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Biomedical subjects

D Howard

Publications and source records attributed to D Howard.

At least 19 recordsLinked to original sources

Regional response differences within the human auditory cortex when listening to words.

The relationship between activity within the human auditory cortices and the presentation rate of heard words was investigated by measuring changes in regional cerebral blood flow with positron emission tomography. We demonstrate that in the primary auditory cortices and middle regions of the superior temporal gyri there is a linear relationship between the rate of presentation of heard words and blood flow response. In contrast, the blood flow response in an area of the left posterior superior temporal gyrus (Wernicke's area) is primarily dependent on the occurrence of words irrespective of their rate of presentation. The primary auditory cortices are associated with the early processing of complex acoustic signals whereas Wernicke's area is associated with the comprehension of heard words. This study demonstrates for the first time that time dependent sensory signals (heard words) detected in the primary auditory cortices are transformed into a time invariant output which is channelled to a functionally specialised region--Wernicke's area. Wernicke's area is therefore distinguished from other areas of the auditory cortex by direct observation of signal transformation rather than by association with a specific behavioural task.

Adult

Asynchronous synthesis of membrane skeletal proteins during terminal maturation of murine erythroblasts.

To study the changes in the synthesis of the major membrane skeletal proteins, their assembly on the membrane, and their turnover during terminal red blood cell maturation in vivo, we have compared early proerythroblasts and late erythroblasts obtained from the spleens of mice at different times after infection with the anemia-inducing strain of Friend virus (FVA). Metabolic labeling of these cells indicates striking differences between early and late erythroblasts. In early erythroblasts, spectrin and ankyrin are synthesized in large amounts in the cytosol with proportionately high levels of spectrin and ankyrin messenger RNA (mRNA). In contrast, only small amounts of these polypeptides are incorporated into the skeleton, which is markedly unstable. In late erythroblasts, however, the synthesis of spectrin and ankyrin and their mRNA levels are substantially reduced, yet the net amounts of these polypeptides assembled in the membrane skeleton are markedly increased, and the membrane skeleton becomes stable with no detectable protein turnover. The mRNA levels and the synthesis of the band 3 and 4.1 proteins are increased considerably in terminally differentiated normoblasts with a concomitant increase in the net amount and the half-life of the newly assembled spectrin and ankyrin. Thus, the increased accumulation of spectrin and ankyrin at the late erythroblast stage is a consequence of an increased recruitment of these proteins on the membrane and an increase in their stability rather than a transcriptional upregulation. This is in contrast to band 3 and 4.1 proteins, which accumulate in direct proportion to their mRNA levels and rates of synthesis. These results suggest a key role for the band 3 and 4.1 proteins in conferring a long-term stability to the membrane skeleton during terminal red blood cell differentiation.

Anemia

Schedule-induced stereotypy.

The phenomena of the induction and entrainment of adjunctive behaviours was investigated in eight people with severe or profound mental retardation who exhibited stereotypic behaviours. The occurrence of collateral behaviours was investigated under extinction and massed reinforcer baselines and a variety of periodic or intermittent schedules of reinforcement for the performance of a simple experimental task. Seven of the eight subjects demonstrated evidence of schedule-induced stereotypic behaviour in the experimental conditions: five of the eight subjects also showed evidence of the entrainment of these behaviours within the first third of the interreinforcement interval. The results are discussed in relation to the analysis and intervention of problem behaviours in people with severe or profound mental retardation.

Adolescent

The cortical localization of the lexicons. Positron emission tomography evidence.

Positron emission tomography was used to investigate changes in regional cerebral blood flow (rCBF) in neurologically normal subjects during word reading and word repetition. The blood flow in these conditions was compared with control conditions where subjects were presented with stimuli of comparable auditory and visual complexity to real words and said the same word on presentation of each stimulus. The control condition for word repetition (hearing spoken words presented backwards) resulted in bilateral activation of the superior temporal gyrus. Word repetition caused a significant increase in rCBF over this control condition in the left superior and middle temporal gyri. The control condition for word reading (seeing stimuli written in 'false fonts', i.e. non-existent letter-like forms) resulted in significant changes in rCBF bilaterally in the striate and extrastriate cortex. Word reading caused a significant increase in blood flow relative to this control in the posterior part of the left middle temporal gyrus. The implications of these results are discussed, and it is argued that they are consistent with localization of a lexicon for spoken word recognition in the middle part of the left superior and middle temporal gyri, and a lexicon for written word recognition in the posterior part of the left middle temporal gyrus.

Adult

Taurine: an essential amino acid to prevent cholestasis in neonates?

