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Biomedical subjects

K L Jones

Publications and source records attributed to K L Jones.

At least 127 records · Page 7Linked to original sources

Ontogeny of morphine withdrawal in the rat.

The present studies examined behavioral changes during precipitated morphine withdrawal in 7- to 42-day-old rat pups. One group of rats was injected with morphine sulfate (10.0 mg/kg) twice daily for 6.5 days. Another group of 7-day-old rats received a lower dose of morphine (3.0 mg/kg). Controls were saline injected or untreated litters (7-day-old pups only). On Day 7, a target pup was injected with saline or naltrexone (0.3-10.0 mg/kg). Preweaning pups were observed in a warm chamber with the litter. Forty-two-day-old rats were tested individually. Morphine-treated pups tested with naltrexone showed significant alterations in behavior that varied at different ages. For example, rolling, stretching, and head and paw moves were observed at the younger ages, whereas burrowing, diarrhea, jumps, teeth chatter, and wet dog shakes occurred in the older rats. These data indicate that morphine-abstinent rats demonstrate withdrawal signs that are within the developmental repertoire of the rat.

Age Factors↗

Relationship between fractional calcium absorption and gastric emptying.

The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61-72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (alpha 6) was calculated from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min sample using only a calibration curve (alpha 1). There were close correlations between radiocalcium absorption on the two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood sample procedure has similar precision to the six-blood sample test.

Acetaminophen↗

Abnormalities of the corpus callosum in children prenatally exposed to alcohol.

For 20 years, it has been known that fetal alcohol syndrome (FAS) is associated with abnormal brain development. Early autopsy studies point to the corpus callosum as one area affected by heavy alcohol exposure. Little is known, however, about the integrity of the brain in alcohol-exposed children who survive the perinatal period. This study was designed to assess the corpus callosum in living children exposed to high doses of alcohol prenatally. Thirteen children with histories of significant prenatal alcohol exposure and 12 normal control children were evaluated using magnetic resonance imaging. Using the midsagittal section, images were measured for the area of the corpus callosum using a computer-assisted measurement technique. In addition to the overall area, five equiangular regions were determined for each corpus callosum. Of the 13 alcohol-exposed children assessed, two had agenesis of the corpus callosum. The remaining alcohol-exposed children had significantly smaller overall callosal areas, as well as smaller regional areas of four of the five callosal regions, when compared with the normal control children. Importantly, when corrected for brain size, three of the five callosal regions were still smaller in the alcohol-exposed children, although overall area of the corpus callosum was no longer significantly different. These results suggest that prenatal exposure to high levels of alcohol is associated with abnormalities of the corpus callosum. They verify callosal agenesis in children with FAS, which previously had only been noted in autopsy reports.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Impact of microfilaremia on maintenance of a hyporesponsive cellular immune response in Brugia-infected gerbils (Meriones unguiculatus).

The purpose of these experiments was to define the significance of the microfilarial stage to the hyporesponsive condition seen in lymphatic filariasis. Two types of experiments were conducted with Brugia pahangi-infected gerbils. In one, in vitro lymphocyte blastogenesis and in vivo granuloma formation in response to parasite antigen were correlated to microfilaremia in chronically infected individuals. In a second set of experiments, the level of in vivo granuloma formation was assessed following chemotherapeutic removal of microfilariae with ivermectin. The results indicated that the microfilarial stage alone is not responsible for the maintenance of the low cellular responses seen during chronic infections in this model. Furthermore, the data suggest that the degree of downregulation of these responses may be related to parasite burden.

Acute Disease↗

Thymidylate synthase binds to c-myc RNA in human colon cancer cells and in vitro.

Using an immunoprecipitation-reverse transcription-PCR technique, we characterized a thymidylate synthase (TS) ribonucleoprotein complex in cultured human colon cancer cells that consists of TS protein and the mRNA of the nuclear oncogene c-myc. TS protein is complexed in intact cells with the C-terminal coding region of c-myc mRNA that includes nucleotide positions 1625 to 1790. RNA electrophoretic gel mobility shift assays confirm a specific interaction between TS protein and c-myc mRNA and provide additional evidence that the C-terminal coding region represents an important cis-acting regulatory element. Further evidence demonstrates that the in vitro translational efficiency of c-myc mRNA is inhibited as a result of its direct interaction with TS protein. In addition, the presence of exogenous c-myc mRNA specifically relieves the inhibitory effects of TS protein on TS mRNA translation.

Base Sequence↗

Effect of drink temperature on antropyloroduodenal motility and gastric electrical activity in humans.

