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Biomedical subjects

D F Keren

Publications and source records attributed to D F Keren.

18 recordsLinked to original sources
PubMed1992

Antigen processing in the mucosal immune system.

The mucosal immune system is concerned with host defense along the moist surfaces of the body which have contact with the external environment. These sites contain specialized lymphoid structures which contain precursors for IgA-synthesizing B lymphocytes and immunoregulatory T lymphocytes which will determine whether oral tolerance or a strong immune response develops against antigens administered orally. The key step to antigen processing in the gastrointestinal tract involves its initial uptake from the gut lumen by specialized follicle associated epithelium called 'M' cells. M cells originate from adjacent crypt epithelium and are interspersed between the absorptive epithelial cells in the follicle-associated epithelium. M cells cells have short, irregular microvilli, are closely associated with lymphocytes, do not have a prominent terminal web, and have only weak alkaline phosphatase activity but strong nonspecific esterase activity. M cells do not express surface MHC class II (HLA-DR) antigens. These cells take up macromolecules, viruses, bacteria and protozoa within 30 minutes from the initial presentation of the antigen to the intestinal lumen. After the initial uptake of antigen by M cells, the antigens are transported into the follicular areas to be processed by dendritic cells and brought into close contact with the antigen-specific precursors for IgA secreting plasma cells. The final result of M cell processing is the production of a vigorous secretory IgA response and local cell-mediated immunity with suppression of a systemic IgG, IgE and delayed-type hypersensitivity to orally-administered antigens.

Animals↗
PubMed1992

Immunofixation to quantify beta 2-transferrin in cerebrospinal fluid to detect leakage of cerebrospinal fluid from skull injury.

beta 2-Transferrin, the desialated form of transferrin normally found only in cerebrospinal fluid (CSF) and aqueous and vitreous humor, is detected by high-resolution immunofixation (IFE). It is not normally found in nasal or aural fluids, saliva, tears, or serum. Detection in nasal fluid has been suggested to document CSF leakage into the nose after skull injury. We measured beta 2-transferrin in 48 samples of CSF. IFE of the CSF was performed on high-resolution agarose gels and stained with Coomassie Blue. beta 2-Transferrin was estimated by quantifying the total transferrin by rate nephelometry and then determining the percentage of transferrin in the beta 2 vs beta 1 region by densitometric scanning of the IFE pattern. We accurately quantified as little beta 2-transferrin as 2.5 mg/L in the CSF samples. The beta 2-transferrin fraction was clearly visible by IFE at concentrations less than 2.5 mg/L, but accurate quantification was difficult. In the samples assayed, the range of beta 2-transferrin was 4.6 +/- 1.9 mg/L. Use of this technique to examine rhinorrhea in a motor-vehicle-accident patient confirmed leakage of CSF into the nasal cavity through a vent in the left olfactory groove.

Adult↗
PubMed1979

Enzyme-linked immunosorbent assay for immunoglobulin G and immunoglobulin A antibodies to Shigella flexneri antigens.

An enzyme-linked immunosorbent assay has been developed to detect class-specific antibodies to Shigella flexneri lipopolysaccharide antigens. This enzyme-linked immunosorbent assay system has been used to measure antibodies present in serum or intestinal secretions without further purification. It is considerably more sensitive than passive hemagglutination, allowing detection of as little as 1.3 ng of specific immunoglobulin G antibody per ml in immune sera. Optimal conditions for this assay are outlined in this report.

Antibodies, Bacterial↗
PubMed1979

Immunofluorescence of deparaffinized, trypsin-treated renal tissues. Preservation of antigens as an adjunct to diagnosis of disease.

