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Biomedical subjects

D Friedman

Publications and source records attributed to D Friedman.

At least 109 records · Page 6Linked to original sources

Pregnancies in an 18-Year Follow-up after Biliopancreatic Diversion.

BACKGROUND: 239 pregnancies occurred in 1136 women who had undergone biliopancreatic diversion (BPD). METHODS: There were 73 abortions, and 14 pregnancies are presently in their course. The 152 term pregnancies (six twins) occurred in 129 women 2-173 months (mean 42.7) after BPD. Mean age and current excess weight were 31.4 years (20-42) and 29.1%(- 6.9-78.2), and mean excess weight loss was 72.9%(30.4-110.5). RESULTS: Mean weight gain during pregnancy was 6.2 kg (-21-25). In 32 patients (21%), parenteral nutritional support was needed. In all the other patients (79%), the usual supplementations were given. Of the newborns, 122 were delivered at term (84.7%) with a mean weight of 2842.4g (1760-4600g) and a mean length of 48.S cm (43-59 cm), while the 22 preterm babies (15.3%) weighed 2151.1 g (1400-3850 g) and had a length of 44.6 cm (33-56 cm). Forty infants (27.8%) were small for gestational age but 17 of them weighed more than 2500 g. Eleven twins (one, abortion at 26th week) were also delivered, with a mean weight of 2088.6 g (1200-3100 g) and a mean length of 45.6 cm (35-50 cm). Delivery was spontaneous in 85 instances (56%), while vacuum extractor was used in one, and 66 cesarean sections were performed. There were two birth malformations, one infant died after surgery for meconium obstruction and two died from unknown causes. Of the 129 women, 35 had been infertile before BPD. CONCLUSIONS: Disappearance of infertility and decrease of pregnancy risk are to be considered among the beneficial effects of weight reduction following BPD.

Journal Article↗

Vertebral artery injury after acute cervical spine trauma: rate of occurrence as detected by MR angiography and assessment of clinical consequences.

OBJECTIVE: The purposes of this study were to assess prospectively the frequency of vertebral artery injuries after major acute cervical spine trauma as determined by MR angiography and to assess the clinical consequences of these injuries. SUBJECTS AND METHODS: During a 6-month period, 37 patients who had major acute nonpenetrating cervical spine trauma were examined with MR imaging, usually within 24 hr of the injury. Routine spin-echo and gradient-echo images were supplemented by two-dimensional time-of-flight MR angiography of the extracranial head and neck vessels. The vertebral arteries were independently assessed by two neuroradiologists for nonvisualization, focal narrowing, or focal widening. Two patients had conventional angiographic correlation. The medical records of these 37 patients were also reviewed to determine the type of spinal injury, neurologic deficit on admission, and evidence of an intracranial neurologic deficit due to vertebral artery injury. The MR angiograms of 37 control subjects were interpreted to help determine the specificity of MR angiography; those studies were assessed only for the presence or absence of the vertebral arteries. RESULTS: Findings on MR angiograms were abnormal in nine patients (24%). In seven cases, one vertebral artery was diagnosed as nonvisualized (occluded) or focally narrowed; one patient had bilateral vertebral artery injuries; and one patient had nonvisualization of the left common carotid and left vertebral arteries. In all 37 control subjects, both vertebral arteries were identified on MR angiograms. A significant difference in the frequency of vertebral artery nonvisualization (occlusion) was found between the trauma and control populations. The patient with bilateral vertebral artery injuries died 2 days after hospital admission of a massive infarction of the right cerebellar hemisphere. The other eight patients with vertebral artery injuries, and the remaining 28 patients with normal findings on MR angiograms, had no intracranial neurologic deficits that could be ascribed to a major arterial injury. CONCLUSION: In our experience, vertebral artery injuries due to major cervical spine trauma as determined by MR angiography are common. Although these vascular abnormalities usually remain clinically occult, a small percentage of patients may suffer devastating neurologic complications of posterior fossa infarction. Noninvasive assessment of the vertebral arteries by means of MR imaging should be an integral part of the evaluation of the acutely injured cervical spine.

Acute Disease↗

20 hot job tracks.

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Data Collection↗

Determination of the catalytic site of creatine kinase by site-directed mutagenesis.

Site-directed mutagenesis was used to alter the amino-acid residues at the presumed catalytic site Cys-283 and ATP binding site Asp-340 of human creatine kinase B cDNA. In addition, a highly conserved arginine residue, Arg-292, was also mutated. Transfection of 0.1 to 1 microgram of recombinant plasmid into COS cells produced increasing creatine kinase activity in the cell lysate. The expression of mutant Cys283-Tyr and Cys283-Ser resulted in complete abolition of homodimer BB isoform enzymatic activity without alteration of the capacity for dimerization. Expression of mutants Arg292-His, Arg292-Leu, and Arg292-Gln produced non-functional homodimers, whereas expression of mutant Arg292-Lys produced a homodimer with enzymatic activity that was 42% of the enzymatic activity of the wild type. Expression of the Asp340-Glu mutant creatine kinase did not alter enzyme activity as compared to the wild type. Following heterodimerization, there was inhibition of the normal subunit by the mutant subunit, for both the BB and the MB dimer. The results showed residues Cys-283 and Arg-292 are essential for enzyme catalysis. The best fit model for the dimer is one in which there is close apposition of the two catalytic sites. The interaction of the individual subunits during dimerization provides a molecular approach for dominant negative modulation of the creatine kinase isozyme system in future genetic manipulative experiments.

