did not take the full dose of ethanol, glucose production rose initially and then fell. In the other, glucose production fell steadily and in both patients blood lactate concentrations rose. Blood glucose concentrations decreased. Patients with this enzyme deficiency are dependent on the gluconeogenic pathway when fasting and, therefore, ethanol may be potentially hazardous.
Enterotoxigenic Bacteroides fragilis caused severe, nonhemorrhagic, watery diarrhea when 10(9) CFU of a porcine or human isolate was administered orogastrically to 3-day-old rabbits. The bacterium colonized the intestinal tract with a predilection for the large intestine (10(9) CFU/g of cecal contents). Diarrhea occurred at an average of 4.6 days postinoculation, and 84% of rabbits were dead or moribund at an average of 8.8 days postinoculation. The disease was characterized by watery diarrhea and dehydration. Severe histologic lesions including inflammation, exfoliation of epithelial cells, and crypt hyperplasia were observed throughout the colon. There was no indication of bacteremia or of bacterial adherence to or invasion of intestinal epithelial cells. Rabbits inoculated with nonenterotoxigenic B. fragilis were colonized with B. fragilis but did not develop clinical disease or intestinal lesions. While the pathogenesis of this disease is undefined, clinical signs of disease and histologic changes were consistent with a mechanism of net secretion of fluid into the small intestine and decreased absorption of fluid from the large intestine. Enteric disease caused by enterotoxigenic B. fragilis in infant rabbits was similar to naturally occurring enteric disease associated with the bacterium in humans and livestock. This study established that enterotoxigenic B. fragilis is enteropathogenic in intact infant rabbits.
Attaching and effacing Escherichia coli (AEEC) adhere to mucosal epithelium in both small and large intestine and induce a distinctive lesion characterized by an irregular scalloped appearance of the epithelial layer. Infection with attaching and effacing E. coli was detected in 14 calves, 7 pigs, 2 lambs, and 3 dogs. Affected animals were from farms and kennels in South Dakota, Minnesota, Iowa, Nebraska, and Wisconsin. Ages of affected animals were calves, 2 days to 4 months; pigs, 1-6 weeks; lambs, 1 week; and dogs, 7-8 weeks. Clinical signs included diarrhea in all animals, but other nonenteric disease problems were present in some animals. Concurrent infection with other enteropathogens was detected in 9 calves and 5 pigs. Infection with AEEC appeared to be the sole cause of illness and death in some animals. There was evidence of intestinal hemorrhage in 5 of the calves and in all 3 dogs. Attaching and effacing lesions varied from small scattered foci to widespread involvement of large areas of intestinal mucosa. Verotoxin was produced by E. coli strains isolated from 9 calves, but not by strains from pigs, lambs, or dogs.
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The virulence of 2 porcine group-A rotavirus isolates was compared. Forty hysterotomy-derived 3-day-old gnotobiotic pigs were inoculated orally with 2 ml of intestinal homogenate containing either the Ohio State University (OSU) or the South Dakota State University (SDSU) strain of porcine rotavirus or were inoculated with medium only. Clinical signs of disease, body weight, distribution of viral antigen, fecal excretion of virus, and histologic lesions (observed by light and scanning electron microscopy) were determined. Morphometric measurements of villi and crypts were made. In pigs inoculated with OSU or SDSU strains, diarrhea began at postinoculation hours (PIH) 19 to 48 and PIH 24 to 54, respectively. None of the virus-infected pigs died as a consequence of infection and all had similar clinical signs of disease, body weight changes, and virus-shedding patterns, regardless of the strain of rotavirus with which they were infected. Microscopic findings in the small intestine of virus-infected pigs were similar, except that the SDSU strain caused more severe villus atrophy and villus fusion in the duodenum at PIH 72 and 168 than was associated with the OSU strain. Viral antigen in the small intestine of pigs infected with either virus was observed by use of immunofluorescence at PIH 24 and 72, but was seldom seen at PIH 168.
The sera of 34 acquired immune deficiency syndrome (AIDS) patients and 20 healthy male homosexuals were examined for the presence of elevated levels of IgA and IgM rheumatoid factor (RF) and compared with results obtained with sera from 23 healthy laboratory volunteers. IgA RF levels were elevated (greater than 3 standard deviation units) in 9 of 34 (26%) patients with AIDS as compared to the panel of laboratory controls. Levels of IgM RF did not differ significantly in the AIDS patients and in the controls. There were no differences in levels of either IgA RF or IgM RF when the homosexual controls were compared with the laboratory volunteers. Sucrose-gradient ultracentrifugation experiments and assays using monoclonal reagents specific for IgA subclasses indicated that the IgA RF was predominantly of the polymeric configuration and restricted to the IgA1 subclass, respectively. Polyethylene glycol (PEG) precipitates of serum enriched for circulating immune complexes (CIC) were also assayed for the presence of IgA RF and IgM RF. Although levels of IgA RF in serum and in PEG precipitates did not correlate with levels of IgA- or IgA/IgG-containing CIC in AIDS patients, levels of IgA RF in both serum and CIC-enriched material were significantly elevated in the AIDS population when compared with the control panel. In contrast, levels of IgM RF in both serum and CIC-enriched material were low and not significantly different from those in healthy controls. These results indicate that both IgA-containing CIC and IgA RF occur in many AIDS patients and raise the possibility that IgA RF may contribute significantly to the formation of immune complexes in this disease.
We asked 26 subjects to recall and describe social situations in which either a close or a distant other performed better or worse than the self at an activity that was either high or low in relevance to the self. Subjects then rated the extent to which they experienced each of 18 different emotions in each situation. They also rated each situation on a series of dimensions that Smith and Ellsworth (1985) found to be consequential for differentiating emotions. In a series of analyses guided by intuitive hypotheses, the Smith and Ellsworth theoretical approach, and a relatively unconstrained, open-ended exploration of the data, the situations were found to vary with respect to the emotions of pride, jealousy or envy, pride in the other, boredom, and happiness. We discuss the results in terms of their relevance to emotion theories and to the self-evaluation maintenance model of social behavior.
Human papillomavirus (HPV) infection of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma was investigated using in situ DNA-DNA hybridisation on histological sections of formalin fixed, paraffin embedded tissue to assess the technique's sensitivity and to assess retrospectively the association between HPV16 and invasive cervical carcinoma. HPV DNA was detected in 16 of 33 biopsy specimens of CIN. Cells containing viral DNA were more numerous than those positive for viral structural proteins. HPV DNA was also present in less differentiated cells deeper in the epithelium. The detection rate in CIN was lower than that reported for other hybridisation techniques such as Southern blotting. In a retrospective study of biopsy specimens of invasive squamous carcinoma of the cervix HPV16 DNA, the virus most commonly associated with cervical malignant disease, was found in 20 of 25 cases, including those dating from as far back as 1932. The level of sensitivity was similar to that reported for other hybridisation techniques. DNA positive cells were focally distributed in the invasive tumours, and most tumour cells were negative for viral DNA, a result consistent with the low copy number found in malignant cells. It is concluded that HPV16 is not a new virus but that its prevalence is a result of changes in sexual behaviour and that in situ hybridisation is useful in the localisation of HPV DNA replication in CIN and invasive carcinoma.
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