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Biomedical subjects

J M Fletcher

Publications and source records attributed to J M Fletcher.

At least 145 records · Page 8Linked to original sources
PubMed1989

CpG islands surround a DNA segment located between translocation breakpoints associated with genitourinary dysplasia and aniridia.

We have isolated a DNA segment absent from all the constitutionally deleted chromosomes 11 of our patients with Wilms tumor. This marker separates two balanced translocations that break in band 11p13: the distal one associated with aniridia (AN2), and the proximal one with genitourinary dysplasia (GUD). The GUD breakpoint maps within the smallest region of overlap (SRO) for the Wilms tumor (WT) gene locus, thus strengthening the previous suggestion of an association between Wilms tumor and other abnormalities of the genitourinary system. The 11p13 translocation breakpoint associated with T-cell acute lymphatic leukemia (T-ALL) is centromeric to the SRO and separated from the WT locus by at least one known gene. This region of the human genome (11p13) is rich in CpG islands that potentially identify genes, some of which may be involved in the various phenotypes associated with the WAGR syndrome. This is consistent with the proposition that the majority of human genes are in G-negative bands.

Animals↗
PubMed1989

Intellectual, motor, and language sequelae following closed head injury in infants and preschoolers.

Examined cognitive and motor performance during the subacute stage of recovery and 8 months postinjury in 21 infants and preschoolers who sustained a closed head injury (CHI). Children sustaining severe CHI, who exhibited impaired consciousness for at least 1 day, were impaired on measures of intelligence, motor, expressive language, and receptive language functions on the baseline and follow-up evaluations relative to children with mild-moderate injuries. Irrespective of injury severity, motor and expressive language functions were the most vulnerable to the effects of CHI. Results are discussed in terms of the rate of development of cognitive functions.

Age Factors↗
PubMed1989

Magnetic resonance imaging after closed head injury in children.

Magnetic resonance imaging (MRI) was performed in a series of 21 children and adolescents who had been hospitalized after sustaining closed head injuries of varying severity at least 6 months previously. Areas of high intensity in the parenchyma were present in 8 of the 11 severely injured patients, whereas MRI findings were normal in all 10 patients with mild-to-moderate head injuries. Lesions involving the subcortical white matter were confined to severely injured patients whose clinical features were compatible with diffuse axonal injury. Neuropsychological assessment disclosed deficits primarily in the severely injured patients; these deficits were significantly associated with persistent lesions visualized by MRI. Serial MRI and neurobehavioral assessment following early injury may be useful in documenting cognitive impairment in relation to structural alterations of the young brain.

Adolescent↗
PubMed1989

Residual abnormalities of insulin secretion and sensitivity after weight loss by obese women.

Changes in plasma insulin and glucose concentrations before and after feeding were measured in six female subjects (post-obese) who had regained a normal body mass after a history of severe obesity (mean weight loss, 37.1 +/- 2.6 kg). The responses of the post-obese group were compared with a group of weight- and age-matched subjects who had not been obese (lean). After an overnight fast subjects were fed a meal at 09.00 h and 13.10 h. Fasting and post-prandial insulin concentrations were lower in post-obese than in lean subjects. Immediately after beginning to eat at 13.10 h all subjects showed a rise in insulin concentration with no change in glucose concentration. In this pre-absorptive period there was no significant difference in insulin concentration between post-obese and lean subjects, although the increment in insulin concentration over baseline values was greater in post-obese subjects (P less than 0.05). It is concluded that abnormalities of insulin secretion and action remain after weight loss by obese subjects. These abnormalities may predispose to hyperphagia and accumulation of excess adiposity.

Adult↗
PubMed1988

Analysis of WAGR deletions and related translocations with gene-specific DNA probes, using FACS-selected cell hybrids.

We used the fluorescence-activated cell sorter (FACS) to select a series of somatic cell hybrids with deleted or translocated chromosome 11 segregated from its normal homolog. Analysis of these cell hybrids with gene-specific probes and for cell-surface marker expression has allowed us to order the markers and define a smallest region of overlap (SRO) for deletions associated with the WAGR (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) region of chromosome 11. Two translocation breakpoints in 11p13 (one associated with familial aniridia and one with a sporadic case of congenital renal dysfunction resulting from urethral and ureteral atresia) map within this SRO.

Animals↗
PubMed1988

The effects of dietary fat content on the growth and body composition of lean and genetically obese Zucker rats adrenalectomized before weaning.

