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Biomedical subjects

J E Hill

Publications and source records attributed to J E Hill.

At least 19 recordsLinked to original sources

Gastric ulcer associated with a Helicobacter-like organism in a cougar (Felis concolor).

A 12-year-old captive female cougar (Felis concolor) died following perforation of a gastric ulcer. Histologically, erosions and ulcers were present in the antral area of the stomach. Fibroplasia and infiltrates of neutrophils bordered the ulcers. Modified Steiner silver stain revealed numerous tightly coiled helical bacteria. The bacteria stained positively with a rabbit polyclonal anti-Helicobacter pylori antibody. Morphology, location, and positive immunohistochemical staining suggests that the organism is a Helicobacter.

Animals

A community waterborne outbreak of salmonellosis and the effectiveness of a boil water order.

OBJECTIVES: A 1993 large water-borne outbreak of Salmonella typhimurium infections in Gideon, Mo, a city of 1100 with an unchlorinated community water supply, was investigated to determine the source of contamination and the effectiveness of an order to boil water. METHODS: A survey of household members in Gideon and the surrounding township produced information on diarrheal illness, water consumption, and compliance with the boil water order. RESULTS: More than 650 persons were ill; 15 were hospitalized, and 7 died. Persons consuming city water were more likely to be ill (relative risk [RR] = 9.1, 95% confidence interval [CI] = 2.9, 28.4), and the attack rate increased with increased water consumption. S. typhimurium was recovered from samples taken from a city fire hydrant and a water storage tower. Persons in 31% (30/ 98) of city households had drunk unboiled water after being informed about the boil water order, including 14 individuals who subsequently became ill. Reasons for noncompliance included "not remembering" (44%) and "disbelieving" (25%) the order. CONCLUSIONS: Communities with deteriorating water systems risk widespread illness unless water supplies are properly operated and maintained. Effective education to improve compliance during boil water orders is needed.

Data Collection

Immunogenicity and safety of recombinant Helicobacter pylori urease in a nonhuman primate.

Groups of squirrel monkeys (Saimiri spp.), predetermined to be free of Helicobacter infections in the gastric mucosa, were immunized orally with 0.5-4.5 mg of Helicobacter pylori recombinant urease (rUrease) and 25-500 micrograms of Escherichia coli heat-labile enterotoxin (LT) adjuvant. Oral immunization with rUrease resulted in a markedly elevated serum immunoglobulin G (IgG) antibody response with peak levels at 45 days after immunization. No significant gastric inflammation or cytotoxicity was evident in rUrease immunized monkeys as determined by light and electron microscopy. Twenty-five micrograms of LT was a sufficient and safe adjuvant dosage, whereas higher dosages resulted in diarrhea and lethargy. Animals developed a serum IgG antibody response to LT that did not impede the production of anti-rUrease antibody levels. The results of this investigation indicate that rUrease is immunogenic in a nonhuman primate.

Adjuvants, Immunologic

Identification and characterization of the v-cath gene of the baculovirus, CfMNPV.

The v-cath gene of the Autographa californica multi-nucleocapsid nuclear polyhedrosis virus (AcMNPV) encodes a cathepsin L-like proteinase which plays a role in the liquefaction of host tissues during a viral infection [1]. We have identified a homologous gene in the spruce budworm virus, Choristoneura fumiferana MNPV (CfMNPV). The CfMNPV v-cath gene is 74% identical to AcMNPV v-cath at the nucleotide sequence level and 80% identical at the level of predicted amino acid sequence. Transcription analysis of the CfMNPV v-cath gene revealed that it is expressed late in infection and that transcription initiates within the consensus baculovirus late-promoter motif.

Amino Acid Sequence

Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis.

Helicobacter pylori, a gram-negative spiral bacterium, is the cause of chronic superficial (type B) gastritis and peptic ulcer disease. The urease enzyme of H. pylori was expressed as an inactive recombinant protein in Escherichia coli, purified as particulate structures of 550-600 kDa molecular mass with a diameter of approximately 12 nm. Given orally, 5 micrograms of urease with an appropriate mucosal adjuvant, such as the labile toxin of E. coli, protected 60%-100% of mice against challenge with virulent Helicobacter felis. Protection correlated with the level of secretory IgA antibodies against urease. Oral administration of antigen was as effective or better than intragastric administration. Parenteral injection of antigen or intragastric administration of high-dose antigen without adjuvant elicited serum IgG but no IgA antibodies and did not confer protection. Recombinant urease as an oral vaccine candidate deserves further investigation as an approach to the prevention of Helicobacter-induced chronic gastroduodenal diseases in humans.

