Lipid peroxidation and Kawasaki disease.
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Biomedical subjects
Publications and source records attributed to J C Burns.
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Level of nitrogen (N) intake and ruminally protected methionine supplementation were evaluated in eight Angus growing steers (initial BW 253+/-21 kg, final BW 296+/-21 kg) in a replicated 4+/-4 Latin square design. The steers were fed two endophyte-free tall fescue (Festuca arundinacea) hays that contained 2.2 (LO) or 2.8% (HI) of DM as N and were either supplemented or not with ruminally protected methionine (10 g metabolizable methionine/d). Diets were fed to provide adequate energy for 0.5 kg ADG and sufficient protein for maintenance (LO), or protein to support 0.5 kg ADG (HI). Following at least 14 d of adjustment, N balance was measured for 6 d. Isotopic urea was infused (15N15N-urea, 0.164 mmol urea N/h) via a jugular catheter for 56 h and urine was collected from 48 to 56 h to measure urea kinetics. Jugular blood was collected during the balance trial, and serum was analyzed for serum urea N (SUN). By design, daily N intake was greater (P < 0.05) for HI (112 g) than for LO (89 g). Compared with LO, steers when fed HI had greater (P < 0.05) daily DMI (4,217 vs 4,151 g), fecal N (34.4 vs 31.2 g), N digested (77.1 vs 57.7 g), urine N (48.3 vs 37.5 g), urine urea N excretion (34.6 vs 24.8 g), and N retained (29.8 vs 21.1 g). When fed HI steers also had higher (P < 0.05) urine urea N concentration (276 vs 219 mM), SUN (8.7 vs 6.7 mM), N digestibility (69.1 vs 64.9%), percentage of urinary N present as urea (71.5 vs 66.7%, P < 0.053), and rate of urea N production (59.6 vs 49.2 g/d) but lower (P < 0.05) percentage of urea N produced that was returned to the ornithine cycle (15.03 vs 19.2 1%) than when fed LO. Methionine supplementation decreased daily urine N (41.2 vs 44.6 g, P = 0.10) and increased both the amount of N retained daily (27.9 vs 23.7 g, P < 0.089) and the percentage of N digested that was retained (40.4 vs 34.6%, P < 0.094). In summary, supplemental methionine met a specific dietary limitation by increasing the amount of digested N that was retained by the steers.
Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood that continues to baffle researchers and clinicians alike. Although the acute illness resolves spontaneously, permanent damage to the coronary arteries occurs in 20-25% of untreated children. The cause of KD remains unknown and there is no specific laboratory test to identify affected children. Nonetheless, high dose intravenous g-globulin plus aspirin administered within the first 10 days of fever significantly reduces the risk of coronary artery damage by unknown mechanisms. KD thus presents a unique dilemma: the disease may be difficult to recognize, there is no diagnostic laboratory test, there is an extremely effective therapy, and there is a 25% chance of serious cardiovascular damage or death if the therapy is not administered. This review will highlight some of the many unanswered questions about KD.
Creation of a shrimp cell line has been an elusive goal. This failure may be due to the composition of the cell culture medium, which may be inadequate to support primary cultured cells. Shrimp hemolymph should contain the nutritional components needed to support cell growth and division. We report here the comprehensive biochemical analysis of hemolymph from the blue shrimp, Penaeus stylirostris (Litopenaeus stylirostris) (see Holthuis, L. B. Shrimps and prawns of the world, in: FAO species catalog. Vol. 1. Rome: Food and Agriculture Organization of the United Nations; 1980), for free amino acids (FAAs), carbohydrates, electrolytes, metals, pH, and osmolality. Levels of hemolymph components were compared to 2xL-15 with 20% fetal bovine serum, a commonly used culture medium for crustacean cells. The FAAs, taurine and proline, and the metals, strontium and zinc, were significantly higher in hemolymph than in the 2 x L-15 medium. In contrast, other FAAs were up to 50 times higher in the 2 x L-15 medium than in the hemolymph. To mimic more closely the hemolymph composition, we created two new media based on either the 0.2 x L-15 or the M199 medium. We compared the microscopic appearance of cells cultured in these media and evaluated deoxyribonucleic acid (DNA) and protein synthesis by 3H-thymidine uptake and 35S-methionine uptake assays. The ovary cells of P. stylirostris cultured in either of the new media formed monolayers, while the cells cultured in 2 x L-15 medium did not. Despite these differences, there was no evidence of sustained DNA or protein synthesis with any of the media. Future studies to establish a shrimp cell line should focus on analysis of the cell cycle and on overcoming the molecular blocks to cell division.
