The incorporation of proline by cultured skin fibroblasts derived from normal individuals and patients with Duchenne muscular dystrophy (DMD) was analyzed by SDS-gel electrophoresis combined with a double-labeling procedure [Pediatr. Res., 12: 887 (1978)]. DMD fibroblasts showed increased proline incorporation into protein of approximately 130 000 daltons which could be degraded partially by collagenase. This difference was observed only at 7 days after seeding, and may be due to slight differences in growth rate as comparison of cells harvested at 2 and 7 days indicated that increased proline incorporation into high molecular weight protein was associated with day 7 cells, whether normal or DMD. During 14 days in culture normal and DMD strains did not differ in protein content, doubling time or incorporation of [3H]leucine and [14C]proline into cellular protein, although the ratio of [14C]proline to [3H]leucine incorporated was greater for DMD fibroblasts at 7 days. Incorporation of [14C]proline and [3H]leucine into extracellular proteins was greater in DMD fibroblast cultures. These subtle differences support the hypothesis that the DMD gene is expressed in fibroblasts.

Cell Differentiation↗

PubMedDate not supplied

Differential distribution of norepinephrine and serotonin along the dorsal-ventral axis of the hippocampal formation.

Norepinephrine (NE) and Serotonin (5-HT) are differentially distributed along the dorsal-ventral axis of the Hippocampal Formation (HF). A kinetic analysis of the uptake of labeled NE and 5-HT was performed to assess the relative density of nerve terminals which accumulate NE and 5-HT (Vmax) and the apparent affinity for uptake (Km). The results reveal a greater density of NE and 5-HT terminals in the ventral HF and a higher Km for 5-HT uptake in the dorsal HF. The results are discussed in terms of potential explanation of reported differences following independent manipulation of the dorsal and ventral hippocampal formation.

Animals↗

PubMedDate not supplied

Inhibition of calcium channel dihydropyridine receptor binding by purified Mojave toxin.

Mojave toxin, the principal toxic component of the venom of the Mojave rattlesnake Crotalus scutulatus scutulatus, is a protein complex of about 22,000 mol. wt. The mechanism of action of this potent (LD50 = 0.039 micrograms/g, mouse, IV) neurotoxin is a matter of conjecture, but physiologic data suggest a presynaptic site of action with disruption of stimulus-secretion coupling and neurotransmitter release. The selectivity of Mojave toxin's effect on several ion channels involved in neurotransmission was assessed in the present study using competitive radioisotopic binding procedures. Synaptic membranes from rat brain were used to assess the toxin's interaction with Ca++ and Cl- channels while membrane fragments from the Torpedo fish electric organ were used to determine toxin interaction with the nicotinic acetylcholine receptor-coupled Na+ channel. Mojave toxin was found to irreversibly inhibit 3H-nitrendipine binding to dihydropyridine receptors associated with Ca++ channels in rat brain, but had no effect on radioligand binding in the Na+ and Cl- channel assays. Saturation analysis of the binding further showed that the effects of MoTX on dihydropyridine binding were noncompetitive, with MoTX producing a decrease in both the affinity and density of 3H-nitrendipine sites. These results are consistent with the hypothesis that MoTX acts selectively on Ca++ channel function and that this interaction occurs via an allosteric mechanism in which MoTX binds to a membrane site that is topologically distinct from the dihydropyridine receptor.

Animals↗

PubMedDate not supplied

Comparison of lindane, bicyclophosphate and picrotoxin binding to the putative chloride channel sites in rat brain and Torpedo electric organ.

The relative potencies of lindane, picrotoxin and several bicyclophosphate derivatives were compared in their ability to compete with 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding sites in membranes derived from Torpedo electric organ and rat brain. Lindane proved to be ten times more potent in competing with 35S-TBPS binding in electric organ than rat brain, while the bicyclophosphate analogs displayed up to three orders of magnitude greater affinity for rat brain over electric organ. GABA inhibited 35S-TBPS binding in rat brain with moderate potency (IC50 = 30 microM), while unlabelled TBPS inhibited the binding of 3H-muscimol to the GABA receptor with an IC50 greater than 100 microM. The GABA receptor antagonist bicuculline increased 35S-TBPS binding in rat brain both in the presence and absence of 30 microM GABA. The results of the study are discussed in the context of a pharmacological discrimination between voltage-sensitive and receptor-gated Cl- channels in nervous tissue, with lindane and the i-propylbicyclophosphate derivative being the most selective compounds for discriminating between them.

Animals↗

PubMedDate not supplied

56K fibroblast protein not specific for Duchenne muscular dystrophy but for skin biopsy site.

Recently, we reported the detection by two-dimensional gel electrophoresis of a 56,000 (56K)-molecular weight polypeptide that was present in cultured skin fibroblasts from normal males but was not detectable in fibroblasts from Duchenne muscular dystrophy (DMD) patients. Since then we have established that the 56K polypeptide is not present in skin fibroblasts from normal females, DMD carrier females, or in normal male fibroblasts obtained from sources other than the Repository for Mutant Human Cell Strains, Montreal. Further inquiry has led to the discovery that all the normal male fibroblast cultures obtained from the Montreal repository had been established from preputial skin. Fibroblast cultures from DMD patients, DMD carriers, as well as other normal individuals, had been derived from non-genital skin biopsies. Thus, the absence of the 56K polypeptide is not specific for DMD, but rather is related to the site of skin biopsy.

