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Biomedical subjects

H J Van Kruiningen

Publications and source records attributed to H J Van Kruiningen.

At least 19 recordsLinked to original sources

The comparative importance of E. coli antigen in granulomatous colitis of Boxer dogs.

Granulomatous colitis of Boxer dogs is characterized by mucosal and submucosal infiltration by abundant large macrophages and lymphocytes and plasma cells. Involved intestine is thickened, corrugated and ulcerated. The macrophages that occur in colon, cecum and regional lymph nodes are PAS-positive, lipid-rich, contain cholesterol, and some of the time can be seen to hold bacteria. Paraffin tissue blocks of formalin-fixed colon and colic lymph nodes from 10 cases were cut at 5 microm and immunostained by a streptavidin-biotin immunoperoxidase technique, employing primary antibodies against Escherichia coli, E. coli 0157: 2, Campylobacter, C. jejuni-coli, Yersinia pseudotuberculosis, Salmonella, Shigella, Pseudomonas and Lawsonia intracellularis. The macrophages in the lamina propria and submucosa, as well as those in aggregates in regional lymph nodes, showed immunoreactivity with polyclonal E. coli antibody in all 10 cases. Tissues lacking granulomas were negative, as were those reacted with the other eight antibodies, with the exception that there was rare focal staining for Campylobacter, Lawsonia and Salmonella in a few dogs. We believe these results identify the causative agent of this granulomatous disease of Boxer dogs, a disease with great histologic and etiologic similarity to granulomatous leptomeningitis of Beagle dogs, and malacoplakia and xanthogranulomatous cholecystitis of man. Macrophages that are immunopositive for E. coli antigen occur in Crohn's disease as well, where their significance is less well understood.

Animals↗

The West Nile virus: its recent emergence in North America.

West Nile fever emerged in New York in the summer of 1999 when seven people, several horses and thousands of wild birds died. It was soon established that the human disease and the mortality of birds were related. Continued surveillance detected West Nile virus in mosquitoes, birds, horses, small mammals, bats and humans, and has shown its spread to several northeastern states. These events confirm the establishment of West Nile virus endemically in the United States.

Aged↗

A clustering of Crohn's disease in Mankato, Minnesota.

Infrequently, clusterings of Crohn's disease (CD) occur that suggest it is transmissible. We studied such a clustering. Graduates of the Mankato West High School Class of 1980 were contacted by mail and asked to respond, by self-addressed postcard, to a six-item questionnaire about inflammatory bowel disease and CD. Responses were followed-up by telephone contact and additional mailings. Two visits were made to Mankato, Minnesota, to interview individuals with CD, to obtain medical records, radiographs, and sera, and to study environmental risk factors. Of the 320 graduates of the class of 1980, 285 were contacted. Seven cases of CD were identified, the equivalent of a prevalence of 2,400/100,000. Concerns were discovered that CD may have emanated from recreational swimming. Fecal coliform counts in excess of 200/dL, the standard above which water is regarded as unsafe for recreational use, had been recorded year after year for the Blue Earth River at Mankato and for the Minnesota River. Recent fecal coliform counts (1993-1995) of Lake Washington, Lake German/Jefferson, and Lake Shetek were greater than 200/dL in 57%, 65%, and 62% of water samples. This clustering, in unrelated individuals, argues against a genetic cause for CD and suggests that environmental transmission occurred.

Adult↗

Virus serology in familial Crohn disease.

BACKGROUND: Recent findings that early-in-life virus infections represent a risk factor for Crohn disease, that exacerbations of disease sometimes appear associated with common viral infections, and, in particular, suggestions that Crohn disease may be the result of persistent infection with measles virus prompted serologic studies for antibody to 19 common viruses, Chlamydia psittaci, and Mycoplasma pneumoniae. METHODS: Sera from 14 affected members of 2 French families with a high frequency of Crohn disease and from age- and sex-matched controls, taken in 1990 and 1992, and from unaffected family members were tested. Complement fixation, enzyme immunoassay, and indirect immunofluorescent tests were used. RESULTS: There were no significant differences between patients and controls or between affected and unaffected family members of family 2, with the exception that affected siblings carried higher antibody titers for mycoplasma one year and for varicella another year. There were no differences in measles IgM and IgG or mumps IgG antibody levels between patients and controls, or between patients and unaffected family members. CONCLUSIONS: Serology failed to find evidence of participation by 19 common viruses, C. psittaci, and M. pneumoniae in Crohn disease. The data do not support the hypothesis that persistent measles virus infection causes Crohn disease.