Genetic polymorphisms influence the magnitude of the cytokine response after an inflammatory stimulus. To determine whether such polymorphisms might play a role in Kawasaki disease (KD), we analyzed white and Japanese children with KD and control populations for two polymorphic loci in which the A allele is associated with high tumor necrosis factor-alpha secretion. The lymphotoxin-alpha+250 A/A genotype was overrepresented among white children with KD compared with controls (0.59 versus 0.36; p = 0.013). The tumor necrosis factor-alpha-308 A/G genotype was overrepresented among whites with KD who had coronary artery abnormalities compared with those with normal echocardiograms (0.36 versus 0.09; p = 0.044). No significant difference was seen at either locus between Japanese children with KD and Japanese controls. The increased frequency of the high secretor alleles in white children with KD suggests that these loci may be related to susceptibility to KD and to outcome after disease.
Grazing ruminants use both visual cues and taste in selecting their diet. Preference during grazing may not be the same when forage is dried for hay and cut into lengths prior to feeding in confinement. Eight cultivars of tall fescue (Festuca arundinacea Schreb.), previously evaluated for preference while grazed, were harvested three times over a period of 2 yr. The hays were air-dried, baled, and passed through a hydraulic bale processor prior to feeding. Five experiments were conducted. All three harvests were evaluated with sheep and the last two also with goats, using six animals each time. During an adaptation phase, hays were offered alone as meals. In the experimental phase, every possible pair of hays (28 pairs) was presented for a meal. Data were analyzed by multidimensional scaling and by traditional analyses. Preference was significant among cultivars in all experiments. Multidimensional scaling showed that selection was based on two criteria with two dimensions being significant. Sheep preferred KENHY followed by KENTUCKY 31 and STARGRAZER but preferenced against BARCEL. HIMAG, MO-96, and C1 were intermediate and MOZARK was variable. Goats were similar to sheep in preferring KENHY followed by STARGRAZER and selected against MOZARK and BARCEL. KENTUCKY 31, HIMAG, MO-96, and C1 were intermediate. In all five experiments, the general association was positive for available carbohydrate fractions and negative for fiber fractions that contribute to cell wall rigidity.
The effects of two forage species and N levels on urea kinetics and whole-body N metabolism were evaluated in eight Angus steers (initial BW 217+/-15 kg). In a replicated, 4 x 4 Latin square design, steers were fed gamagrass (Tripsacum dactyloides L.) or switchgrass (Panicum virgatum L.), each of which had 56.2 (LO) or 168.5 (HI) kg of N fertilization per hectare. Diets provided adequate energy for 0.5 kg ADG. Nitrogen balance and urea kinetics were measured from d 22 to 27 of each period. Urine samples collected during intravenous infusion of bis 15N urea were used to calculate production and recycling of urea N from relative abundance of urea isotopomers. Jugular blood serum was analyzed for serum urea N (SUN). Gamagrass differed from switchgrass (P < 0.05) in daily DMI (4,273 vs 4,185 g), N intake (72 vs 67 g), DM digestibility (61.0 vs 63.6%), fecal N (30.6 vs 28.3 g/d), urine urea N (10.5 vs 8.0 g/d), and percentage of urinary N present as urea N (53.5 vs 40.0%). After adjustment for differences in N intake, fecal N still tended to be greater (P < 0.09) for gamagrass than for switchgrass. The LO differed from the HI (P < 0.01) in daily N intake (63 vs 76 g), DM digestibility (61.3 vs 63.3%), urine N (13.6 vs 25.9 g/d), and N retained as a percentage of N digested (57.3 vs 43.5%). Compared to switchgrass, gamagrass had greater SUN, N digestibility, and N digested as N level increased (forage x N level interactions, P < 0.05). As N level increased, N retention increased from 19.5 to 23.5 g/d in gamagrass and decreased from 20.5 to 18.1 g/d in switchgrass (interaction, P < 0.07). The HI group was greater than the LO intake group (P < 0.03) in endogenous production of urea N (44.4 vs 34.0 g/d), gut entry rate of urea N (31.6 vs 28.2 g/d), and the amount of urea N that re-entered the ornithine cycle (9.4 vs 7.9 g/d). However, the percentage of urea N entering the gastrointestinal tract that was recycled was constant among treatments (29.1%), indicating that almost 70% of the urea N that entered the gastrointestinal tract was potentially available for anabolic purposes of the steers as a component of microbial products that were absorbed or excreted in the feces. In summary, N levels affected N metabolism of steers more when they were fed gamagrass than when they were fed switchgrass. Although the absolute amounts of N moving through the system changed with variations in intake, the proportions remained similar, with a greater efficiency of N use at low N intakes.
