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Biomedical subjects

J Morrow

Publications and source records attributed to J Morrow.

At least 19 recordsLinked to original sources

The gene for an inherited form of deafness maps to chromosome 5q31.

Primary--i.e., nonsyndromal-postlingual deafness is inherited as an autosomal dominant phenotype in a large kindred in Costa Rica. Genetically susceptible individuals begin to lose hearing at low frequencies at about age 10 years, after language and speaking are learned. Deafness inevitably progresses by age 30 years to bilateral hearing loss of all frequencies. Intelligence, fertility, and life expectancy are normal. The family traces its ancestry to an affected founder born in Costa Rica in 1754. We have mapped the gene for deafness in this kindred to chromosome 5q31, between the markers IL9 and GRL, by linkage analysis involving 99 informative relatives.

Base Sequence

Toe walking and language development.

Neurodevelopmental markers that are present early in childhood may identify children at risk for later developmental disabilities. This paper attempts to clarify the relationship between one such proposed marker, toe walking, and language development in a general pediatric population. One hundred sixty-three children being seen for well-child visits were included in the study. Information from each child's caretaker was obtained for language development and a history of toe walking; observation of toe walking during the visit was also included. The frequency of toe walking was 24%. Language quotients were calculated and compared for toe walkers (n = 39) and non-toe walkers (n = 127). The mean language quotient for toe walkers tended to be consistently lower than that for non-toe walkers. The specificity of toe walking for low language scores was 85% but had a sensitivity of only 32%. Although an association between toe walking and language delay is supported by the present data, the association does not appear to be clinically significant.

Age Factors

Minor malformations, hyperactivity, and learning disabilities.

Standardized minor malformation scores have been reported to predict and identify children with attentional problems and hyperactivity. The reason why this marker works for only a subset of children with attention deficit hyperactivity disorder remains unclear. The dysmorphology scores on all children presenting for a multidisciplinary team evaluation of developmental disorders were examined for diagnostic correlations after children with chromosomal disorders and recognized dysmorphic syndromes were excluded. For 1233 subjects, the mean minor malformation score was 2.94 (SD = 2.05). A significant association between minor malformation scores and IQ (mean = 80.95, SD = 23.67) was accounted for by the group with IQs greater than 100 exhibiting the higher dysmorphology scores. An analysis of variance revealed no significant association between minor malformation scores and hyperactivity or attention deficit disorder. Indeed, the presence of an attention deficit disorder yielded lower mean dysmorphology scores. When the minor malformation scores were compared for those subgroups of children with and without specific learning disabilities, the learning-disabled subjects had significantly higher dysmorphology scores. Minor dysmorphic features do not relate to the presence or absence of attentional problems or hyperactivity in referred children. Rather they appear to characterize that subpopulation of children with attention deficit disorder and learning disabilities as well as a group of learning-disabled children without attentional disorders.

Adolescent

Neuropeptide Y, a putative cotransmitter in noradrenergic neurons, induces mast cell degranulation but not prostaglandin D2 release.

Recent evidence suggests that neural transmitters, including neuropeptides, may modulate the release of mast cell mediators. Because neuropeptide Y (NPY) has recently been recognized as a putative cotransmitter in noradrenergic neurons, we studied the effect of NPY on purified rat peritoneal mast cells. NPY induced mast cell degranulation, as assessed by a dose-dependent increase in net release of beta-hexosaminidase. The concentration that produced 50% of the maximal effect, approximately 10 mumol/L, evoked a 40% +/- 3% release. As previously reported for other neuropeptides, release was fast with maximal release already achieved at 60 seconds. Release was at 4 degrees C. In contrast to its effects on mast cell degranulation, NPY had no effect on the generation of prostaglandin D2, the major mast cell cyclooxygenase product. By comparison, the calcium ionophore A23187, at doses (4 mumol/L) that evoked comparable release of beta-hexosaminidase, stimulated a net release of 37 +/- 9 ng of PGD2 per 10(6) mast cells. These results raise the possibility that NPY may act as a modulator between the autonomic nervous system and mast cells. The results also imply that with neuropeptide stimulation, the release of preformed and newly formed mast cell mediators are mediated through independent pathways.

Animals

The development of a seizure severity scale as an outcome measure in epilepsy.

In controlled trials of antiepileptic drugs (AEDs) seizure frequency is often the only variable considered. With little prospect of improving assessment of AEDs, using seizure counts as the only end-point, there is a need for the development of new outcome measures. Clinical experience indicates that seizure severity is equally important to the patient and, by preventing seizure spread, AEDs can influence seizure severity without necessarily reducing seizure frequency. A scale capable of measuring seizure severity and change of severity attributable to treatment could be a useful additional outcome measure. Such a scale should exhibit the basic properties of validity and reliability. An easily administrable 16-point scale, containing 2 subscales--perception of control and ictal/post-ictal effects--has been developed. This scale has been tested on a patient population (n = 159) representative of that seen in trials of novel AEDs. Using standardised statistical methods, the scale has been shown to be both reliable and valid.