Adolescent↗

Recovery and identification of West Nile virus from a hawk in winter.

West Nile virus was recovered from the brain of a red-tailed hawk that died in Westchester County, N.Y., in February 2000. Multiple foci of glial cells, lymphocytes, and a few pyknotic nuclei were observed in the brain. Three to 4 days after inoculation of Vero cells with brain homogenates, cytopathic changes were detected. The presence of West Nile virus antigen in fixed cells or cell lysates was revealed by fluorescent antibody testing or enzyme-linked immunosorbent assay, respectively. Furthermore, Reverse transcriptase-PCR with primers specific for the NS3 gene of West Nile virus resulted in an amplicon of the expected size (470 bp). Electron microscopy of thin sections of infected Vero cells revealed the presence of viral particles approximately 40 nm in diameter, within cytoplasmic vesicles. The demonstration of infection with the West Nile virus in the dead of the winter, long after mosquitoes ceased to be active, is significant in that it testifies to the survival of the virus in the region beyond mosquito season and suggests another route of transmission: in this case, prey to predator.

Animals↗

Gastric intramural hematoma and hemoperitoneum in a captive northern fur seal.

A 16-yr-old adult male northern fur seal (Callorhinus ursinus) was found dead in its outdoor pool in November 1995. The animal was maintained at Mystic Aquarium (Mystic, Connecticut, USA) from March 1980 to November 1995. Gross necropsy findings included hemoperitoneum and locally extensive gastric intramural hemorrhage that involved the posterior fundic, antral, and pyloric regions and extended into the duodenum. The gastric mural thickening grossly resembled hemangioma, and the gastric serosa was ruptured at the site of maximal mural expansion. In histologic sections of the stomach, a cribiform network of fibrin, which encompassed numerous variably-sized aggregates of closely packed erythrocytes, markedly expanded the submucosa. No vascular endothelium was identified in serial histologic sections of the expanded gastric submucosa stained with hematoxylin and eosin or immunohistochemically with antibodies to vimentin and Factor VIII-related antigen, establishing an absence of hemangioma. Carstairs' and Weigert's histochemical stains confirmed that the framework expanding the submucosa was fibrin. Although the appearance of the gastric wall resembled hemangioma, a population of neoplastic endothelial cells was not identified within the submucosal expansion of hemorrhage and fibrin, and microscopic evidence was most consistent with the diagnosis of gastric intramural hematoma. This lesion is a rare pathologic event that has not been reported in marine mammals, but one that should be included in diagnostic considerations of hemoperitoneum and gastric mural expansion.

Animals↗

Isolation of West Nile virus from mosquitoes, crows, and a Cooper's hawk in Connecticut.

West Nile (WN) virus, a mosquito-transmitted virus native to Africa, Asia, and Europe, was isolated from two species of mosquitoes, Culex pipiens and Aedes vexans, and from brain tissues of 28 American crows, Corvus brachyrhynchos, and one Cooper's hawk, Accipiter cooperii, in Connecticut. A portion of the genome of virus isolates from four different hosts was sequenced and analyzed by comparative phylogenetic analysis. Our isolates from Connecticut were similar to one another and most closely related to two WN isolates from Romania (2.8 and 3.6 percent difference). If established in North America, WN virus will likely have severe effects on human health and on the health of populations of birds.

Aedes↗

Molecular characterization of the myxosporean associated with parasitic encephalitis of farmed Atlantic salmon Salmo salar in Ireland.

