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Biomedical subjects

J Mann

Publications and source records attributed to J Mann.

At least 91 records · Page 5Linked to original sources

Mice transgenic for human carcinoembryonic antigen as a model for immunotherapy.

Mice transgenic for the human carcinoembryonic antigen (CEA) gene were prepared for use as a preclinical model for immunotherapy. A 32.6-kb fragment containing the complete human CEA gene and flanking sequences was isolated from a genomic cosmid clone and used to produce transgenic C57BL/6 mice. A homozygous line was established that was designated C57BL/6J-TgN(CEAGe)18FJP. Southern blot analysis showed that this line contained intact copies of the cosmid clone, with approximately 19 integrated copies at one chromosomal location. A mouse-human chimeric anti-CEA monoclonal antibody was used to examine CEA expression by immunohistochemical staining of frozen tissue sections. In the cecum and colon, approximately 20% of the luminal epithelial cells had strong cytoplasmic staining, whereas occasional glands showed intense staining. CEA was also expressed in gastric foveolar cells, whereas small intestine villi had only a few (<1%) positive cells. CEA was not found by immunohistochemistry in other tissues of the digestive tract, nor was it found in a wide range of other tissues or organs. Concordance in results was obtained between immunohistochemistry and analysis of tissue extracts by enzyme immunoassay. The lone exception was the testis, which was positive only by enzyme immunoassay. Expression of human CEA was not observed in tissues derived from nontransgenic mice. The fecal content of CEA in transgenic mice was approximately 100-fold less than that observed for humans. Circulating CEA was not detected. A CEA-transfected syngeneic murine colon carcinoma cell line, MC-38, was prepared that had stable expression of CEA in vitro and in vivo. The molecular size of CEA produced by CEA-transfected MC-38 cells and by the colon of transgenic mice was similar to that obtained with CEA purified from human colon tumors. Anti-CEA antibody appeared in nontransgenic but not transgenic mice bearing transfected MC-38 tumors. These findings demonstrate that CEA distribution and its properties in tissues of mice transgenic for the human CEA gene are similar to that observed in human tissues. As in humans, immune responsiveness to CEA, as reflected by antibody formation, was not detectable in transgenic mice bearing CEA-positive tumors. Thus, CEA transgenic mice may serve as a useful model for studying the efficacy and safety of various immunotherapy strategies directed at this tumor self-antigen.

Adenocarcinoma↗

Natal attraction: allomaternal care and mother-infant separations in wild bottlenose dolphins.

To determine whether allomaternal care occurs among bottlenose dolphins, we examined patterns of association and mother-infant separations for eight infants (164.4 focal h) during the first 3 months of life. During the first week of life, three inexperienced females (nullipara and mothers of infants that did not survive the newborn period) attempted to take infants from their mothers 13 times. Mothers responded by rapidly retrieving the infant and threatening the female. By the second week, mothers consistently allowed the same females to escort their infants to tens of metres away from them, suggesting that such separations were no longer risky, possibly because infants had imprinted on their mothers. To determine whether escorts benefited mothers after the first week, we compared maternal behaviour when infants were away from their mothers, but alone (solitary separations), to when infants were away, but with escorts (social separations). Mothers were less likely to forage and were more likely to engage in non-foraging activities (socialize, rest or travel) when infants were with young escorts (other dependent infants) compared with when infants were alone. When infants were with older (juvenile or adult) escorts, maternal activity did not differ significantly compared with when infants were alone. This result suggests that escorts did not benefit mothers by allowing them to forage. Inexperienced females that never raised an infant were more likely to escort newborns than were parous experienced females, supporting the 'learning to parent' hypothesis. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.

A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Chromosomes, Human, Pair 17↗

American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12.

