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Biomedical subjects

J G Morris

Publications and source records attributed to J G Morris.

At least 127 records · Page 7Linked to original sources

Optimizing the pattern of essential amino acids as the sole source of dietary nitrogen supports near-maximal growth in kittens.

Most experiments conducted to determine the optimal essential amino acid (EAA) nitrogen to total nitrogen (E:T) ratio in rats, chicks and other species have shown that weight gain and nitrogen retention are optimal when the ratio is between 0.5 and 0.65. Two experiments were conducted to determine if weight gains of kittens fed EAA as a sole source of dietary nitrogen were equivalent to those of kittens fed a control diet that contained equal amounts of EAA and dispensable amino acids (DAA). In the first experiment, kittens fed diets that contained only EAA lost weight. Amino acid analysis of plasma showed that the concentration of methionine was 9.1 times that of controls, supporting the premise that the weight loss that occurred was the result of an adverse effect of excess methionine. Also, plasma threonine and arginine were elevated whereas proline and asparagine were very low. In the second experiment, feeding lower concentrations of methionine and arginine in a diet containing only EAA resulted in weight gains and nitrogen retention that were not significantly different from results for kittens fed the control diet (E:T ratio = 0.5). The addition of proline and asparagine to this EAA diet or their removal from the control diet did not improve or reduce weight gain or nitrogen retention. It is concluded that the decreased weight gain found in kittens (and probably other species) fed only EAA is the result of an adverse effect of excesses of methionine and possibly other EAA, and not the inability to synthesize DAA. If excesses of certain EAA are avoided, near-maximal weight gain can be achieved without any DAA in the diet.

Amino Acids, Essential↗

Emerging foodborne pathogens: Escherichia coli O157:H7 as a model of entry of a new pathogen into the food supply of the developed world.

There would appear to be little argument that the large outbreaks of E. coli O157:H7 which have occurred since the early 1980s represent a distinct, new phenomenon. The number of reported cases have increased dramatically, starting from zero in 1981; however, it is also clear that this increase in reported cases is in part an artifact of improved surveillance and reporting. Available data suggest that E. coli O157:H7 infections were present prior to 1982, although numbers appear to have been small. At a molecular level, the organism shows evidence of clonal origin, but there is not the striking clonality, with virtually identical pulsed-field gel electrophoresis and ribotyping patterns, which has been seen in situations such as the emergence of Vibrio cholerae O139 Bengal in the Indian subcontinent in 1992 or the introduction of V. cholerae O1 into naïve populations in South America in 1991 (127-129). Findings are more consistent with the image of an organism which arose from a common ancestor, but which has had time to become distributed geographically and to show some evidence of genetic divergence. While this is an "emerging" infection, at least in terms of its distribution and public recognition, it is unlikely that it will be possible to identify the "first" O157:H7 case or to track the clonal spread of the organism through cattle or human populations.

Animals↗

Controversies in the treatment of Parkinson's disease.

Although theoretical reasons exist for believing that selegiline slows the progression of Parkinson's disease, this has not been shown in clinical trials. Selegiline improves the symptoms of Parkinson's disease, allowing the introduction of levodopa to be delayed in de-novo patients and, later, for levodopa to be used at a lower dose. It does not lessen the long-term problems of dyskinesia and fluctuations associated with levodopa therapy. The report of an increased mortality associated with selegiline therapy awaits further evaluation. Of the dopamine agonists, pergolide appears to be more potent than bromocriptine; cabergoline looks promising. The catechol-O-methyltransferase inhibitors, tolcapone and entacopone, prolong the duration of action of levodopa and also show promise. The main objective in the drug treatment of Parkinson's disease remains the optimization of the dose and frequency of levodopa administration.

Antiparkinson Agents↗

Vitamin K deficiency in cats fed commercial fish-based diets.

Clinical signs of vitamin K deficiency have been observed in cats offered two commercial canned diets high in salmon or tuna. Some of the queens and kittens offered these diets had died while survivors had increased coagulation times. Necropsies revealed hepatic and, or, gastrointestinal haemorrhages. Coagulation times of survivors returned to normal after vitamin K therapy. The purpose of this study was to induce a vitamin K deficiency in kittens and determine the dietary requirement. Kittens were offered vitamin K-deficient purified diets containing antibiotics and, or, substances inherent in canned fish diets that may have contributed to the deficiency. Clinical signs of vitamin K deficiency were not observed, even though one purified diet contained only 4 micrograms K1/kg diet compared with 60 micrograms in the commercial tuna diet. Therefore, a minimum vitamin K requirement could not be determined using purified diets; nevertheless, canned commercial diets formulated primarily with fish should contain more than 60 micrograms K1/kg diet.

