PubMed Health⌕ Search

Biomedical subjects

H M Lederman

Publications and source records attributed to H M Lederman.

At least 37 records · Page 2Linked to original sources
PubMed1999

HIV-1-specific cytolytic T-lymphocyte activity correlates with lower viral load, higher CD4 count, and CD8+CD38-DR- phenotype: comparison of statistical methods for measurement.

OBJECTIVES: The objective of this study was to use novel statistical methods to determine the correlation between HIV-1-specific cytolytic T-lymphocyte (CTL) activity and HIV-1 plasma viral load, in a blinded study of HIV-infected patients at various stages of clinical disease. METHODS: Peripheral blood mononuclear cells (PBMC) were collected and stored at enrollment and 2 weeks later, from 15 HIV-infected individuals who were receiving stable antiretroviral therapy for the previous 6 weeks and during the study period. HIV-1-specific CTL activity was measured using an antigen-specific PBMC in vitro stimulation method. Measurements of plasma viral load, as well as CD4+ and CD8+ T lymphocytes expressing T-cell activation markers (DR and CD38) were also performed at each time point. CTL activity was quantified using three separate statistical methods: area under the net HIV-specific lysis curve (AUC), lytic units (LU20), and linear regression (LR) of net HIV-specific lysis. RESULTS: HIV-1 nef-, pol- and gag-specific CTL activity (AUC method) was significantly higher in subjects with a plasma viral load < or = 30,000 RNA copies/ml, than in those with viral load >30,000 RNA copies/ml. When plasma viral load was analyzed as a continuous variable, there was a strong correlation between higher CTL activity and lower viral load for nef (r2 = .77; p < .001), pol (r2 = .63; p < .001) and gag (r2 = 0.75; p < .001) targets by the AUC, but not for the LU20 analysis. Using the LR analysis, which is less dependent on in vitro PBMC growth than the AUC analysis, an independent association was demonstrated between nef- and gag-specific CTL activity and lower viral load. Measurement of CTL activity was also significantly correlated with a higher percentage of circulating CD8+DR-CD38- T lymphocytes. CONCLUSIONS: In this blinded study using an in vitro stimulation of frozen PBMC, higher HIV-1 nef-, pol-, and gag-specific CTL activity correlated with lower plasma viral load, particularly in patients with a CD4 count <500 cells/mm3. Two new statistical methods for estimating CTL activity, AUC and LR analyses, were superior to the standard lytic unit (LU20) method for demonstrating this correlation. These data also demonstrated that higher circulating CD8+ T lymphocytes with a DR-CD38-phenotype, correlate with a lower plasma viral and load and higher HIV-specific CTL activity. This suggests that lymphocytes with this double-negative phenotype may include circulating HIV-specific CD8+ CTL.

ADP-ribosyl Cyclase↗
PubMed1999

Ocular motor abnormalities in ataxia telangiectasia.

Although abnormal eye movements are a prominent feature of ataxia telangiectasia, the characteristics of the oculomotor dysfunction in the disease have been reported only in small groups of patients. We have examined eye movements clinically in 56 patients with ataxia telangiectasia, and obtained electrooculographic recordings of eye movements in 33 subjects. Deficits were observed in the eye movement systems that stabilize images on the retina, including pursuit, gaze holding, convergence, vestibular and optokinetic slow phases, and cancellation of vestibular slow phases. Abnormalities in the systems that maintain fixation and shift gaze were also prominent, including abnormal reflexive and voluntary saccades (characterized by prolonged latency, hypometric amplitude, and the use of head movements to initiate gaze shifts), impaired fixation, and a reduction in vestibular and optokinetic quick phases. The abnormalities in image stabilization most likely result from dysfunction in the cerebellar flocculus and paraflocculus. The basis of the saccadic and fixation disturbance is less certain but may be the result of abnormal supranuclear control of the superior colliculus resulting from dysfunction in the cerebellar vermis or the basal ganglia.