The present study compares formalin-fixed, deparaffinized and trypsin-treated (DTT) renal tissue sections with frozen sections for detecting immune complex deposition. Both DTT and frozen sections from 52 renal biopsies were stained directly with fluorescein isothiocyanate-conjugated antihuman IgG, IgM, IgA, fibrinogen, and C3. DTT sections alone were stained indirectly for C3 using a double conjugate technique. Antigen presence or absence on DTT section was accurately detected in 90 per cent of biopsies for immunoglobulins and fibrinogen and in 75 per cent for C3 when compared to frozen section. Furthermore, antigen deposition was found in 21 per cent of biopsies only on DTT sections (usually because frozen tissue lacked glomeruli). Frozen sections alone were treated with reagents of the fixation-embedding process and directly stained for IgM and C3 to determine antigen stability. Alkaline or neutral formalin pH helped maximize antigen preservation. DTT sections are a valuable tissue source for adjunctive diagnosis of renal disease.

Antigen-Antibody Complex↗
PubMed1978

Bridging hepatic necrosis. Etiology and prognosis.

The probable etiology and outcome of bridging hepatic necrosis found on a liver biopsy performed within three months of the onset of clinical illness was evaluated in 42 consecutive patients with this finding. Eighteen of the patients (43%) had a probable drug etiology for their hepatitis. Ten patients had HBSAG-positive acute hepatitis. Fourteen patients had neither drug-induced disease nor proven HBSAg-positive hepatitis. One patient from the drug-induced group died, but the other 17 had complete clinical recovery. Eight of ten in the hepatitis B antigen-postive group cleared their antigen and had complete clinical recovery. Chronic hepatitis developed in two who remained persistently HGSAg positive. Eight of the patients in the group with unknown etiology recovered, while six developed evidence of active chronic liver disease. This incidence of active chronic liver disease is significantly greater than that found in the drug-induced group (P less than 0.02). We conclude that drug-induced hepatitiis accounts for a significant proportion of patients of acute hepatitis who have bridging hepatic necrosis on liver biopsy. However, in these drug-induced cases the finding of bridging hepatic necrosis does not appear to be associated with an increased risk of development of active chronic liver disease.

Acute Disease↗
PubMed1978

A modification of the automated immune precipitin method for quantitation of human serum immunoglobulins.

The use of the automated immune precipitin method to measure human serum immunoglobulins has been reported by several groups. The authors encountered difficulties in evaluating the technic even when they incorporated such recent modifications as the use of polyethylene glycol to enhance the reaction. By altering the flow pattern and prediluting each specimen, they were able to increase sampling rate, decrease processing time, and decrease the frequency of line obstructions while obtaining reproducible standard curves without using polyethylene glycol. There was good correlation between the results obtained by their modification of the technic and those obtained by the Fahey radial immunodiffusion method. As with other automated immune precipitin systems, abnormally high values gave characteristic notched peaks and lipemic specimens were centrifuged in order to obtain the infranatant for quantitation. The present modification of the automated immune precipitin system provides a rapid, simple and efficient method to quantitate human serum immunoglobulins.

Automation↗
PubMed1978

Local (immunoglobulin A) immune response by the intestine to cholera toxin and its partial suppression with combined systemic and intra-intestinal immunization.

Chronically isolated Thiry-Vella (T-V) ileal loops in rabbits were used to study the local and systemic immune response to purified cholera toxin (CT). Immunization consisted of intraloop (i.l.), subcutaneous (s.c.), or combined i.l. and s.c. inoculation of CT. Fluid from the loops and sera were tested for neutralization of CT by the blueing test and for relative content of isotype-specific (immunoglobulins A [IgA] and G [IgG]) anti-CT. To demonstrate protection against CT, fluid production by the chronic T-V loops was measured after challenge with CT; an "acute" loop prepared from adjacent intestine at the time of challenge was also tested in some animals. The highest neutralizing titers in loop fluids were found in animals receiving i.l. or i.l. and s.c. inoculations, whereas titers in sera were highest in rabbits receiving s.c. or i.l. and s.c. inoculations. IgA anti-CT in fluids became greatest after i.l. inoculation alone and was lowest in s.c. animals. Combined s.c. and i.l. immunization was accompanied by reduced content of IgA anti-CT in fluids as compared with that obtained with i.l. inoculation alone. This finding strongly suggested a suppressive effect on local immunization by s.c. inoculation. While this suppression may have been due to a direct (toxigenic) effect of CT on lymphocytes, an immunogenic mechanism, probably mediated through suppressor T cells, is favored. Little IgG anti-CT was detected in any loop fluids, but high levels were found in sera after two s.c. inoculations or four i.l. inoculations. Neutralization titers for the fluid specimens showed much better correlation with IgA anti-CT values than with IgG anti-CT values. The chronic and acute T-V loops showed protection against fluid production after exposure to CT in systemically and locally immunized animals. However, IgG anti-CT usually appeared in both loops; leakage of serum antibodies because of surgical manipulation was felt, therefore, to invalidate these protection results as a demonstration of local immunity. In challenge studies in undisturbed chronic loops, only local immunization alone was found to result in definite protection.