Animals↗

Distribution of Vibrio vulnificus in the Chesapeake Bay.

Vibrio vulnificus is a potentially lethal human pathogen capable of producing septicemia in susceptible persons. Disease is almost always associated with consumption of seafood, particularly raw oysters, or with exposure of wounds to seawater. An oligonucleotide DNA probe (V. vulnificus alkaline phosphatase-labeled DNA probe [VVAP]), previously shown to be highly specific for V. vulnificus, was used to enumerate this species in environmental samples collected from the Chesapeake Bay between April 1991 and December 1992. Total aerobic, heterotrophic, culturable bacteria were enumerated by plate counts on nonselective medium. The number of V. vulnificus organisms was determined by colony lifts of spread plates for subsequent hybridization with VVAP. V. vulnificus was not detected in any samples collected during February and March (water temperature of < 8 degrees C) but was found in 80% of the water samples collected during May, July, September, and December (water temperature of > 8 degrees C), with concentrations ranging from 3.0 x 10(1) to 2.1 x 10(2)/ml (ca. 8% of the total culturable heterotrophic bacteria). In a multiple regression analysis, increased V. vulnificus concentrations were correlated with lower salinities and with isolation from samples collected closer to the bottom. Isolation from oysters was demonstrable when water temperatures were 7.6 degrees C, with concentrations ranging from 1.0 x 10(3) to 4.7 x 10(4)/g (ca. 12% of total culturable bacteria). In samples collected in May and July, V. vulnificus was identified in seven of seven plankton samples and four of nine sediment samples. Our data demonstrate that V. vulnificus is a widespread and important component of the bacterial population of the Chesapeake Bay, with counts that are comparable to those reported from the Gulf of Mexico.

Animals↗

Preclinical immunoprophylactic and immunotherapeutic efficacy of antisera to capsular polysaccharide-tetanus toxoid conjugate vaccines of Vibrio vulnificus.

Vibrio vulnificus is an oyster-associated bacterial pathogen that causes life-threatening fulminating septicemia and necrotizing wound infections in humans. The capsular polysaccharide of V. vulnificus (VvPS) is critical for virulence. Previously we showed that active immunization of mice with a VvPS-tetanus toxoid (VvPS-TTa) conjugate vaccine conferred significantly higher protection against subsequent lethal challenge than immunization with VvPS alone. In the current study, we examined the utility of immunoprophylaxis or immunotherapy with hyperimmune antisera elicited by VvPS-TTa and VvPS-TTb conjugate vaccines prepared by different synthetic schemes. First we demonstrated that the Ribi adjuvant significantly enhanced the murine antibody response (P < or = 0.02) to both conjugates. Subsequently, high-titered polyclonal antisera were raised to VvPS-TTa and VvPS-TTb conjugate vaccines by using Ribi adjuvant or Freund's adjuvants. Antisera were observed to have protective effects when administered before and after acute lethal infection. All animals receiving prophylactic antisera intraperitoneally 24 h before lethal challenge with homologous carbotype 1 were protected, while 73 to 100% of control mice succumbed. Immunotherapy was also effective, with survival rates of 60 to 73% seen among mice when antisera were administered 2 h after bacterial challenge, at a time when symptoms of infection were already apparent. The protective effect of capsular antiserum appeared to be serotype specific. Antisera to the, carbotype 1 VvPS-TTa vaccine did not confer cross-protection against lethal challenge with carbotype 2 V. vulnificus despite partial structural similarity and a weak serological cross-reaction between the two carbotypes. Immune globulins induced by a potential multivalent VvPS conjugate vaccine composed of clinically prevalent carbotypes may have utility in the management of V. vulnificus infections and deserve further evaluation.

Animals↗

Analysis of clinical and environment Yersinia isolates in the Republic of Georgia.

