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J R Hamilton

Publications and source records attributed to J R Hamilton.

At least 19 recordsLinked to original sources
PubMed1992

Differences in Ca(2+)-mediation of hypotonic and Na(+)-nutrient regulatory volume decrease in suspensions of jejunal enterocytes.

We determined differences in the Ca2+ signalling of K+ and Cl- conductances required for Regulatory Volume Decrease (RVD) in jejunal villus enterocytes passively swollen (0.5 or 0.95.isotonic) compared with swelling because of the absorption of D-glucose (D-Glc) or L-Alanine (L-Ala). Cell volume was measured using electronic cell sizing. In nominally Ca(2+)-free medium containing EGTA (100 microM) RVD after 0.5 or 0.95.isotonic challenge was prevented. L-Ala swelling and subsequent RVD was influenced in Ca(2+)-free medium. Villus cells were incubated with 10 microM of the acetomethoxy derivative of 1,2.bis (2-aminophenoxy) ethane N,N,N1,N1 tetracetic acid (BAPTA-AM) and RVD after 0.5.isotonic swelling or L-Ala swelling was prevented. Niguldipine (0.1 microM), nifedipine (5 microM), diltiazem (100 microM), Ni2+, and Co2+ (1 mM) all prevented hypotonic RVD but had no effect on RVD after L-Ala addition. Charybdotoxin (25 nM) a potent inhibitor of Ca(2+)-activated K+ channels, had no effect on hypotonic RVD but prevented RVD of villus cells swollen by D-Glc. We used the calmodulin antagonists, naphthalene sulfonamide derivatives W-7 and W-13, to assess calmodulin activation of K+ and Cl- conductance in these two models. L-Ala swelling and subsequent RVD was not influenced by 25 microM W-7; hypotonic RVD was prevented by 25 microM W-7 or 100 microM W-13. The W-13 inhibition of RVD was by-passed with 0.5 microM gramicidin. Our data show that hypotonic RVD requires extracellular Ca2+ and that the K+ conductance activated is not charybdotoxin sensitive but requires calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prevalence of measles antibodies in adults with HIV infection: possible risk factors of measles seronegativity.

OBJECTIVES: To determine the prevalence of measles (rubeola) immunity in a group of HIV-1-infected adults and to examine predictors of measles seronegativity in this population. SETTING: County hospital outpatient clinic and public-health department early HIV intervention clinic. PATIENTS: A total of 262 HIV-infected adults presenting to outpatient clinics between September 1990 and January 1991. INTERVENTIONS: Patients were screened for the presence of measles immunoglobulin G antibody, as measured by an enzyme-linked immunosorbent assay (ELISA). Pertinent clinical and immunologic information was recorded. Univariate and multivariate analyses were performed to identify possible risk factors for measles seronegativity. MAIN OUTCOME MEASURE: Measles seronegativity, as defined by a lack of detectable antibody (ELISA predicted index value < 1.0). RESULTS: Thirteen (5%) patients lacked serologic evidence of immunity. Risk factors for measles seronegativity included year of birth in 1957 or later, Caucasian (non-Hispanic) race and oral hairy leukoplakia. Factors associated with progressive HIV disease (other than hairy leukoplakia) were not associated with a lack of existing immunity. CONCLUSIONS: A high prevalence (95%) of measles antibody was found in this large group of HIV-infected adults. Young, white individuals born in 1957 or later were at the greatest risk for measles seronegativity, but declining immunity due to progressive HIV infection did not appear to be associated with a lack of antibody. Self-reported histories of measles infection or immunization were not reliable predictors of measles immunity.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effect of protein kinase C inhibitors on Cl- conductance required for volume regulation after L-alanine cotransport.

We used electronic cell sizing and Cl- efflux measurements in guinea pig jejunal enterocytes to study activation of Cl- conductance under two experimental conditions, regulatory volume decrease (RVD) after passive hypotonic swelling and volume regulation during Na(+)-alanine cotransport. RVD after a hypotonic (0.5 x isotonic) challenge was not affected by the protein kinase C (PKC) inhibitor 100 microM 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). Volume decrease after cell swelling in response to L-Ala (25 mM) was prevented by H-7 (P less than 0.05) or the more potent PKC inhibitor 10 nM staurosporine (P less than 0.001). L-Ala stimulated biphasic 36Cl efflux, a rapid efflux over 60 s which was inhibited by H-7 (P less than 0.01) and the Cl(-)-channel blocker anthracene-9-carboxylic acid (9-AC) (P less than 0.005). In contrast, after hypotonic dilution the rate of 36Cl efflux increased (P less than 0.005); H-7 had no effect but 9-AC inhibited the increase (P less than 0.01). Gramicidin (0.5 microM) added to cells maximally swollen by L-Ala in Cl(-)-containing medium caused 2 degree swelling (P less than 0.001), but 10 nM staurosporine reduced this 2 degree swelling (P less than 0.001). Addition of phorbol ester or synthetic diacylglycerol to villus cells under isotonic conditions, after gramicidin addition, caused cell swelling (P less than 0.005) that was inhibited by staurosporine (P less than 0.05). We concluded that PKC does not activate Cl- conductance for hypotonic RVD but that Na(+)-nutrient cotransport is a physiological stimulus for PKC to activate Cl- conductance necessary for volume regulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Effect of osmotic swelling on K+ conductance in jejunal crypt epithelial cells.

