Reactivity of aggregated immunoglobulin in Crohn's disease.
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Animals↗
Biomedical subjects
K M Das
Publications and source records attributed to K M Das.
Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis.
We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis.
Adolescent↗
Double-J catheter for transgastric cystogastrostomy.
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Catheterization↗
Hybridomas using athymic nude mouse injected with Crohn's disease (CD) tissue filtrate. Immunoreactivity of the hybridomas with CD sera.
Injections of Crohn's disease (CD) tissue filtrates produce lymphoma and hyperplastic lymph nodes from plasma cell hyperplasia (PCH) in athymic nude (nu/nu) mice; these lymphoid tissue contain an antigen(s) recognized by CD serum/gamma G immunoglobulin (IgG). To immortalize the "CD-reactive antigen(s)," the authors fused the lymphoid cells from a CD tissue filtrate primed nu/nu mouse with nonsecretory mouse myeloma cells. Hybrids were screened and selected based on their reactivity with CD serum IgG, but not with control serum IgG in an indirect immunofluorescence assay (IF). Two CD-positive hybridomas were examined by IF with sera from 47 CD, 38 ulcerative colitis (UC), 13 controls with other gastrointestinal diseases, 19 with autoimmune diseases, and 21 normal subjects. Sera from 16 CD patients (34%) reacted with the two hybridomas, but only one of 38 UC sera and none of the 53 other disease or normal control sera reacted. The immunoreactivity of CD sera was significantly higher than UC sera (P less than 0.01) and each of the other groups (P less than 0.007). Using immunoperoxidase techniques at light and electron microscopic levels, the authors localized CD-associated antigen(s) in the plasma membrane of the two hybridomas. Further characterization of these hybridomas and the immunoreactive protein(s) may provide an important probe(s) for the diagnosis and the understanding of the pathogenesis of CD.
Animals↗
Recurrent massive upper gastrointestinal hemorrhage due to Strongyloides stercoralis infection.
A 29-yr-old black male immigrant from Africa presented with recurrent life-threatening upper gastrointestinal bleeding due to massive duodenal infection by Strongyloides stercoralis. The diagnosis was missed by repeated examinations of fresh stool specimens for ova and parasites and by an initial esophagogastroduodenoscopy. The diagnosis was made by pathologic examination of a duodenal biopsy and of a duodenal aspirate obtained at a second esophagogastroduodenoscopy. This has been previously reported as a cause of massive upper gastrointestinal hemorrhage in four cases. Patients with obscure gastrointestinal bleeding who have travelled or lived in an endemic area should have a duodenal aspiration performed at esophagogastroduodenoscopy.
Adult↗
Double-blind placebo-controlled study of olsalazine in the treatment of ulcerative colitis.
Olsalazine is a compound consisting of two 5-amino salicylate (5-ASA) molecules linked by an azo bond, which, administered orally, is split by colonic bacteria to liberate 5-ASA. It lacks the sulfapyridine moiety found in sulfasalazine. Using a specific protocol, we conducted a randomized, double-blind, placebo-controlled trial of olsalazine in patients with symptomatic ulcerative colitis. Inclusion criteria included mild to moderate disease with involvement of more than 15 cm of colon, visible blood in stools, and the discontinuation of all other medications prior to and during the study. Patients were given oral olsalazine 3.0 g/day or placebo for 4 wk. Patients were evaluated clinically, by laboratory analysis and by colonoscopic evaluation, at entry and at 4 wk. Additional clinical and laboratory evaluations were performed at 2 wk. Fifteen patients entered the study. Of the seven patients randomized to olsalazine, four (57%) improved clinically and by colonoscopic scoring, one showed no improvement in either, and two (29%) withdrew after developing severe watery diarrhea. Of the eight patients treated with placebo, two (25%) improved clinically but were without colonscopic improvement and six (75%) worsened, of whom four withdrew early because of worsening symptoms of colitis. Seven of eight placebo patients were then treated with olsalazine on an open basis. Of these seven, five (71%) improved clinically and colonoscopically and two (29%) withdrew because of severe watery diarrhea. Overall, of 14 patients treated with Olsalazine, nine (64%) improved, one showed no improvement, and four (29%) discontinued because of persistent watery diarrhea. No other serious side effects were noted. Minor side effects included transient diarrhea, flares of acne, and anxiety attacks which resolved despite continuation of the drug.
