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At least 613 records · Page 34Linked to original sources
PubMed1999

Effect of moist vs. dry bonding to normal vs. caries-affected dentin with Scotchbond Multi-Purpose Plus.

Recent research in dentin bonding demonstrated the superiority of moist bonding over dry bonding on normal dentin, but it is unclear if this technique is also superior in bonding to caries-affected dentin. The purpose of this study was to evaluate the SEM appearance and bond strength of Scotchbond Multi-Purpose Plus (SMPP) to normal vs. caries-affected dentin bonded under moist vs. dry conditions, with and without polyalkenoic acid in the primer. Extracted carious human third molars were ground down by means of 600-grit SiC paper until the carious dentin no longer stained with caries detector solution. The flat surfaces were then primed, bonded, and built up with resin composite. After soaking in water for 1 day, the teeth were serially sectioned vertically into 5 or 6 slabs 0.7 mm thick. The bonded caries-affected areas were isolated by means of an ultrafine diamond bur to create an hourglass configuration with a cross-sectional area of 0.9 mm2. Bonded normal dentin was isolated the same way. Each specimen was attached to a Bencor device and tested in tension to failure. SMPP bonds to dry, normal dentin were only half as strong (21+/-10 MPa, x +/- SD) as those made to moist, normal dentin (42+/-9 MPa, p<0.01). There was no significant difference between bonds made to normal vs. caries-affected dentin by means of the moist technique (42+/-9 vs. 48+/-4 MPa, respectively). Removal of the polyalkenoic acid from the primer lowered (p<0.05) the bond strength of SMPP to caries-affected dentin (38+/-8 MPa). The benefits of moist bonding extend to caries-affected dentin. The polyalkenoic acid in the SMPP primer contributes to the high bond strength that can be achieved to caries-affected dentin.

Analysis of Variance↗
PubMed2001

Affective illness in children and adolescents: patterns of presentation in relation to pubertal maturation and family history.

Affective illness is now recognized as a common problem in all age groups, and the various patterns have been well documented in adults. The objective of this study was to evaluate the patterns of affective illness in children and determine changes with increasing age and family history. One hundred children/adolescents with affective illness (72 boys and 28 girls; age range 2-20 years; mean age 10 years), who were consecutively referred to the Pediatric Behavioral Neurology Program, Children's Medical Center at Dallas, were evaluated for the pattern and course of affective illness symptoms, family history, and pubertal stage. Seven patterns of affective illness were identified. In the 65 prepubertal children (Tanner stage 1), disorders with hypomanic/manic symptomatology were most common (47/65, 72%): mania (2/65, 3%), hypomania (8/65, 12%), cyclothymia (11/65, 17%), juvenile rapid-cycling bipolar disorder/ultradian cycling bipolar disorder (8/65, 12%), and dysthymia with bipolar features (18/65, 28%). In contrast, the 26 fully pubertal adolescents (Tanner stages 3-5) had a predominance of patterns with only depressive symptomatology (16/26, 61%): dysthymia (4/26, 15%) and depression (12/26, 46%), along with juvenile rapid-cycling bipolar disorder/ultradian cycling bipolar disorder (6/26, 23%). Affective illness, alcoholism, and drug abuse were prominent in the family histories, regardless of the child's pattern of symptoms. Family histories of character disorder and Briquet's syndrome were also common, but thought disorder, suicide, and homicide were infrequent. This study supports the clinical observation that the presentation of affective illness changes with age: manic features predominate in younger children, whereas depressive symptomatology is more evident with pubertal maturation.

Adolescent↗
PubMed2001

Contribution of education to health and life satisfaction in older adults mediated by negative affect.

OBJECTIVES: The authors developed a model of relationships between two enduring attributes (educational attainment and negative affect) and two indicators of successful aging (health and life satisfaction). METHODS: A probability sample of 1,177 participants (age 55 and older) were interviewed four times at 6-month intervals. Structural equation models were developed based on the authors' hypothetical model proposing a mediating effect of negative affect between health and successful aging. RESULTS: As predicted, education and negative affect both were directly related to health and life satisfaction. Also, as predicted, negative affect mediated the relationship between education and successful aging indicators. DISCUSSION: Education appears to confer a lifelong advantage for healthy aging. Part of this advantage is accounted for by the relationship between education and trait negative affect. Higher educational attainment is related to lower levels of trait negative affect; lower negative affect results in better health and life satisfaction.

Aged↗
PubMed2003

Clinical and surgical data of affected members of a classic CFEOM I family.