To further elucidate differences in ion transport properties between jejunal crypt and villus cells, we compared the responses of purified cell suspensions to hypotonic stress using electronic cell sizing to evaluate volume changes and 86Rb and 36Cl efflux. After hypotonic swelling, villus enterocytes undergo a regulatory volume decrease (RVD) due to the loss of K+ and Cl- through volume-activated conductances. After 0.6x isotonic challenge in Na(+)-free medium, crypt cells exhibited only partial RVD, with t1/2 congruent to 15 min. The addition of a cation ionophore, gramicidin (0.25 microM), to hypotonically swollen crypt cells caused an accelerated RVD, which was complete with t1/2 congruent to 5 min. Crypt epithelial cells showed no volume-activated 86Rb efflux, but villus enterocytes had an increased rate of 86Rb efflux after hypotonic dilution (P less than 0.001). Gramicidin added to hypotonically diluted crypt cells greatly increased the rate of 86Rb efflux compared with controls. Both villus (30 s; P less than 0.005) and crypt (2 min; P less than 0.001) cells exhibited volume-activated 36Cl efflux in absence of gramicidin. Cl- channel blockers anthracene-9-carboxylate (9-AC, 300 microM) and indanyloxyacetic acid (IAA-94, 100 microM) prevented crypt RVD (P less than 0.001) in the presence of gramicidin. Ouabain (P less than 0.001) or K(+)-free Na(+)-containing medium, but not Ba2+ (5 mM) or quinine (100 microM), prevented crypt partial RVD. We conclude that crypt cells lack volume-activated K+ conductance. The RVD exhibited by crypt cells, although partial, was due to Cl- loss through a volume-activated Cl- conductance and Na+ loss via Na(+)-K(+)-ATPase.

Animals↗
PubMed1991

Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes.

We studied cell-volume changes caused by adding corticostatin (CS) or defensin-like peptides to villus enterocytes isolated in suspension from guinea pig jejunum. Guinea pig CS (10(-9) M) added to villus cells in Na(+)-containing medium reduced volume, but immediate cell swelling was caused by 10(-6) M guinea pig CS. In Na(+)-free N-methyl-D-glucamine-containing medium 10(-9) M guinea pig CS accelerated the initial rate of shrinkage compared with cells in N-methyl-D-glucamine-containing medium alone as well as causing greater cell shrinkage. Guinea pig CS-stimulated cell shrinkage was prevented by a Ca2(+)-channel blocker--5 microM nifedipine, by chelation of extracellular Ca2+ with 100 microM EGTA, or by omega-conotoxin (10(-9) M). The Ca2+ ionophore A23187 (2.5 microM) reduced volume when added to villus cells in N-methyl-D-glucamine-containing medium; this action was prevented by EGTA, or quinine--an inhibitor of K+ conductance, or 9-anthracenecarboxylic acid--a Cl- channel blocker, suggesting that the volume reduction occurred because K+ and Cl- conductances were activated. Guinea pig CS-stimulated volume reduction was also prevented by 100 microM quinine or 9-anthracenecarboxylic acid. We conclude that jejunal villus enterocytes possess a Ca2(+)-activated Cl- conductance and a K+ conductance that need not be stretch-activated. Corticostatic peptides cause volume reduction in villus cells by activating L-type Ca2+ channels; other defensin-like peptides were without effect.

Amino Acid Sequence↗
PubMed1991

Volume regulation initiated by Na(+)-nutrient cotransport in isolated mammalian villus enterocytes.