Adult↗
Estimation of 5-aminosalicylic acid and its metabolite in human serum by front-face fluorometry: a simple and sensitive method.
Salicylazosulfapyridine (SASP), commonly used in the treatment of inflammatory bowel disease, breaks down in the colon into sulfapyridine and 5-aminosalicylic acid (5-ASA), the active moiety of SASP. We report a sensitive method to measure 5-ASA and its known major metabolite acetyl 5-ASA (Ac-5-ASA) directly from the serum without any extraction procedure. Using front-face fluorometry, 5-ASA and Ac-5-ASA were detected at the excitation wavelength of 310 nm with emission maxima at 475 nm and 440 nm, respectively. Standard curves were obtained by adding known amounts of 5-ASA and Ac-5-ASA to several individual and pooled human sera. Presence of sulfapyridine (0 to 20 micrograms/ml) and SASP (0 to 15 micrograms/ml) in the serum did not interfere with the assays. Five microliters of acetic anhydride was added to the serum to convert all 5-ASA to Ac-5-ASA. The difference in the spectrum before and after addition of acetic anhydride represented the concentration of free 5-ASA. The values thus estimated were within 1% of the expected readings from the standard curves. This assay was compared with the organic extraction method for the determination of free and acetylated 5-ASA in sera of patients given olsalazine (azodisalicylate). The results demonstrate that direct analysis of the sera by front-face fluorometry enables us to measure 5-ASA and Ac-5-ASA at levels as low as 0.1 micrograms/ml in serum, making this method at least 10-fold more sensitive than the current available extraction methods.
Aminosalicylic Acids↗
Ultrasound in obstructive jaundice.
One hundred and twenty-five consecutive patients with obstructive jaundice were prospectively studied by ultrasonography to determine the level and cause of obstruction. These were diagnosed precisely in 80 (72%) and 52 patients (41.6%) respectively. The results were compared with cholangiography. The final diagnosis was established at surgery (97 cases) and fine needle aspiration cytology (28 cases). While US is an excellent screening modality in distinguishing obstructive and non-obstructive jaundice, cholangiography is still the gold standard for determining the precise anatomic level and cause of obstruction.
Adult↗
Rapid development of pancreatitis following reuse of 6-mercaptopurine.
A patient with Crohn's disease developed acute pancreatitis 4 h after retaking one 50 mg dose of orally administered 6-mercaptopurine (6-MP). All seven previously reported patients who were rechallenged with 50 mg or more of 6-MP developed pancreatitis within 48 h. These findings suggest that 6-MP can produce pancreatitis due to an idiosyncratic immune-mediated response. Patients with this complication should not reuse 6-MP.
Adult↗
Sera-reactivity in inflammatory bowel disease: frequency of recognition of Crohn's disease tissue primed nude mouse lymphoid tissue in an interinstitutional blinded study.
We used a double-blinded interinstitutional study with an indirect immunofluorescence assay to evaluate the immunoreactivity of Crohn's disease (CD) sera against hyperplastic and malignant lymph nodes from nude mice primed with CD tissue filtrates. We assessed the reactivity for potential usefulness as a serodiagnostic test by using sera from different clinical subgroups of patients with inflammatory bowel disease. The immunoreactivity of 86 coded sera from ambulatory patients treated at the Mount Sinai Medical Center were examined-29 from patients with CD, 25 from patients with ulcerative colitis (UC), 21 from disease controls, and 11 from normal controls. Each serum was tested at the Albert Einstein College of Medicine against lymph nodes from at least two of six nude mice inoculated with CD tissue filtrates or CD filtrate-induced lymphoma. There was positive immunofluorescent staining in 11 of 29 (38%) CD patients, 4 of 25 (16%) UC patients, 1 of 21 (4.8%) disease controls, and 0 of 11 normal volunteers. Statistically significant differences in immunoreactivity were seen between CD patients compared to non-inflammatory-bowel-disease controls (p = 0.007) and to normals (p = 0.02).