BACKGROUND: Congenital fibiosis of the extraocular muscles (CFEOMI) refers to a group of congenital eye movement disorders that are characterized by non-progressive restrictive ophthalmoplegia. We present clinical and surgical data on affected members of a classic CFEOMI family. METHODS: Ten members of a fifteen-member, three-generation Italian family affected by classic CFEOM participated in this study. Each affected family member underwent ophthalmologic (corrected visual acuity, pupillary function, anterior segment and fundus examination), orthoptic (cover test, cover-uncover test, prism alternate cover test), and preoperative examinations. Eight of the ten affected members had surgery and underwent postoperative examinations. Surgical procedures are listed. RESULTS: All affected members were born with varying degrees of bilateral ptosis and ophthalmoplegia with both eyes fixed in a hypotropic position (classic CFEOM). The affected members clinical data prior to surgery, surgery procedures and postoperative outcomes are presented. On 14 operated eyes to correct ptosis there was an improvement in 12 eyes. In addition, the head position improved in all patients. CONCLUSIONS: Surgery is effective at improving ptosis in the majority of patients with classic CFEOM. However, the surgical approach should be individualized to each patient, as inherited CFEOM exhibits variable expressivity and the clinical features may differ markedly between affected individuals, even within the same family.

Adolescent↗
PubMed2004

Catastrophizing and pain sensitivity among chronic pain patients: moderating effects of sensory and affect focus.

BACKGROUND: Pain catastrophizing is a particularly harmful cognitive factor among patients with chronic pain, but little is known of mechanisms linking this factor to pain and disability. PURPOSE: The study examined whether attentional focus on sensory versus affective information about pain constitutes a pathway by which catastrophizing affects responses to painful stimuli. METHODS: Participants were 82 chronic pain patients assigned randomly to sensory focus, affect focus, or control conditions. They underwent cold pressors first prior to and then following an information focus manipulation, and they completed the Pain Catastrophizing Scale (PCS). RESULTS: Regressions produced significant Condition x PCS interaction effects on threshold and tolerance change from first to second cold pressor, such that PCS scores were significantly and negatively related to these changes in both sensory and affect focus conditions, but not in the control condition. Only a main effect for PCS scores emerged for self-reported pain changes. Solving regression equations for hypothetical PCS values (+- 1 SD from the mean) revealed that (a) high catastrophizers decreased threshold and tolerance in the affect focus condition and showed no appreciable changes in sensory focus and (b) low catastrophziers showed increases in threshold and tolerance in sensory focus, but no appreciable changes in affect focus. Further, the degree to which patients focused on emotions during pain partly mediated effects of PCS scores on threshold and tolerance changes. CONCLUSION: Catastrophizing about pain may affect pain severity and distress of chronic pain patients through a bias toward processing the most disturbing elements of a painful stimulus.

Adult↗
PubMed2001

Cognition, negative affectivity and substance use in adolescent boys with and without a family history of a substance use disorder.

OBJECTIVE: The purpose of this study was to test a model of substance use in adolescent males. The model is based on the premise that cognitive distortions and poor constructive thinking represent weaknesses in the ability to adaptively cope with everyday problems. It is postulated that failures in adaptive coping result in increased negative affectivity (e.g., frustration, anger, and anxiety), which fosters substance use as a means of alleviating unpleasant feelings. METHOD: Subjects (N = 276) were 15- to 17-year-old males with a positive (FHP; n = 118) or a negative (FHN; n = 158) family history of a substance use disorder (SUD). Subjects completed self-report measures of constructive thinking, cognitive distortions, negative affectivity, substance use frequency and substance use problems. RESULTS: Negative affectivity mediated the relations between constructive thinking and both substance use variables, in separate analyses, for the FNP and FHN groups. Negative affectivity also moderated the relation between constructive thinking and substance use frequency, such that constructive thinking was negatively related to substance use frequency but only for individuals high in negative affectivity. CONCLUSIONS: Poor constructive thinking skills are related to increased substance use in adolescent males, in part through an association with greater negative affectivity. SUD treatment and prevention efforts may benefit from strategies aimed at improving constructive thinking abilities and reducing negative affectivity.

Adolescent↗
PubMed2001

Enhanced activity of osteoblast differentiation factor (PEBP2alphaA2/CBFa1) in affected sutural osteoblasts from patients with nonsyndromic craniosynostosis.