Kawasaki disease is an acute self-limited vasculitis of infancy and early hildhood that is now the leading cause of acquired heart disease in children in the United States and Japan. An infectious cause is suspected, although the etiology remains unknown. Children typically are seen with the acute onset of fever followed by signs of mucosal inflammation and vasodilatation that evolve over the first week of the illness. Laboratory tests reveal a marked systemic inflammatory response. If untreated, 1 in 4 children will develop permanent damage to the coronary arteries. Intravenous gamma globulin in conjunction with aspirin is effective in reducing the inflammation and preventing coronary artery abnormalities if administered within the first 10 days of illness. This poses a difficult situation for the pediatric care provider who must distinguish Kawasaki disease from other rash/fever syndromes in a timely manner so that appropriate therapy can be initiated.
Computer-assisted analysis of the oral brush biopsy is a recently introduced tool that determines the significance of an oral lesion. The oral brush biopsy is minimally invasive, requires no anesthesia, and definitively distinguishes benign from precancerous and cancerous lesions. Oral brush biopsy specimens are analyzed with the aid of a highly specialized neural network-based computer system specifically designed to detect oral epithelial precancerous and cancerous cells.
We purified and sequenced infectious hypodermal and hematopoietic necrosis virus (IHHNV), a small DNA virus of shrimp, from wild Penaeus stylirostris. The virion has a buoyant density of 1.45 as determined by cesium chloride gradient. Analysis of 3873 nucleotides of the viral genome revealed three large open reading frames (ORFs) and parts of the noncoding termini of the viral genome. The left, mid, and right ORFs on the complementary (plus) strand have potential coding capacities of 666 amino acids (aa) (75.77 kDa), 363 aa (42.11 kDa), and 329 aa (37.48 kDa), respectively. The overall genomic organization is similar to that of the mosquito brevidensoviruses. The left ORF most likely encodes the major nonstructural (NS) protein (NS-1) since it contains conserved replication initiator motifs and NTP-binding and helicase domains similar to those in NS-1 from all other parvoviruses. The IHHNV putative NS-1 shares the highest aa sequence homology with the NS-1 of mosquito brevidensoviruses, Aedes densovirus and Aedes albopictus parvovirus. A search for putative splicing sites revealed that the N-terminal region of NS-1 is very likely located in a small ORF upstream of the left ORF. The right ORF is presumed to encode structural polypeptides (VPs), as in other parvoviruses. Two putative promoters, located upstream of the left and right ORFs, are presumed to regulate expression of NS and VP genes, respectively. Thus, IHHNV is closely related to densoviruses of the genus Brevidensovirus in the family Parvoviridae, and we therefore propose to rename this virus Penaeus stylirostris densovirus (PstDNV).
BACKGROUND: The time course and rate of recovery of myocardial dysfunction in association with Kawasaki disease in response to intravenous gamma-globulin is unknown and may provide mechanistic clues. METHODS AND RESULTS: The acute changes in myocardial contractility in 25 patients with Kawasaki disease were evaluated by noninvasive stress-shortening and stress-velocity analysis. Echocardiograms were performed before and then daily for 4 days during which the patients received gamma-globulin 1.6 to 2 g/kg. Before treatment, contractility was abnormally low (<2 SD) in 14 patients (56%). Contractility increased significantly (2 SD increase) in 17 (68%), including 13 of 14 with depressed contractility and 4 whose initial contractility fell within normal limits. Of the 14 patients with depressed contractility, 8 (57%) normalized within 24 hours and a further 5 (35.7%) normalized within 6 months. A clinical response to treatment (fall in C-reactive protein by 50% and/or resolution of fever within 4 days) was seen in 22 patients (88%). Contractility increased in 17 of the 22 clinical responders and was normal before therapy in the other 5. The 3 patients who did not respond clinically also had no change in contractility with gamma-globulin therapy. Long-term (more than 12 months) follow-up was available in 19 patients. All patients had normal contractility at late follow-up. CONCLUSIONS: More than half the patients with Kawasaki disease have abnormal contractility at presentation. Myocardial response to gamma-globulin therapy is associated with rapid improvement in myocardial mechanics, with a high concordance between the clinical and myocardial response to therapy. The speed of recovery suggests that depressed contractility in patients with Kawasaki disease is caused by a rapidly reversible process such as circulating toxins or activated cytokines. Long-term outcome is good even in those patients with slow recovery of myocardial function.
We describe 10 patients who developed a psoriatic skin eruption during either the acute or convalescent phase of Kawasaki disease. The skin eruption was pustular in 3 patients, but more typical psoriasiform skin lesions were seen in the remaining 7 patients. No patient has yet developed chronic psoriasis.