BACKGROUND & AIMS: Two European genome-wide screens for inflammatory bowel disease have identified two significant regions of linkage on chromosomes 16 (IBD1) and 12 (IBD2) and two regions with suggestive levels of significance (chromosomes 3p and 7q). The aim of this study was to determine if there was evidence for linkage to these regions in non-Jewish and Ashkenazi Jewish families multiplex for Crohn's disease from the United States. METHODS: One hundred forty-eight affected relative pairs, 34% Ashkenazim, were genotyped with 10-14 highly polymorphic markers overlying each candidate region. Nonparametric multipoint and two-point linkage analyses were performed. RESULTS: Significant evidence for replication of linkage was found only for the chromosome 16 locus, IBD1, maximal at D16S769 (nonparametric linkage score [NPL], 2.49; P = 0.007). Analysis by ethnicity showed stronger evidence for Ashkenazim (D16S769; NPL = 2. 52; P = 0.007) than for non-Jewish white populations (D16S401; NPL = 1.40; P = 0.082). There was no significant evidence for replication on chromosome 12 (IBD2). Minimal evidence for extension of linkage evidence was observed for the chromosomes 3p and 7q regions. CONCLUSIONS: American families, particularly Ashkenazim, have significant evidence for the Crohn's disease susceptibility locus, IBD1, on chromosome 16, but not for IBD2 on chromosome 12.

Chromosome Mapping↗

Intestinal Cryptosporidium sp. infection in the Egyptian tortoise, Testudo kleinmanni.

An adult Egyptian tortoise (Testudo kleinmanni) presented with clinical signs of enteritis and died 5 weeks after initiation of antibiotic therapy. Histological examination of the small intestine revealed heavy infection with Cryptosporidium sp.; over 80% of epithelial cells harboured the pathogen. No Cryptosporidium developmental stages were present in the stomach or the lungs. The intestinal lamina propria and mucosa were infiltrated by heterophils, lymphocytes and macrophages. The present study constitutes the first report of Cryptosporidium sp. infection in T. kleinmanni, and the first histological documentation of intestinal cryptosporidiosis in Chelonia.

Animals↗

10 years' neuroblastoma screening in Europe: preliminary results of a clinical and biological review from the Study Group for Evaluation of Neuroblastoma Screening in Europe (SENSE).

Between January 1986 and May 1996, 870,313 children were tested in European neuroblastoma (NB) screening programmes. Among these children, 82 cases of NB (age range 4-24 months, median 11 months) were detected by screening. 83% of the patients had localised NB and 17% were diagnosed with generalised NB (stage 4, 10%; stage 4s, 7%). Unfavourable biological markers (MYCN amplification, loss of heterozygosity (LOH) 1p36, DNA di/tetraploidy) were observed in 14% of 76 biologically examined cases. The median follow-up time of all the patients was 21.5 months (range 1-101 months). To date, 69 patients are in complete remission (CR) and 2 patients have died due to therapy (stage 4, 1 patient; stage 3, 1 patient with unfavourable markers). Apart from screened patients, 16 other patients with NB were found who had previously had a normal screening test, i.e. 'false negative' patients (age range 10-41 months, median 31.5 months). The median interval between screening and diagnosis was 24.5 months (range 6-35 months). 11 of the 'false negative' patients suffered from generalised NB (stage 4) and 5 had localised NB at diagnosis. Unfavourable biological markers were observed in 7/12 patients. 5 patients have died, 2 achieved partial remission and 9 CR. 9 of the 11 patients with unfavourable biological markers diagnosed due to NB screening are currently in CR. It is very likely that, among the patients without unfavourable biological markers, we detected tumours which may have regressed spontaneously. These children may have undergone 'unnecessary,' but unavoidable, diagnostic procedures and therapy. To reduce the number of 'false negative' patients, a later screening could be helpful and should be evaluated.

Age Distribution↗

Plasma D-dimer measurement in patients with suspected DVT--a means of avoiding unnecessary venography.

OBJECTIVES: To assess the applicability of plasma D-dimer levels in the exclusion of a DVT. DESIGN: Consecutive cohort of patients. MATERIALS AND METHODS: Eighty consecutive patients presenting to the radiology department with a clinical diagnosis of DVT were included. Citrated blood samples were taken from all patients before radiological investigation, plasma isolated and frozen for subsequent testing. The patients then underwent venography (duplex scan was also used in some cases). Plasma samples were tested using the NycoCard D-Dimer. NycoCard Reader was used to estimate the D-dimer concentrations. RESULTS: A DVT was diagnosed in 29 cases (36.7%). Plasma D-dimer levels had a sensitivity of 96% (only one false negative), specificity of 40%, positive predictive value of 48%, and negative predictive value of 95% when compared to venography. CONCLUSIONS: A normal plasma D-dimer level could be used as an exclusion test for DVT avoiding complications of venography and saving time and money.