OBJECTIVE: Nonsyndromic craniosynostosis is characterized by premature closure of one or more cranial sutures in infants. The purpose of this investigation was to evaluate cellular and molecular events that lead to pathogenesis of nonsyndromic craniosynostosis. DESIGN: This study utilized discarded samples of normal and affected cranial sutures from 12 patients (7 boys, 5 girls) with nonsyndromic craniosynostosis. RESULTS: Histological evaluation of affected sutures revealed complete osseous obliteration instead of a zone of connective tissue and osteogenic cells as seen in normal sutures. Although proliferation of normal and affected osteoblasts did not vary substantially, elevated osteocalcin production and increased in vitro bone nodule formation indicated that the differentiation and the bone-forming potential of affected osteoblasts was significantly higher than that of normal cells. We therefore investigated the levels and activity of Cbfa1, a transcription factor that plays an integral role in osteoblast differentiation. Northern blot analysis of messenger RNA from both normal and affected sutural osteoblasts revealed a twofold increase in the expression of Cbfa1 in affected cells. This increase in the level of Cbfa1 transcript correlated with an increase in its transcriptional activity on the osteocalcin gene promoter, as assessed using gene transfer methods. CONCLUSION: Our results indicated that osteoblasts from synostosed sutures exhibit an increased potential for differentiation and bone formation. The increased level and activity of Cbfa1 could play a vital role in the aberrant function of these affected osteoblasts and may explain their altered behavior compared to the normal cells.

Alkaline Phosphatase↗
PubMed1999

Acute aerobic exercise and affect: current status, problems and prospects regarding dose-response.

One of the assumptions underlying recent physical activity recommendations is that lower doses of activity (i.e. intensity and duration) are more enjoyable for the average person, thus leading to higher involvement and adherence rates. However, the veracity of this hypothesis can be questioned, since little is actually known regarding the association between activity doses and affective responses. The few preliminary attempts at the conceptual delineation of the dose-response relationship, all centred around an 'inverted-U' notion, are reviewed and criticised as lacking empirical foundation. Available meta-analyses, as well as the empirical literature on the role of exercise intensity and duration, are examined. Increased intensity appears to be associated with reduced positivity of affect during and immediately following an exercise bout. Intensity effects appear to be attenuated during recovery. Fitness and training status appear to become significant mediators of the exercise-affect relationship only at high intensities. With intensity being kept constant, different exercise bout durations have not been shown to have a differential impact on pre- to post-exercise affective changes. Recommendations for future research include: (i) a shift from categorical to dimensional conceptualisations and operationalisations of affect; (ii) the examination of psychological theories on the association between activation and affect (e.g. extraversion-introversion, sensation seeking, type A behaviour pattern and related self-evaluative tendencies, reversal theory, optimal stimulation theory, multidimensional activation theory and self-efficacy); (iii) the systematic and theory-based examination of in-task and post-exercise affective responses; (iv) the incorporation of the parameter of fitness and/or activity status in research designs; and (v) the re-evaluation of methods for selecting exercise intensity levels.

Emotions↗
PubMed1996

Internal resourcefulness, task demands, coping, and dysphoric affect among caregivers of the frail elderly.

Internal resourcefulness is defined as the repertoire of skills and behaviors individuals employ to deal with negative affective states. The relationships among caregivers' internal resourcefulness, demands of the caregiving situation, and caregivers' self-reported coping behaviors were examined relative to changes in dysphoric affect over time. Primary caregivers of the frail elderly (N = 143) completed the following measures, at two time periods, approximately four months apart: Rosenbaum's Self Control Schedule, assessing internal resourcefulness; Poulshock and Deimling's list of tasks carried out for the frail elder; Zarit et al.'s Memory and Behavior Problem Check List assessing caregiver burden; Moos et al.'s Indices of Coping; and Beck et al.'s Depression Inventory as a means of assessing dysphoric affect. Although caregivers' reactions to the care recipients' annoying behaviors predicted negative affect at time 1 and avoidant coping behavior predicted negative affect at times 1 and 2, internal resourcefulness was the only significant predictor of changes in dysphoric affect over time. Decreased dysphoric affect among caregivers was linked to possession of a larger initial set of internal resources to deal with negative internal experiences.

Adaptation, Psychological↗
PubMed1990

Personality correlates and cyclicity in positive and negative affect.