1. Lean (Fa/-) and obese (fa/fa) Zucker rats were adrenalectomized or sham-operated at 18 d of age (3 d before weaning). After weaning the rats were fed ad lib. on semi-synthetic diets containing either a low (8 g/kg) or a high (178 g/kg) proportion of fat. Other groups of sham-operated rats were given the same amount eaten by adrenalectomized animals (restricted intake). Rats were killed at 40 d of age. 2. Adrenalectomy reduced the body lipid content of lean and obese rats compared with intact animals fed ad lib. or given a restricted intake. Adrenalectomized obese rats contained more body lipid than intact or adrenalectomized lean rats. 3. Sham-operated obese rats given a restricted intake had less body protein than similarly treated lean animals and this phenotypic difference was abolished by adrenalectomy. 4. There were no effects of diet on growth or body composition of intact or adrenalectomized rats. 5. It is concluded that preweaning adrenalectomy prevented development of the obese phenotype when rats were fed on either diet. Comparison of these results with a previous study, in which adrenalectomized Zucker rats were fed on a stock diet (Fletcher, 1986b), showed, however, that feeding either of the semi-synthetic diets caused greater deposition of body lipid in obese rats.

Adrenalectomy↗
PubMed1988

Classification in neuropsychology: a theoretical framework and research paradigm.

Classification research is not well understood in neuropsychology. A major purpose of classification research is to establish and investigate inclusion and exclusion criteria for group formation. Therefore, classification represents the foundations of clinical assessment as well as traditional contrasting groups research designs in neuropsychology. Null results in neuropsychological research do not pinpoint the basis for the absence of group differences. The most frequent research focuses on the original theory or the validity of the dependent variables. Classification research focuses on a third potential problem area, which has received little attention: poor subject classifications (invalid independent variables). The purpose of this paper is to describe a general theoretical framework and outline a set of decisions for conducting classification research in neuropsychology.

Brain Damage, Chronic↗
PubMed1988

Discriminant validity of lateral sensorimotor tests in children.

The discriminant validity of left- (LH) and right-hand (RH) sensorimotor measures from a comprehensive neuropsychological battery was tested using confirmatory factor analysis. A group of children (primarily learning disabled) was divided into analysis (n = 488) and cross-validation (n = 400) samples and the following measures were taken for both the LH and the RH Tactile Perception, Finger Agnosia, Fingertip Number Writing, Tactile Form Recognition, Finger Tapping, Grip Strength, Grooved Pegboard, and Mazes. RH- and LH scores from these tests, and scores from five WISC subtests (Information, Similarities, Vocabulary, Block Design, and Object Assembly) were analyzed in a series of four nested confirmatory factor models. Models distinguished between LH and RH skill factors, and/or between simple- and complex-skill factors. Models were compared using incremental fit ratios and chi 2 difference tests (Bentler & Bonnett, 1980). Model comparisons revealed little evidence for discriminant validity of LH and RH measures, but strong support for distinctions between measures of simple- and complex-skills. These findings were replicated in the cross-validation sample.

Adolescent↗
PubMed1988

Neurobehavioral effects of central nervous system prophylactic treatment of cancer in children.

This article reviews 41 studies of the effects of prophylactic CNS treatment on the neurobehavioral development of children with cancer. This research is classified according to studies of (a) children in treatment; (b) long-term survivors; and (c) longitudinal follow-ups of children from the time of diagnosis. Studies vary considerably in design, sample, and outcome variables, so firm conclusions regarding the morbidity of CNS prophylaxis are not currently possible. However, the studies do suggest that CNS prophylaxis does impair cognitive development, particularly when cranial radiation therapy is part of the treatment. There is also evidence of greater impairment in younger children and some suggestion of more frequent impairment of non-language skills relative to language skills. The possible relationships among age, radiation, and non-language cognitive skills may be linked to disruption of white matter CNS structures apparent on autopsy and cerebral tomography following treatment.

Adolescent↗
PubMed1988

Neuropsychological effects of childhood cancer treatment.

The potential neuropsychological effects of treatment were investigated in 124 childhood cancer patients. Children were classified into groups on the basis of treatment modality and treatment status. All patients received systemic chemotherapy. Other treatment modalities included intrathecal chemotherapy and intrathecal chemotherapy plus central nervous system radiation therapy. Treatment status was determined by whether children were newly diagnosed patients in active treatment or long-term survivors of cancer. This classification resulted in five groups; group 1 (n = 29)--children with newly diagnosed disease who were receiving intrathecal chemotherapy; group 2 (n = 21)--children with newly diagnosed disease who were receiving systemic chemotherapy without central nervous system treatment; group 3 (n = 24)--long-term survivors who had received intrathecal chemotherapy; group 4 (n = 25)--long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy; and group 5 (n = 25)--long-term survivors who had received systemic chemotherapy only (no specific central nervous system treatment). Groups were compared by using multivariate analysis of variance on sets of neuropsychological test variables that represent major cognitive domains. Results of comparisons indicated significant group differences for most dependent-variable sets. Follow-up pairwise comparisons showed that the group of long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy consistently obtained lower test scores than the other four groups. These findings are consistent with results of previous studies, thus indicating that intrathecal chemotherapy plus cranial radiotherapy is associated with significant effects on neuropsychological performance. Comparisons among newly diagnosed and long-term groups of patients who did not receive cranial radiotherapy yielded null results on measures of higher-order cognitive functions. However, significant group differences were observed on measures of fine-motor and visual-motor skills; newly diagnosed groups obtained lower scores than the nonirradiated long-term survivor groups. Findings were attributed to chemotherapy-induced peripheral neuropathy that differentially affected the newly diagnosed groups.