Adjuvants, Immunologic

Characterization of the baculovirus Choristoneura fumiferana multicapsid nuclear polyhedrosis virus p10 gene indicates that the polypeptide contains a coiled-coil domain.

The DNA sequence and transcription pattern of the p10 gene from the spruce budworm baculovirus Choristoneura fumiferana multicapsid nuclear polyhedrosis virus (CfMNPV) were analysed. The CfMNPV p10 gene codes for a protein 81 amino acids in length: this is the shortest p10 peptide identified thus far. A novel characteristic of the CfMNPV p10 gene is that it contains tandem late initiation sites (TAAG) having different temporal transcription patterns. Comparative analysis of CfMNPV p10 and the amino acid sequences of other p10 gene products showed that they each appear to have a similar N-terminal structure: an amphipathic alpha-helical terminus which condenses as coiled-coil multimers. Another feature of the p10 N terminus is that the central region of the coiled-coil domain resembles a bend or hairpin loop and could fold into a hairpin or form a bent rod structure. The condensation of p10 monomers to coiled-coil multimers is likely to be a step leading to the formation of p10 fibrous bodies in infected cells.

Amino Acid Sequence

Evaluation of formalin-inactivated Clostridium difficile vaccines administered by parenteral and mucosal routes of immunization in hamsters.

Clostridium difficile produces toxins that cause inflammation, necrosis, and fluid in the intestine and is the most important cause of nosocomial antibiotic-associated diarrhea and colitis. We evaluated C. difficile antigens as vaccines to protect against systemic and intestinal disease in a hamster model of clindamycin colitis. Formalin-inactivated culture filtrates from a highly toxigenic strain were administered by mucosal routes (intranasal, intragastric, and rectal) with cholera toxin as a mucosal adjuvant. A preparation of culture filtrate and killed whole cells was also tested rectally. The toxoid was also tested parenterally (subcutaneously and intraperitoneally) and by a combination of three intranasal immunizations followed by a combined intranasal-intraperitoneal boost. Serum antibodies against toxins A and B and whole-cell antigen were measured by enzyme-linked immunosorbent assay, neutralization of cytotoxic activity, and bacterial agglutination. The two rectal immunization regimens induced low antibody responses and protected only 20% of hamsters against death and 0% against diarrhea. The intragastric regimen induced high antibody responses but low protection, 40% against death and 0% against diarrhea. Hamsters immunized by the intranasal, intraperitoneal, and subcutaneous routes were 100% protected against death and partially protected (40, 40, and 20%, respectively) against diarrhea. Among the latter groups, intraperitoneally immunized animals had the highest serum anticytotoxic activity and the highest agglutinating antibody responses. Hamsters immunized intranasally and revaccinated intraperitoneally were 100% protected against both death and diarrhea. Protection against death and diarrhea correlated with antibody responses to all antigens tested. The results indicate that optimal protection against C. difficile disease can be achieved with combined parenteral and mucosal immunization.

Administration, Intranasal

Spontaneous equine pulmonary granular cell tumors: morphologic, histochemical, and immunohistochemical characterization.

Spontaneous equine pulmonary granular cell tumors were diagnosed in six mature horses at slaughter. These tumors were grossly recognized as multiple (5/6) or single (1/6) creamy white, firm nodules. The tumors, located adjacent to bronchi and bronchioles, often invaded airways, resulting in partial to complete occlusion of the lumina. Neoplastic cells were rounded to polyhedral with numerous eosinophilic cytoplasmic granules that reacted uniformly positive with S-100 and neuron-specific enolase antibodies and multifocally with glial fibrillary acidic protein antibodies. These cells were negative for muscle-specific actin, lysozyme, cytokeratin, chromogranin A, and myelin basic protein antigens and did not stain with silver by the Grimelius technique. Uniformly blue-green and scattered pink intracytoplasmic granules were evident with luxol fast blue and periodic acid-Schiff counterstain for myelin and myelin breakdown products. Histochemical and immunohistochemical staining results of these tumors suggest that they are composed primarily of myelinating Schwann cells with lesser numbers of scattered nonmyelinating Schwann cells. The morphologic features of the equine pulmonary granular cell tumors are strikingly similar to those of endobronchial granular cell tumors of human beings.

Animals

Modelling the dynamic ventilatory response to hypoxia in normal subjects.