Base Sequence↗

Atrial natriuretic peptide response to postural change and medication in familial dysautonomia.

Circulating atrial natriuretic peptide (ANP) was assayed before and after postural change and exercise in 54 patients with familial dysautonomia (FD) and 20 controls. ANP levels were compared with blood pressure, heart rate, plasma catecholamines and parameters of renal function. Compared with controls supine FD subjects had elevated blood pressures, heart rates and ANP levels (39 +/- 4 pg/ml vs. 23 +/- 3 pg/ml, p < 0.01). With the erect posture and exercise in FD subjects, blood pressure fell below control values, with ANP lowered. In FD subjects, blood pressure was correlated with ANP levels when supine and when erect and with heart rate post exercise. In controls, ANP levels did not correlate with other parameters. In FD patients on metoclopramide, supine and erect blood pressure and ANP levels were higher. FD subjects treated with fludrocortisone, had elevated supine and erect noradrenaline (p < 0.05 and p = 0.06); and those on diazepam had lower erect and post exercise noradrenaline (p < 0.05), but ANP levels were similar. In conclusion, sympathetic denervation may increase FD patients' responsiveness to other regulators of cardiovascular integrity, such as ANP. In addition, circulating ANP and catecholamines in FD subjects appear to be influenced by commonly used medications, such as metoclopramide.

Adolescent↗

ERP amplitude and scalp distribution to target and novel events: effects of temporal order in young, middle-aged and older adults.

Event-related brain potentials (ERPs) were recorded from young (mean age = 24.1), middle-aged (48.7) and older (69.7) adults during a version of the oddball paradigm, in which 48 unique, unexpected novel stimuli were interspersed with equally rare instructed targets. As older relative to younger adults are thought to differ in their ability to inhibit the processing of task irrelevant information, we expected, based on previous work, that novel stimuli would retain their 'novelty' longer in older than in younger adults. To assess this, P3 amplitude and scalp topography elicited by novels and targets were analyzed as a function of stimulus number (n = 6) within the block and as a function of block number (n = 4). The results were in line with the prediction: While the younger adults' P3 scalp distribution shifted from a relatively more frontal to a relatively more posterior focus as a function of novel number within the block, this was not evident in the scalp topographies of the older adults. Coupled with the older adults' elevated false alarm rates to novel stimuli, the data are consistent with a change in frontal lobe function with increases in age.

Adult↗

Implicit retrieval processes in cued recall: implications for aging effects in memory.

Aging produces deficits in what has come to be called explicit or direct memory, in which subjects must consciously retrieve information from long-term memory. In contrast, many studies have shown that when implicit or indirect memory is tested, old and young subjects perform equivalently. The present study manipulated orienting instructions (structural vs. semantic) for indirect (stem completion) and direct (cued recall) memory tasks for both young and old subjects. Contrary to previous research, older subjects produced equivalent performance to young subjects on the direct test as well as on the indirect test, and performance of both groups was worse in the direct than indirect test. In addition, semantic orienting activity at study led to greater learning on the indirect test than structural orienting for both groups, although the levels of processing effect was greater for the direct test. We attribute the unexpected lack of age difference on the direct test to its difficulty, which led subjects to adopt an implicit (generate + recognize) rather than an explicit retrieval strategy during the cued recall task. Because the elderly are not impaired with regard to either implicit retrieval or recognition, this strategy produced equivalent performance in the two groups.

Adult↗

Event-related potentials (ERPs) as indicators of risk for schizophrenia.

Evidence is reviewed concerning the viability of cognitive event-related potential (ERP) indices to serve as psychophysiological markers for liability to schizophrenia and schizophrenia-related disorders. Methodologic problems that hinder the establishment of ERPs as such markers are also detailed. The ERP data from prospective high-risk and family-transmission paradigms were subjected to criteria that have been used to establish the marker status of a psychobiological variable. It is concluded that (1) there is a clear need for more studies of ERP component stability and of transmission of ERP parameters within normal families; (2) multiple tasks (in addition to the oddball experiment) must be used to probe the range of information-processing deficits in the schizophrenic syndrome; (3) investigators should pay greater attention to the scalp distribution of ERP components; and (4) profiles of multiple ERP indices may be required to enhance the probability of achieving diagnostic specificity.

Arousal↗

Brain event-related potential correlates of overfocused attention in obsessive-compulsive disorder.