Adolescent

A prospective study of depression and posttraumatic stress symptoms after a natural disaster: the 1989 Loma Prieta Earthquake.

Measures of emotional health and styles of responding to negative moods were obtained for 137 students 14 days before the Loma Prieta earthquake. A follow-up was done 10 days again 7 weeks after the earthquake to test predictions about which of the students would show the most enduring symptoms of depression and posttraumatic stress. Regression analysis showed that students who, before the earthquake, already had elevated levels of depression and stress symptoms and a ruminative style of responding to their symptoms had more depression and stress symptoms for both follow-ups. Students who were exposed to more dangerous or difficult circumstances because of the earthquake also had elevated symptom levels 10 days after the earthquake. Similarly, students who, during the 10 days after the earthquake, had more ruminations about the earthquake were still more likely to have high levels of depressive and stress symptoms 7 weeks after the earthquake.

Adaptation, Psychological

Accuracy of pulse oximeters in estimating heart rate at rest and during exercise.

Pulse oximeters are being widely used for non-invasive, simultaneous assessment of haemoglobin oxygen saturation. They are reliable, accurate, relatively inexpensive and portable. Pulse oximeters are often used for estimating heart rate at rest and during exercise. However, at present the data available to validate their use as heart rate monitors are not sufficient. We evaluated the accuracy of two oximeters (Radiometer, ear and finger probe; Ohmeda 3700, ear probe) in monitoring heart rate during incremental exercise by comparing the pulse oximeters with simultaneous ECG readings. Data were collected on eight men (713 heart rate readings) during graded cycle ergometer and treadmill exercise to volitional fatigue. Analysis by linear regression revealed that general oximeter readings significantly correlated with those of ECG (r = 0.91, P less than 0.0001). However, comparison of heart rate at each level of work showed that oximeter readings significantly (P less than 0.05) under-estimated rates above 155 beats/min. These results indicate that the use of pulse oximeters as heart rate monitors during strenuous exercise is questionable. This inaccuracy may well originate from the instability of the probes, sweating, other artefacts during exercise, and measurement of different components in the cardiovascular cycle.

Adult

Rare HRAS alleles and susceptibility to human breast cancer.

The suggestion that inherited rare alleles at the HRAS oncogene locus might be associated with susceptibility to breast cancer led us to test linkage of HRAS and the neighboring region of 11p15 to breast cancer susceptibility in 12 high-risk families. Linkage could be excluded within 17 cM of HRAS; the lod score for close linkage to HRAS was -19.9. In addition, rare HRAS alleles segregated independently of breast cancer in 8 families in which both occurred. Among unrelated breast cancer patients not selected for family history, rare HRAS alleles were slightly, but not significantly, more frequent than among controls (0.11 vs 0.04, P = 0.11). The HRAS region of 11p is not the site of a primary alteration leading to breast cancer.

Alleles

Effects of responses to depression on the remediation of depressive affect.

The effects of different types of responses to a depressed mood on the duration and severity of the mood were examined. On the basis of Nolen-Hoeksema's (1987) response styles theory of depression, it was hypothesized that distracting, active responses would be more effective in alleviating a depressed mood than would ruminative, passive responses. A depressed mood was induced in 35 male and 34 female Ss, and subjects were randomly assigned to engage in 1 of 4 types of responses: an active task that distracted them from their mood; a passive, distracting task; an active task designed to lead to ruminations about their mood; or a passive, ruminative task. As predicted, the greatest remediation of depressed mood was found in Ss in the distracting-active response condition, followed in order by the distracting-passive, ruminative-active, and ruminative-passive response conditions. Degree of rumination had a greater impact on remediation of depressive affect than level of activity, with greater rumination leading to lesser remediation of depressive affect. In addition, the effects of the response tasks were limited to depressed mood. The implications of these results for interventions with depressed persons are discussed.

Adaptation, Psychological

The requirement of DNA synthesis for the induction of alkaline phosphatase by bromodeoxyuridine in a derivative of the HeLa cell line.

Non-lethal concentrations of bromodeoxyuridine induce a 2- to 5-fold increase in the specific activity of alkaline phosphatase in a HeLa subclone, S3G. Experiments employing 10-hour pulses of BRdU showed that 48 hours were required before induction commenced, and that maximal induction was attained by 96 hours. Under conditions in which DNA synthesis was prevented with hydroxyurea induction did not occur. Upon removal of hydroxyurea both DNA synthesis and induction were rapidly reestablished. Furthermore, experiments employing radiolabelled BRdU demonstrated that the kinetics of the induction process paralleled the incorporation of the analogue into cellular DNA. These results indicate that DNA synthesis, or some process intimately linked to DNA synthesis, is required for the induction of alkaline phosphatase, and suggest that the mode of the induction may be through the incorporation of the analogue into cellular DNA.