OBJECTIVE: To review the evidence that taurine can prevent cholestasis in neonates. DATA SOURCES: MEDLINE and EMBASE searches were conducted to identify both animal and human data regarding taurine's role in bile acid conjugation and liver disease (key terms: taurine, children less than two years old). STUDY SELECTION: Emphasis was placed on human data supplemented by relevant animal data. DATA SYNTHESIS: Taurine appears to more effectively conjugate bile acids than glycine, and the end-products of conjugation are more soluble. Taurine deficiency may increase glyco-conjugates of bile acids and result in cholestasis. Although the cause of neonatal cholestasis probably is multifactorial, there are data indicating that adequate taurine may prevent cholestasis in neonates. CONCLUSIONS: Taurine should be considered an essential amino acid for neonates and should be included in total parenteral nutrition solutions for these patients.

Amino Acids, Essential

Frozen phonology thawed: the analysis and remediation of a developmental disorder of real word phonology.

A 5-year-old boy presented with very deviant phonological production, as well as some delay in acquisition of vocabulary for comprehension. Investigations showed that, in contrast to his very limited phonological system in word production and naming, he was able to repeat a variety of non-words with reasonable accuracy using a variety of syllable structures. A period of therapy aimed at improving his phonological segmentation skills resulted in dramatic improvement in real word production to the same level that he showed with non-words. This improvement was specific to the domain of treatment--real word phonology--demonstrating that the effects were a result of the therapy regimen. The reasons for this dissociation between the phonology of real words and non-words are discussed. It is concluded that the child's pattern of performance is incompatible with theories which assume that a single phonological representation is used both for word recognition and for output. His deficit appears to lie in a failure to update the underlying phonological representations used to drive spoken output as his phonological abilities develop--his lexical phonology was 'frozen'.

Child, Preschool

Language activation studies with positron emission tomography.

Behavioural tasks produce changes in regional cerebral blood flow (rCBF), the result of increased local neural activity. These changes can be measured with positron emission tomography (PET). Language activation studies by means of PET are being used to relate regional patterns of cerebral activation to information-processing models of speech and reading. Significant activation confined to both superior temporal gyri has been observed when normal subjects hear words played backwards, listen to non-words, and perform category judgements on pairs of heard real words. Prestriate cortex is activated by seeing strings of letter-like symbols, consonant strings, pronounceable non-words and real words, with additional activation in left medial prestriate cortex in response to the non-words and real words. Left posterior superior temporal gyrus (PSTG), left dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA) are engaged when subjects retrieve verbs from memory to match nouns. Finally, primary sensorimotor cortex is activated during articulation. There is particular interest at present in the precise roles of left PSTG and DLPFC in single-word comprehension and generation, and interpretation of the results depends critically on the design of the single-word tasks used for behavioural activation.

Aphasia

Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience.

To determine whether pregnancy is associated with an increased rate of flare in patients with systemic lupus erythematosus (SLE), we prospectively studied 40 pregnancies in 37 women with SLE. The women were evaluated on a monthly basis in the Hopkins Lupus Pregnancy Center. Flare was designated using a previously developed quantitative definition, i.e., a change of greater than 1.0 in the physician's global assessment (scale of 0-3) since the preceding visit or during the last 93 days. Flare occurred in 24 (60%) of the pregnancies. Flares presented most commonly as constitutional symptoms, renal involvement, or involvement of skin or joints. Comparison of the rates of flare in the same patients after delivery and in nonpregnant SLE patients showed a significant increase in the rate of flare during pregnancy (P less than 0.001 and P less than 0.0001, respectively). We conclude that flare of lupus during pregnancy is common and occurs significantly more frequently than does flare in nonpregnant SLE patients or in the same patients after pregnancy.

Adult

The determination of myeloperoxidase activity in liver.

Myeloperoxidase (MPO) is an enzyme found in granulocytes of neutrophils, but not in mammalian tissues. Previous studies have directly correlated MPO activity with neutrophil accumulation in tissues. This study presents a method for determining MPO activity in liver. Neutrophil accumulation in rat liver was provoked by creating partial ischemia followed by reperfusion. Liver homogenates prepared by a standard procedure showed no MPO activity. The homogenate was applied to Sephadex G100 and DEAE Sepharose CL6B columns which separated MPO activity from inhibitory activity. The inhibitor was identified as catalase based upon its elution from the columns and removal with 3-amino- 1,2,4-triazole (AT), a catalase inhibitor. Based upon these findings, it was determined that full MPO activity can be assayed in unfractionated liver homogenates by first inactivating catalase with AT.

Amitrole

Neuropsychological studies of auditory-visual fusion illusions. Four case studies and their implications.