There is little information on the motor mechanisms underlying the effects of meal temperature on gastric emptying. The effects on antropyloric pressures and the surface electrogastrogram of ingesting drinks at 4 degrees C, 37 degrees C, and 50 degrees C (350 ml normal saline and 50 ml low calorie (7 kj) orange cordial) given in randomised order were measured over 60 minutes in 12 normal volunteers (10 men and 2 women, aged 18-55 years). The warm and cold drinks suppressed antral pressure waves (p < 0.05), altered the organisation of antropyloric pressure waves (p < 0.05), stimulated isolated pyloric pressure waves (p < 0.05), and increased electrogastrogram frequency (p < 0.05) when compared with the 37 degrees C drink. These changes were greatest in the first 30 minutes after ingestion and greater (p < 0.05) with the 4 degrees C drink. Temperature has major effects on postprandial antropyloroduodenal motility in normal subjects. Both cold and warm drinks stimulate a pattern of motility associated with retardation of transpyloric flow.

Adolescent↗

Gastric emptying of oil and aqueous meal components in pancreatic insufficiency: effects of posture and on appetite.

The aims of this study were to evaluate the effects of posture on gastric emptying, intragastric distribution, and satiation after a meal containing oil and aqueous phases in patients with exocrine pancreatic insufficiency. Five patients with cystic fibrosis (CF) consumed 60 ml 99mTc-labeled (V)-thiocyanate olive oil and 290 ml 113mIn-labeled diethylenetriaminepentaacetic acid soup while sitting and while lying in the left lateral decubitus position. Hunger and fullness before and after the meal were recorded. Results were compared with those obtained in 11 normal volunteers. In both postures emptying of oil was faster (P < 0.01) in CF patients. Emptying of the aqueous phase was faster (P < 0.01) in CF patients in the decubitus position. In normal subjects there was no overall difference in emptying of oil between the two postures, whereas emptying of the aqueous phase was delayed (P < 0.01) in the decubitus position. In CF patients emptying of oil was faster (P < 0.01) in the decubitus position, and emptying of the aqueous phase was only slightly faster (P < 0.05) in the sitting position. For both postures there was greater retention (P < 0.05) of oil in the proximal stomach in normal subjects than CF patients. Hunger decreased (P < 0.05) after the meal in the control subjects, but there was no change in CF patients. These results indicate that in CF patients with pancreatic exocrine insufficiency 1) gastric emptying of nonhomogenized fat is faster than normal, 2) gravity affects gastric emptying of oil, and 3) effects of a fatty meal on hunger are reduced.

Adult↗

Relationships between gastric emptying, intragastric meal distribution and blood glucose concentrations in diabetes mellitus.

UNLABELLED: The aim of this study was to evaluate the prevalence of disordered intragastric meal distribution and the relationships between gastric emptying, intragastric distribution, glycemic control and gastrointestinal symptoms in diabetes mellitus. METHODS: Eighty-six patients with diabetes mellitus had measurements of gastric emptying and intragastric distribution of a radioisotopically labeled solid/liquid meal (100 g beef and 150 ml 10% dextrose), glycemic control (plasma glucose concentrations), upper gastrointestinal symptoms (questionnaire) and autonomic nerve function (cardiovascular reflexes). Results were compared to those obtained in 20 normal volunteers. RESULTS: Solid and liquid gastric emptying were delayed in the diabetic patients and correlated weakly. Intragastric meal distribution was also often abnormal, with increased retention of both solid and liquid in the proximal stomach and increased retention of solid but not liquid in the distal stomach. In all patients with increased retention of solid in the proximal stomach, emptying from the total stomach was delayed. Gastric emptying of liquid was slower in those subjects who had a mean plasma glucose > 15 mmol/liter during the gastric emptying measurement, when compared to the remainder of the group. CONCLUSION: In patients with diabetes mellitus, there is poor relationship between solid and liquid gastric emptying and intragastric meal distribution is frequently abnormal. Interpretation of the results of gastric emptying measurements should consider meal composition and plasma glucose concentrations.

Blood Glucose↗

The effect of reducing reagents on binding of thymidylate synthase protein to thymidylate synthase messenger RNA.

Human thymidylate synthase (TS) protein specifically binds to its own TS mRNA and functions as a translational repressor. In the presence of reducing agents, the RNA binding activity of TS protein is significantly enhanced. In contrast, treatment of TS protein with the oxidizing agent diamide inhibits RNA binding. Scatchard analysis reveals that in the presence of the reducing agent 2-mercaptoethanol, the TS protein/TS mRNA interaction changes from low (Kd = 66 nM) to high (Kd = 2.6 nM) apparent affinity. The catalytic activity of TS is increased by up to 6.5-fold in the presence of 2-mercaptoethanol. These studies demonstrate that the interaction between TS protein and its target TS mRNA is sensitive to the presence of reducing reagents and is dependent upon a reversible sulfhydryl switch mechanism.