Alkaline Phosphatase

An evaluation of some theories of the mechanism of aging.

Two theories of aging are considered in this review. Although there exists substantial experimental evidence in support of the somatic mutation and error catastrophe hypotheses, several experiments have been published which are extremely difficult to reconcile with these models, at least in their simplest forms. These include the observation that biochemical and morphological degenerative changes observed in fibroblasts aged in vitro do not resemble alterations observed in cells obtained from aged donors, and the fact that tissues transplanted serially through different hosts do not decline in vigor in the manner predicted by the somatic mutation theory. Although biochemical and mutational alterations appear to accumulate in fibroblasts aged in vitro (in support of the error catastrophe model), there are substantial problems with the interpretation of such experiments, and some observations (such as the lack of increase in translational error in hemoglboin synthesis as a function of age) seem to argue directly against the error catastrophe theory. Some alternative theoretical and experimental possibilities are discussed, including the concept of programmed aging as the cause of senescence.

Age Factors

Ototoxicity in neonates treated with gentamicin and kanamycin: results of a four-year controlled follow-up study.

This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants. Audiometric, vestibular, and psychometric evaluations were performed on gentamicin-treated, kanamycin-treated, and untreated, matched control infants and children. No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy. Performances on the Illinois Test of Psycholinguistic Abilities, Beery Test of Visual Motor Integration, the Peabody Picture Vocabulary Test, and on fine and gross motor examinations were comparable for the three study groups.

Audiometry

Spontaneous mutation rate to thioguanine resistance is decreased in polyploid hamster cells.

The mutation rate to thioguanine resistance was 3.11 X 10(-6) in a near diploid V79 hamster cell line and 7.58 X 10(-8) in a near tetraploid derivative produced with colchicine. The specific activities of glucose-6-phosphate dehydrogenase and phosphoglycerate kinase of the tetraploid line were greater than that of the diploid which suggests that twice the number of active X chromosomes were present in the tetraploid. These results are compatible with the hypothesis that spontaneous variants resistant to thioguanine arise through mutation and chromosomal segregation, as has been suggested for induced mutations in tetraploid hamster cells.

Cell Line

Bromodeoxyuridine induced variations in the level of alkaline phosphatase in several human heteroploid cell lines.

The level of alkaline phosphatase in a number of established cell lines of human origin can be modified by exposure to non-lethal concentrations of bromodeoxyuridine (BRdU). In the several cell lines examined an inverse relationship between amount of induction and constitutive level of the enzyme was observed. Thus, the H.Ep 2 line, which had the highest basal level of enzyme, was reversibly repressed following exposure to the drug, whereas other cell lines with relatively low constitutive enzyme levels were induced to a maximum of 10-fold following exposure. Initiation of induction required from 24 to 48 hours, and as short an exposure ("pulse") as five hours was sufficient to produce induction. Exposure to visible light had no effect upon the repression of alkaline phosphatase in H.Ep 2 by BRdU. Induction did not occur in non-dividing, serum starved cells. The time course of induction by BRdU and hydrocortisone was similar, and simultaneous exposure of the cells to both agents resulted in no greater induction than that observed with either drug alone. Experiments utilizing mitomycin C yielded significant induction in the presence of this agent alone, and somewhat less induction when both mitomycin C and BRdU were added simultaneously. These results suggest that DNA synthesis is required for BRdU were added simultaneously. These results suggest that DNA synthesis is required for BRdU-mediated induction of alkaline phosphatase.

Alkaline Phosphatase

Purine uptake by azaguanine-resistant Chinese hamster cells.

In this study the resistance of a number of lines of Chinese hamster ovary cells to azaguanine is examined. Those which are drug resistant by virtue of a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) fail to take up any exogenous hypoxanthine or azaguanine. A second class of drug resistant cells which grow in the reverse selective HAT medium and have levels of HPRT in the range of the wild type parent line take up these purines at lower rates than the nonresistant cells and incorporate smaller amounts of them into trichloracetic acidinsoluble constituents. The results suggest that their basis for resistance resides in lowered incorporation of azaguanine into DNA and RNA, possibly due to a mofified HPRT molecule which accepts hypoxanthine, but not azaguanine as a substrate.

Amino Acids

Mutagenesis studies on cultured mammalian cells. The sensitivity of the asparagine-requiring phenotype to several chemical agents.

The effect of several chemical agents on the mutation frequency from asparagine dependence to asparagine independence has been studied in Jensen sarcoma cells. It was found that ethylmethanesulfonate brought about a dramatic exponential increase, while nitrosoguanidine was not lighly effective as a mutagen, causing only a modest increase in mutation frequency, and quinacrine HCl was ineffective. The results presented here are compared with those obtained in other systems and with our previous work on the effects of UV on mutation induction in the asparagine system. They suggest that the basis of the asparagine requirement of mammalian cell lines resides in a specific genetic alteration in nuclear DNA which is corrected by the mutagenic action of the agents tested here.

Asparagine