We have developed a mathematical model to describe the dynamic ventilatory response to hypoxia. The ventilatory response to both transient (two to three breaths nitrogen) and 3 min step change hypoxic stimuli were measured in ten normal subjects during moderate exercise (oxygen consumption 0.96 +/- 0.08 1 min-1). The simplest model relating ventilation to ear oxygen saturation which adequately described the responses in all subjects consisted of two linear differential equations in parallel; both using the fall in oxygen saturation as input, and with the outputs summed to give the rise in ventilation. One equation had a fast time constant (< 3 sec), and the other a slow time constant. Non-linear terms included were (i) a "saturating" effect, similar to that described by the Michaelis-Menten equation, reducing the gain of the equation with the slow time constant as oxygen saturation falls, and (ii) "inhibition" or "potentiation" of the gain of the equation with a slow time constant as the output of the fast time constant equation increased. Repeated measurements in four subjects showed intra- and inter-subject variability for all parameters, with significant between-subject variability for the gain of the fast time constant equation. The final model structure is similar to that describing the peripheral chemoreceptor-mediated hypoxic ventilatory response in anaesthetized cats.

Adult

Identification of the gp67 gene of a baculovirus pathogenic to the spruce budworm, Choristoneura fumiferana multinucleocapsid nuclear polyhedrosis virus.

The baculovirus gp67 gene encodes a pH-dependent membrane fusion protein and has been identified in both Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) and Orygia pseudotsugata MNPV (OpMNPV). We have identified a homologous gene in the spruce budworm virus, Choristoneura fumiferana MNPV (CfMNPV). The CfMNPV gp67 gene is 79% identical to AcMNPV gp67 at the level of nucleotide sequence and 82% identical at the level of predicted amino acid sequence. As with OpMNPV and AcMNPV gp67, the CfMNPV gp67 protein is found exclusively in the budded virus phenotype of the baculovirus.

Amino Acid Sequence

Observations and thoughts on infection control practices in Russia.

Members of the American Society of Ophthalmic Registered Nurses (ASORN), as a delegation of ophthalmic nurses for the People to People Citizen Ambassador Program, had the opportunity to visit five ophthalmic facilities in St. Petersburg and Moscow in August 1993. Russian hosts described their operations through a translator and then provided tours and answered questions. Unrestricted photographs were allowed. This article describes a perspective of infection control practices as observed and documents statements or responses made to questions that were posed. Generalizations cannot be made from this brief encounter, but comparisons and thoughts are presented.

Humans

Nucleotide sequence of the p74 gene of a baculovirus pathogenic to the spruce budworm, Choristoneura fumiferana multicapsid nuclear polyhedrosis virus.

Polypeptide p74 has been found to be essential for production of virulent occlusion bodies of the baculovirus Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV). Hybridization with AcMNPV-derived probes has led to the location of the p74 gene in the spruce budworm virus, Choristoneura fumiferana MNPV. Sequence data indicate that CfMNPV p74 is 73% identical to AcMNPV at the nucleotide level and 77% identical at the amino acid level. Elements of predicted secondary structure are also conserved.

Amino Acid Sequence

The Tc2 transposon of Caenorhabditis elegans has the structure of a self-regulated element.

We have analyzed the sequence of the Tc2 transposon of the nematode Caenorhabditis elegans. The Tc2 element is 2,074 bp in length and has perfect inverted terminal repeats of 24 bp. The structure of this element suggests that it may have the capacity to code for a transposase protein and/or for regulatory functions. Three large reading frames on one strand exhibit nonrandom codon usage and may represent exons. The first open coding region is preceded by a potential CAAT box, TATA box, and consensus heat shock sequence. In addition to its inverted terminal repeats, Tc2 has an unusual structural feature: subterminal degenerate direct repeats that are arranged in an irregular overlapping pattern. We have also examined the insertion sites of two Tc2 elements previously identified as the cause of restriction fragment length polymorphisms. Both insertions generated a target site duplication of 2 bp. One element had inserted inside the inverted terminal repeat of another transposon, splitting it into two unequal parts.

Animals

Salmonellosis in gerbils induced by nonrelated experimental procedure.

An outbreak of salmonellosis in a gerbil colony was investigated. The clinical, bacteriologic, and pathologic findings are reported. Clinical signs included an occasional sudden death, depression, emaciation, dehydration, rough hair coat, and testicular enlargement. Not every sign was observed in every infected gerbil. At necropsy, 11 animals had lesions consistent with salmonellosis. Histopathologic lesions consisted of interstitial pneumonia, hepatic and splenic necrosis, meningitis, and suppurative orchitis. Splenic and intestinal amyloidosis were also noted. Salmonella, group D, was recovered from gerbil feces, a container in which adult mosquitos were reared, filarial inoculum, and a cockroach. An epizootiologic investigation led to salmonella-infected cockroaches as the possible source of animal contamination via mosquitos and the subsequent filarial inoculum.

Animals