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Biomedical subjects

E Jackson

Publications and source records attributed to E Jackson.

At least 55 records · Page 3Linked to original sources

Dietary protein influences upon immunity to Nematodirus battus infection in lambs.

Several indices of the immune response to Nematodirus battus infection in lambs offered differing levels of dietary protein were quantified. Lambs were offered either a complete basal ruminant diet (13.2% crude protein (CP)) or the same diet supplemented with fish meal as a source of rumen bypass protein (18.3% CP). Lambs from each dietary treatment group were given either a 7-week continuous trickle infection with N. battus L3 or remained uninfected. All lambs were drenched with anthelmintic at week 8 post-infection (PI), challenged with a single dose of 30,000 N. battus L3 1 week later, and killed 9 days post-challenge (PC). Previous infection induced a significant reduction in worm burdens (p < 0.001) and enhancement of immune responses when compared to challenge controls. Among previously infected lambs, protein supplementation did not reduce worm burdens significantly, although there was a trend for fewer worms in the supplemented lambs. However, a significant increase in mucosal globule leucocyte (p < 0.05) and eosinophil (p < 0.05) numbers was evident. Supplementation (p < 0.05) and previous infection (p < 0.001) both enhanced serum anti-worm IgG titres over time. Peripheral blood eosinophil counts were not affected by supplementation but were significantly elevated over time as a result of previous infection (p < 0.001). Since there were no significant differences in worm burdens of supplemented and unsupplemented previously infected lambs, it was of interest to determine whether lambs possessed an innate ability to regulate their parasite burden. Hence they were re-grouped based on an arbitrary cut-off burden of 1000 worms. High responders (HR) had burdens below 1000 worms, while low responders (LR) had burdens above this value and challenge controls were pooled. The data were re-analyzed based on these groupings and showed significant reduction in worm burdens between all three groups (p < 0.001). Globule leucocytes were the only cell type that appeared to be significantly more abundant in the intestinal mucosa of HR (p < 0.001). Serum antibody responses (p < 0.05) and peripheral blood eosinophil counts (p < 0.01) were significantly elevated over time in accord with the degree of responsiveness. The results of this study suggest that supplementation of protein upon an adequate basal diet of lambs previously exposed to N. battus does not significantly enhance worm regulation despite significant increases in cellular and antibody responses. The immunity acquired is characterized by reduction in worm burdens, elevated anti-worm antibodies and a cellular inflammatory response. The identification of HR and LR essentially shows that when the protein supply is adequate, the predominant host effect influencing the pathogenicity of the parasites is the level of genetically determined susceptibility of the host.

Analysis of Variance↗

The response of breeding doses to nematodiasis: segregation into "responders" and "non-responders".

Responder and non-responder does were identified from a flock of 95 Scottish cashmere 2-6 year-old does exposed to natural nematode infection over a 12-month period. Every 5 weeks, the does were faecal sampled for worm-egg counts prior to anthelmintic treatment. Responsive and non-responsive individuals were identified on the basis of their cumulative faecal egg count (FEC) rankings: the 8 lowest and 8 highest rankings were deemed to be responders and non-responders, respectively. Retrospective analysis showed that the mean egg count of the 8 responders was significantly lower than that of the 8 non-responders. The selected responders and non-responders were subsequently housed together with 8 randomly selected does from a control line, and given a mixed trickle challenge with Teladorsagia circumcincta and Trichostrongylus vitrinus larvae (L3). Mean responders FEC was significantly lower following artificial infection than that of non-responder and unselected does. Peripheral eosinophilia was significantly greater in responders in the first 3 weeks of this infection. On day 60, the infection was terminated with anthelmintic and 7 days later the goats were given a single challenge of 50,000 T. circumcincta L3. The mean responder worm burden was lower, and exhibited greater evidence of retardation of worm development, than those of non-responder and unselected does. Responders had significantly more mast cells and globule leukocytes post-challenge than did the other 2 groups. These results suggest that under the conditions encountered in this experiment, it is possible to segregate goats into responders and non-responders using simple parasitological criteria, as individual responsiveness is a relatively repeatable phenomenon.

Animal Feed↗

Effect of dietary protein on the regulation of populations of Nematodirus battus by lambs.