Adult↗

The nature and extent of jaw involvement in Gaucher disease: observations in a series of 28 patients.

A wide variety of osteoarticular pathoses plague the clinical course of many patients with Gaucher disease. Osseous lesions involving the jaws have been described, usually as isolated case reports. The purpose of this study was to ascertain the nature and extent of mandibulo-maxillofacial pathosis in 28 patients with documented Gaucher disease by means of panoramic radiography. Twenty-five of the 28 patients displayed radiographic evidence of jaw involvement. The most prevalent finding was gross widening of marrow spaces; frank radiolucencies, endosteal scalloping, cortical thinning, root resorption, and inferior displacement of the mandibular canal or effacement of its cortices were also seen. A previously unreported finding was delayed eruption of permanent teeth, which was seen in more than one half of the patients who were under 20 years of age. Osseous changes throughout the jaws may be more common than previously suspected and may alert the dentist to the presence of the disease.

Adolescent↗

A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects.

OBJECTIVE: To compare two low fat diets one rich in walnuts on parameters of lipid metabolism in a group of hyperlipidaemic subjects. DESIGN: A randomised cross over study. SETTING: Department of Human Nutrition, University of Otago, Dunedin, New Zealand SUBJECTS: Twenty one men with mean (s.d.) levels of total and LDL cholesterol of 6.58 (0.60) and 4.63 (0.58) respectively. INTERVENTIONS: For two periods of four weeks subjects were asked to consume two low fat diets (fat 30% total energy), one containing, on average, 78 g/d walnuts. Walnuts obtained through Lincoln University and the Walnut Growers Group (South Canterbury). RESULTS: Participants reported a higher total fat intake on the walnut diet (38% compared with 30% on the low fat diet P < 0.01) The most consistent change in fatty acid profile of triacylglycerol, phospholipid and cholesterol ester on the walnut diet was a significant (P < 0.01) increase in linoleic acid. Triacylglycerol linolenate also increased significantly (P < 0.01). Total and LDL cholesterol were lower on both experimental diets than at baseline, 0.25 mmol/l and 0.36 mmol/l respectively on the walnut diet and 0.13 mmol/l and 0.20 mmol/l respectively on the low fat diet. High density lipoprotein cholesterol was higher on both the walnut and low fat diets when compared to baseline (0.15 mmol/l and 0.12 mmol/l, respectively). When comparing the walnut and low fat diets only apo B was significantly lower (P < 0.05) on the walnut diet. CONCLUSIONS: Despite an unintended increase in the total fat intake on the walnut diet, fatty acid profile of the major lipid fractions showed changes which might be expected to reduce risk of cardiovascular disease. The reduction of apolipoprotein B suggests a reduction in lipoprotein mediated risk, the relatively low myristic acid content of both diets perhaps explaining the absence of more extensive differences in lipoprotein levels on the two diets.

Adult↗

Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels.

OBJECTIVE: The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. DESIGN: The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. SUBJECTS: Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. INTERVENTIONS: Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. RESULTS: Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. CONCLUSIONS: These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.

Adult↗

Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies.