During seasonal epizootics of neurologic disease and mass mortality in the summers of 1992, 1993 and 1994 on a sea-farm in Ireland, Atlantic salmon Salmo salar smolts suffered from encephalitis associated with infection by a neurotropic parasite. Based on ultrastructural studies, this neurotropic parasite was identified as an intercellular presporogonic multicellular developmental stage of a histozoic myxosporean, possibly a Myxobolus species. In order to generate sequence data for phylogenetic comparisons to substantiate the present morphological identification of this myxosporean in the absence of detectable sporogony, polymerase chain reaction (PCR), Southern blot hybridization, dideoxynucleotide chain-termination DNA sequencing, and in situ hybridization (ISH) were used in concert to characterize segments of the small subunit ribosomal RNA (SSU rRNA) gene. Oligonucleotide primers were created from sequences of the SSU rRNA gene of M. cerebralis and were employed in PCR experiments using DNA extracted from formalin-fixed paraffin-embedded tissue sections of brains from Atlantic salmon smolts in which the myxosporean had been detected by light microscopy. Five segments of the SSU rRNA gene of the myxosporean, ranging in length from 187 to 287 base pairs, were amplified, detected by hybridization with sequence-specific probes, and sequenced. Consensus sequences from these segments were aligned to create a partial sequence of the SSU rRNA gene of the myxosporean. Assessments of sequence identity were made between this partial sequence and sequences of SSU rRNA genes from 7 myxosporeans, including Ceratomyxa shasta, Henneguya doori, M. arcticus, M. cerebralis, M. insidiosus, M. neurobius, and M. squamalis. The partial SSU rRNA gene sequence from the myxosporean had more sequence identity with SSU rRNA gene sequences from neurotropic and myotropic species of Myxobolus than to those from epitheliotropic species of Myxobolus or Henneguya, or the enterotropic species of Ceratomyxa, and was identical to regions of the SSU rRNA gene of M. cerebralis. Digoxigenin-labeled oligonucleotide DNA probes complementary to multiple segments of the SSU rRNA gene of M. cerebralis hybridized with DNA of the parasite in histologic sections of brain in ISH experiments, demonstrating definitively that the segments of genome amplified were from the organisms identified by histology and ultrastructural analysis. Based on sequence data derived entirely from genetic material of extrasporogonic stages, the SSU rDNA sequence identity discovered in this study supports the hypothesis that the myxosporean associated with encephalitis of farmed Atlantic salmon smolts is a neurotropic species of the genus Myxobolus, with sequences identical to those of M. cerebralis.

Animals↗

Reporting of vancomycin-resistant enterococci in Connecticut: implementation and validation of a state-based surveillance system.

OBJECTIVE: To assess state-based surveillance for isolation from a sterile site of vancomycin-resistant enterococci (VRE) in Connecticut. DESIGN: Clinical laboratory reporting (passive surveillance) of VRE isolates to the Connecticut Department of Public Health (CDPH) was followed by state-initiated validation, laboratory proficiency testing, and review of hospital demographic characteristics. SETTINGS: All 45 clinical laboratories and all 37 (36 for 1995 and 1996) acute-care hospitals in Connecticut were included in the study. MAIN OUTCOME MEASURES: The outcome measures included determination of the statewide incidence of VRE and the accuracy of passive reporting, determination of clinical laboratory proficiency in detecting VRE, and analysis of hospital characteristics that might be associated with an increased incidence of VRE. RESULTS: During 1994 through 1996, 29 (78%) of 37 hospital-affiliated clinical laboratories and 1 (11%) of 9 commercial or other laboratories in Connecticut reported to the CDPH the isolation of VRE from sterile sites; 158 isolates were reported for these 3 years. Based on verification, we discovered that these laboratories actually detected 58 VRE isolates in 1994, 104 in 1995, and 104 in 1996 (total, 266). The age-standardized incidence rate of VRE was 14.1 cases per million population in 1994 and 26.8 cases per million population for both 1995 and 1996. Laboratory proficiency testing revealed that high-level vancomycin resistance was identified accurately and that low- and moderate-level resistance was not detected. The incidence of VRE isolates was three times greater in hospitals with over 300 beds compared with categories of hospitals with fewer beds. Increases in the number of VRE isolates were at least twice as likely in hospitals located in areas with a higher population density, or with a residency program or trauma center in the hospital. CONCLUSIONS: Passive reporting of VRE isolates from sterile sites markedly underestimated the actual number of iso lates, as determined in a statewide reporting system. Statewide passive surveillance systems for routine or emerging pathogens must be validated and laboratory proficiency ensured if results are to be accurate and substantial underreporting is to be corrected.

Adolescent↗

Lack of support for a common etiology in Johne's disease of animals and Crohn's disease in humans.

The superficial similarity of Johne's disease to Crohn's disease led to the hypothesis that, like the former. Crohn's disease was caused by Mycobacterium paratuberculosis. Detailed pathologic comparisons, however, reveal little similarity between these two entities, including the lack of important extraintestinal manifestations. Attempts to recover M. paratuberculosis by culture have only rarely succeeded and the significance of spheroplasts that appear more frequently on culture is seriously in question. Five immunocytochemistry studies have failed to find mycobacterial antigens in diseased tissues and the five most recent polymerase chain reaction (PCR) attempts to find genomic evidence of M. paratuberculosis were uniformly negative. Numerous serologic studies failed to demonstrate antibody to M. paratuberculosis and attempts to show cell-mediated immunity were also unrewarding. Inoculation of numerous experimental animals with Crohn's disease tissue has failed to induce Johne's disease, and inoculation of various animal species with M. paratuberculosis has equally failed to result in Crohn's disease. Controlled studies of the treatment of Crohn's disease with antimycobacterial agents have generally resulted in no improvement, and most studies that have shown a positive response are either uncontrolled or include broad-spectrum antibiotics that may be acting on pathogens other than mycobacteria. Finally, although Johne's disease is common in farm animals, and infected animals shed M. paratuberculosis in large numbers, no record of zoonotic transmission has been recorded.

