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Biomedical subjects

J A White

Publications and source records attributed to J A White.

At least 19 recordsLinked to original sources

Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14.

Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) was obtained with the marker D14S43 at 14q24.3. One early-onset family yielded a lod score of 4.89 (theta = 0.0). When no assumptions were made about age-dependent penetrance, significant results were still obtained (Zmax = 5.94, theta = 0.0), despite the loss of power to detect linkage under these conditions. Results for the Volga German families were either negative or nonsignificant for markers in this region. Thus, evidence indicates a familial Alzheimer's disease locus on chromosome 14.

Alzheimer Disease

The parameter identification problem for the somatic shunt model.

The somatic shunt model, a generalized version of the Rall equivalent cylinder model, is used commonly to describe the passive electrotonic properties of neurons. Procedures for determining the parameters of the somatic shunt model that best describe a given neuron typically rely on the response of the cell to a small step of hyperpolarizing current injected by an intrasomatic recording electrode. In this study it is shown that the problem of estimating model parameters for the somatic shunt model using physiological data is ill-posed, in that very small errors in measured data can lead to large and unpredictable errors in parameter estimates. If the somatic shunt is assumed to be a real property of the intact neuron, the effects of these errors are not severe when predicting EPSP waveshapes resulting from synaptic input at a given location. However, if the somatic shunt is assumed to be a consequence of a leakage pathway around the recording electrode, and a correction for the shunt is applied, then the instability of the inverse problem can introduce large errors in estimates of EPSP waveshape as a function of synaptic location in the intact cell. Morphological constraints can be used to improve the accuracy of the inversion procedure in terms of both parameter estimates and predicted EPSP responses.

Mathematics

Cooperativity of SV40 T antigen and ras in progressive stages of transformation of human fibroblasts.

Human diploid fibroblasts immortalized by SV40 T antigen provide an experimental system for studying the progression and synergism in transformation by secondary oncogenes. We have utilized the human fibroblast line HAL, which was immortalized with an orgin-defective SV40 genome encoding a temperature-sensitive T antigen, to study the cooperativity between SV40 T antigen and the ras oncogene in the progression of transformation. This study demonstrates that HAL cells possess characteristic growth patterns, requiring 10% serum, are anchorage dependent, and express a temperature-sensitive T antigen. HAL cells rely on the normal functioning of T antigen for continual growth and therefore do not proliferate at 39 degrees C. Three new derivatives of the HAL cell line were generated by microinjection of the ras oncogene. The cell line v-ras-HAL was derived by microinjection of HAL cells with v-Ha-ras DNA. The cell lines c-rasSVneo-HAL and c-rasLTRhygro-HAL were established by microinjection of HAL cells with the plasmids pSV2neoT24 or fpHVT24, respectively, wherein the ras gene is transcriptionally regulated by the cellular promoter and driven by either the SV40 enhancer or an upstream LTR enhancer. The three ras containing cell lines grow in reduced serum concentrations (0 to 5%), are anchorage independent, and express both T antigen and ras p21. The v-ras-HAL and c-rasSVneo-HAL cell lines are still dependent upon the normal functioning of T antigen for continual growth at 39 degrees C, however the c-rasLTRhygro-HAL cell line does proliferate at 39 degrees C in 10% serum-containing medium. Therefore, we propose that neither v-Ha-ras nor c-ras can replace T antigen at 39 degrees C; rather T antigen and ras cooperate in progressive stages of transformation of human fibroblasts.

Antigens, Polyomavirus Transforming

Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region.

A large number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease. Previous studies have identified three mutations at APP codon 717 which are pathogenic for Alzheimer disease (AD). Samples from affected subjects were examined for mutations in exons 16 and 17 of the APP gene. A combination of direct sequencing and single-strand conformational polymorphism analysis was used. Sporadic AD and normal controls were also examined by the same methods. Five sequence variants were identified. One variant at APP codon 693 resulted in a Glu-->Gly change. This is the same codon as the hereditary cerebral hemorrhage with amyloidosis-Dutch type Glu-->Gln mutation. Another single-base change at APP codon 708 did not alter the amino acid encoded at this site. Two point mutations and a 6-bp deletion were identified in the intronic sequences surrounding exon 17. None of the variants could be unambiguously determined to be responsible for FAD. The larger families were also analyzed by testing for linkage of FAD to a highly polymorphic short tandem repeat marker (D21S210) that is tightly linked to APP. Highly negative LOD scores were obtained for the family groups tested, and linkage was formally excluded beyond theta = .10 for the Volga German kindreds, theta = .20 for early-onset non-Volga Germans, and theta = .10 for late-onset families. LOD scores for linkage of FAD to markers centromeric to APP (D21S1/S11, D21S13, and D21S215) were also negative in the three family groups. These studies show that APP mutations account for AD in only a small fraction of FAD kindreds.

Adult

Primary immunodeficiencies.

Primary immunodeficiencies are rare immune system disorders that present with recurrent and chronic infections of the head and neck. Otitis media, sinusitis, and upper respiratory tract infections develop frequently and present in early childhood. The purpose of this report is to classify and define the primary immunodeficiencies as well as to examine the clinical manifestations, evaluation, and treatment of these disorders.

Diagnosis, Differential

Eagle's syndrome: the Ochsner experience.