Adolescent↗
PubMed1999

Blomstrand chondrodysplasia: a lethal sclerosing skeletal dysplasia. Case report and review.

We report a female stillborn with typical clinical, radiological, and anatomopathological features of Blomstrand chondrodysplasia. The main findings in this lethal osteochondrodysplasia are osteosclerosis and advanced skeletal maturation. Autosomal recessive inheritance has been proposed because of parental consanguinity of affected siblings in all reported cases, including this one. Histopathological study of the bones confirmed the advanced skeletal maturation radiological features. We also review this rare lethal osteochondrodysplasia.

Adult↗
PubMed1999

Oligo-/monoclonal gammopathy and hypergammaglobulinemia in ataxia-telangiectasia. A study of 90 patients.

We investigated the presence of hypergammaglobulinemia and oligo-/monoclonal gammopathy in 90 patients (from 80 families) with ataxia-telangiectasia ranging in age from 2 to 29 years. Of the 90 patients, 38.8% displayed hypergammaglobulinemia. An isolated increase in IgM was the most common finding (23.3%) followed by a simultaneous increase in IgM and IgG (8.8%), an isolated increase in IgA (3.3%), an elevated level of IgG (2.2%) and a concomitant increase in IgM and IgA (1.1%), respectively. Seven of the patients (8.1%) had oligo-/monoclonal gammopathy. The gammopathies included all major immunoglobulin isotypes. Chemotherapeutic intervention in 2 cases precipitated the emergence of new clones within a matter of weeks. Further investigation of oligo-/monoclonal gammopathies in these patients may lead to a clearer understanding of the clinical course and provide further insight into the underlying mechanisms of B-cell abnormalities in ataxia-telangiectasia.

Adolescent↗
PubMed1999

Supply, use, and abuse of intravenous immunoglobulin.

Intravenous immunoglobulin is used as a replacement therapy in primary immunodeficiency diseases as well as an immunomodulatory agent in a variety of autoimmune and inflammatory disorders. The mechanisms of intravenous immunoglobulin action are complex and, for some disorders, not well understood. This paper reviews the recent literature and discusses approved, new, and controversial indications for intravenous immunoglobulin therapy, with special emphasis on its mechanism of action.

Autoimmune Diseases↗
PubMed1999

Magnetic resonance findings in amyotrophic lateral sclerosis using a spin echo magnetization transfer sequence. Preliminary report.

We present the magnetic resonance (MR) findings of five patients with amyotrophic lateral sclerosis (ALS) using a spin-echo sequence with an additional magnetization transfer (MT) pulse on T1-weighted images (T1 SE/MT). These findings were absent in the control group and consisted of hyperintensity of the corticospinal tract. Moreover we discuss the principles and the use of this fast but simple MR technique in the diagnosis of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Thymoma and cellular immune deficiency in an adolescent.

Thymoma has been associated with both humoral immunodeficiency and cellular immunodeficiency, but the latter association has never been described in the pediatric age group. We report a 15-year-old female with thymoma, recalcitrant oropharyngeal candidiasis, recurrent generalized cutaneous herpes simplex virus type 2 infection, recurrent pneumonia and myasthenia gravis. Pathology of the thymic lesion showed a 10x5x6 cm extensively hyalinized mass with residual regions of spindle cell predominant and lymphocyte-rich thymoma. There was no evidence of humoral immunodeficiency but there was clinical and laboratory evidence of cellular immunodeficiency with cutaneous anergy and absence of T cell proliferation to Candida antigen. Six weeks after the thymoma was resected, she was no longer anergic and Candida proliferation was normal, although she continued to experience infections. This is the first reported pediatric patient with an association of cellular immunodeficiency with thymoma.

Adolescent↗
PubMed1998

Adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency in common variable immunodeficiency.

The clinical presentations of adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency are widely variable and include clinical and immunologic findings compatible with common variable immunodeficiency. The screening of 44 patients with common variable immunodeficiency failed to identify any individuals with deficiencies of these enzymes.

