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Biomedical subjects

L James

Publications and source records attributed to L James.

At least 73 records · Page 4Linked to original sources
PubMed1993

A physical map of the human APP gene in YACs.

Several point mutations within exons 16 and 17 of the amyloid precursor protein (APP) gene have been reported that are associated with Alzheimer's disease in a small number of familial cases. To determine the size of the APP gene and the organization of the exons within human genomic DNA, we have characterized 11 Yeast Artificial Chromosome (YAC) recombinants containing human APP gene sequences. The smallest YAC insert was 125 kb, and the largest was 1.4 Mb. The YACs were screened by polymerase chain reaction amplification of APP exons to determine which of the 18 exons coding for APP770 were present. Four of the YACs (D110G1, D110G6, D110E9, and B142F9) contain all 18 exons and at least part of the promoter. Construction of an overlapping map of the gene with all of the YACs demonstrated that 3 of the 11 YACs were chimeric. The orientation and position of the coding sequence on the map was determined by probing digests of the YAC DNA with exon PCR products and the vector arms. The coding region of the APP gene spans approximately 400 kb of genomic DNA.

Amyloid beta-Protein Precursor↗
PubMed1993

Somatostatin inhibits secretin-induced canine pancreatic response via a cholinergic mechanism.

BACKGROUND: Somatostatin inhibits pancreatic exocrine secretion in intact animals but not in vitro, suggesting an indirect effect. The present study examined the influence of extrapancreatic nerves and intrapancreatic cholinergic activity on somatostatin-induced inhibition of pancreatic exocrine secretion in conscious dogs. METHODS: Seven dogs underwent extrapancreatic denervation and creation of pancreatic fistulae, while a second group of 6 dogs had pancreatic fistulae created without denervation. The pancreatic responses to graded doses of secretin (16-500 ng.kg-1.h-1), both alone and during background infusions of somatostatin-14 (400 and 800 pmol/L.kg-1.hr-1), were determined in all dogs. The secretin dose response was then repeated with a continuous infusion of bethanechol (90 micrograms.kg-1.h-1) both with and without somatostatin-14 (800 pmol/L.kg-1.h-1). RESULTS: Secretin-induced bicarbonate and protein outputs were significantly inhibited by somatostatin-14 in both the innervated and denervated animals. The inhibitory effects of somatostatin-14 were partially reversed by bethanechol in the innervated animals and completely reversed in the denervated animals. Bethanechol alone potentiated secretin-induced bicarbonate output from both the innervated and denervated pancreas. CONCLUSIONS: The data suggest that extrapancreatic nerves do not mediate the inhibitory effects of somatostatin-14. Rather, somatostatin-14 appears to inhibit secretin-induced pancreatic response by an intrapancreatic cholinergic mechanism.

Animals↗
PubMed1993

Effect of pancreatic denervation and atropine on the pancreatic response to secretin.

To study the influence of extrapancreatic nerves and intrapancreatic cholinergic activity on the pancreatic response to secretin, six dogs underwent extrapancreatic denervation and creation of pancreatic fistulae. A second group of six dogs had pancreatic fistulae created without pancreatic denervation. The pancreatic exocrine response to graded doses of secretin (16-500 ng/kg/h) was determined, both alone and during a background infusion of cholecystokinin-octapeptide (CCK8, 50 ng/kg/h). All studies were replicated during administration of atropine (10 micrograms/kg/h). Secretin-induced bicarbonate output was significantly inhibited by atropine in both the innervated and denervated groups. Combined secretin and CCK8 elicited a dose-dependent increase in bicarbonate output and a sustained increase in protein output in both groups, regardless of atropine. In addition, potentiation of secretin-induced bicarbonate output by CCK8 was observed despite both extrinsic pancreatic denervation and administration of atropine. We conclude that endogenous intrapancreatic cholinergic activity influences the pancreatic response to secretin. Potentiation of secretin-induced bicarbonate output by CCK, however, is not dependent on neural mediation.

Animals↗
PubMed1993

Characterization of the protein encoded by the flt3 (flk2) receptor-like tyrosine kinase gene.