Binding Sites↗

Offspring of women infected with varicella during pregnancy: a prospective study.

Despite the well-recognized association between maternal varicella infection and a specific pattern of malformation in the offspring referred to as fetal varicella syndrome, the full spectrum of this disorder as well as its frequency in the offspring of women infected with varicella during pregnancy is unknown. In order to resolve these issues, we have evaluated pregnancy outcome in 194 women who contacted us during pregnancy, soon after the onset of their infection: 132 (68%) during the 1st trimester and 171 (88%) prior to the onset of the 20th week, the most critical period relative to fetal susceptibility. Of those 171 women, there were 146 liveborn babies, 6 spontaneous abortions, 7 therapeutic abortions (one because of an anencephalic fetus), 2 stillborn infants, and nine pregnancies lost to follow-up. Of the 146 liveborn births, there were 2 with features consistent with the fetal varicella syndrome: one a child with mild cutaneous scars on her face, arms, and legs, Horner syndrome involving her left eye and a scar on her retina, leading to blindness in that eye; and the other, a child with horizontal nystagmus who is otherwise normal at 1 year of age. An additional four liveborn infants had a single major malformation which included unilateral microtia, bowel obstruction secondary to an ileal band, bilateral double ureters, and a thyroglossal duct cyst. This study suggests that prenatal varicella infection is associated with a wider spectrum of severity than has been previously appreciated and indicates that maternal varicella infection prior to the 20th week of pregnancy is associated with only a small risk for the developing fetus.

Adult↗

Anabolic effect of human growth hormone: management of inherited disorders of catabolic pathways.

The effects of growth hormone treatment and dietary alanine supplementation, individually and in combination, were studied in five patients with organic acidemias. Three patients had propionic acidemia, one had 3-hydroxyisobutyric acidemia, and one had a defect in isoleucine metabolism. Two patients with propionic acidemia had decreased growth hormone secretion in response to provocative stimuli (intravenous L-arginine and oral levodopa or clonidine); the remaining subjects had sufficient growth hormone secretion. Three of four subjects in whom IGF1 was measured showed subnormal concentrations at baseline (including two with normal growth hormone secretory responses). All patients showed an increase in linear growth with growth hormone. In the four patients studied, all had a significant increase in nitrogen retention over baseline with alanine or growth hormone alone, or with the combination of growth hormone and alanine, with a much greater effect of growth hormone. Lean body mass and body fat composition tended to become normal with treatment. Protein tolerance increased, and when the patients' dietary protein intakes were increased between 20 and 60% they maintained positive nitrogen balance, without a significant increase in metabolite excretion. One patient with propionic acidemia expired during the time of the study, following a course of recurrent pancreatitis and an episode of acute basal ganglia infarction. All of the other subjects showed clinical improvement (decreased incidence of ketoacidotic episodes and decreased frequency of hospital admission and school absence) during treatment, and even the patient who expired remained metabolically stable up to and through the terminal event. We conclude that growth hormone may be of value in the management of patients with organic acidemia.

3-Hydroxybutyric Acid↗

M-band structure, M-bridge interactions and contraction speed in vertebrate cardiac muscles.

Cardiac muscle M-band structures in several mammals (guinea pig, rabbit, rat and cow) and also from three teleosts (plaice, carp and roach), have been studied using electron microscopy and image processing. Axial structure seen in negatively stained isolated myofibrils or negatively stained cryo-sections shows the presence of five strong M-bridge lines (M6, M4, M1, M4' and M6') except in the case of the teleost M-bands in which the central M-line (M1) is absent, giving a four-line M-band. The M4 (M4') lines are consistently strong in all muscles, supporting the suggestion that bridges at this position are important for the structural integrity of the A-band myosin filament lattice. Across the vertebrate kingdom, cardiac M-band ultrastructure appears to correlate roughly with heartbeat frequency, just as in skeletal muscles it correlates with contraction speed, reinforcing the suggestion that some M-band components may have a significant physiological role. Apart from rat heart, which is relatively fast and has a conventional five-line M-band with M1 and M4 approximately equal, the rabbit, guinea pig and beef heart M-bands from a new 1 + 4 class; M1 is relatively very much stronger than M4. Transverse sections of the teleost (roach) cardiac A-band show a simple lattice arrangement of myosin filaments, just as teleost skeletal muscles. Almost all other vertebrate striated muscles, including mammalian heart muscles, have a statistical superlattice structure. The high degree of filament lattice order in teleost cardiac muscles indicates their potential usefulness for ultrastructural studies. It is shown that, in four-line M-bands in which the central (M1) M-bridges are missing, interactions at M4 (M4') are sufficient to define the different myosin filament orientations in simple lattice and superlattice A-bands. However the presence of M1 bridges may improve the axial order of the A-band.