We assessed ion transport during regulatory volume decrease (RVD) in jejunal villus enterocytes, isolated in suspension from guinea pig jejunum and swollen by exposure to L-alanine (L-Ala) or D-glucose (D-Glc) in the presence of Na+. Cell volume was measured electronically. Relative volume of cells (rel vol: cell vol/isotonic vol) within 1 min of L-Ala (20 mM) addition increased (1.10 +/- 0.03, P less than 0.005), but by 5 min there was no difference between cells in L-Ala or 20 mM D-Ala (0.95 +/- 0.02). Cell shrinkage after maximal swelling was greater with L-Ala than with D-Ala (14 +/- 4 vs. 2 +/- 1%, P less than 0.01). Initial swelling generated by L-Ala required extracellular Na+ (P less than 0.02). Volume increased 30 s after D-Glc (20 mM), and cells were larger than cells treated with L-Glc (1.04 +/- 0.01 vs. 0.95 +/- 0.01, P less than 0.001); subsequent cell shrinkage was complete in 2 min (8 +/- 2%, P less than 0.05). Swelling generated by methyl alpha-D-glucoside was prevented by 0.1 mM phloridzin (P less than 0.05). RVD after D-Glc swelling was prevented by inhibitors of K+ channels, 5 mM Ba2+ (P less than 0.001), 100 microM quinine (P less than 0.005), or 25 mM TEA (P less than 0.02), but the same inhibitors completely prevented L-Ala swelling. All inhibitors had no effect on L-Ala uptake into brush-border membrane vesicles in presence of Na+ gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1991

Separate K+ and Cl- transport pathways are activated for regulatory volume decrease in jejunal villus cells.

We assessed ion transport mechanisms operative during regulatory volume decrease (RVD) in jejunal villus enterocytes, isolated in suspension from guinea pig jejunum and examined with electronic cell sizing. Immediately after reduction of osmolarity (153 mosmol/kg medium) enterocytes swelled, but within 5 min they shrank by 50%. This RVD, which was complete by 20 min, was unaffected by Li+ substitution for Na+ or by Na(+)-free (N-methyl-D-glucose, NMDG+) medium. Passive loss of K+ is required for RVD because both the magnitude and direction of RVD changed when external [K+] varied. Increasing K+ permeability with gramicidin (0.5 microM) accelerated RVD in NMDG+ medium (10.0 +/- 0.8 vs. 6.2 +/- 0.4% min-1, P less than 0.01) suggesting that K+ loss is rate limiting for RVD. Inhibition of K(+)- and Ca2(+)-activated K+ conductance with Ba2+ (5 mM, P less than 0.005), quinine (100 microM, P less than 0.005), or apamin (1 microM, P less than 0.005) prevented RVD. Inhibition of Cl- conductance with 9-anthracenecarboxylic acid (100 microM, P less than 0.005) or dipyridamole (75 microM, P less than 0.005) also prevented RVD. In isotonic HCO3(-)-buffered medium, the addition of gramicidin to cells generated conditions in which anion permeability was rate limiting for cell swelling. This swelling was inhibited 97% by 100 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In K(+)-free, HCO3(-)-buffered medium containing DIDS and gramicidin hypotonic swelling resulted in continued (secondary) swelling (rel vol 1.19 +/- 0.01 vs. 1.25 +/- 0.02, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

A clinical study of young infants after small intestinal resection.

We prospectively studied 15 infants who, before 3 months of age, underwent resection of the small intestine-proximal in 3 infants, mid in 6, and distal in 6. Two died before one year of age. Many required prolonged parenteral nutrition, but by one year, 12 of the 13 survivors were on oral feedings only, and seven were above the third percentile for height and weight. Developmental delay occurred in the early postoperative period but diminished with time. There was compensatory adaptation of the remaining gut, shown by improving fat and B12 absorption and duodenal bile-salt concentrations. Bacterial contamination complicating end-to-side anastomoses occurred in two cases (P), gastric hyperacidity in four of 12 (1P, 3M), and hyperoxaluria in eight of 14 (1P, 5M, 2D). Studies of immune competence revealed normal cellular immune function (11/11), transient hypogammaglobulinemia (3/14), hypocomplementemia (1/12), and serum autoantibodies (3/10). Thus, massive resection of the small intestine did not preclude spontaneous improvement in absorptive function, growth, and development.

Child Development↗
PubMed1979

Evaluation of a detoxification service of habitual drunken offenders.

The progress of 52 chronic alcoholic habitual drunken offenders who were offered a detoxification, assessment and referral service as an alternative to penal management for their public drunkenness was compared over a year with 48 control subjects, and each group's progress in the experimental year was compared with that in the previous year. The 'detoxification' patients were found not to have benefited as regards their alcoholism or episodes of drunkenness, though their periods of abstinence were longer. There were significant improvements in their accommodation and self-reported quality of life, and it is likely that their physical and perhaps mental health improved.