The Center for Infectious Diseases Control, Georgian Ministry of Health, isolated 2,493 Yersinia enterocolitica and Y. enterocolitica-like strains, 22 Y. pestis strains, and 21 Y. pseudotuberculosis strains from 130,574 clinical and environmental samples. Analysis of 100 Y. enterocolitica and Y. enterocolitica-like strains showed none to be within traditional pathogenic biogroups or serogroups, and none carried genetic markers for virulence. However, some strains were enterotoxigenic in infant mice, while others were associated with prolonged carriage in adult mice.

Adult↗

Diffuse Lewy body disease: clinical features in nine cases without coexistent Alzheimer's disease.

OBJECTIVE: To further elucidate the relation between diffuse Lewy body disease and Parkinson's disease. METHODS AND RESULTS: The clinical features of nine cases of pure diffuse Lewy body disease without pathological evidence of coexisting Alzheimer's neuritic pathology were reported. All patients were aged less than 70 years at onset (mean 62 years). Five patients presented with clinical features, which included assymetric resting tremor had levodopa responsiveness, which were initially indistinguishable from idiopathic Parkinson's disease. All five patients later became demented (mean of three years after presentation). Two further patients presented with parkinsonism and dementia and two patients presented with dementia and developed parkinsonism at a later stage. Hallucinations appeared 2.5-9 years after the onset of symptoms in six patients and were a presenting feature in one patient. All patients met the pathological criteria of idiopathic Parkinson's disease, with respect to the midbrain changes, in addition to having diffuse cortical Lewy bodies. CONCLUSIONS: Diffuse Lewy body disease may present a parkinsonism, dementia, or both depending on whether the Lewy body pathology begins in the midbrain, the cortex, or both together. When it begins in the midbrain, diffuse Lewy body disease is indistinguishable initially from idiopathic Parkinson's disease. Diffuse Lewy body disease may be a common cause of dementia complicating Parkinson's disease.

Aged↗

Loss of Helicobacter pylori hemagglutination with serial laboratory passage and correlation of hemagglutination with gastric epithelial cell adherence.

Adherence of Helicobacter pylori to gastric epithelial cells is thought to be important in the pathogenesis of infection and may be essential to maintain lifelong colonization. However, the factors responsible for adherence to gastric epithelial cells in vivo have not been characterized, and the significance of adherence to standard epithelial cell lines is unclear. Hemagglutination is also thought to be important in H. pylori adherence. However, no studies have clearly linked H. pylori hemagglutination or adherence to cultured epithelial cells to primary gastric epithelial cell adherence. Furthermore, it is not clear whether laboratory strains which have undergone multiple passages lose potential colonization factors. In this study, we examined the effect of serial laboratory passage on hemagglutination and correlated the hemagglutination characteristics of H. pylori strains to primary gastric cell adherence. Variable expression of hemagglutination was seen with serial laboratory passage of 15 strains. After 100 serial laboratory passages, all strains had lost hemagglutination activity. Hemagglutination was seen in association with adherence to primary gastric cells in vitro isolated from 2 patients. An association with ultrastructural intimate adherence was seen with HEp-2 cells, but not with gastric adenocarcinoma cells. Ultrastructural adherence was seen in corresponding antral biopsies of patients whose strains were hemagglutination positive, but hemagglutination was not associated with gastric inflammation. These data indicate that H. pylori hemagglutination is lost with serial passage and that hemagglutination may play a role in the attachment of H. pylori to gastric epithelial cells, but the role of adherence to chronic gastric inflammation is unclear.

Adenocarcinoma↗

Escherichia coli transcytosis in a Caco-2 cell model: implications in neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder of preterm infants. Other than an association with prematurity and gastrointestinal feeding, no single factor or mechanism has been consistently linked to this disease. We have previously demonstrated that Escherichia coli isolates obtained from the stool of infants with NEC caused NEC-like injury in a weanling rabbit ileal loop model; this injury, in turn, could be blocked by coinfection with selected Gram(+) bacteria (Enterococcus faecium) isolated from asymptomatic controls. Using Caco-2 cells in a trans-well system, we now demonstrate that the same E. coli isolates can cross epithelial cell monolayers in the absence of ultrastructural change or damage. These results with E. coli contrast with those seen with Salmonella typhimurium, which passed through the monolayer at a higher rate and were associated with striking ultrastructural damage. Transcytosis of E. coli was reduced 3-5-fold in the presence of E. faecium previously shown to block NEC-like injury in the loop model. There was a mild increase in the rate of E. coli transcytosis when studies were conducted with younger, undifferentiated cells; these immature cells had no brush border, had decreased production of brush border-specific enzymes, but retained well defined tight junctions, as demonstrated by transepithelial electrical resistance and electron microscopy. A further reduction/ complete blockage of E. coli transcytosis was observed when E. faecium was used as the coinfectant in studies with these undifferentiated cells. We hypothesize that the ability of E. coli to cross epithelial cell layer is a critical initial step in the cascade of events which lead ultimately to NEC; blockage or reduction in E. coli transcytosis in the presence of certain Gram(+) organisms may play a significant role in prevention of NEC.