Actin Cytoskeleton↗

Distal spinal cord pathology in the VATER association.

Herein the authors report the pathology of six cases of VATER association and tethered spinal cord that underwent operative intervention for removal of lipomas of the conusfilum terminale and/or release of the tethered cord. In five of the six patients, the excised filum terminale consistently showed excessive mature adipose tissue, normal blood vessels, small myelinated nerve fibers, and fibrous connective tissue. One patient had mature lobulated adipose tissue and vessels only. It is concluded that patients with the VATER association who present with distal spinal cord pathology consistently have abnormal involution of the filum terminale, the hallmark being an abnormal collection of mature fat, thickening of the filum, and extension of the fat into the conus medullaris.

Abnormalities, Multiple↗

Identification of a thymidylate synthase ribonucleoprotein complex in human colon cancer cells.

Translation of thymidylate synthase (TS) mRNA is controlled by its own protein product, TS, in an autoregulatory manner. Direct binding of TS protein to two different cis-acting elements on the TS mRNA is associated with this translational regulation. In this study, an immunoprecipitation-reverse transcription-PCR technique was used to identify a TS ribonucleoprotein (RNP) complex in cultured human colon cancer cells. Using antibodies specific for TS protein, we show that TS is complexed in vivo with its own TS RNA. Furthermore, evidence demonstrating a direct interaction between the mRNA of the nuclear oncogene c-myc and TS protein is presented.

Base Sequence↗

Lysosomal enzyme activities in Chediak-Higashi syndrome: evaluation of lymphoblastoid cell lines and review of the literature.

Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency disorder characterized by giant lysosomal granules in all granule-containing cells. Prior examination of lysosomal enzyme activities in granulocytes and other cells derived from patients with CHS have revealed multiple abnormalities, with the predominant finding being diminished activity of many of the enzymes tested. Abnormalities in lysosomal enzyme activity are also found in animal models of CHS (cattle, aleutian mink, and beige mice). In this study, we have examined lymphoblastoid cell lines derived from a patient with CHS and from an individual heterozygous for the CHS gene for acid phosphatase, beta-glucuronidase, and alpha-mannosidase activity. These cell lines have recently been shown to be satisfactory in vitro models for the disease. Acid phosphatase activity was increased in the heterozygous-derived cell line when compared to control while other enzyme activities were normal both in the CHS- and heterozygous-derived cell lines. We have reviewed the literature and summarized published abnormalities of lysosomal enzyme activities in humans and animals with CHS.

Acid Phosphatase↗

Incidence of renal anomalies in children prenatally exposed to ethanol.

OBJECTIVE: Based on a number of studies involving animals as well as human case reports indicating an association between prenatal ethanol exposure and renal malformations, it has been suggested that children with fetal alcohol syndrome (FAS) should be screened for renal anomalies. The purpose of this study was to evaluate a group of children prenatally exposed to alcohol to determine the incidence of renal anomalies and to evaluate the need for such a screening procedure. METHODS: Renal ultrasounds were performed on a total of 84 patients (68 children, 13 adolescents, and three adults). In addition to screening for malformations, renal size was studied. Data were analyzed using both chronologic and height-age as determinants of kidney size. PATIENTS: Of these 84 patients, 51 (61%) had FAS, and 33 (39%) had a history of prenatal ethanol exposure but did not have FAS. RESULTS: Three (3.6%) patients (one with FAS, two with prenatal ethanol exposure who did not have FAS) had significant renal abnormalities. This incidence was not significantly different from that found in ultrasound screening of newborns. The kidneys of children with both FAS and prenatal ethanol exposure who did not have FAS were significantly smaller than normal for both chronologic and height-age. When children were compared across chronologic ages, those with FAS had significantly smaller kidneys than those who had no evidence of FAS. After adjusting for height, the difference between these two groups was no longer significant. CONCLUSIONS: Based on these data, children prenatally exposed to ethanol do not need to be screened for renal anomalies.

Abnormalities, Drug-Induced↗