Animals↗
PubMed1976

Arizona hinshawii osteomyelitis with antecedent enteric fever and sepsis. A case report with a review of the literature.

A case of Arizona osteomyelitis of the spine which occurred 11 months after an episode of gastroenteritis and enteric fever is presented. As close biochemical and antigenic relative of Salmonella, Arizona infection produces a similar clinical course with gastrointestinal manifestations frequently preceding localized infections by several months. The boney lesion in the present case and in three of the four other cases of Arizona osteomyelitis described in the literature was a chronic inflammation which may have a xanthomatous component. The bone destruction caused by Arizona infection is less severe than that of tuberculosis or pyogenic osteomyelitis. Proposed treatment of Arizona osteomyelitis consists of debridement of the localized infection and long term antimicrobial therapy.

Child, Preschool↗
PubMed1976

Challenge of dogs with live enterotoxigenic Escherichia coli and effects of repeated challenges on fluid secretion in jejunal Thiry-Vella loops.

Dogs were evaluated as experimental models for the study of diarrheal disease produced by enterotoxigenic Escherichia coli. Although a suitable whole model for orogastric bacterial challenge could not be developed, chronic jejunal Thiry-Vella loops were used to study the secretory effects of multiple jejunal challenges with enterotoxin of either Vibrio cholerae or E. coli. The heat-stable and heat-labile E. coli enterotoxins could be differentiated clearly in this model. Sequential weekly challenges over a four-week period showed a significant decrease in loop secretory response to homologous enterotoxin, although levels of antitoxin in serum remained unchanged, a finding suggesting a local immune response. Dogs challenged with E. coli enterotoxin were markedly protected against subsequent challenge with V. cholerae enterotoxin; the converse was not true. Histologic studies of the loops showed only minimal atrophy, and results of absorption studies in the loops were normal. These studies suggest that mongrel dogs are resistant to colonization by enterotoxigenic E. coli and partially resistant to challenge with enterotoxin, perhaps on an immune basis due to prior antigenic exposure. Multiple challenges with enterotoxin effect a decreased secretory response; this finding also suggests a local immune mechanism.

Animals↗
PubMed1976

Whipple's disease: demonstration by immunofluorescence of similar bacterial antigens in macrophages from three cases.

Although it is widely accepted that Whipple's disease is caused by microorganisms, there is little agreement as to the exact nature of those microbes. Several different types of bacteria have been reported from patients with Whipple's disease causing some workers to speculate that Whipple's disease may be due to a variety of microorganisms. Using an indirect immunofluorescence technique, we have demonstrated bacterial antigens in the granules of the foamy macrophages from three patients with Whipple's disease. The macrophages in each case stained with several types of antibacterial grouping sera. Jejunal biopsies from three normal subjects and one from a patient with celiac-like disease did not show significant reactions with any of the antisera. When these same antisera were reacted with homologous and heterologous bacteria, numerous cross-reactions were seen. However, each organism only reacted with certain antisera resulting in a distinctive pattern of reaction which could identify it. Therefore, if a different organism was present in each case of Whipple's disease, the antisera should give dissimilar reactions from case to case, but if the same type of microbe was present in each case, a similar pattern of reaction should be seen. In fact, the reactions were remarkably similar from case to case. These results suggest that a single, antigenically definable microorganism is present in the jejunal tissue of patients with Whipple's disease.