Analysis of Variance↗

A new route of transmission for Escherichia coli: infection from dry fermented salami.

OBJECTIVES: This study evaluated the production of dry fermented salami associated with an outbreak of Escherichia coli O157.H7 infection in Washington State and California. METHODS: Facility inspections, review of plant monitoring data, food handler interviews, and microbiological testing of salami products were conducted. RESULTS: Production methods complied with federal requirements and industry-developed good manufacturing practices. No evidence suggested that postprocessing contamination occurred. Calculations suggested that the infectious dose was smaller than 50 E. coli O157:H7 bacteria. CONCLUSIONS: Dry fermented salami can serve as a vehicle of transmission for O157:H7 strains. Our investigation and prior laboratory studies suggest that E. coli O157:H7 can survive currently accepted processing methods.

Adult↗

Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center.

OBJECTIVES: To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of vancomycin. DESIGN: Problem identification based on descriptive studies, point-prevalence surveys, and case-control studies and followed by specific interventions and evaluation of the response to these interventions. SETTING: University medical center. PARTICIPANTS: All patients hospitalized between May 1992 and June 1994 (59,196 admissions). MAIN RESULTS: 75 active infections attributed to vancomycin-resistant enterococci were identified. Thirty-one patients (41%) had bloodstream infections and 6 (8%) died. The incidence of active infection was highest in the organ transplantation unit (13.2 infections/1000 admissions). In the point-prevalence studies, vancomycin-resistant enterococci were isolated from 20% of a random sample of hospitalized patients in July, August, and September 1993 (adjusted prevalence, 16.9%). Case-control studies showed significant associations between colonization and infection and 1) receipt of antimicrobial agents, particularly vancomycin, and 2) severity of illness. Although several small case clusters had isolates with identical banding patterns on pulsed field gel electrophoresis, at least 45 different banding patterns were noted among medical center isolates. Interventions took place in November and December 1993. Vancomycin restriction policies resulted in a 59% decrease in intravenous vancomycin use and an 85% decrease in oral vancomycin use. Point-prevalence surveys done in April, May, and June 1994 showed a consistent 20% level of colonization with vancomycin-resistant enterococci strains (adjusted prevalence, 18.7%). No significant changes were seen in rates of vancomycin-resistant enterococci infection. CONCLUSIONS: Vancomycin-resistant enterococci are an important cause of illness and death in the study institution, particularly among organ transplant recipients and other seriously ill persons; they have also become a common intestinal colonizer among hospitalized patients. The diversity of isolates (based on molecular typing studies) suggests that resistant organisms have been introduced from multiple sources. Interventions that effectively lower the overall level of colonization with vancomycin-resistant enterococci must still be identified.

Case-Control Studies↗

Elevation of plasma cholecystokinin (CCK) immunoreactivity by fat, protein, and amino acids in the cat, a carnivore.

The cat requires a diet high in protein and certain nutrients that are found only in animal tissue. It is possible that secretogogues of intestinal CCK in the cat may be different from those observed in non-carnivorous species. Plasma CCK concentrations were determined in cats (n = 6) given by oral-gastric tube either casein, whey protein, corn oil, or corn starch suspended in water. CCK was measured by RIA with a tyrosine sulfate-specific, C-terminal antibody, DINO. HPLC of plasma revealed that most CCK-immunoreactivity (CCK-LI) was associated with CCK-33 and a late eluting peak, presumably CCK-58. Casein, whey protein, and corn oil increased (P < 0.05) post-administration plasma CCK-LI, and at least for casein, the effect was dose related. An amino acid mixture approximating the residue composition of casein increased plasma CCK-LI (P < 0.05), however, the increase tended to be less than that caused by casein. Evaluation of post-administration levels of plasma amino acids indicated that intact protein and amino acids in the intestinal lumen affect CCK release by different mechanisms. Collectively, the results indicated that although cats are carnivores cats and humans secrete CCK in response to the same nutrients.