OBJECTIVE: To compare the mortality rates of vegetarians and non-vegetarians. DESIGN: Collaborative analysis using original data from five prospective studies. Death rate ratios for vegetarians compared to non-vegetarians were calculated for ischaemic heart disease, cerebrovascular disease, cancers of the stomach, large bowel, lung, breast and prostate, and for all causes of death. All results were adjusted for age, sex and smoking. A random effects model was used to calculate pooled estimates of effect for all studies combined. SETTING: USA, UK and Germany. SUBJECTS: 76,172 men and women aged 16-89 years at recruitment. Vegetarians were those who did not eat any meat or fish (n = 27,808). Non-vegetarians were from a similar background to the vegetarians within each study. RESULTS: After a mean of 10.6 years of follow-up there were 8330 deaths before the age of 90 years, including 2264 deaths from ischaemic heart disease. In comparison with non-vegetarians, vegetarians had a 24% reduction in mortality from ischaemic heart disease (death rate ratio 0.76, 95% CI 0.62-0.94). The reduction in mortality among vegetarians varied significantly with age at death: rate ratios for vegetarians compared to non-vegetarians were 0.55 (95% CI 0.35-0.85), 0.69 (95% CI 0.53-0.90) and 0.92 (95% CI 0.73-1.16) for deaths from ischaemic heart disease at ages <65, 65-79 and 80-89 years, respectively. When the non-vegetarians were divided into regular meat eaters (who ate meat at least once a week) and semi-vegetarians (who ate fish only or ate meat less than once a week), the ischaemic heart disease death rate ratios compared to regular meat eaters were 0.78 (95% CI 0.68-0.89) in semi-vegetarians and 0.66 (95% CI 0.53-0.83) in vegetarians (test for trend P< 0.001). There were no significant differences between vegetarians and non-vegetarians in mortality from the other causes of death examined. CONCLUSION: Vegetarians have a lower risk of dying from ischaemic heart disease than non-vegetarians.

Adolescent↗

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design.

Essential hypertension is a major Public Health issue. Although the number of treated hypertensive patients has increased, only 25% of treated patients have their blood pressure levels under control. The benefit of treating hypertension has been proven, but cardiovascular morbidity and mortality rates remain high. The ideal antihypertensive drug should not only normalize blood pressure levels, but also reduce the associated cardiovascular morbidity and mortality rates. The role of angiotensin II in systemic hypertension and its complications has been recently redefined. The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated, especially the role of angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use Evaluation) is the only one comparing an angiotensin II antagonist (valsartan) with a third-generation calcium channel blocker (amlodipine). The main hypothesis of the VALUE trial is that, for an equivalent decrease in blood pressure, valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity. VALUE is a prospective, multinational, multicentre, double-blind, randomized, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration scheme. VALUE involves 14,400 patients in over 30 countries, who will be followed for 4 years or until 1450 patients experience a primary endpoint. The population to be included in VALUE consists of hypertensive men and women, aged 50 years or older, and at a relatively high risk of sustaining a cardiovascular event. The high risk profile is defined taking into account age, gender, and a list of cardiovascular risk factors and disease factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum creatinine. Disease factors include documented history of myocardial infarction, peripheral vascular disease, stroke or transient ischaemic attack, or the presence of left ventricular hypertrophy with strain on the ECG. A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients. The trial started on 10 September 1997.

Aged↗

Care tracker: a new approach to nursing care in ambulatory settings.

The shift from inpatient to ambulatory settings and the increasingly large and diverse numbers of ambulatory clients require reengineering and cost-effective approaches to managing ambulatory care. With data on 921 encounters in 12 ambulatory clinics, we developed CARE TRACKER, an instrument to describe nursing encounters by type, intervention, staff, time, and cost. Distinguishing nursing from medical interventions is an appreciable improvement over the traditional practice of bundling nursing as part of overhead costs. If managers can track the care delivered, they can better calculate staffing requirements, staff mix, inservice needs, and the costs of their existing and projected services.

Ambulatory Care↗

The description of a unique population with a very high prevalence of localized juvenile periodontitis.