Animals↗
Sulfasalazine therapy in inflammatory bowel disease.
Sulfasalazine currently is the most commonly prescribed medication for inflammatory bowel disease. Insights into the pharmacokinetics, their side effects and mechanism and their possible mode of action has led to rational basis for its clinical use and the development of new related agents. This review summarizes these aspects and discusses the future role of sulfasalazine in the face of new oral preparations.
Chemical Phenomena↗
Turner's syndrome and inflammatory bowel disease: a case report with immunologic studies.
A patient with Turner's syndrome who developed ulcerative colitis (UC) is reported, and reports from the literature of 16 cases of Turner's syndrome with inflammatory bowel disease (IBD) are reviewed. Most of the patients previously described had severe disease. Half of the patients had ulcerative colitis and half had Crohn's disease (CD). Of those with Crohn's, most had colonic involvement. Of note, also, half of the patients had an isochromosome for the long arm of X which usually is found in only 17% of all patients with Turner's syndrome. A high incidence of autoimmune diseases is associated with this syndrome. We demonstrate the presence of specific anticolonic antibodies in this patient and propose some possible explanations for the association of this particular chromosomal disorder with autoimmune diseases.
Adult↗
Generalized lipodystrophy.
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Adipose Tissue↗
The production and characterization of monoclonal antibodies to a human colonic antigen associated with ulcerative colitis: cellular localization of the antigen by using the monoclonal antibody.
We detected in human colon extracts a 40 kDa protein(s) that specifically reacts with tissue-bound IgG obtained from the colon of patients with ulcerative colitis or CCA-IgG. Using the hybridoma technology, we developed monoclonal antibodies to this 40 kDa protein. The specific immunoreactivity of one of the monoclonal antibodies (7E12H12, IgM isotype) against the 40 kDa protein was demonstrated both by ELISA and by immunotransblot. Competitive binding experiments showed that CCA-IgG inhibits the binding of 7E12H12 to the 40 kDa protein, suggesting the recognition of common epitope(s) on the 40 kDa protein by the monoclonal antibody and CCA-IgG. 7E12H12 was used to determine cellular localization of the 40 kDa protein. Biopsy tissue specimens from colon, esophagus, stomach, duodenum, jejunum, ileum, liver, pancreas, lungs, kidneys, salivary, and mammary glands were obtained. Tissue specimens were fixed in 4% paraformaldehyde or in 10% formalin. Sections were sequentially incubated with the hybridoma supernatant, biotinylated anti-mouse IgM, avidin-biotin-peroxidase complex, and 3,3'-diaminobenzidine. An unrelated hybridoma supernatant was used as control. The monoclonal antibody exclusively recognized colonic epithelial cells both in the crypt and on the luminal surface. Immunoreactivity was present on the plasma membrane chiefly along the basolateral areas of the cells. Plasma membrane localization of the 40 kDa protein was confirmed by immunoelectron microscopy. All colonic mucosal biopsy specimens from both adult and fetal colon reacted with the monoclonal antibody. None of the biopsy specimens from stomach, duodenum, jejunum, ileum, liver, pancreas, or non-gastrointestinal tissue reacted with the antibody, confirming the organ specificity of the 40 kDa protein. The interaction between this colonic epithelial membrane protein and the CCA-IgG may play an important role in the pathogenesis of ulcerative colitis.
Antibodies, Monoclonal↗
Demonstration of Crohn's disease tissue-specific proteins by enzyme-linked immunosorbent assay (ELISA).
