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Biomedical subjects

M Mody

Publications and source records attributed to M Mody.

29 records · Page 2Linked to original sources
PubMed1998

Reticulated platelet counts in the assessment of thrombocytopenic disorders.

Reticulated platelets (RP) are the youngest platelets in the circulation and can be measured by analysing the RNA content of platelets from whole blood or platelet-rich plasma by flow cytometry. Increased RP are indicative of increased production of platelets. Despite the current lack of standardization for the measurement of RP, it is useful in the assessment of patients with ITP by aiding the distinction of these patients from those with decreased platelet production. RP counts also have a role in the assessment of the complicated patient with multiple possible aetiologies for thrombocytopenia. Measurement of the RP count may hold predictive value for marrow recovery following myelosuppressive or myeloablative chemotherapy, and may play a role in monitoring the administration of the various thrombopoietins currently under clinical trial.

Blood Platelets↗
PubMed1997

Speech perception deficits in poor readers: auditory processing or phonological coding?

Poor readers are inferior to normal-reading peers in aspects of speech perception. Two hypotheses have been proposed to account for their deficits: (i) a speech-specific failure in phonological representation and (ii) a general deficit in auditory "temporal processing," such that they cannot easily perceive the rapid spectral changes of formant transitions at the onset of stop-vowel syllables. To test these hypotheses, two groups of second-grade children (20 "good readers," 20 "poor readers"), matched for age and intelligence, were selected to differ significantly on a /ba/-/da/ temporal order judgment (TOJ) task, said to be diagnostic of a temporal processing deficit. Three experiments then showed that the groups did not differ in: (i) TOJ when /ba/ and /da/ were paired with more easily discriminated syllables (/ba/-/sa/, /da/-/fa/); (ii) discriminating nonspeech sine wave analogs of the second and third formants of /ba/ and /da/; (iii) sensitivity to brief transitional cues varying along a synthetic speech continuum. Thus, poor readers' difficulties with /ba/-/da/ reflected perceptual confusion between phonetically similar, though phonologically contrastive, syllables rather than difficulty in perceiving rapid spectral changes. The results are consistent with a speech-specific, not a general auditory, deficit.

Child↗
PubMed1997

Flow cytometric analysis of platelets from children with the Wiskott-Aldrich syndrome reveals defects in platelet development, activation and structure.

The pathophysiology of platelet dysfunction in the Wiskott-Aldrich immune deficiency syndrome (WAS) remains unclear. Using flow cytometry, we have characterized the functional properties of platelets from 10 children with WAS. Patients with WAS had thrombocytopenia, small platelets, increased platelet-associated IgG and reduced platelet-dense granule content. Levels of reticulated 'young' platelets were normal in the WAS patients. Although the mean numbers of platelet glycoprotein (GP) Ib, GPIIbIIIa and GPIV molecules per platelet appeared lower in WAS patients than in healthy controls, analysis of similar-sized platelets revealed the mean number of GPIb molecules per platelet to be comparable in patients and normal controls. Surface GPIIbIIIa and GPIV expression was, however, significantly lower on the WAS platelets than on normal platelets. Compared with normal platelets, WAS platelets showed a reduced ability to modulate GPIIbIIIa expression following thrombin stimulation. In addition, thrombin- and ADP-induced expression of CD62P and CD63 was defective in WAS platelets. Phallacidin staining of the WAS platelets revealed less F-actin content than in normal platelets. Together, these data suggest that the reduced platelet number and function in WAS reflects, at least in part, a defect in bone marrow production as well as an intrinsic platelet abnormality.

Actins↗
PubMed1996

Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity.