Amino Acids↗

Ubiquitin-positive achromatic neurons in corticobasal degeneration.

A 66-year-old woman presented with an alien limb syndrome without dementia. The course of her illness was unremitting and at autopsy 6 years later her diagnosis was confirmed as corticobasal degeneration without Alzheimer-type pathology. Although the presence of ballooned achromatic cortical neurons and cell loss from the substantia nigra distinguishes such patients, the site and density of achromatic neurons has not previously been quantified. We show that immunohistochemistry for the cell stress protein ubiquitin selectively stains these achromatic neurons, whereas they do not stain for abnormally phosphorylated tau protein. Phosphorylated neurofilament antibodies recognise both ballooned and non-ballooned neurons. In this case, high densities of ubiquitin-positive ballooned neurons were found in frontal cortical regions with the highest densities in layers V and VI of the anterior cingulate cortex. In addition, high densities of ubiquitin-positive ballooned neurons were found in the insular cortex, claustrum and amygdala. These results confirm past reports of frontal pathology, but show that there is also considerable pathology in insular and parahippocampal cortical regions and some subcortical regions. Our findings suggest that the distribution and staining characteristics of ballooned neurons in corticobasal degeneration may help to differentiate these cases pathologically, while the absence of dementia appears to be an important clinical criterion.

Aged↗

Clinical and immunologic characteristics of Vibrio cholerae O139 Bengal infection in North American volunteers.

Vibrio cholerae O139 Bengal has recently emerged as a cause of epidemic cholera in Asia. To evaluate clinical and immunologic responses to infection, V. cholerae O139 Bengal AI1837 was administered to healthy adult North American volunteers. Two of 4 persons ingesting 10(4) cfu became ill (incubation period, 48 h; mean diarrheal stool, 1873 g), as did 7 of 9 persons receiving 10(6) cfu (incubation period, 28 h; mean diarrheal stool, 4548 g). Ill volunteers did not demonstrate a vibriocidal antibody response to the challenge strain or other V. cholerae. Three months later, volunteers were rechallenged with the homologous O139 Bengal strain. Only 1 of 6 persons who had been ill on initial challenge had diarrhea, compared with 11 of 13 controls (P = .01; protective efficacy = 80%). V. cholerae O139 Bengal can cause severe diarrhea typical of cholera, with clinical characteristics and a dose-response similar to those seen with V. cholerae O1 El Tor. A moderately high level of protection against subsequent disease is provided by initial clinical infection.

Adult↗

Diets causing taurine depletion in cats substantially elevate postprandial plasma cholecystokinin concentration.

Excessive secretion of the intestinal hormone cholecystokinin (CCK) was postulated to cause diet-related taurine depletion in cats. To test this hypothesis, plasma CCK-like immunoreactivity (CCK-LI) was measured in cats given four diets, two purified and two canned, that contained similar concentrations of protein, fat, moisture and taurine but produced variable rates of taurine depletion. Plasma CCK-LI was measured by RIA with a tyrosine-sulfate specific, C-terminal anti-serum, validated for use in cat plasma. As indicated by measurements of taurine in whole blood and urine, a purified diet containing casein maintained body taurine, whereas the same diet containing soybean protein and a commercial canned diet preserved either by freezing or cooking depleted body taurine. Preprandial and peak postprandial plasma CCK-LI in cats given the casein-containing diet were 10.6 +/- 1.4 and 27.6 +/- 4.8 pmol/L, respectively, approximately two- to tenfold greater than those reported in humans. Integrated postprandial plasma CCK-LI was less for cats given the casein diet than cats given both forms of the canned diet; it tended to be lower in cats given the casein diet than in cats given the soy protein diet. A negative linear correlation was observed between apparent nitrogen digestibilities of the diets and integrated plasma CCK-LI. The results indicated that diets that cause taurine depletion have lower protein digestibilities and cause greater endocrine secretion of CCK than diets that maintain body taurine status.

Animals↗