The current study investigated over time variation of Positive and Negative Affect and the relation between mood level and personality characteristics. 68 male undergraduate volunteers completed the Multidimensional Personality Questionnaire and then recorded mood ratings daily over a 29-day period. Spectra time series analyses showed a distinct and significant seven-day cycle for Positive Affect and Negative Affect, with the peak in Negative Affect occurring approximately three days after that of Positive Affect. Positive Affect was significantly correlated with scores on Well-being, Social Closeness, Social Potency, and Absorption scales of the questionnaire, while Negative Affect was significantly related to scores on the Stress-Reaction, Alienation, and Aggression scales.

Adult↗
PubMed1995

Demography of DSM-III borderline personality disorder (PD): a comparison with Axis II PDs, affective illness and schizophrenia convergent and discriminant validation.

Demographic characteristics of borderline personality disorder (PD) defined according to DSM-III criteria were compared with those found for schizophrenia, affective illness, and other Axis II PDs. Borderline PD, unlike affective illness and most other Axis II PDs, usually occurs before the age of 30. By contrast to antisocial PD and schizophrenia, borderline PD usually occurs after the age of 25. For borderline PD (N = 280) average age was significantly more homogeneous compared with affective illness (N = 157) and Axis II PDs (N = 71) across 9 studies. By contrast, variability for 63 predominantly male schizophrenics in 3 studies was significantly less, reflecting the younger age at admission compared with borderline PD (N = 84). According to predictions based upon an age-of-risk hypothesis (Dahl, 1985) for 106 borderline PD patients, a significantly lower percentage were > or = 40 years of age than diagnostic controls (N = 181) predominantly with DSM-III affective illness. Borderline PD is predominantly diagnosed in females either single or who have been divorced compared with Axis II PDs and affective illness, to a lesser extent. Unlike antisocial PD, as well as schizophrenia, the preponderance of male and single/divorced patients usually occur significantly less than for borderline PD. Borderline PD usually occur significantly less than Axis II PDs, affective illness and schizophrenia and ethnic minorities, particularly Afro-Americans. These differences in ethnic/racial distribution are explained in terms of two hypotheses. From the perspective of demographic variables, borderline PD closely converges with neither (a) schizophrenia, (b) antisocial PC, (c) other Axis II PDs, nor (d) affective illness. Evidence for discriminant and convergent validation of these data is provided by (a) cluster analyses and intersample pairwise contrasts, as well as comparisons with (b) clinical samples selected on the basis of DSM-III-R and criteria of the (c) Diagnostic Interview for Borderline Patients, (d) a longitudinal case registry study conducted in Denmark, and (e) prospective surveys conducted among (i) North Carolina community residents and (ii) first degree (nonpatients) relatives of psychiatric patients in Iowa.

Adult↗
PubMed1994

Attitudes towards co-workers affected by occupational hearing loss. II: Focus groups interviews.

This study was undertaken as a complement to a questionnaire inquiry on attitudes towards co-workers affected by occupational hearing loss (OHL). Four groups of 7 to 11 volunteer participants were recruited among respondents to the questionnaire inquiry. They were interviewed using a focus group technique. Scenarios were prepared to serve as a basis for asking questions aimed at three major objectives: (a) to characterize workers' perception of a co-worker who has an impairment involving no visible signs; (b) to identify the conditions that trigger social withdrawal and isolation behaviour among people affected by OHL, and the conditions that might make the latter decide to seek help; and (c) to define the type and methods of help that might minimize social withdrawal and isolation among hearing impaired workers. The interviews were taped and transcribed verbatim for content analysis using a phenomenological-interpretative framework. The findings can be summarized by the following description of the perception of the problem of OHL among industrial workers. The strong fear of being stigmatized leads those affected by OHL to conceal its manifestations and consequences in their everyday life. As a result, significant others, co-workers, employers and the general population are not aware of such manifestations. Within the workplace, the problem of OHL is generally seen as being inconsequential. In daily interactions among co-workers, its effects are ignored. Within the family, hearing difficulties are often not interpreted as such but they nevertheless affect the workers' significant others. People do not know how to facilitate communication with a person affected by OHL. A large scale multi-target awareness programme is proposed to demarginalize workers affected by OHL. Implications of the findings are drawn in such areas as characterization of attitudes toward workers with hearing impairment, rehabilitation for those affected by OHL, and prevention of OHL.

Adult↗
PubMed2004

Detection of quantitative trait loci affecting milk production, health, and reproductive traits in Holstein cattle.

