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Biomedical subjects

C L Smith

Publications and source records attributed to C L Smith.

At least 325 records · Page 18Linked to original sources

Survey of the use of colonoscopy in inflammatory bowel disease.

In a survey of patients with inflammatory bowel disease (IBD), colonoscopy with multiple biopsies has been shown to be superior to either colonoscopy alone or barium studies in assessing disease extent. Thus, of a total of 149 patients, 23 (15%) were considered to have total colitis on barium enema, 51 (34%) on macroscopic colonoscopy appearance compared to 92 (62%) on biopsy. Furthermore, radiological assessment of "skip lesions" was shown to be unreliable. Although it remains to be seen whether the more accurate delineation of disease extent achieved by endoscopy is advantageous in terms of clinical management, it may have implications for our understanding of the disease.

Biopsy↗

Medical evaluation and management of calcium nephrolithiasis.

Stone disease is a common medical problem, frequently recurs, and is associated with significant morbidity. Because appropriate medical therapy significantly decreases stone recurrence, this disorder must not be ignored by nonurologists. Even the single stone-former should be offered a metabolic evaluation.

Acidosis, Renal Tubular↗

When should the stone patient be evaluated? Early evaluation of single stone formers.

Nephrolithiasis is a common disease, associated with high morbidity in terms of hospitalization and surgery, and probably low, but nonetheless present, mortality. Evaluation is low in risk to the patient, is probably cost-effective, and nearly always reveals one or more abnormalities which, when specifically treated, will alter the natural history of the disease process.

Female↗

An evaluation of the one-day NBT-PABA/14C-PABA in the assessment of pancreatic exocrine insufficiency.

The one-day NBT-PABA/14C-PABA has been performed on 58 consecutive subjects with suspected or established pancreatic disease. 23 of these were normal subjects, 12 were subsequently shown to have other gastrointestinal disease and 23 had proven pancreatic disease. A PABA excretion index (PEI) has been calculated and, using our lower limit of normality (0.61), the test has shown an overall sensitivity of 83% and specificity of 89%. False positives were a particular problem in the other gastrointestinal disease group (25%). There was a close correlation between PEI and Lundh mean tryptic activity (r = 0.89). These results indicate that this test is a satisfactory screening test for pancreatic exocrine disease and is easier to perform with less likelihood of error than many other non-invasive tests of pancreatic function.

4-Aminobenzoic Acid↗

A comparison between the use of a shadow shield whole body counter and an uncollimated gamma camera ain the assessment of the seven-day retention of SeHCAT.

We have compared the 7-day retention of the radioisotope bile salt analogue SeHCAT (75Se-23-selena-25-homotaurocholate), by whole body counting and by uncollimated gamma camera measurement, in phantoms and in 25 patients with inflammatory bowel disease. The results correlate with a linear correlation coefficient of 0.96. An uncollimated gamma camera can be used to assess bile acid malabsorption when a whole body radioactivity monitor is not available.

Colitis, Ulcerative↗

The development and postnatal organization of motor nuclei in the rat thoracic spinal cord.

The topographic organization of the motor nuclei supplying individual thoracic muscles in postnatal rats was investigated by horseradish peroxidase (HRP) labelling from the periphery. To determine whether aspects of the same organization are apparent at early developmental stages, we used HRP to label neurons contributing axons to the two primary rami of thoracic nerves in rat fetuses ranging in age from the 13th day of gestation to birth. This developmental period includes stages during which peripheral nerves and muscles are forming. The results show that motoneurons in the appropriate positions in the ventral horn have axons in each primary ramus even at stages prior to the innervation of muscle. However, in fetuses at certain developmental stages, there are also neurons located outside the motor nuclei which send axons into the peripheral nerves.

Animals↗

The development and postnatal organization of primary afferent projections to the rat thoracic spinal cord.

Primary afferent projections to the thoracic spinal cord in fetal and postnatal rats were labelled by applying horseradish peroxidase (HRP) to the central stumps of cut peripheral nerves. Diaminobenzidine (DAB) and tetramethyl benzidine (TMB) histochemical processing procedures were used to reveal the HRP reaction product. In postnatal rats, individual muscle nerves were labelled to reveal the organization of muscle afferent projections to the motor nuclei. The terminals of muscle afferents were distributed widely across the dendritic arbors of motoneurons supplying the same muscles. No spatial segregation of the terminations of different populations of muscle afferents was discernable. Afferents supplying different regions of the skin were labelled by applying HRP to the dorsal and ventral primary rami of the spinal nerves. Afferents in the dorsal rami projected to lateral portions of both the ipsilateral and contralateral dorsal horns while afferents in the ventral rami projected to the medial portions of both dorsal horns. The projections of the dorsal rami were shifted caudally relative to those of the ventral rami. This relationship reflects the fact that the regions of skin innervated by the dorsal rami are displaced caudally relative to those innervated by the corresponding ventral rami. In fetuses, dorsal rami were labelled alone or in combination with ventral rami. These experiments disclosed the time course of development of the projections to different laminae of the spinal gray matter and revealed that afferents in the two primary rami project to appropriate regions in the ipsilateral and contralateral dorsal horns from the very outset.