We have developed rabbit polyclonal antibodies to the C-terminus of the flt3-encoded protein, which is a member of the receptor tyrosine kinase family. Immunoprecipitation using this antiserum brings down two protein bands, a major band of 143 kDa and a less abundant, more diffuse, band of 158 kDa. Pulse-chase analysis of flt3 protein from transfected COS-7 cells shows that the larger band is derived from the smaller one and presumably represents maturation of the protein from a glycosylated high-mannose form to a complex carbohydrate form. N-glycosidase F digestion confirmed the presence of N-linked carbohydrates, and cell-surface labeling of flt3-transfected cells indicated that the 158-kDa glycoprotein is the species found on the cell surface. A mutated form of the flt3 protein that was defective in its glycosylational processing was identified. Western blotting of the immunoprecipitated flt3 protein showed that it is heavily phosphorylated on tyrosine, and that this phosphorylation probably occurs in the absence of ligand. In this regard, the flt3 protein resembles the c-erbB2 protein, which is also highly phosphorylated in the absence of ligand. These data suggest that the flt3 receptor regulates the growth and differentiation of cells via an as yet unknown ligand.

Amino Acid Sequence↗
PubMed1991

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.

Alzheimer Disease↗
PubMed1991

Partial characterization of the fructose-induced defect in very-low-density lipoprotein triglyceride metabolism.

Very-low-density lipoprotein triglyceride (VLDL-TG) catabolism was studied in rats receiving either fructose or glucose as a 10% drinking solution. Consumption of either of the hexoses for 16 hours significantly elevated postheparin plasma (PHP) lipoprotein lipase (LPL) activity compared with normal control animals. Prolonged feeding of the carbohydrates for 14 days abolished the higher LPL activities, which were similar to control levels. PHP hepatic lipase (HL) activity was significantly reduced in carbohydrate-fed rats compared with control animals despite the duration of feeding. The kinetic parameters Km and Vmax cannot be obtained with lipoproteins and so the first-order rate constant (k1) of triglyceride hydrolysis was used to assess the effectiveness of VLDL-TG as substrates for endothelial lipases. VLDL-TG from fructose and VLDL-TG from glucose donors was lipolyzed with PHP LPL and HL from normal rats. The k1 (fraction of VLDL-TG lipolyzed) of VLDL-TG was found to be lower when donors had been fed fructose compared with VLDL that had come from glucose-fed donors. Rates of VLDL-TG removal from fructose and glucose donors were determined simultaneously in perfused livers of normal control, fructose-fed, and glucose-fed animals. Livers of fructose-fed animals cleared VLDL-TG at a slower rate than livers from glucose-fed or control rats. VLDL-TG from fructose-fed rats was cleared less effectively than VLDL-TG from glucose-fed rats in livers of both control and glucose-fed animals. We conclude that an impairment in the ability of fructose-fed rats to hydrolyze VLDL-TG, and of their livers to remove VLDL-TG, may in part explain fructose-induced hypertriglyceridemia.

Animals↗
PubMed1991

Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer.

A weekly, intensive chemotherapy regimen has been used to treat 70 patients with small-cell lung cancer (SCLC). Forty-five patients had limited disease (LD) and 25 extensive disease (ED) with good prognostic features. The regimen consisted of cisplatin 50 mg/m2 intravenously (IV) day 1 and etoposide 75 mg/m2 IV days 1 and 2, alternating weekly with ifosfamide 2 g/m2 IV day 8 and doxorubicin 25 mg/m2 IV day 8, for a total of 12 weeks. Dose modifications were made according to defined hematologic criteria. Responding patients with limited disease subsequently received mediastinal radiotherapy. Overall response to chemotherapy was 91% with a complete response (CR) rate of 50%. Forty-five patients with limited disease (LD) achieved an overall response rate of 91% with a CR rate of 51%, and 25 patients with extensive disease (ED) achieved an overall response rate of 92% with a CR rate of 48%. Median survival for the whole group was 54 weeks (LD, 58 weeks; ED, 42 weeks). Hematologic toxicity was predictable, without the wide fluctuations in WBC count seen in conventional 3-weekly regimens. In all, one quarter of treatment courses were delayed, most frequently because of leukopenia. Dose reductions were required in 63% of cases. The average delivered dose intensity was calculated and shown to be 73% of projected. Nonhematologic toxicity was mild with nausea and vomiting being the most common. This weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3-weekly chemotherapy in a randomized study.

Adult↗
PubMed1991

Colonic volvulus. The Army Medical Center experience 1983-1987.