Animals↗

Epizootiology, pathology, and ultrastructure of the myxosporean associated with parasitic encephalitis of farmed Atlantic salmon Salmo salar in Ireland.

In 1995 at a sea-farm in Ireland, Atlantic salmon Salmo salar smolts were introduced in the spring and autumn into 2 marine rearing sites, one with and one without recent histories of neurologic disease and mass mortality believed to be due to parasitic encephalitis. In order to monitor disease, determine the onset and anatomic distribution of parasites and encephalitis, and determine the ultrastructure and identity of the parasite, randomly selected smolts were necropsied from both sites at intervals of 1 to 3 d for periods of 1 to 2 mo, and clinical signs and cumulative mortalities were monitored. The prevalences of parasites and encephalitis were assessed by light microscopy, and sections of brain were examined by transmission electron microscopy. No clinical signs of neurologic disease were observed, but parasites and encephalitis were detected in smolts from both sites, with prevalences of each that were significantly greater in smolts from the site with recent disease. Based on light microscopy, the parasite was first detected in smolts sampled at 26 d post-introduction. Parasites were detected with significantly greater frequency in the optic tectum of the mesencephalon than in the diencephalon, metencephalon, and myelencephalon, and were not detected in the telencephalon. Foci of non-suppurative encephalitis were detected with significantly greater frequency in the myelencephalon than in each of the other 4 anatomic subdivisions. In each anatomic subdivision the prevalence of encephalitis was significantly greater than that of parasitic infection. The ultrastructure of the parasite was consistent with that of a histozoic presporogonic multicellular developmental stage of a myxosporean, characterized by intercellular branching tubular structures containing generative cells arranged individually or in cell-in-cell doublets. Parasitic stages were located between bundles of axons, with compression of axons along segments of their plasmalemma. No mature spores were detected.

Animals↗

Mucosal and systemic antibody responses to a C4/V3 construct following DNA vaccination of rabbits via the Peyer's patch.

A plasmid encoding T1-SP10MN(A), a peptide derived from immunodominant regions of human immunodeficiency virus type 1 gp120, was delivered to rabbit Peyer's patches using a helium-driven gene gun. Six weeks thereafter, 2 of 5 animals were given an intradermal booster immunization. Blood, feces, and vaginal washes were collected weekly and assayed by ELISA. High titer T1-SP10MN(A)-specific fecal and vaginal secretory IgA responses were observed, and the response appeared to be augmented following dermal booster immunizations. Specific serum IgG was also detected within 1 week of immunization and remained elevated through week 20 in the 2 animals receiving dermal boosts (titers > or = 6400). This study establishes the Peyer's patch as a promising target tissue for DNA vaccination and demonstrates the efficacy of gene gun-mediated delivery of foreign DNA to a mucosal tissue for the induction of an immune response.

AIDS Vaccines↗

Mucosal immune response to an HIV C4/V3 peptide following nasal or intestinal immunization of rabbits.

The HIV env-encoded synthetic peptide T1-SP10MN(A) contains immunodominant epitopes of the C4/V3 regions of gp120. The mucosal immunogenicity of this peptide in various vaccine preparations was first tested in rabbits using chronically isolated Thiry-Vella (T-V) ileal loops. Intestinal and serum samples collected from rabbits immunized via T-V loops demonstrated secretory IgA (S-IgA) and IgG anti-T1-SP10MN(A), respectively, when assayed by ELISA. Intranasal delivery of the peptide supplemented with cholera toxin (CT) resulted in serum IgG and S-IgA anti-T1-SP10MN(A) in vaginal and nasal secretions. This study further demonstrates the utility of rabbits as a convenient animal model for HIV vaccine research and the relationship between nasal immunization and vaginal immunity.

AIDS Vaccines↗

Mucosal unresponsiveness to aflatoxin B1 is not broken by cholera toxin.