We report putative quantitative trait loci affecting female fertility and milk production traits using the merged data from two research groups that conducted independent genome scans in Dairy Bull DNA Repository grandsire families to identify quantitative trait loci (QTL) affecting economically important traits. Six families used by both groups had been genotyped for 367 microsatellite markers covering 2713.5 cM of the cattle genome (90%), with an average spacing of 7.4 cM. Phenotypic traits included PTA for pregnancy rate and daughter deviations for milk, protein and fat yields, protein and fat percentages, somatic cell score, and productive life. Analysis of the merged dataset identified putative quantitative trait loci that were not detected in the separate studies, and the pregnancy rate PTA estimates that recently became available allowed detection of pregnancy rate QTL for the first time. Sixty-one putative significant marker effects were identified within families, and 13 were identified across families. Highly significant effects were found on chromosome 3 affecting fat percentage and protein yield, on chromosome 6 affecting protein and fat percentages, on chromosome 14 affecting fat percentage, on chromosome 18 affecting pregnancy rate, and on chromosome 20 affecting protein percentage. Within-family analysis detected putative QTL associated with pregnancy rate on six chromosomes, with the effect on chromosome 18 being the most significant statistically. These findings may help identify the most useful markers available for QTL detection and, eventually, for marker-assisted selection for improvement of these economically important traits.

Animals↗
PubMed1999

[Affective, somatoform and anxiety disorders in Germany--initial results of an additional federal survey of "psychiatric disorders"].

BACKGROUND AND AIMS: The paper informs about methods and field survey procedures used in the German National Health Interview and Examination Survey--Mental Health Supplement (GHS-MHS)--and provides 12-month prevalence estimates of affective, anxiety and somatoform disorders in the general population. Such data have previously not been available for Germany on a nationwide level. METHODS: Findings are based on a two-stage design: In the first stage all the 7124 participants of the German National Health Interview and Examination Survey (core survey) completed the Composite International Diagnostic-Screener (CIDS) for mental disorders. In the second stage 4181 probands (all screen-positive and a random sample of 50% of the screen-negative subjects) were interviewed with the full Composite International Diagnostic Interview (DIA-X-M-CIDI) by clinical interviewers. The overall response rate was 87.6%. RESULTS: Affective (12-months prevalence estimate: 6.3%), anxiety (9%) and somatoform disorders (7.5%) are widespread in all age groups (18 to 65 years) of the German population; women are significantly more often affected than men. The prevalence rates of somatoform and affective disorders were found to be significantly lower in the former East German Länder as compared to the former West, whereas no such difference was found with regard to anxiety disorders. All disorders resulted in considerable reduction of work productivity during the past month; affective disorders reported on average 1.3 days/month total impairment and 7.2 days/month partial impairment, indicated significantly higher reduction in work productivity than anxiety and somatoform disorders. CONCLUSIONS: Affective, somatoform and anxiety disorders are highly prevalent mental disorders (total: 17.3%) in the German population. The result of a lower morbidity of affective and somatoform disorders in former East Germany was unexpected and requires further clarification. The findings on impairment of work productivity emphasize the economic impact of psychiatric disorders on society.

Adolescent↗
PubMed2000

Non-thermic skin affections.

The Centre for Burns can help by its means (material, technical and personal) in the treatment of burns with extensive and deep losses of the skin cover and other tissue structures and in some affections with a different etiology (non-thermic affections). Indicated for admission are, in particular, extensive exfoliative affections--Stevens-Johnson's syndrome (SJS), Lyell's syndrome--toxic epidermal necrolysis (TEN) and staphylococcal scalded skin syndrome (SSSS), deep skin and tissue affections associated with fulminant purpura (PF), possibly other affections (epidermolysis bullosa, posttraumatic avulsions etc.). The similarity with burn injuries with loss of the skin cover grade II is typical, in particular in exfoliative affections with a need for adequate fluid replacement in the acute stage and aseptic surgical treatment of the affected area from the onset of the disease. In conditions leading to full thickness skin loss, in addition to general treatment rapid plastic surgical interventions dominate.

Child↗
PubMed2002

In vitro pharmacological characterizations of the anti-angiogenic and anti-tumor cell migration properties mediated by microtubule-affecting drugs, with special emphasis on the organization of the actin cytoskeleton.