Colonic volvulus was first described in 1836 by von Rokitansky. The condition has been a formidable one, fraught with innumerable complications responsible for many deaths. Even with advances in surgical technology, mortalities have remained high. Often the diagnosis is delayed for hours or even days after presentation, and serious concomitant systemic diseases are often present. Treatment has been controversial, particularly the role of elective resection following successful nonoperative reduction. The Army Medical Center experience with colonic volvulus from 1983 through 1987 is reviewed. Fifty-four patients at the eight medical centers carried this diagnosis. Their presenting signs and symptoms are discussed. The Army patients are compared and contrasted with reviews presented in the surgical literature, and conclusions are made to give guidelines for diagnosis and treatment.

Adolescent↗
PubMed1990

Augmentation of auditory evoked potentials in somatization disorder.

Sensory input regulation was examined in terms of augmenting/reducing of auditory evoked potentials in 10 patients with somatization disorder (8 males and 2 females) and 10 age- and sex-matched normal controls. The slope of P1-N1 amplitude change as a function of stimulus intensity was greater in patients compared with controls, suggesting an enhanced central nervous system response to sensory input. Taken together with previous findings of a failure to habituate to incoming stimuli in a similar group of patients, and evidence obtained in somatizers of both over-responding to background stimuli in a simple tone-discrimination task and enhanced parietal activation during selective attention, this finding suggests disturbances in the processes of attention and in the regulation of afferent stimuli in somatization disorder, and may help explain the multiple and chronic complaints characteristic of patients with the disorder.

Acoustic Stimulation↗
PubMed1989

A modified selective attention auditory event-related potential paradigm suitable for the clinical setting.

Auditory event-related potentials (ERPs) were recorded without practice sessions using a selective attention ERP paradigm modified from Hillyard et al. (1973) in 20 normal individuals who varied across wide ranges of age and educational background. The results concur with previous findings concerning the effects of selective attention on both the earlier and later phases of the ERP waveform. Attended stimuli elicited a larger N1 deflection compared with unattended stimuli. Processing negativity was also elicited by attended stimuli, but not by unattended stimuli. Mismatch negativity (N2) was evident in waveforms to signals as compared with standards, and a late positivity (P3) followed N2 only in waveforms to attended signals. This paradigm may be appropriate for evaluating suspected attentional dysfunctions in clinical populations.

Acoustic Stimulation↗
PubMed1988

Laser balloon angioplasty: effect of constant temperature versus constant power on tissue weld strength.

Thermal fusion of intimal plaque with the arterial wall during coronary balloon angioplasty may significantly reduce the incidence of abrupt closure and may reduce the occurrence of delayed restenosis by improvement of luminal size and shape. Although Nd:YAG laser energy has been shown to be effective in the thermal fusion of plaque-arterial wall separations in vitro, the most efficient manner of energy delivery for rapid achievement of therapeutically useful equilibrium tissue temperature during laser exposure has not been defined. A comparison of weld strength achieved was therefore made between two formats of laser delivery: constant power vs. decremental power with an initial high dose followed by the minimal serial decrements necessary to maintain tissue temperature constant for 15 seconds. One hundred sixty-six tissue discs of human postmortem aorta of 11 mm diameter were studied. Intimal plaque was separated from the media, the two layers were juxtaposed, a force of 4 pounds was applied, and a fiberoptic-delivered laser beam was directed perpendicular to the tissue over a 3-mm-diameter nominal spot size. Weld strength was measured as the shear force required to separate completely the two tissue layers. The mean weld strength (75 g) achieved by use of the decremental power format was significantly higher (P less than .01) than the mean strength (32 g and 56 g) achieved by using constant power for 20 and 30 seconds, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1988

Computerized axial tomographic reconstruction of coronary tree cross sections from a small number of cineradiographic views.

Three-dimensional reconstruction of the coronary tree from a conventional cineangiographic study is limited, in part, by the small number of available cineangiographic views. The potential utility of a maximum entropy iterative algorithm (MENT) for reconstruction of myocardial planes perpendicular to the axis of cineangiographic rotation from a small number (n = 6-18) of cineangiographic views was tested in vitro. The coronary arteries of postmortem human, canine, and calf hearts were filled with a silicone/thorium oxide mold to simulate in vivo angiographic contrast. Thirty-five-millimeter cineradiographs of each heart were obtained at 10 degrees intervals over 180 degrees about a myocardial central axis of rotation under exposure conditions which simulated the clinical setting. Projection data were derived from cinedensitometric scans across the entire myocardial shadow, perpendicular to the axis of rotation in each view, after 512 X 512 digitization with a vidicon camera/digitizer interfaced to a VAX computer. Comparison of MENT-reconstructed images with corresponding anatomic myocardial cross sections indicate that as few as 6 to 12 views can be used to reconstruct the cross sections of the multiple coronary branches (n = 6-11) within a plane of reconstruction.