BACKGROUND: The etiology of Kawasaki syndrome (KS), the leading cause of acquired coronary artery disease in children, is unknown. Recent studies have suggested that Chlamydia pneumoniae, a common respiratory pathogen associated with an increased risk of heart disease, might lead to KS. OBJECTIVE: To assess whether KS was associated with an elevated risk of having a current or antecedent infection with C. pneumoniae. METHODS: Blood, urine and pharyngeal specimens from KS patients in San Diego County, CA, during a period of high KS incidence were analyzed for evidence of recent C. pneumoniae infection by culture, PCR and serology. Specimens collected from two control groups, family members of KS patients and age-matched children attending outpatient clinics for well child visits, were similarly analyzed. RESULTS: Thirteen cases were identified. Forty-five outpatient controls and an average of three family members per patient were enrolled in the study. All specimens tested negative for the presence of C. pneumoniae by PCR and culture except for one blood specimen from the mother of a case-patient. Serologic analysis of patients and a subset of outpatient and family controls revealed no evidence of current C. pneumoniae infection; 4 of 13 adult family controls had IgG titers consistent with past exposure to C. pneumoniae. Case patients were no more likely than outpatient controls to have had a respiratory illness in the preceding 2 months (11 of 13 patients vs. 35 of 45 controls; odds ratio, 1.57; 95% confidence interval, 0.3 to 11.9). CONCLUSIONS: We found no evidence that C. pneumoniae infection was associated with KS.
BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in children in the United States. By monitoring trends in patient numbers and demographics during a 5-year period, we were able to explore the relationship between climate, ethnicity, socioeconomic status and susceptibility to KD. METHODS: We conducted active surveillance for all patients hospitalized with KD in San Diego County from 1994 through 1998. Data on seasonal variation in monthly rainfall and temperature were obtained from the US Meteorological Service. Patient sex, age, date of admission and self-reported ethnicity were identified from patient medical records. Socioeconomic status was assessed on the basis of insurance status among patients hospitalized at a single institution. RESULTS: During the 5-year period there were 169 cases of KD in San Diego County. The overall annual incidence of KD in children < 5 years of age ranged from 8.0 to 15.4/100 000. KD incidence was inversely associated with average monthly temperature (r = -0.47, P < 0.001) and positively associated with average monthly precipitation (r = -0.52, P < 0.001). Asian/Pacific Islanders < 5 years of age were 2.7 times as likely and Hispanics were one-third as likely to be hospitalized for KD than children from all other ethnic groups combined. Children with private or military insurance in all ethnic groups were more likely to have a diagnosis of KD than children with government assistance or no insurance. After controlling for insurance status, only Asian/Pacific Islanders remained at increased risk (rate ratio, 2.14) for KD relative to all other ethnic groups combined. CONCLUSION: KD is a common childhood vasculitis of unknown etiology. The skewed ethnic distribution and seasonality are consistent with the hypothesis that KD is an infectious disease that is influenced by environmental and genetic factors.
The inability to stably introduce and express foreign genes has hampered basic research in molluscan species. We cultured cells from dissociated embryos of the Pacific oyster, Crassostrea gigas, and infected these primary cultures with pantropic retroviral vectors containing the envelope glycoprotein of vesicular stomatitis virus. Luciferase transgene expression mediated by different heterologous promoters was demonstrated for at least 9 d after infection of the cells. Surprisingly, the promoter reproducibly mediating the highest level of luciferase expression was the retroviral promoter (U3 region of long terminal repeat) from the Moloney murine leukemia virus. The infection efficiency using a low multiplicity of infection (0.05) was estimated by quantitative polymerase chain reaction to be between 0.1-0.5%. This system will facilitate studies of gene expression and regulation and should be widely applicable to other molluscan species.
Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause of acquired heart disease among children in North America and Japan. Although an infectious agent is suspected, the cause remains unknown. However, significant progress has been made toward understanding the natural history of the disease and therapeutic interventions have been developed that halt the immune-mediated destruction of the arterial wall. We present a brief history of KD, review progress in research on the disease, and suggest avenues for future study. Kawasaki saw his first case of KD in January 1961 and published his first report in Japanese in 1967. Whether cases existed in Japan before that time is currently under study. The most significant controversy in the 1960s in Japan was whether the rash and fever sign/symptom complex described by Kawasaki was connected to subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka and pediatrician Takajiro Yamamoto disputed the early assertion of Kawasaki that KD was a self-limited illness with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases of sudden cardiac death after KD. By the time of the first English-language publication by Kawasaki in 1974, the link between KD and coronary artery vasculitis was well-established. KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles Children's Hospital, retrospectively diagnosed a 1971 autopsy case as KD. The similarity between KD and infantile periarteritis nodosa (IPN) was apparent to these pathologists, as it had been to Tanaka earlier. What remains unknown is the reason for the simultaneous recognition of this disease around the world in the 1960s and 1970s. There are several possible explanations. KD may have been a new disease that emerged in Japan and emanated to the Western World through Hawaii, where the disease is prevalent among Asian children. Alternatively, KD and IPN may be part of the spectrum of the same disease and clinically mild KD masqueraded as other diseases, such as scarlet fever in the preantibiotic era. Case reports of IPN from Western Europe extend back to at least the 19th century, but, thus far, cases of IPN have not been discovered in Japan before World War II. Perhaps the factors responsible for KD were introduced into Japan after the World War II and then reemerged in a more virulent form that subsequently spread through the industrialized Western world. It is also possible that improvements in health care and, in particular, the use of antibiotics to treat infections caused by organisms including toxin-producing bacteria reduced the burden of rash/fever illness and allowed KD to be recognized as a distinct clinical entity. Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide surveys in Japan. These have indicated that: 1) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; 2) there are approximately 5,000 to 6,000 new cases each year; 3) current estimates of incidence rates are 120 to 150 cases per 100,000 children <5 years old; 4) KD is 1.5 times more common in males and 85% of cases occur in children <5 years old; and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for Disease Control and Prevention published a case definition based on Kawasaki's original criteria. The Centers for Disease Control and Prevention developed a computerized database in 1984, and a passive reporting system currently exists in 22 states. Regional investigations and national surveys suggest an annual incidence of 4 to 15 cases per 100 000 children <5 years o
Effect of preservation method on intake and chewing behavior was examined using a first, late vegetative harvest (mid-June) of Kanlow switchgrass (Panicum virgatum L.). For silage (S), forage was harvested with a commercial field chopper (1.5 to 4 cm average chop length) and ensiled directly in silos 1.2 m in diameter and 3.6 m in height. For hay (H), forage was harvested with a flail-chopper (7 to 15 cm average chop length) and cured as hay in a drier at 77 degrees C. Diets of H and S were fed to six Hereford steers (338+/-5 kg) in a single crossover experiment. Chewing behavior was monitored for 4 d with a computerized system. At feeding, H was higher in DM and contained greater concentrations (DM basis) of NDF, CP, and hemicellulose, but lower concentrations of ADF and cellulose, and had lower in vitro DM disappearance values. Steers fed S had higher intakes of DM (P < .02) and NDF (P < .04) and consumed less water from the water supply (P < .01) than animals fed H. However, total amount of water (from water supply and feed) consumed per kilogram of DMI did not differ between diets. Crude protein intake was similar between diets. Preservation method had no effect on eating time, number of boli ruminated, bolus duration, and number of rumination chews per bolus. Steers fed S made fewer eating chews (P < .10) and ruminated for a longer time (P < .05) while making a greater number of rumination chews (P < .04) than steers fed H. Rumination intercycle time was slightly shorter in steers fed H (P < .05) than in steers fed S. When expressed per kilogram of NDF intake, steers fed S spent less time eating (P < .03) and made fewer eating chews (P < .02) than steers fed H; however, rumination time, number of rumination chews, and number of boli ruminated were not affected by preservation method. Steers fed S ingested feed at a greater rate (P < .03), excreted smaller fecal particles (P < .03), had meals of shorter duration (P < .06), spent less time eating during main meals (meals following feed distribution: P < .05), had more rumination periods (P < .01), and a shorter morning (P < .06) latency time (interval between end of main meal and onset of rumination) than steers fed H. These results indicate that preservation method with its concomitant differences in chop length affected forage chemical composition and voluntary intake, and that differences in chewing behavior occurred mostly during eating.
Transformation of Entamoeba histolytica has been previously reported, but the foreign genes have all been replicated episomally. Pantropic retroviral vectors based on the Moloney murine leukemia virus with the envelope glycoprotein of vesicular stomatitis virus (VSV-G) have an extremely broad host range and can be concentrated to high titer. To investigate whether these pseudotyped, pantropic vectors can mediate gene transfer and expression in E. histolytica, we constructed a retroviral vector, in which a hygromycin phosphotransferase is expressed from the E. histolytica actin promoter. Data confirm the infection, integration, and expression of a foreign gene mediated by the provirus. To our knowledge, this is the most evolutionarily distant example of successful integration and expression of a mammalian retrovirus. Pantropic retroviral vectors may thus facilitate genetic analysis in species lacking transformation systems.