Two groups of seven and two groups of six lambs were offered either a complete basal ruminant diet (13.2 per cent crude protein [CP]) (groups 2 and 4) or the same diet supplemented with fish meal (18.3 per cent CP) (groups 1 and 3). Groups 1 and 2 were infected daily for seven weeks with Nematodirus battus larvae (L3) and groups 3 and 4 served as uninfected challenge controls. All the groups were treated with anthelmintic in the eighth week, challenged with a single dose of 30,000 N battus L3 one week later and killed nine days after the challenge. Although protein supplementation tended to enhance the regulation of the population of N battus in the lambs which had been infected continuously, the effect was not statistically significant. The worm burdens in both the groups of previously infected lambs were significantly reduced both in number and size (P < 0.001) and they had a lower proportion of male worms than the uninfected challenge controls. The lambs could be segregated into high or low responders on the basis of their worm burdens, and there was a significant reduction in worm burdens (P < 0.001) and size (P < 0.01) in parallel with the lambs' responsiveness. The identification of high and low responders shows that when the dietary protein supply is adequate the predominant effect of the host on the pathogenicity of its parasites is the host's genetically-determined susceptibility.

Animal Feed↗

Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer.

The purpose of this study was to determine the effect of the first rat monoclonal antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I clinical trial in patients with unresectable squamous cell carcinomas. This antibody effectively blocks the binding of EGF, transforming growth factor (TGF)-alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice. Eleven patients with squamous cell carcinoma of the head and neck and nine patients with squamous cell carcinoma of the lung, whose tumours expressed EGFR, were recruited. Groups of three patients were treated with 2.5 mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg. All patients were evaluated for toxicity using WHO criteria. Patients' sera were tested for the clearance of MAb ICR62 and the development of human anti-rat antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and two at 100 mg doses) and of these only the former two were anti-idiotypic responses. In four patients receiving doses of ICR62 at 40 mg or greater, biopsies were obtained from metastatic lesions 24 h later and examined for the localisation of ICR62 using anti-rat antibody reagent. In these patients we showed the localisation of MAb ICR62 to the membranes of tumour cells; this appeared to be more prominent at the higher dose of 100 mg. On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses.

Adult↗

Blood conservation in acute care and critical care.

Blood conservation has evolved into an important issue in hospital-based medicine. Increased awareness of and worry about transfusion-associated diseases have prompted a focus on this important area. New technologies, including continuous intraarterial monitoring devices, microchemical technologies, new drug development (recombinant human erythropoietin and aprotinin) and intraoperative salvage techniques have made the concept of clinically important blood conservation possible. In this article, the authors review clinically important areas regarding blood conservation, which are subsequently detailed in this issue of AACN Clinical Issues. Emphasis is placed on the need for blood conservation in acute and critical care practice and the technologies available to achieve this goal.

Blood Loss, Surgical↗

Psychotic symptoms in Parkinson's disease patients with dementia.

OBJECTIVE: To assess the prevalence of psychotic symptoms in a group of patients with Parkinson's disease (PD) and dementia and examine the association of psychotic symptoms with neuropsychiatric problems, the level of distress reported by caregivers, and cognitive and functional impairment. DESIGN: The psychotic and nonpsychotic patients with PD dementia were compared on a series of demographic, neuropsychiatric, behavioral, caregiver complaint, and cognitive measures. SETTING: The database from nine university-based State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTCs). PARTICIPANTS: 101 patients diagnosed with PD. RESULTS: A total of 36 of the 101 patients (35.6%) had either hallucinations, delusions, or both. The psychotic patients had significantly more insomnia, confusion, agitation, personality changes, and self-care problems and were noted by their caregivers to be significantly more unmanageable at home than their nonpsychotic counterparts. On cognitive scales, psychotic patients were significantly more impaired. CONCLUSION: Many patients with PD and dementia experience psychosis. Psychotic symptoms in PD dementia patients are associated with major behavioral, cognitive, and functional problems.

Activities of Daily Living↗

A critical assessment of uncalibrated respiratory inductance plethysmography (Respitrace) for the measurement of tidal breathing parameters in newborns and infants.