The aim of the present work is to investigate whether microtubule-affecting drugs including vincristine, vinblastine, vindesine and vinorelbine are able to produce an anti-angiogenic effect at non-cytotoxic doses in the same way of taxol. The cytotoxic effects were determined by means of the colorimetric MTT assay, and the anti-angiogenic effects on HUVEC cells growing on Matrigel and forming capillary networks. Sixteen additional drugs (camptothecin, SN38, topothecan, adriamycin, daunomycin, etoposide, bleomycin, melphalan, mitomycin C, TNP-470, cisplatin, carboplatin, 5-fluorouracil, methotrexate, suramin and batimastat) were used as control in order to test the specificity of the microtubule-affecting drug effects. We also investigated by means of videomicroscopy whether microtubule-affecting drugs could produce anti-migratory effects at non-cytotoxic doses on tumor cells. Finally, we used computer-assisted fluorescence microscopy to characterize the influence of microtubule-affecting drugs on the polymerization/depolymerization dynamics of the actin cytoskeleton in tumor cells. Our results show that taxol, vincristine and vindesine behave similarly in their ability to reduce the capillary network formation by HUVEC cells cultured on Matrigel. These anti-angiogenic effects appear at non-cytotoxic concentrations. In contrast, vinblastine and vinorelbine produce apparent anti-angiogenic effects by direct cytotoxicity. Microtubule-affecting agents are also able to significantly reduce the level of migration of tumor cells at non-cytotoxic concentrations, some of these effects may occur via modifications to the actin cytoskeleton organization. Several types of microtubule-affecting agents could be used as anti-angiogenic agents by administering them at non-cytotoxic concentrations, and some microtubule-affecting agents abandoned in pharmacological assays could turn out to be potent anti-migratory drugs acting on tumor cells, though without being too cytotoxic.

Actins↗
PubMedDate not supplied

Caries-risk factors for Hispanic children affected by early childhood caries.

PURPOSE: The purpose of this study was to examine factors associated with early childhood caries (ECC) and to develop a profile of risk factors for Hispanic families affected by this condition. METHODS: Sixty Hispanic families with at least 1 child affected by ECC and 60 Hispanic families without any affected children were included in the study. Data was collected using a parent-completed questionnaire which gathered information about family demographics, dental care and hygiene practices, and feeding practices of the children. RESULTS: Parents in families without ECC were significantly more likely to have visited the dentist recently and the children were less likely to sleep while feeding compared to families with an ECC-affected child. Within families affected by ECC, siblings with ECC were significantly more likely to use the bottle and to sleep while feeding compared with their siblings without ECC. Fifty-five percent of the subject families had more than 1 child affected by ECC. However, odds ratios did not indicate an increased risk of ECC among younger siblings in the presence of affected older siblings. CONCLUSIONS: The current study, while supporting the long-held belief that feeding practices influence the susceptibility and course of ECC, demonstrates the role of other nonfeeding practices.

Boston↗
PubMed1992

Affected paroxysmal nocturnal hemoglobinuria T lymphocytes harbor a common defect in assembly of N-acetyl-D-glucosamine inositol phospholipid corresponding to that in class A Thy-1- murine lymphoma mutants.

Deficient expression of glycoinositol phospholipid (GPI) anchored proteins in affected paroxysmal nocturnal hemoglobinuria (PNH) cells has been traced to a defect in GPI anchor assembly. In a previous study (Schubert, J., Schmidt, R. E., and Medof, M. E. (1993) J. Biol. Chem., in press) we characterized the biosynthesis of putative Man-containing GPI anchor precursors in normal peripheral blood lymphocytes and investigated assembly of these intracellular GPI intermediates in CD48- affected and CD48+ unaffected T and natural killer cell lines of PNH patients. We found that affected T cells from five patients exhibited a uniform defect in which dolichol-phosphoryl-Man was synthesized but no GPI mannolipids were expressed. In this study, membranes of patients' affected T cells were labeled with UDP-[3H]GlcNAc to evaluate earlier steps in GPI synthesis, and intact cells were fused to Thy-1- murine lymphoma mutants harboring different defects in early GPI assembly to test for the presence of corresponding or complementary lesions. In all cases, affected cell membranes failed to assemble GlcNAc-inositol phospholipid, the initial precursor of GPI anchor structures, and the intact cells failed to complement class A mutants while complementing other classes. Affected polymorphonuclear leukocytes from three additional patients of different origin were then labeled with [3H]Man and the labeling patterns found to correspond to those obtained with the T lymphocytes. Taken together the data indicate that the genetic lesion in PNH cells resides in a DNA element which: 1) encodes a product required for the synthesis of GlcNAc-inositol phospholipid, 2) corresponds to that altered in class A Thy-1- murine lymphoma mutants, and 3) is commonly affected in different patients.

Acetylglucosamine↗