Afferent Pathways↗

Climate and the evolution of brachycephalization.

Significant associations of cranial shape for 82 ethnic groups and seven climate variables are described. Variation among current populations is partially attributed to cold adaptation throughout the Pleistocene. Application of data files tabulated by the authors is described for a number of problems. Temporal distribution of 115 specimens indicates a geometric trend (CI = 76.7-1.96 log time X 10(3) ). Cranial indices are summarized within alternative taxonomic models and between climatic ecotypes. Evidence supports the hypothesis of cold adaptation among "Classic" Neandertals. Limitations of the thermodynamic model are discussed. It is probable that a decrease of the cranial index occurs from the Middle to Upper Paleolithic. During the Holocene, the index increases under all climatic conditions.

Adaptation, Biological↗

Failure to demonstrate altered gastric emptying in irritable bowel syndrome.

In irritable bowel syndrome (IBS), abnormalities of motility have been observed in the esophagus and small bowel, as well as in the colon. In order to investigate gastric function, gastric emptying has been measured in 25 patients with strictly defined IBS and compared with 25 age- and sex-matched controls. A standard radioisotope method for measuring gastric emptying has been employed. There was no significant difference between the two groups (T1/2 gastric emptying, IBS subjects 99.3 +/- 9.4 min, control subjects 104.0 +/- 11.9 min, mean +/- SEM), nor was there any major correlation between different symptom patterns and altered gastric emptying times. The results of the present investigation suggest that future studies on abnormalities in IBS should investigate other aspects of gastric motor function.

Adult↗

Characterization of an antigenic determinant of the glycoprotein that correlates with pathogenicity of rabies virus.

The pathogenicity of fixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies have been used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them, whereas nonpathogenic strains fail to react with these monoclonal antibodies and are not neutralized by them. Antigenic variants of the rabies virus with altered glycoprotein were selected by growing virus in the presence of one monoclonal antibody, 194-2. All variants that lost their ability to react with this antibody and an additional antibody, 248-8, were found to be nonpathogenic for adult mice. Analysis of tryptic peptides of the glycoproteins of pathogenic parent virus and nonpathogenic variants and the amino acid sequence of a specific variant tryptic peptide revealed that the change in pathogenicity corresponded to an amino acid substitution at position 333 of the glycoprotein molecule. The nucleotide sequence of the nonpathogenic variant glycoprotein gene contained a base change that confirmed the single amino acid substitution in the tryptic peptide replacing arginine-333 in the parental glycoprotein. We conclude that arginine-333 is essential for the integrity of an antigenic determinant and for the ability of rabies viruses to produce lethal infection in adult mice.

Amino Acid Sequence↗

recF-dependent induction of recA synthesis by coumermycin, a specific inhibitor of the B subunit of DNA gyrase.

Genetic and biochemical studies on enzymes known to be involved in regulating DNA supercoiling yield a complex spectrum of effects on the Escherichia coli SOS system. Previous studies indicated that only inhibition of DNA gyrase by antibiotics that act on the DNA gyrase A subunit results in turning on the E. coli SOS system. Here we show that coumermycin, an antibiotic that acts on the DNA gyrase B subunit, can also induce. Like nalidixic acid induction, coumermycin induction is dependent on the recBC DNase. In both cases induction apparently results from a response of the cell to the DNA gyrase-inhibitor complex rather than just the loss of DNA gyrase activity. However, unlike induction by the DNA gyrase A-specific antibiotics, coumermycin induction also requires the recF gene product. This demonstrates a functional relationship between DNA gyrase and the recF gene product.

Aminocoumarins↗

Adaptive doses of MNNG efficiently induce a recA-trp gene fusion.