Biopsy↗

PubMedDate not supplied

Music enhances category fluency in healthy older adults and Alzheimer's disease patients.

Exposure to some music, in particular classical music, has been reported to produce transient increases in cognitive performance. The authors investigated the effect of listening to an excerpt of Vivaldi's Four Seasons on category fluency in healthy older adult controls and Alzheimer's disease patients. In a counterbalanced repeated-measure design, participants completed two, 1-min category fluency tasks whilst listening to an excerpt of Vivaldi and two, 1-min category fluency tasks without music. The authors report a positive effect of music on category fluency, with performance in the music condition exceeding performance without music in both the healthy older adult control participants and the Alzheimer's disease patients. In keeping with previous reports, the authors conclude that music enhances attentional processes, and that this can be demonstrated in Alzheimer's disease.

Aged↗

PubMedDate not supplied

Parents' and teachers' differing views of short children's behaviour.

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Adolescent↗

PubMedDate not supplied

Factors related to grade retention in children with short stature.

A recent study by Holmes et al. (1982) revealed a high degree (23%) of grade retention in a group of children with significant short stature secondary to growth hormone deficiency (GHD), constitutional delay (CD); or Turner's Syndrome (TS). Parents indicated in a free response format that 'immaturity' and 'small size' were the reasons for retention. The present follow-up study obtained academic achievement data on 47 of the 56 short children from the Holmes et al. (1982) study to assess what role academic factors, not spontaneously mentioned by parents, may have had in the retention decision. Results indicated that despite repeating a year in the primary grades, the group of retained children were still functioning 6 months below grade expectation, compared to grade appropriate achievement in the never-retained group. Parents and teachers were both accurate in their perceptions of children's academic achievement. Behavioural ratings by teachers indicated more adjustment difficulties for retained children, while parent ratings of behaviour showed a similar high level of problems for short children regardless of retention status. Although both groups of children possessed average intellectual abilities, the retained children obtained lower IQ scores than the never retained children. In summary, a majority of short children were achieving appropriate grade levels, but a substantial minority were experiencing under-achievement, behaviour problems, and grade retention, despite average intelligence.

Achievement↗

PubMedDate not supplied

Validity of urine glucose measurements for estimating plasma glucose concentration.

Both physicians and diabetic patients have traditionally relied on measurement of glycosuria as an indirect method of estimating plasma glucose concentration to guide adjustment of insulin and diet therapy. Our observations on the correlation between mean plasma glucose concentration with simultaneous urine glucose concentration or excretion rate re-emphasize the limitations of this approach. Although our observations show a significant correlation (P less than 0.0001) between plasma glucose concentration and urine glucose concentration or urine glucose excretion rate, the wide confidence limits [95% confidence limits (minimum) +/- 150 mg/dl] on plasma glucose concentration estimated from urine glucose measurements limit the clinical applicability of such estimates. Differences among subjects in the renal resorption of glucose contribute to the wide variance of estimates. However, significant variability in renal glucose resorption within individuals is documented, further reinforcing the limitations of urine glucose determinations for reliable estimates of plasma glucose concentrations. Diabetologists need to reconsider the applicability of urine glucose measurements in evaluation of adequacy of therapy and in adjustment of insulin dosage.

Adolescent↗

PubMedDate not supplied

Verbal fluency and naming performance in type I diabetes at different blood glucose concentrations.

The effect of serum glucose alterations on selected verbal skills was examined in a group of diabetic men between 18 and 35 yr of age. An artificial insulin infusion system was used to set and maintain glucose concentrations during testing at each of three levels: hypoglycemia (55 mg/dl), euglycemia (110 mg/dl), and hyperglycemia (300 mg/dl). Subjects were used as their own controls, with performance at euglycemia serving as the comparison standard. A double-blind crossover design was employed as described in Holmes et al. (see ref. 14). Results showed significantly disrupted naming or labeling skills at hypoglycemia, with a trend toward poorer performance at hyperglycemia. During hypoglycemia, rate of responding was slowed from 6% to 18%, compared with euglycemic performance, but accuracy was not impaired. In contrast, word recognition skills were not affected by deviations in glucose. These performance effects were not correlated with duration of disease except for one of the five tests administered. This one exception, on the most difficult task, was less notable than the general finding of no relation between disease duration (from 6 mo to 17.5 yr) and test performance. Thus, in addition to considering long-term consequences of blood glucose alterations, clinicians and diabetic patients may wish to consider acute neuropsychological consequences of disrupted euglycemia.

Adolescent↗

PubMedDate not supplied

The role of the orthopaedic surgeon in the treatment of amputees.

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Amputation, Surgical↗