Patients with both acute and chronic autoimmune thrombocytopenic purpura (AITP) have in vitro lymphocyte defects in the form of platelet-stimulated proliferation and cytokine secretion. A blinded study was performed to determine if these defects are related to serum cytokine levels and/or platelet antigen expression. Compared with controls, 53% of children with chronic AITP, but only 9% of those with acute AITP, had increased serum interleukin-2 (IL-2), interferon-gamma, and/or IL-10; however, none of the patients had detectible serum levels of IL-4 or IL-6, cytokine patterns suggesting and early CD4+ Th0 and Th1 cell activation. In children with chronic AITP, the levels of serum IL-2 correlated with in vitro platelet-stimulated IL-2 production. Few (17%) patients with AITP showed platelet activation, as measured by CD62 expression, or abnormal expression levels of platelet membrane glycoprotein (GP) IIbIIIa, but abnormal GPIb levels were observed in one-third of children with AITP. In contrast to normal controls and patients with nonimmune thrombocytopenia, a significant number of children with acute (80%), chronic (71%), or chronic-complex (55%) AITP and GPIb+ peripheral blood cells expressing HLA-DR. HLA-DR was variably coexpressed on distinct smaller and larger-sized GPIb+ cell populations with CD41, CD45, CD14, CD80, and/or glycophorin molecules. GPIb+ cells isolated from spleens of patients with chronic AITP had high expression (49% +/- 30%) of HLA-DR and splenic T cells had a high level of in vitro platelet-stimulated IL-2 secretion compared with controls. Platelet HLA-DR expression correlated inversely with platelet count, but not with therapy, serum cytokines, or in vitro lymphocyte antiplatelet reactivity. The results indicate that platelet HLA-DR expression is a common occurrence in patients with immune thrombocytopenia, whereas a large subpopulation of children with chronic AITP can be identified by increased serum cytokine levels and in vitro platelet-stimulated IL-2 secretion by lymphocytes, suggesting that differences exist in the immune pathogenesis of acute and chronic AITP, particularly at the level of platelet reactive T cells.

Acute Disease↗
PubMed1996

Platelet-surface glycoproteins in healthy and preeclamptic mothers and their newborn infants.

Preeclampsia, a common complication of pregnancy, contributes significantly to maternal and fetal morbidity and mortality. It may lead to both quantitative and qualitative defects of maternal and neonatal platelets. In this prospective study, flow cytometry has been used to study expression of platelet-surface glycoproteins (GPs) on maternal and neonatal platelets of both healthy and preeclamptic subjects. We studied 15 preeclamptic women, 20-44 y of age, and their newborns (median gestational age, 32 wk; range, 26-38) and seven healthy women (aged 26-41 y) and their healthy newborns (median gestational age, 38 wk; range, 38-42). Compared with their healthy and preeclamptic mothers, resting platelets from neonates expressed significantly less CD41 and CD9. Thrombin activation resulted in significant increases in platelet-surface expression of CD62P, CD63, CD41, CD9, and CD36 in neonates and their healthy mothers. Compared with neonates of healthy mothers, platelets from neonates of preeclamptic mothers expressed lower levels of CD62P, CD63, CD9, and CD36 on activated platelets. These findings suggest that preeclampsia influences the expression of platelet-surface GPs on neonatal and maternal platelets, which may affect platelet function, leading to an additional risk for bleeding in thrombocytopenic neonates of mothers with preeclampsia.

Adult↗
PubMed1993

FO gives voicing information even with unambiguous voice onset times.

The voiced/voiceless distinction for English utterance-initial stop consonants is primarily realized as differences in the voice onset time (VOT), which is largely signaled by the time between the stop burst and the onset of voicing. The voicing of stops has also been shown to affect the vowel's FO after release, with voiceless stops being associated with higher FO. When the VOT is ambiguous, these FO "perturbations" have been shown to affect voicing judgments. This is to be expected of what can be considered a redundant feature, that is, that it should carry a distinction in cases where the primary feature is neutralized. However, when the voicing judgments were made as quickly as possible, an inappropriate FO was found to slow response time even for unambiguous VOTs. This was true both of FO contours and level FO differences. These results reinforce the plausibility of tonogenesis, and they add further weight to the claim that listeners make full use of the signal given to them, even when overt labeling would seem to indicate otherwise.

Audiometry↗
PubMed1993

Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes.