Theories on the etiology of Crohn's disease have included extrinsic agents and intrinsic bowel wall defects. We sought to determine the presence of immunoreactive antigens specific to Crohn's disease tissue by modifying the enzyme-linked immunosorbent assay. Tissue proteins were extracted from four patients with Crohn's disease and from four normal segments of colon from patients with colonic cancer. These tissue extracts were further purified on Con A Sepharose 4B affinity column. The glycoproteins eluted from this column were adsorbed by polystyrene plates as antigen and tested against 85 sera from patients with Crohn's disease, ulcerative colitis, other diarrheal diseases, and normal subjects. Sera from 48 patients with Crohn's disease showed significantly greater recognition of Crohn's disease tissue glycoproteins than sera from 27 disease controls (P less than 0.0125) and 10 normal subjects. These Crohn's disease sera also showed preferential recognition of glycoproteins extracted from Crohn's disease tissue compared to glycoproteins from normal colonic tissue (P less than 0.0005). The nature of these immunoreactive proteins, whether extrinsic or intrinsic, is not yet known. The ELISA may help in further characterization of Crohn's disease tissue-specific glycoprotein(s) and to develop a clinically useful serological test.
Antigens↗
Development of a monoclonal antibody specifically reactive to gastrointestinal goblet cells.
A mouse monoclonal antibody (7E6A5) of IgG isotype, reacting specifically with mucin-producing goblet cells of the human gastrointestinal tract, has been developed. 7E6A5 reacts by an ELISA with colonic protein eluted from a DEAE column. A screening by immunoperoxidase assay of 76 specimens from 19 different human tissues showed that the immunoreactivity of 7E6A5 was confined exclusively in the globules of goblet cells in the colon, the appendix, and the small intestine. Nongoblet small and large intestinal epithelial cells did not react. Immunoelectron microscopy demonstrated the reactivity with mucin droplets in a homogeneous granular pattern inside the globules of goblet cells. Mucus-secreting cells from remaining parts of the gastrointestinal tract and other mucus-secreting organs such as respiratory, genitourinary tracts, salivary and mammary glands did not show any reactivity to 7E6A5. These findings indicate that the antigen recognized by 7E6A5 is shared by the goblet cells of both the small and large intestines and is unique to them. The monoclonal antibody may be useful in the study of function of mucus-secreting goblet cells and may represent an important tool in the evaluation of diseases such as ulcerative colitis, colon cancer, and intestinal metaplasia in gastric mucosa that are associated with quantitative changes in goblet cell numbers or with qualitative differences in mucin secretion.
Antibodies, Monoclonal↗
Unusual sites of upper gastrointestinal variceal bleeding.
When patients with portal hypertension bleed from varices, these are most commonly located in the esophagus and gastric fundus. However, varices can develop anywhere in the upper or lower gastrointestinal tract. Oftentimes if an active upper gastrointestinal bleeding site is not evident at the time of endoscopy, bleeding is attributed to any esophageal or gastric varices that are present. This supposition may not always be true as illustrated in the two patients presented here. Likewise, the absence of esophagogastric varices in a patient with portal hypertension does not preclude the presence of varices elsewhere. Endoscopic examination of the second and third portion of the duodenum can sometimes be helpful in accurately locating the bleeding site.
Adult↗
Immunofluorescence assay using Crohn's disease tissue-injected athymic nude mouse lymph nodes in the diagnosis of inflammatory bowel diseases.
Sometimes, even after extensive investigative efforts, the diagnosis of inflammatory bowel disease remains in doubt. The accurate diagnosis is important if appropriate therapy is to be instituted. A simple indirect immunofluorescence assay that tests the patient's serum against lymphoid tissues from athymic nude (nu/nu) mice receiving injections of filtrates of Crohn's disease tissue is proposed. Eighty percent of serum samples from patients with active, symptomatic Crohn's disease give positive results of immunofluorescence when tested with these lymphoid tissues. The false-positive rate has been very low (less than 10 percent). Because this assay is fairly sensitive and least invasive, it was used for the clarification of many puzzling cases that were seen at the Albert Einstein College of Medicine over the past three years. Ten of these cases were selected for illustration and discussion and are presented in this report.
Adult↗