A hypothesis of overfocused attention in obsessive-compulsive disorder was investigated by measuring auditory event-related potentials (ERPs) during a selective attention task. Unmedicated patients (n = 18) with this disorder showed significantly larger attention-related processing negativity (PN), with earlier onset and longer duration, than did normal controls (n = 15). In the N200 region (160-250 ms), PN was larger in patients with fewer nonspecific neurological soft signs. This task, however, did not yield any group differences in mismatch negativity (N2a) or classical N200 (N2b). P300 amplitudes for attended targets were smaller for patient than normal groups, but the reverse was true for P300 and positive slow wave amplitudes for unattended nontargets. Collectively, these ERP abnormalities suggest a misallocation of cognitive resources. Because of the importance of the frontal lobe in the control of selective attention, PN enhancement in patients with obsessive-compulsive disorder may reflect hyperactivation of this region. This conceptualization is consistent with recent functional neuroimaging findings.

Adult↗

A theory of the value of children.

This paper uses a non-standard value assumption--uncertainty reduction--to explain parenthood. We begin by reviewing the inadequacies of normative and standard rational choice explanations of shifts in fertility behavior. Then we propose a theory of the value of children based on the uncertainty-reduction assumption. Next we generate a range of hypotheses that follow both from this assumption and from a subsidiary assumption of marital solidarity enhancement. Finally, we explore the extent to which implications based on these new ideas are supported by the relevant empirical literature.

Adolescent↗

Studies on the substrate specificity of the proteinase of equine infectious anemia virus using oligopeptide substrates.

The proteinase of the equine infectious anemia virus (EIAV), a lentivirus closely related to human immunodeficiency virus (HIV), was purified from concentrated virus. The specificity of the enzyme was characterized using oligopeptides representing naturally occurring cleavage sites in the Gag and Gag-Pol polyproteins. The length of the substrate binding pocket was found to be 1-2 residues longer than that of HIV proteinases. Although the EIAV and HIV proteinases cleaved most of the peptides at the same bond, some were hydrolyzed by only the EIAV enzyme. Oligopeptides representing cleavage sites in the nucleocapsid protein were also found to be substrates of the EIAV proteinase. However, these peptides were not hydrolyzed by the HIV proteinases. While peptides representing the corresponding sequences in the first cysteine arrays of the nucleocapsid proteins of HIV-1 and HIV-2 were substrates of the proteinases, peptides representing the homologous sequences in the second Cys arrays were resistant against the proteolytic attack. A three-dimensional model of the EIAV proteinase built on the basis of homology with HIV-1 proteinase was used to interpret the differences. In addition to the oligopeptides representing cleavage sites in the Gag and Gag-Pol polyproteins, the EIAV proteinase was also able to cleave an oligopeptide mimicking a cleavage site in the transmembrane protein. Our results suggest that the specificity of lentiviral proteinases share common characteristics, although substantial differences may exist in hydrolysis of some peptides.

Amino Acid Sequence↗

Molecular model of equine infectious anemia virus proteinase and kinetic measurements for peptide substrates with single amino acid substitutions.

A molecular model has been built of the equine infectious anemia virus (EIAV) proteinase on the basis of the crystal structures of the related Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV) proteinases. The 104 residue long EIAV proteinase has 30 identical and 11 similar amino acids compared to those in HIV-1 proteinase and 25 identical and 18 similar amino acids compared to RSV proteinase. The overall structure is predicted to be close to that of HIV-1 proteinase. Two regions show differences: there are 6 additional residues leading to the tip of the flap, which is predicted to be involved in interactions with substrate, and there is a single residue deletion in the beta b' strand at a position equivalent to residue 60 in HIV-1 proteinase. The conformation of the residues leading to the flap was modeled by analogy to the corresponding region of RSV proteinase. The peptide substrate, VSQNYPIVQ, was modeled by analogy to the inhibitors in the co-crystal structures of HIV-1 proteinase, and the residues forming the substrate binding sites of EIAV proteinase were identified. EIAV proteinase showed several non-conservative substitutions in these residues compared to HIV-1 proteinase: Thr 30 instead of Asp in subsites S2, S2', S4, and S4', Ile 54 instead of Gly 48 in subsites S1, S1', S3, and S3', Arg 79 instead of Thr 74 in S4 and S4', and Ile 85 instead of Thr 80 in subsites S1 and S1'.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Neonatal hemochromatosis associated with maternal autoantibodies against Ro/SS-A and La/SS-B ribonucleoproteins.

Liver disease in the fetus and neonate may be associated with maternal Sjögren's syndrome (neonatal lupus erythematosus). The infant of a mother with Sjögren's syndrome and high anti-Ro/SS-A and anti-La/SS-B antibody titers presented at 2 1/2 weeks of age with overwhelming hepatic insufficiency and died at 6 weeks of age. Autopsy confirmed the antemortem diagnosis of neonatal hemochromatosis. We discuss the possibility of a relationship between these two conditions.

Adult↗