Algorithms↗
PubMed1988

The P300 event related potential component in the diagnosis of dementia.

Several studies have suggested that delays in the latency of the P300 ERP component are highly sensitive and specific to dementia and that ERP measurements may become a useful clinical tool in aiding diagnosis. This study examines the sensitivity of P300 measurements to dementia and addresses several methodological issues that limit previous research. Twenty-four patients with dementia diagnosed according to ICD-10 criteria were compared with 100 normal controls, 31 of whom were older than 60. An auditory oddball paradigm was employed to elicit the P300. Mean P300 latency did not differ significantly between the two groups. When individual subjects were examined only 13% of patients with dementia fell outside the two standard error band of the regression of P300 latency on age derived from controls. Thus, this study has not demonstrated clinically useful abnormalities of the P300 component in dementia.

Adolescent↗
PubMed1988

Microanalysis of the amino-acid sequence of monomeric beta-lactoglobulin I from donkey (Equus asinus) milk. The primary structure and its homology with a superfamily of hydrophobic molecule transporters.

The complete primary structure of donkey beta-lactoglobulin I was determined by pulsed-liquid phase microsequencing of tryptic peptides. The protein has been isolated in monomeric form and it corresponds to monomeric beta-lactoglobulin of type I. With the inclusion of donkey beta-lactoglobulin I there are 13% common residues amongst the members of the beta-lactoglobulin family. Donkey beta-lactoglobulin I is homologous to the retinol-binding protein, bilin-binding protein and five other proteins belonging to the new superfamily of hydrophobic molecule transporters. A rapid method for peptide isolation and the strategy for microsequencing of this protein have been described.

Amino Acid Sequence↗
PubMed1987

L-carnitine treatment in the hyperlipidemic rabbit.

A study was designed to examine the hypolipidemic effect of L-carnitine treatment (4 weeks, 170 mg/kg/d) in rabbits fed a high fat diet (5% corn oil/0.5% cholesterol, w/w). Eight weeks of exposure to the high fat diet significantly increased plasma total cholesterol and triglycerides. VLDL associated triglycerides, cholesterol, apo-B, and total protein were also significantly increased with the diet. There was no change in HDL-cholesterol levels. Plasma concentration of carnitine (free, acyl, and total) all increased significantly with the high fat diet. The content of free, short-chain, and total carnitine were decreased in the liver whereas the content of long-chain acylcarnitines was increased. The diet generated a significant steatosis within the livers of these animals. Four weeks of treatment of L-carnitine reduced the extent of the liver steatosis and significantly decreased plasma total cholesterol, triglycerides, VLDL associated triglycerides, cholesterol, and total protein. HDL-cholesterol levels were unaffected by the treatment. All plasma fractions of carnitine (free, acetyl, acyl, and total) were significantly increased above those levels seen after 8 weeks of the high fat diet alone. The content of liver carnitine and its esters was normalized following treatment. The high fat diet decreased liver HMG-CoA reductase activity and increased the activities of 7-alpha-hydroxylase and acylcholesterol acyltransferase (ACAT). L-Carnitine treatment blunted the magnitude of the diet induced increase in 7 alpha-hydroxylase activity, yet overall the activity still remained elevated relative to controls. ACAT activity increased (1.5 times) with the high fat diet and increased further (4.5 times) following carnitine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evoked response potentials and regional cerebral blood flow in somatization disorder.

Somatization disorder (SMD) is a chronic condition characterized by multiple complaints which are not due to any apparent organic illness but frequently involve pain. This study employs computer-aided imaging technologies to examine brain function in thousandths of a second (event-related brain potentials) and over a number of minutes (regional cerebral blood flow). Fourteen patients with SMD and 14 normal controls were investigated. Results from both studies suggest that patients with SMD have a dysfunction in the processes of attention, compared to normal controls.

Adult↗