The paraoxonase/arylesterase gene is located close to the cystic fibrosis gene on chromosome 7. Human serum contains two paraoxonase/arylesterase allozymes, A and B, which differ in their substrate specificities and kinetic properties. Purified A, AB, and B esterases were digested with trypsin, and the resultant peptides were compared by high-performance liquid chromatography. The elution profiles were very similar for all three samples, except for (1) one peptide (i.e., peptide A) seen only in the A and AB profiles and (2) another peptide (i.e., peptide B) seen only in the B and AB profiles. Sequencing revealed that peptide A had glutamine at amino acid position 191, whereas peptide B was generated by cleavage on the carboxy side of position 191, presumably because there was a basic (trypsin-specific) amino acid at that position. Working independently, our laboratory and one other laboratory have sequenced the coding region for paraoxonase from human liver cDNA libraries and have identified two polymorphic sites: Arg/Gln at position 191 and Leu/Met at position 54. Using PCR amplification and direct sequencing of nucleotides in both polymorphic regions with genomic DNA, we have estimated the allelic frequencies and have determined their concordance with the serum paraoxonase allozyme phenotypes in 27 unrelated adults and in 16 members of a three-generation pedigree. Among unrelated individuals, the Met/Leu polymorphism at position 54 did not correlate with the serum esterase phenotype. In contrast, the particular amino acid at position 191 correlated perfectly with serum phenotypes: A-type individuals had Gln at position 191, and B-type individuals had Arg at position 191; AB-type serum was found only with the heterozygous (Arg/Gln) combination. Pedigree analysis showed both polymorphisms to be inherited in the expected Mendelian manner and confirmed that only the 191 polymorphism showed concordance with the serum paraoxonase/arylesterase phenotypes.

Amino Acid Sequence↗
PubMed1990

Gradient effects of fundamental frequency on stop consonant voicing judgments.

The post-stop-release rise or fall of fundamental frequency (F0) is known to affect voicing judgments of syllables with ambiguous voice onset times (VOTs). In 1986, Silverman claimed that the critical factor was not direction of F0 change but rather its direction relative to the intonational contour. He further claimed that only F0s that start above and fall to the contour have an effect proportional to the size of the frequency change; F0s that rise to the contour by different amounts were claimed to be equivalent. In our first experiment, we examined the effect on voicing judgments of five onset F0s preceding a single, flat contour. Only falling F0s were differentiated in the first set of judgments, but after increased exposure to the syllables, even F0s below the contour differentially affected the voicing judgment. In a second experiment, the contour of the final part of the syllable was flat, rising or falling. F0 contour affected the judgments, as did onset F0s, but the two factors did not interact, indicating that the onset values were not being judged by reference to the contours. However, the contour which was predicted to result in more voiceless judgments also ended at a higher F0 in the vowel, and another effect of voicing is that the F0 is higher throughout the vowel after voiceless stops. In a third experiment, F0 contours were created to contrast contour and mean F0. The effect of the F0 during the vocalic segment appeared to be attributable to the average F0 rather than the contour. In all three experiments, the F0 onset values contributed to the voicing judgment whether they were above or below the putative intonation contour. The contribution of the lower F0s, while significant, was not as great as that of the higher F0s, which argues for a noncategorical contribution of intonation.

Cues↗
PubMedDate not supplied

Comparison of platelet immunity in patients with SLE and with ITP.

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.

Adult↗
PubMedDate not supplied

Speech perception deficits in poor readers: a reply to Denenberg's critique.

We reply to Denenberg's (1999) recent critique of our work (Mody, Studdert-Kennedy, & Brady, 1997). Denenberg mounted two main lines of criticism, one concerning characteristics of the population sampled for the experimental group, and the other a statistical critique, concerning (a) violation of parametric assumptions for use of the F distribution and (b) our supposed acceptance of the null hypothesis of no differences between experimental and control groups. We show that the first criticism stemmed from a misunderstanding of the experimental hypothesis and that the second can be answered by both parametric and nonparametric comparisons across conditions within the experimental group, without reference to the control group. Thus, our original conclusion stands: The difficulty with rapid /ba/-/da/ discrimination that some children with reading impairment may experience does not stem from difficulty in discriminating the rapid spectral transitions at stop-vowel syllable onsets.

Child↗