A heard speech sound which is not the same as the synchronized speech sound can sometimes give rise to an illusory phonological percept. Typically, a heard /ba/ combines with a seen /ga/ to give the impression that /da/ has been heard (McGurk, H. and MacDonald, J. Nature Lond. 264, 746-748, 1976). We report the susceptibility to this illusion of four individuals with localized brain lesions affecting perceptual function. We compare their performance to that of ten control subjects and relate these findings to the efficiency of processing seen and heard speech in separate and combined modalities. The pattern of performance strongly suggests LH specialization for the phonological integration of seen and heard speech. The putative site of such integration can be effectively isolated from unilateral and from bilateral inputs and may be driven by either modality.

Adult

Periosteal osteosarcoma of the maxilla: a case report and review of literature.

Juxtacortical osteosarcomas, including periosteal and parosteal subtypes, are uncommon neoplasms of the jaws. In long bones, the biologic behavior of the periosteal variant is reported to be more aggressive than the parosteal tumor. Juxtacortical osteosarcoma of the jaws appears to have a slightly more favorable prognosis than in long bones, although a larger series of cases needs to be evaluated before a definitive conclusion concerning the behavior of juxtacortical osteosarcoma of the jaws can be made.

Aged

A human minisatellite sequence reveals DNA polymorphism in the equine species.

Southern blot analysis of equine DNA's digested with the restriction endonuclease Hinfl hybridized with a 32 PdCTP labeled human VNTR probe revealed a highly polymorphic pattern of restriction fragments upon autoradiography. The horses were unrelated individuals of the quarter horse breed. This heterologous probe can thus be used in the equine species for individual identification and pedigree analysis.

Animals

Why don't Broca's aphasics cue themselves? An investigation of phonemic cueing and tip of the tongue information.

This study investigates whether Broca's aphasics have the information processing abilities necessary to generate and use their own phonemic cues. Twenty patients were studied; ten benefited from phonemic cues given by the therapist. Phonemic cues were most effective with the patients whose naming was most severely impaired. Six patients could indicate the initial letter of words which they could not produce; three of these patients had no knowledge of any relationship between orthography and phonology, so information about the initial letter must be orthographic and not phonological. Only two patients had any success in giving the sounds of written letters. None of the 20 patients had all three abilities needed to use their own cues: giving the first letter of the name, sounding the letter, and utilizing a phonemic cue. The possibility of relearning letter-to-sound correspondences is considered.

Aphasia

Incantations in the dark: Medicaid, managed care, and maternity care.

Public program reforms in the 1980s have substantially increased the numbers of poor pregnant women potentially eligible for Medicaid coverage. Structural deficiencies in the Medicaid program, together with inadequate arrangements in managed-care plans, however, have not led to generally acceptable levels of maternity care. Demonstration projects indicate that Medicaid can be modified cost effectively to underwrite early, continuous, and comprehensive care delivery. Recommendations are suggested for eligibility guarantees, enrollment safeguards, benefit and treatment protocols, provider recruitment, quality control, and sufficient payment rates to overcome barriers to adequate levels of material health care.

Delivery of Health Care

A monoclonal antibody to exfoliated surface vesicles that recognizes a membrane-associated erythroid burst-promoting activity.

A monoclonal antibody (MoAb) recognizing a membrane-associated erythroid burst-promoting factor was prepared by immunizing BALB/c mice with plasma membrane-derived vesicles exfoliated from lymphocytes under serum-free conditions. Hybrids secreting antibody reactive with lymphocyte plasma membranes were formally cloned and IgG was purified from monoclonal supernatants or from BALB/c mouse ascites fluid. Two clones (D3-E4 and D3-G9) were found to suppress burst forming unit-erythroid (BFU-E) proliferation when added directly to serum-free human marrow culture. Inhibition to a level of 100% was observed in a dose-dependent fashion over a wide range of antibody concentrations (0-200 micrograms/mL). Neither antibody altered the proliferation of colony forming unit-granulocyte macrophage (CFU-GM) or colony forming unit-granulocyte-erythroid-monocyte-megakaryocyte (CFU-GEMM) progenitor cells in human bone marrow culture. The D3-E4 clone was found to produce an IgG1 antibody which adsorbs an erythroid burst-promoting activity (BPA) from supernatants of, and octylglucoside extracts of shed vesicles present in, serum-free, lymphocyte conditioned medium (LCM), and which recognizes a vesicular protein of Mr approximate 30,000 on immunoblots of membrane proteins electrophoresed on sodium dodecyl sulfate (SDS)/polyacrylamide and transferred to nitrocellulose. In contrast, the D3-G9 clone was found to produce an IgG1 cytotoxic antibody. These antibodies will be important to the study of cell-cell and growth factor-cell interactions in vitro.

Animals

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Adult