We have compared results obtained with an uncalibrated respiratory inductance plethysmograph (RIP) with those of a face mask and pneumotachograph (PNT) for the computerized measurement of the time to reach peak tidal expiratory flow as a ratio of total expiratory time (tPTEF:tE). Simultaneous measurements were made in 32 healthy neonates aged 0-3 weeks, 35 healthy infants aged 5-82 weeks, and 28 infants aged 15-94 weeks with physician diagnosed recurrent wheeze. The group mean (+/- SD) values of tPTEF:TE determined using a PNT were 0.455 (+/- 0.129), 0.263 (+/- 0.077), and 0.232 (+/- 0.089) for the neonates, healthy infants and infants with recurrent wheeze respectively. RIP gave mean (+/- SD) values that were 0.055 (+/- 0.044) and 0.025 (+/- 0.104) lower than the PNT in healthy neonates and infants with recurrent wheeze respectively; RIP values were 0.002 (+/- 0.073) higher in the healthy infants over 4 weeks of age than measurements by PNT. Although the difference between the two measurements was not related to the thoracoabdominal phase angle, as measured from Lissajous figures, examination of the RIP ribcage and abdominal signals revealed that many healthy subjects, while appearing clinically in phase, had ribcage and abdominal signals that differed markedly from each other in terms of convexity/concavity during early expiration. This may explain the lack of agreement between the two methods. We conclude that uncalibrated RIP should be used with caution for the determination of tPTEF:tE, even in subjects whose ribcage and abdomen appear to move synchronously. The measurement of tPTEF:tE did not differentiate between the healthy infants and infants with recurrent wheezing.

Data Interpretation, Statistical↗

Primary structure of the variable regions encoding antibody to NG2, a tumour-specific antigen on the rat chondrosarcoma HSN. Correlation of idiotypic specificities with amino acid sequences.

Eight syngeneic rat monoclonal antibodies that recognize structurally overlapping epitopes on the chondroitin proteoglycan NG2, a tumour-specific antigen on the chemically induced rat chondrosarcoma HSN, have been analysed for the sequence of their immunoglobulin heavy (H) and light (L) chain variable (V) regions. This analysis defined five groups of antibodies which are very similar for both the H and L chains and revealed that a wide range of different V regions are capable of binding to the same antigenic determinant. However, three mAbs, 11/160, ALN/12/17 and ALN/9/94, which recognize a sequential epitope, were found to use almost identical heavy (V-D-J) and light (V-J) chains in regions demonstrating an exclusivity in specific protein-protein interaction for this particular epitope. Two other mAbs, ALN/11/53 and AL/3/12, used similar V and J segments but totally different D regions. With the exception of the pair ALN/11/53 and AL/3/12, this grouping of antibodies matches that derived from the idiotypic specificity study we have reported previously. The reactivity pattern of Ab1 11/160, ALN/12/17 and ALN/9/94 with six anti-idiotopic mAbs raised against 11/160 demonstrated that the idiotope recognized by Ab2 HIM/3/41 was defined by a single amino acid, Asn, at position 52 within the CDR2 loop of the VH region; whereas the D region of Ab1 ALN/11/53 was implicated as the structural correlate of idiotypy. The substitution of AsnH52 influenced the Id recognition but Ag binding was not affected suggesting that Ab2 HIM/3/41 did not mimic the NG2 Ag.

Amino Acid Sequence↗

IgA nephropathy: long-term prognosis for pediatric patients.

OBJECTIVE: The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years. METHODS: Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients. RESULTS: Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were. CONCLUSION: With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patient's care is transferred to a physician caring for adults.

Adolescent↗

Physicians and immigrant patients. Cross-cultural communication.

OBJECTIVE: To formulate recommendations for facilitating communication and helping prevent misunderstandings during cross-cultural patient-physician interactions. DESIGN: Qualitative study using content and semantic analyses of information supplied in focus groups. SETTING: All family physician respondents were associated with departments of family medicine at two urban hospitals and had expressed interest in this study; all immigrant patients were recruited from the English-as-a-Second-Language program at a community agency. PARTICIPANTS: Thirteen immigrant patients, distributed in two groups (one of seven women and one man and one of three men and two women), and five family physicians (two women and three men). MAIN OUTCOME MEASURES: Responses to prepared questions asked in focus groups. RESULTS: Family physicians thought that understanding patients' cultures better would improve quality of care. Patients did not always understand why their physicians asked questions about their culture, sometimes finding these questions irrelevant or intrusive. Comments were used to formulate recommendations for patient-physician interactions. CONCLUSIONS: Physicians and patients are aware of culture as a factor in their relationships but differ on its importance to quality of care.