Eagle fully described the syndrome that bears his name in 1948. He noted that the typical patient had undergone tonsillectomy in the past. Although reported in the literature, the carotid artery syndrome is frequently overlooked in patients manifesting craniofacial or pharyngeal pain but who have not undergone tonsillectomy. Cases representative of the variety of patients with Eagle's syndrome treated at the Ochsner Clinic Department of Otolaryngology are presented. The diversity of symptoms and its rather uncommon occurrence often make the diagnosis of Eagle's syndrome elusive. The anatomy and embryology of the stylohyoid complex is discussed, as well as the symptoms, differential diagnosis, workup, and treatment of Eagle's syndrome. We hope to refamiliarize the clinician with this condition in order that it be considered in the assessment of patients with craniofacial pain.

Adult

Management of blunt pancreatic trauma. A report of 3 cases.

Three cases in which the sole injury was a major pancreatic laceration secondary to closed abdominal injury are presented, and the literature on major closed injuries of the pancreas is reviewed. The diagnosis, surgical management and complications of closed injuries of the pancreas are discussed. Delay in diagnosis, inadequate surgery and failure to recognize common complications of pancreatic injury are responsible for the current high mortality rates for this form of closed abdominal trauma.

Adult

Serum insulin and glucose response to graded exercise in adults. Part I: the influence of fitness status.

The effect of acute exercise upon serum immunoreactive insulin levels (IRI) and serum glucose concentrations (GC) was studied in groups of middle-aged men of contrasting physical fitness status. Two groups of subjects, one active and one sedentary (both N = 11, mean age 44 years), performed a graded cycle ergometer exercise test in the post-absorptive state. Venous blood samples were taken at rest, during low and high work intensities, and after recovery. The response of serum IRI to exercise was similar in both groups of subjects with significant increases observed during exercise followed by a return to resting values during recovery. However, the magnitude of serum IRI response was lower in the active group. In contrast, the sedentary group demonstrated little or no change in serum GC during exercise, whereas significant increases in serum GC were observed during exercise in the active group.

Adult

Serum insulin and glucose response to graded exercise in adults. Part II. The effect of exercise conditioning.

The effect of conditioning to severe exercise upon serum immunoreactive insulin levels (IRI) and serum glucose concentrations (GC) was studied in active and sedentary groups of middle-aged men. The responses of serum IRI and serum GC were determined during graded cycle ergometer exercise which required similar low and high relative work intensities, before (pre) and after (post) a four month physical fitness programme. Both groups demonstrated a marked decline in serum IRI during high intensity exercise from pre to post tests, and a tendency to maintain serum, GC (sedentary group) or elevate serum GC (active group) during exercise, following the conditioning programme. The data provides evidence of a bi-directional response of serum IRI and serum GC to graded exercise, with only minor modifications in the response patterns resulting from exercise conditioning.

Blood Glucose

Multivariate interrelationships of selected physiological and biochemical variables associated with physical fitness status.

The interrelationships between selected physiological, metabolic and hormonal variables were investigated in active and sedentary middle-aged males during consecutive periods of rest, graded exercise on a bicycle ergometer, and recovery. Venous blood samples were drawn during each phase of the activity which was performed in the post-absorptive state. Data were analysed using correlational and factorial analysis techniques, and further evaluated by discriminant function procedures. Significant correlational relationships were evident among physiological, metabolic and hormonal variables, and factor analysis identified four factors at each phase of activity which accounted for as much as 69% of the common extracted variance. These factors described physiological function and hormone-metabolite behaviour during each phase of activity. Discriminant function allowed fitness classification of subjects using only the hormone-metabolite data, thus identifying specific biochemical correlates of the fitness groupings which had been established by physiological criteria alone.

Adrenal Cortex Hormones

First aid for shark attack victims.

A first-aid kit designed for the treatment of shark attack victims is presented. Emphasis is placed on the control of massive haemorrhage, the restoration of plasma volume and the transfer of the patient to hospital after initial shoch has been treated on the beach.

Animals

Pancreatic ascites: report of two cases.

Two cases of pancreatic ascites are reported in which endoscopic retrograde and operative pancreatography were used to demonstrate the source of leakage from the duct system. Both patients were successfully treated by surgery. The management of patients with pancreatic ascites is discussed.

Acute Disease

Effect of physical fitness on the adrenocortical response to exercise stress.

Serum corticosteroid (S.C.) responses were compared in two groups of middle-aged male subjects, one sedentary, one active (both N = 11, mean age 44 years), who performed graded bicycle ergometer exercise before (pre) and after (post) a 4 month physical fitness program. Pre-training exercise involved low and high work intensities which required similar percentage of predicted Vo2 max for the sedentary and active groups. Post-training exercise at identical work loads which resulted in lower work intensities due to training effects, was followed by increased work loads demanding higher work intensities in order to accommodate for the increased work capacity of the respective groups. The sedentary group (pre) and the active group (post) showed significant elevations in S.C. during high intensity exercise and recovery. The active group had significantly lower S.C. during low and high intensity exercise and recovery (pre), and during rest and low intensity exercise (post). The sedentary group had significantly lower S.C. at identical work loads which resulted in a reduction of relative work intensity from pre to post-traing tests. Results suggest both fitness status and training effects in the adrenocortical response to exercise stress, although psychological factors may be involved.

Adrenal Cortex Hormones