Adenosine Deaminase↗
PubMed1998

Measurement of induced cytokines in AIDS clinical trials using whole blood: a preliminary report. ACTG Inducible Cytokines Focus Group. AIDS Clinical Trials Group.

Measures of immune function have become increasingly important as endpoints in AIDS clinical trials, with respect to both modulation and reconstitution of immunity by experimental therapies. Measurement of immune function in this setting requires the development of robust analytic approaches suitable for the clinical laboratory. Experiments were performed to evaluate the suitability of using cultured heparinized ("whole") blood for induction of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), two cytokines critical in AIDS pathogenesis. TNF-alpha expression ranged from 229 to 769 pg/ml in lipopolysaccharide (LPS)-stimulated cultures and was not detected in unstimulated cultures. IFN-gamma expression ranged from 0 to 112,000 pg/ml in phytohemagglutinin A (PHA)-stimulated cultures and from 0 to 789 pg/ml in antigen-stimulated cultures. The mean coefficient of variation observed in three weekly determinations was 0.47 for TNF-alpha and ranged from 0.12 to 1.73 for IFN-gamma. These values indicate that sample sizes of 8, 24, and 29 subjects would be sufficient to detect twofold changes in LPS-induced TNF-alpha and in PHA- and antigen-induced IFN-gamma respectively, if two baseline and two treatment determinations were obtained, and if the interpatient variability of changes in true levels from baseline to follow-up is negligible compared to the variability in the three weekly measurements. Measurement of LPS-induced TNF-alpha and mitogen- or antigen-induced IFN-gamma can be performed simply and reproducibly in human immunodeficiency virus-infected persons by the whole-blood culture method. Further studies are warranted to determine the effect of overnight shipping on assay reproducibility and to determine the extent to which responses can be reliably detected in subjects with low CD4 cell numbers.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Consequences of the delayed diagnosis of ataxia-telangiectasia.

OBJECTIVES: Ataxia-telangiectasia (AT) is a rare, autosomal recessive neurodegenerative disorder in which the diagnosis is obvious when ataxia and telangiectasia are both present. However, the diagnosis can be made upon the onset of ataxia and before the appearance of telangiectasia if confirmed by laboratory tests. Early diagnosis is important for genetic counseling, appropriate care, and avoidance of unnecessary tests. The purpose of this study is to identify factors responsible for delays in the diagnosis of AT. DESIGN: The records of all patients seen at the Ataxia-Telangiectasia Clinical Center from July 1, 1995 to April 1, 1997 were reviewed to determine age of onset of gait abnormality, recognition of telangiectasia, and diagnosis. RESULTS: In 48 patients with AT, who were the index cases in their respective families, the median age of diagnosis (78 months) occurred after the onset of gait abnormalities (15 months) and closely corresponded to the development of telangiectasia (72 months). In the majority of cases (34/48), telangiectasia appeared before the diagnosis was established. The most common misdiagnosis was cerebral palsy (29/48 cases). Twenty-one children (4 with AT) were born after the start of symptoms in the index case, but before the establishment of a diagnosis. CONCLUSIONS: The term AT, although a concise and memorable label for the disorder, is also a barrier to early diagnosis. We recommend the use of routine serum alpha-fetoprotein testing for all children with persistent ataxia.

Adolescent↗
PubMed1997

Adenosine deaminase deficiency in adults.