Adult↗

The chondroitin sulfate proteoglycan NG2 is a tumour-specific antigen on the chemically induced rat chondrosarcoma HSN.

N-terminal sequences of 19 and 11 amino acids obtained from 2 different tryptic fragments of the tumour-specific antigen on the chemically induced rat chondrosarcoma HSN show a 100% homology with the rat chondroitin sulfate proteoglycan NG2. Using a scheme of overlapping oligonucleotide primers we have cloned by PCR amplification the cDNA for the specific antigen of the HSN tumour that is immunogenic in immunocompetent CBH/Cbi rats and now report that its cDNA sequence is identical to that of NG2. The cDNA codes for a transmembrane protein of 2,325 amino acids with a large extracellular domain of 2,224 amino acids containing 2 cysteine-rich regions, a transmembrane domain (25 amino acids) and a short cytoplasmic tail (76 amino acids). The tumour-specific determinant was found to lie between amino acid residues 556 and 992 on the core glycoprotein.

Amino Acid Sequence↗

Outcome after maternal varicella infection in the first 20 weeks of pregnancy.

BACKGROUND: Infection with the varicella-zoster virus during pregnancy can produce an embryopathy characterized by limb hypoplasia, eye and brain damage, and skin lesions. The risk is greatest when infection occurs during the first 20 weeks of pregnancy, but the magnitude of the risk is uncertain. METHODS: We studied 106 women with clinically diagnosed varicella infection in the first 20 weeks of pregnancy and compared the outcomes with those in 106 age-matched, nonexposed controls. RESULTS: Among the women with varicella, there was a trend toward more elective terminations of pregnancy (14 percent, vs. 7.5 percent among the controls; P = 0.1), corresponding to a significantly higher perception of teratogenic risk (P = 0.03). The proportions of miscarriages and live births and the mean birth weights were similar in the two study groups; there were more premature births (< or = 37 weeks) among the women with varicella infection (14.3 percent vs. 5.6 percent, P = 0.05). Congenital defects occurred in four infants born to the women with varicella (varicella embryopathy, hydrocephalus, meningocele and clubfeet, and hammer toe) and two infants born to the controls (ventricular septal defect and hip dislocation). The risk of varicella embryopathy after infection in the first 20 weeks was 1.2 percent (95 percent confidence interval, 0 to 2.4 percent). When we pooled our results with those from other prospective studies, the mean risk of embryopathy after infection with varicella-zoster virus in the first trimester was 2.2 percent (95 percent confidence interval, 0 to 4.6 percent). CONCLUSIONS: The absolute risk of embryopathy after maternal varicella infection in the first 20 weeks of pregnancy is about 2 percent.

Chickenpox↗

Increasing the length of the expiratory limb of the Ayre's T-piece: implications for remote mechanical ventilation in infants and young children.

We have assessed the effect of lengthening the expiratory limb of an Ayre's T-piece from 0.5 to 10 m for ventilation with a Nuffield series 200 ventilator and Newton valve, as this equipment is potentially suitable for infants and young children during anaesthesia for magnetic resonance imaging (MRI). We used lung models with compliances and resistances representative of the respiratory system with intubated trachea of a neonate, infant and child weighing 15-20 kg. The effects on ventilation were small, being greatest with the largest lung model where the longer T-piece resulted in a reduction in tidal volume from 261 to 236 ml and an increase in intrinsic and extrinsic positive end-expiratory pressure from 0.20 to 0.32 kPa and from 0.14 to 0.25 kPa, respectively. Such changes are unlikely to be clinically important and can be obviated by using the ventilator with the standard valve in children weighing 15-20 kg.

Air Pressure↗

Evaluation of a clinic for pregnant adolescents.