The recA gene product plays a critical role in the Escherichia coli SOS system. To facilitate studies of the regulation of the recA operon, we constructed a gene fusion between the recA operon and the Salmonella trp operon. This gene fusion closely mimics the behavior of the authentic recA operon in vivo. Using the gene fusion, we looked at the effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on recA expression. In contrast to the expectations from previous work, we found that low (0.5 microgram/ml) adaptive doses of MNNG induce the recA-trp gene fusion as efficiently as other SOS inducers without inducing either lambda or phi 80 prophages. These results are a clear example of the ability of some agents to induce a subset of the SOS-dependent operons. They force a reevaluation of many of the arguments that have led to the conclusion that the SOS and adaptive responses are completely independent.

Anthranilate Synthase↗

Mutagenicity and DNA damage induced by arylamines in the Salmonella/hepatocyte system.

Coincubation of isolated, intact rat hepatocytes with Salmonella typhimurium tester strain TA 98 (Salmonella/hepatocyte system) has been employed to determine both bacterial mutagenicity and DNA damage in rat hepatocytes following treatment with 2-acetylaminofluorene (AAF) and its derivatives. In vivo pretreatment of rats with either 2,3,7,8-tetrachlorodibenzodioxin or 3-methylcholanthrene markedly increased both DNA damage and bacterial mutation frequency upon incubation of AAF or 2-aminofluorene (AF) in this system. The increase in damage to the hepatocyte DNA was more pronounced after AAF treatment than following AF exposure, while the increase in bacterial mutation frequency was greater after AF treatment. Treatment of hepatocytes with paraoxon prior to exposure to N-hydroxy-2-acetylaminofluorene (N-OH-AAF) or N-acetoxy-2-acetylaminofluorene (N-OAc-AAF) partially inhibited both DNA damage and the bacterial mutagenicity caused by these agents. Treatment of primary rat hepatocytes with 2-hydroxy-2-aminofluorene (N-OH-AF) causes a low level of DNA breaks. Substitution of primary rat hepatocytes with highly differentiated rat hepatoma cells (Reuber H4-II-E) revealed a low level of DNA breakage after exposure to N-OH-AAF whereas treatment with either N-OAc-AAF or N-OH-AF induced a dose dependent increase in DNA breaks. Pretreatment of the Reuber cells with paraoxon inhibited the DNA damage caused by N-OAc-AAF whereas the DNA damage induced by N-OH-AF was increased after paraoxon treatment. Employing host cells with differing metabolic capacity, such as Reuber vs. primary hepatocytes, in the Salmonella/hepatocyte system, may allow a determination of the relative importance of different metabolic pathways in mutagenicity and/or genotoxicity of arylamines.

2-Acetylaminofluorene↗

The absorption and conjugation of methyldopa in patients with coeliac and Crohn's diseases during treatment.

The absorption and elimination of a single 500 mg dose of methyldopa has been studied after oral administration to 10 normal volunteers, 10 patients with coeliac disease, who were on a gluten-free diet, and to five patients with Crohn's disease. In patients with Crohn's disease the percentage of the dose recovered in urine (24%) was about one-half of normal (50%). This decreased absorption was associated with reduced plasma concentrations of both free and conjugated methyldopa and a decreased pharmacological response. In patients with coeliac disease the percentage of dose recovered in urine (43%) was similar to normals, indicating a normal absorption of the drug. However, the plasma concentrations of both free and conjugated methyldopa were significantly higher than normal, although there was no increase in drug-related effects. These findings confirm the importance of using indices other than drug plasma concentrations in the assessment of bioavailability in disease states.

Adult↗

Delay in diagnosis of adult coeliac disease.

The delay in diagnosis of 106 patients with adult coeliac disease, diagnosed between 1976 and 1980, was studied. Overall, delay in diagnosis was 11 +/- 10.6 years, being considerably greater in females (12.8 +/- 7.8 years) than in males (3.5 +/- 9.8 years). Most of this delay occurred prior to hospital referral, although that following referral to hospital clinics was still significant (1.8 +/- 4.8 years). The most common presenting complaints were lassitude (75%) anaemia (65%) and flatulence (50%). Typical gastro-intestinal symptoms were relatively uncommon and mild, but when present led to a more speedy diagnosis. It is concluded that, despite advances in modern diagnostic procedures, little progress has been made in hastening the diagnosis of coeliac disease.

Aged↗

The misdiagnosis of common bile duct stones with ultrasound.

Ultrasound is now widely used to demonstrate the presence of gall-stones in the gall bladder and common bile duct in jaundiced patients. The ultrasound appearance of gall-stones is characteristic and consists of strong, bright reflections with shadowing distally, though stones smaller than 3 or 4 mm may not always show shadowing. We report our experience with large common bile duct stones which do not show the characteristic features of gall-stones and so may be misdiagnosed as tumour masses. The possible reasons for these appearances are discussed.

Adenoma, Bile Duct↗