The reported prevalence of localized juvenile periodontitis (LJP) amongst teenagers and young adults varies greatly. The etiology of LJP has been related to Actinobacillus actinomycetemcomitans (Aa), and it has also been suggested that there may be a transmission of Aa within families resulting in the familial distribution of the disease. This study describes the high prevalence of LJP in adolescents, 12-20 years of age, from a group of nuclear families living and functioning in a closed, closely knit community. The survey was carried out on a population of teenagers that had attended the same school and their siblings. All students attending that school and their siblings were examined. They were given a periodontal examination and a questionnaire relating to their demographic details and their personal oral hygiene habits. The periodontal examination was limited to the incisors and first molar teeth. Plaque index (PlI), gingival index (GI), the presence or absence of bleeding on probing (BOP), probing pocket depth (PPD) and recession were measured. All patients having at least two of the examined sites with probing pocket depth > or =5 mm or one site > or =6 mm were considered as possible sufferers from LJP and had a full mouth periapical radiographic survey carried out using a paralleling technique to confirm the diagnosis. At the sites with probing pocket depth > or =5 mm, a Shei ruler was used to measure the % of the root coronal to the alveolar bone. A cut off point of > or =20% was used as a measure of true bone loss confirming the clinical diagnosis of LJP. 86 individuals from 30 families comprised the population of interest. There were 44 males and 42 females with a mean age of 14.7+/-2.3. Of the 86 individuals examined, 33 individuals from 15 families were diagnosed as having LJP (38.4%). None of the individuals examined showed any evidence of the generalized form of juvenile periodontitis. The mean age of the LJP patients was 15+/-2.3 yrs. with a 1:1.75 male to female ratio. Except for 2 pairs of families with genetic ties, no familial connections could be traced between the different nuclear families affected by LJP despite repeated and intensive questioning. There were no significant differences in the PlI and the GI between the groups while the LJP group had significantly higher BOP, PPD and PAL than the non-LJP group. These finding strongly suggest an environmental influence in the etiology of the disease.

Adolescent↗

Dental caries prevalence and treatment need in Chiriqui Province, Panama.

A pathfinder pilot survey was conducted in rural Chiriqui Province, Panama, using standard WHO methodology, in order to estimate dental caries prevalence and treatment need. Examinations for caries and treatment need were performed by six trained, experienced examiners. From a convenience sample of 2,597 subjects, a stratified cluster sample was constructed using index ages 12 and 15 years and age groups 35-44 and 65-74 years. The results showed a mean Decayed, Missing and Filled Teeth index (DMFT) of 4.08 for 12 year olds, 6.40 for 15 year olds, 13.20 for the 35-44 age group, and 18.88 for the 65-74 age group (P < 0.001). No statistically significant differences by gender were found. These findings rank rural Panama with Mexico and Haiti when compared to the results of other Central American community studies. The percentage of caries free 12 year olds was 6.8 per cent. Of the total sample, 74.7 per cent of individuals would require one or multiple surface restorations and 47.9 per cent would require at least one extraction. Restorative need was greatest in the 15 year olds. The severity of dental caries in this sample was moderately severe and the treatment need extraordinarily high.

Adolescent↗

Periodontal health and the role of the dental hygienist.

This study was conducted to evaluate the influence of hygienist services in an Israeli kibbutz (communal settlement) upon periodontal disease levels and periodontal treatment needs. The Periodontal Index (PI) and the Community Periodontal Index of Treatment Needs (CPITN) were utilised to examine 412 subjects of which 202 adult participants resided in a kibbutz employing a hygienist and 210 participants resided in one of three kibbutzim lacking a history of hygienist employment. Examinations were conducted by two calibrated examiners. Results revealed a gradual increase in the CPITN and PI scores with age and generally statistically significantly higher periodontal pathology and treatment need scores among the population not employing a dental hygienist (especially within the 35-44 age grouping). The results of this study suggest that employment of a dental hygienist may be an effective approach to lower the burden of periodontal disease within a community.

Adult↗

Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor.

Macromolecular contrast medium-enhanced magnetic resonance imaging (MRI) and tumor-volume measurements were applied to monitor the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody on microvascular characteristics and tumor growth of MDA-MB-435 human breast cancer cells implanted in nude rats. Administration of anti-VEGF antibody (three 1 mg doses at 3-day intervals) induced significant reductions in tumor growth rates (p < 0.05) and in MRI-assayed microvascular permeabilities (p < 0.05). Results of the study were consistent with previous observations that new microvessels formed in response to angiogenesis are hyperpermeable, and with the hypothesis that hyperpermeability is a mechanistic element in angiogenesis. Variations in tumor-vessel hyperpermeability can be measured by contrast-enhanced MRI, which may prove useful for assessing antiangiogenesis therapy.

Adenocarcinoma↗