Rabbits immunized via chronically isolated ileal loops with aflatoxin B1 (AFB) conjugated to porcine thyroglobulin (TG) mixed with the mucosal adjuvant cholera toxin (CT) produced very small mucosal antibody responses to AFB. Strong mucosal and systemic antibody responses to CT and TG were generated by this immunization protocol, suggesting that the observed unresponsiveness was specific to AFB. Parenteral immunization with AFB-TG produced strong serum IgG anti-AFB responses, indicating that the conjugate preparation was immunogenic and that the rabbits possess the requisite systemic B and T cell repertoires to recognize and respond to AFB. This mucosal unresponsiveness was distinct from oral tolerance, as animals immunized mucosally with AFB-TG mixed with CT produced vigorous serum IgG anti-AFB responses upon subsequent parenteral immunization with AFB-TG. In vitro mitogen stimulation of lymphocytes isolated from Peyer's patches and mesenteric lymph nodes of unimmunized rabbits revealed the presence of AFB-specific B cells at levels comparable with these found in the spleen. These observations indicate that unresponsiveness to AFB is hapten-specific, restricted to the mucosa, and refractory to the adjuvancy of CI.

Adjuvants, Immunologic↗

The role of Peyer's patches in the age-related incidence of Crohn's disease.

Recently researchers have suggested that clinical subsets of Crohn's disease occur, which are variously described as inflammatory, fibrostenotic, and fistulizing. In addition, it has been observed that within families with multiple cases, often there is concordance of the site and type of disease. The lesions of Crohn's disease occur in segments that suggest that distribution of Peyer's patches. When the age-related incidence of Crohn's disease was plotted for all countries from which such data were available, the peaks of greatest case frequency occurred at ages 15 to 25 years and paralleled a similar peak representing the number of Peyer's patches as a function of age. This correlation suggests that Crohn's disease may develop as an inflammatory process specifically targeting these important lymphoid structures. Similar peaks of activity in the adolescent to early adult years occur for appendicitis and tonsillitis.

Adolescent↗

Mucosal inflammation in pediatric diversion colitis: a quantitative analysis.

BACKGROUND: Diversion colitis commonly occurs in bypassed segments of colorectum, and has been described qualitatively in Hirschsprung's disease patients with colostomies. The objective of this study was to characterize quantitatively the changes in the inflammatory cell population in the mucosa of children with diversion colitis. METHODS: Paraffin blocks of well-oriented, full-thickness colorectal tissues were obtained from 15 children with diversion colitis (all with Hirschsprung's disease), four pediatric controls and four adult controls. Sections were immunostained for B and T lymphocytes, macrophages, IgG, IgM, and IgA. Measurements were made referent to a standard length of muscularis mucosae. Lymphoid follicles were counted and the areas occupied by B and T cells were determined by image analysis. Cells in the interfollicular lamina propria were counted separately, but IgA-containing plasma cells were too abundant to enumerate. RESULTS: Pediatric diversion colitis was characterized by enlarged and more numerous lymphoid follicles with approximately four times as many B lymphocytes and twice as many T lymphocytes in the follicular compartment of the mucosa when compared to pediatric controls. The interfollicular mucosa was thickened (499 +/- 27 versus 380 +/- 56 microns) and contained approximately six times as many B cells and eight times as many T cells as controls. Macrophages and plasma cells containing IgG and IgM were not significantly increased. CONCLUSIONS: These findings extend the qualitative observations of increased follicular and lamina propria lymphoid tissue in bypassed segments of colon, and are consistent with the hypothesis of persistent antigenic stimulation of the mucosa-associated lymphoid tissue.

Adult↗

Emergence of raccoon rabies in Connecticut, 1991-1994: spatial and temporal characteristics of animal infection and human contact.

The North American raccoon rabies epizootic continues to expand, now affecting most of New England. In 1990, raccoons became the vertebrate most often reported rabid in the United States. Emergence of this zoonosis poses increasing, but poorly defined risks to humans. This study analyzed various demographic, environmental, and behavioral factors associated with animal infection and human exposure before and during the epizootic in Connecticut. Rabies virus infections among terrestrial vertebrates were analyzed from 1985 through 1994. From March 1991, when the first case was diagnosed, through December 1994, 2,522 of 13,147 animals tested were found positive for rabies viral antigen. Forty-seven percent of the raccoons tested were infected, representing 88.0% of all animals found positive. Domestic animals constituted only 1.7% of positive test results, but 40.6% of the tests performed. The epizootic wave of transmission advanced approximately 30 km/year. Most rabies-positive wild animals were taken from private properties, usually near houses. Possible human exposures involved 939 people on 556 occasions through direct contact (20.7%) or indirectly through another animal (79.3%). Of 3,239 domestic animals exposed to rabies-positive wild animals, 18.4% lacked vaccination. Rabies has become enzootic in Connecticut and risk to humans and animals persists. The public health burden is considerable, yet knowledge is lacking to develop sustainable prevention strategies.

Animals↗