Adolescent↗
PubMed1988

A prospective study of neuropsychological sequelae in children with brain tumors.

Surgery and radiotherapy are the primary modalities of treatment for pediatric brain tumors. Despite the widespread use of these treatments, little is known of their acute effects (within one year posttreatment) on neuropsychological functions. An understanding of acute treatment effects may provide valuable feedback to neurosurgeons and a baseline against which delayed sequelae may be evaluated. This study compares pre- and posttherapy neuropsychological test performance of pediatric brain tumor patients categorized into two groups on the basis of treatment modalities: surgery (n = 7) and radiotherapy (n = 7). Treatment groups were composed of children aged 56 to 196 months at the time of evaluation with heterogeneous tumor diagnoses and locations. Comparisons of pretherapy findings with normative values using confidence intervals indicated that both groups performed within the average range on most measures. Outstanding deficits at baseline were observed on tests of fine-motor, psychomotor, and timed language skills, and are likely to be attributable to tumor-related effects. Comparisons of pre- versus posttherapy neuropsychological test findings indicated no significant interval changes for either group. Results suggest that surgery and radiotherapy are not associated with acute effects on neuropsychological functions.

Adolescent↗
PubMed1988

Memory functioning during the first year after closed head injury in children and adolescents.

Effects of the severity of closed head injury (CHI) on verbal learning and memory and visual recognition memory were studied at base line and on a 1-year follow-up examination in 58 pediatric admissions sampled from three age ranges, 6-8, 9-12, and 13-15 years. Within each age range, recovery of memory was compared in patients with mild to moderate CHI and survivors of severe injury. Consistent with previous findings obtained in head-injured children sampled from a wide age range, the present study confirms that memory deficit persists at least 1 year after severe CHI. Impairment of visual recognition memory was directly related to severity of CHI in all three age ranges. The severity of CHI was directly related to initial and residual verbal memory deficit in adolescents, but this effect was inconsistent in children. We suggest that the cerebral substrate for visual recognition memory was well established in all three age ranges and thus was vulnerable to the effects of injury. In contrast, verbal memory skills were undergoing rapid development in the adolescents, but were still immature in children. Extended follow-up could conceivably demonstrate the late appearance of verbal memory deficit in the children who had apparent sparing of function.

Adolescent↗
PubMed1988

The parasympathetic nervous system and glucocorticoid-mediated hyperinsulinaemia in the genetically obese (fa/fa) Zucker rat.

Lean (Fa/-) and genetically obese (fa/fa) Zucker rats were adrenalectomized at 18 days of age (3 days before weaning) before the onset of hyperinsulinaemia. At 40-41 days of age, basal and glucose-stimulated insulin concentrations did not differ significantly between lean and obese rats. Plasma insulin and glucose concentrations were higher in both phenotypes 24 h after administration of corticosterone (2.0 mg at 12-h intervals). Corticosterone-treated obese rats had higher basal and glucose-stimulated insulin levels than similarly treated lean animals, although plasma glucose concentrations did not differ between phenotypes. The basal plasma insulin concentration of obese rats treated with corticosterone for 24 h was reduced 15, 30 and 45 min after injection of atropine (0.3 mg) without any significant change in the plasma glucose level. Injection of atropine (0.3 mg) 20 min before a glucose load prevented the greater increment in plasma insulin concentration of corticosterone-treated obese rats compared with similarly treated lean animals. Atropine administration (0.3 mg) to intact obese rats at 40 days of age reduced, but did not abolish, their hyperinsulinaemia compared with intact lean animals. It is concluded that (1) pre-weaning adrenalectomy prevents the development of hyperinsulinaemia in genetically obese rats, (2) corticosterone replacement for only 24 h restores the hyperinsulinaemia of obese rats, (3) the differential effects of corticosterone on insulin secretion by lean and obese rats are mediated by the parasympathetic nervous system and (4) the parasympathetic nervous system contributes to, but is not the only cause of, hyperinsulinaemia in intact obese rats.

Adrenalectomy↗
PubMed1987

Sacciform cells in the epidermis of the brown trout, Salmo trutta, and the Arctic char, Salvelinus alpinus.

Sacciform cells containing an acidophilic, proteinaceous secretion, were identified in the epidermis of the brown trout and Arctic char. This cell type increased in number during the chronic stages of infestation by the ectoparasitic flagellate, Ichthyobodo sp., in immature brown trout, and decreased during sexual maturation in male brown trout and char. It is suggested that the salmonid sacciform cell produces a secretion which protects the fish against infestation or damage by skin parasites.

Animals↗