Alcoholism↗
PubMed1979

Determinants of diarrhea in viral enteritis. The role of ion transport and epithelial changes in the ileum in transmissible gastroenteritis in piglets.

To understand mechanisms of viral diarrhea further, we studied ileal ion transport in vitro in relation to mucosal changes and epithelial differentiation in transmissible gastroenteritis in piglets, an invasive viral enteritis thought to involve mainly proximal intestine. In infected pigs, at the height of diarrhea, short-circuited ileal epithelium failed actively to transport Na+ and Cl-, and there was a defect of glucose-mediated Na+ transport. The Cl- secretory response to theophylline remained intact. Conductance measurements indicate that paracellular permeability may be reduced and transcellular transport may be altered. A mucosal lesion was observed at the time of the transport changes, characterized by villus blunting, crypt hyperplasia, and immature crypt-type enterocytes on the villus epithelium, deficient in disaccharidase and (Na+, K+)ATPase activity but rich in thymidine kinase. Consideration of the major determinants of diarrhea in this invasive enteritis must take into account not only altered mucosal function and differentiation but also the extent of intestinal involvement, including the ileum, a major site of fluid absorption in the intestine.

Animals↗
PubMed1978

Intestinal function in infants with severe congenital heart disease.

We evaluated digestive tract function in 21 young infants with severe congenital heart disease. One group had congestive heart failure and ventricular septal defect or single ventricle; the other had cyanosis and transposition of the great arteries. Enteric protein loss was excessive in eight patients, and steatorrhea was found in five. These abnormalities were mild and not related to the type or severity of the cardiac lesion. Available evidence points to a need of these babies for calories in excess of normal requirements for weight. The present study suggests that in designing dietary regimens for these very sick patients, their potential for defective gastrointestinal function must be considered. Because no consistent pattern of abnormalities in apparent, each patient who fails to thrive may deserve gastroenterologic evaluation.

Body Weight↗
PubMed1978

Synergistic infection with murine cytomegalovirus and Pseudomonas aeruginosa in mice.

A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 0--20% lethal inoculum of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (90%--100%) within 48 hr after an intravenous injection of a 0--20% lethal inoculum of Pseudomonas aeruginosa. The current study demonstrated that mice infected with murine CMV alone had high titers of virus in multiple organs over a 20-day period, whereas mice injected with P. aeruginosa alone had a self-limited infection confined to the kidney. In the combined murine CMV-P. aeruginosa infection, titers of virus in tissues were changed very little. In contrast, P. aeruginosa was recovered in high concentrations from multiple organs, a finding which demonstrated a progressive systemic infection closely resembling that produced by a 100% lethal inoculum of P. aeruginosa alone in normal mice. An increased mortality rate due to P. aeruginosa in murine CMV-infected mice was dependent on inoculation of live bacteria and could not be explained by enhanced susceptibility to endotoxin. These results indicate that murine CMF markedly enhanced the suceptibility of mice to infection with P. aeruginosa and suggest that the virus altered mechanisms of host resistance important in recovery from bacterial infections.

Animals↗
PubMed1978

Familial enteropathy: a syndrome of protracted diarrhea from birth, failure to thrive, and hypoplastic villus atrophy.

We have studied 5 infants with persistent severe diarrhea from birth and marked abnormalities of absorption associated with failure to thrive leading to death in 4 infants. Three had siblings who died and a sibling of a 4th is ill at present, all with a similar illness; 2 were the products of consanguinous marriages. Exhaustive investigation failed to identify a recognized disease entity in any patient. Steatorrhea, sugar malabsorption, dehydration, and acidosis were severe in all patients, whatever the diet fed. Total parenteral nutrition was used, but excessive stool water and electrolyte losses persisted even when nothing was fed by mouth. There was no evidence of a hematological or consistent immunological defect in any infant and no abnormalities of intestinal hormones were noted. In the duodenal mucosa of all infants we saw similar abnormalities characterized by villus atrophy, crypt hypoplasia without an increase in mitoses or inflammatory cell infiltrate in the lamina propria and in villus enterocytes absence of a brush border, increase in lysosome-like inclusions, and autophagocytosis. In 3 infants studied by marker perfusion of the proximal jejunum we found abnormal glucose absorption and a blunted response of Na+ absorption to actively transported nonelectrolytes; in 2 there was net secretion of Na+ and H2O in the basal state. Our patients evidently suffered from a congenital enteropathy which caused profound defects in their capacity to assimilate nutrients. The similar structural lesion seen in the small intestinal epithelium of all of our cases undoubtedly contributed to their compromised intestinal function, but the pathogenesis of this disorder, if indeed it is a single disease, remains obscure.

Acidosis↗