Adult↗
PubMed1975

Atrophy of villi with hypertrophy and hyperplasia of Paneth cells in isolated (thiry-Vella) ileal loops in rabbits. Light-microscopic studies.

Thiry-Vella loops in rabbit ileum were prepared by a new technique and were studied 18 hr to 49 days postisolation. The loops became grossly shortened after 14 days. Histologically, some shortening and blunting of villi was detectable as early as 4 days postisolation, and with prolonged isolation the changes became marked. Reduction in epithelial cell height and in brush border thickness were noted, and goblet cells were increased somewhat in size and prominence. Yet there was only slightly increased chronic inflammation in the mucosa and acute inflammation was uncommon, suggesting that mucosal injury was minimal. Furthermore, mean epithelial mitotic indices for the crypts did not rise and were generally reduced. Striking hyperplasia and hypertrophy of Paneth cells associated with mitotic figures in Paneth cells accompanied the atrophic changes in the villi. Reimplantation of loops into the bowel 3 weeks after isolation led to complete reversal of all changes, including hyperplasia of Paneth cells. On the other hand, regular perfusion of loops with a solution containing a large variety of nutrient substances failed to reverse the mucosal changes. It was concluded that atrophy of villi in isolated ileum of the rabbit occurred mainly because one or more substances contained in the chyme are needed to maintain normal mucosal architecture. These substances probably help regulate epithelial cell turnover and may well be endogenous in origin. Loss of substances in the chyme after loop isolation may also have led to Paneth cell hyperplasia. Alternatively, the Paneth cell changes and atrophy of villi might have been related in a cause and effect way.

Animals↗
PubMed1975

Intercurrent cytomegalovirus colitis in a patient with ulcerative colitis.

Acute intercurrent CMV colitis developed in a patient with UC who was receiving prednisone. CMV infection was suggested by light and electron microscopic study of a rectal biopsy taken during the acute episode and was confirmed by serology done nine months later. The microscopic studies of plastic-embedded tissues demonstrated that infected cells were concentrated in a subendothelial location and were presumably macrophages. Epithelial and endothelial cells were not involved. Steroid therapy and the inflammation and repair process (granulartion tissue) of active UC may have predisposed the present patient to CMV colitis. CMV infection has been reported to be more common in patients with UC than in the general population. Detection of CMV colitis in patients with UC could be of special importance since alteration of immunosuppressive therapy may be indicated.

Acute Disease↗
PubMedDate not supplied

Characterization of the mucosal immune response to 2-acetylaminofluorene-protein conjugates.

Many environmental carcinogens gain access to the body only after traversing a mucosal surface. Due to their small size, most carcinogens are not recognized by the immune system and pass unhindered from the external to the internal environment. In previous studies, we demonstrated that secretory IgA directed against the carcinogen 2-acetylaminofluorene (AAF) can be elicited by covalently coupling AAF to the mucosal immunogen cholera toxin (CT). Rabbit intestines receiving secretions containing secretory IgA anti-AAF demonstrated a marked reduction in transmucosal absorption of carcinogen from the intestinal lumen to the mesenteric blood supply. In actively immune animals, however, recent data suggests that the disposition of luminal carcinogen may be influenced by the relative abundance of serum versus mucosally-based immunoglobulins. Our objective was to quantify the amount and isotype distribution of antibodies produced in response to AAF-carrier protein conjugates administered via different routes; using traditional parenteral carrier proteins and routes of administration, compared to mucosal carrier proteins and routes of administration. Administration of AAF-cholera toxin conjugates to isolated ileal (Thiry-Vella) loops in rabbits elicited a vigorous sIgA anti-AAF response in ileal secretions, with low levels of serum or intestinal IgG, or serum-based IgA produced concomitantly. All parenteral immunization protocols generated extremely high titers of serum IgG anti-AAF, with only moderate levels of sIgA produced concomitantly, even when mucosal boosting followed parenteral priming. When AAF-CT mucosal boosts were administered after intraperitoneal priming, a dramatic rise in serum, not secretory IgA was observed.

2-Acetylaminofluorene↗