A random retrospective review of the Teen Obstetrical Parenting Perinatal Services (TOPPS) clinic medical records for 1985 to 1989 was completed on 120 adolescent mothers (30 charts for each year). The purpose of this study was to evaluate maternal and infant outcomes related to the goals of the TOPPS clinic located at University Hospital on the UAMS campus in Little Rock, Arkansas. The clinic was cofounded by Lee Lee Doyle, Ph.D., who is now professor of obstetrics/gynecology at UAMS, and Betty Rouse, R.N., M.N.Sc., who is a clinical associate professor at UAMS, College of Nursing. The outcomes measured were nutritional status as measured by maternal weight gain, infant birth weight, gestational age and Apgar scores. Referrals to appropriate agencies during pregnancy were also reviewed. Analysis of the data revealed that 31% of clients received documented nutritional counseling, 60.2% of the babies were healthy (88% term and 87% appropriate for gestational age), and documented referrals (i.e. WIC, AFDC, Medicaid, etc.) were made in 32% of the cases. Conclusions were that both mothers and infants had positive outcomes. Documentation of referrals needs to be improved or rationale stated for non-referral.

Adolescent↗

Beryllium competitively inhibits brain myo-inositol monophosphatase, but unlike lithium does not enhance agonist-induced inositol phosphate accumulation.

Despite limiting side-effects, lithium is the drug of choice for the treatment of bipolar depression. Its action may be due, in part, to its ability to dampen phosphatidylinositol turnover by inhibiting myo-inositol monophosphatase. Beryllium has been identified as a potent inhibitor of partially purified myo-inositol monophosphatase isolated from rat brain (Ki = 150 nM), bovine brain (Ki = 35 nM), and from the human neuroblastoma cell line SK-N-SH (Ki = 85 nM). It is over three orders of magnitude more potent than LiCl (Ki = 0.5-1.2 mM). Kinetic analysis reveals that beryllium is a competitive inhibitor of myo-inositol monophosphatase, in contrast with lithium which is an uncompetitive inhibitor. Inhibition of exogenous [3H]inositol phosphate hydrolysis by beryllium (IC50 = 250-300 nM) was observed to the same maximal extent as that seen with lithium in permeabilized SK-N-SH cells, reflecting inhibition of cellular myo-inositol monophosphatase. However, in contrast with that observed with lithium, agonist-induced accumulation of inositol phosphate was not observed with beryllium in permeabilized and non-permeabilized SK-N-SH cells and in rat brain slices. Similar results were obtained in permeabilized SK-N-SH cells when GTP-gamma-S was used as an alternative stimulator of inositol phosphate accumulation. The disparity in the actions of beryllium and lithium suggest that either (1) selective inhibition of myo-inositol monophosphatase does not completely explain the action of lithium on the phosphatidylinositol cycle, or (2) that uncompetitive inhibition of myo-inositol monophosphatase is a necessary requirement to observe functional lithium mimetic activity.

Animals↗

Rhesus monkey lipoprotein(a) binds to lysine Sepharose and U937 monocytoid cells less efficiently than human lipoprotein(a). Evidence for the dominant role of kringle 4(37).

Rhesus lipoprotein(a) (Lp[a]) binds less efficiently than human Lp(a) to lysine-Sepharose and to cultured U937 cells. Studies using elastase-derived plasminogen fragments indicated that neither kringle 5 nor the protease domain of Lp(a) are required in these interactions pointing at an involvement of the K4 region. Comparative structural analyses of both the human and simian apo(a) K4 domain, together with molecular modeling studies, supported the conclusion that K4(37) plays a dominant role in the lysine binding function of apo(a) and that the presence of arginine 72 rather than tryptophan in this kringle can account for the functional deficiency observed with rhesus Lp(a). These in vitro results suggest that rhesus Lp(a) may be less thrombogenic than human Lp(a).

Affinity Labels↗

Prevalence of anthelmintic-resistant nematodes in fibre-producing goats in Scotland.

Six cashmere goat herds in Scotland were surveyed to assess the prevalence of anthelmintic resistance and the species of nematode involved. Resistance was determined in vivo by a faecal egg count reduction test and in vitro using an egg hatch assay and specific faecal egg identification techniques. Benzimidazole resistance was present in five of the herds, insufficient eggs were obtained from the other herd to draw firm conclusions. Teladorsagia (Ostertagia) species predominated in four of the five herds in which resistance was detected and Haemonchus contorus was the dominant species in the other.

Animals↗