Adenosine deaminase (ADA) deficiency typically causes severe combined immunodeficiency (SCID) in infants. We report metabolic, immunologic, and genetic findings in two ADA-deficient adults with distinct phenotypes. Patient no. 1 (39 years of age) had combined immunodeficiency. She had frequent infections, lymphopenia, and recurrent hepatitis as a child but did relatively well in her second and third decades. Then she developed chronic sinopulmonary infections, including tuberculosis, and hepatobiliary disease; she died of viral leukoencephalopathy at 40 years of age. Patient no. 2, a healthy 28-year-old man with normal immune function, was identified after his niece died of SCID. Both patients lacked erythrocyte ADA activity but had only modestly elevated deoxyadenosine nucleotides. Both were heteroallelic for missense mutations: patient no. 1, G216R and P126Q (novel); patient no. 2, R101Q and A215T. Three of these mutations eliminated ADA activity, but A215T reduced activity by only 85%. Owing to a single nucleotide change in the middle of exon 7, A215T also appeared to induce exon 7 skipping. ADA deficiency is treatable and should be considered in older patients with unexplained lymphopenia and immune deficiency, who may also manifest autoimmunity or unexplained hepatobiliary disease. Metabolic status and genotype may help in assessing prognosis of more mildly affected patients.

Adenosine Deaminase↗
PubMed1997

Defective antigen-induced lymphocyte proliferation in the X-linked hyper-IgM syndrome.

We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.

Antigens↗
PubMed1997

Ultrasonography in the early diagnosis of hip joint involvement in juvenile rheumatoid arthritis.

OBJECTIVE: To determine the value of ultrasonography in detection of early alterations and subsequent evolution of hip joint disease in patients with juvenile rheumatoid arthritis (JRA). METHODS: Hip joints of 53 patients were evaluated clinically, by conventional radiography and ultrasound. Ten children free of signs/symptoms related to rheumatic diseases were chosen as a control group. Nine patients were followed up 28 months after baseline examinations. The clinical, radiological, and ultrasound evaluations were repeated. RESULTS: Conventional radiography showed alterations in 10 patients (18.9%) who had shown clinical manifestations of advanced disease of the hip joint while ultrasound detected abnormalities in asymptomatic patients who had had normal radiographs. Ultrasound revealed the occurrence of 47.2% involvement in the hips of patients with JRA. Thus, ultrasound was apparently more sensitive than conventional radiographs in diagnosing changes in the hip joints of patients with JRA. Further, such involvement was found with greater frequency in the systemic and polyarticular types of JRA, in children less than 5 years of age, in those with longer duration of disease, and in those who belonged to a poorer functional class. In 3 of 9 patients who initially had normal radiographs and altered ultrasound, we found severe hip alterations upon reevaluation by radiography, after a period ranging from 21 to 39 months. CONCLUSION: Ultrasonography is a method of diagnosis that must be considered in hip joint evaluation of patients with JRA.

Adolescent↗
PubMed1997

Antibody levels to diphtheria, tetanus, and rubella in infants vaccinated while on PD: a Study of the Pediatric Peritoneal Dialysis Study Consortium.

To determine whether infants who receive routine childhood immunizations while on chronic peritoneal dialysis (CPD) develop protective antibody levels/titers, we measured antibody levels/titers in infants vaccinated with diphtheria/tetanus/pertussis (DTP) and measles/mumps/rubella (MMR) while on CPD. Eight CPD patients (median age 19 months, range 9-39 months) had measurement of antibody to diphtheria and tetanus toxoids. Seven of the 8 (88%) had protective levels of IgG antibody to both toxoids. The single patient who did not have protective antibody to either diphtheria or tetanus had a low total serum IgG. However, 3 other patients who had low IgG had protective antibody levels. Serial measurements of antibody to tetanus and diphtheria were obtained in 3 of the 8 patients. All maintained protective levels to both diphtheria and tetanus toxoids for as long as 24 months postvaccination. Antibody to rubella was also measured in 5 CPD patients (median 29 months, range 19-39 months), and all had protective antibody titers despite the fact that 3 had low total serum levels. In conclusion, most but not all infants immunized while on CPD have protective antibody levels/titers to diphtherial, tetanus, rubella. Alteration of the routine schedule for immunizations does not appear to be necessary. However, periodic measurements of antibody may be indicated, particularly to live vial vaccines, prior to transplantation.

Antibodies, Bacterial↗