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Biomedical subjects

T L Miller

Publications and source records attributed to T L Miller.

At least 19 recordsLinked to original sources
PubMed1995

Gastrostomy tube supplementation for HIV-infected children.

OBJECTIVE: Malnutrition is common in pediatric human immunodeficiency virus (HIV) infection, and little is known of effective nutritional interventions. We sought to determine whether enteral supplementation with gastrostomy tube feedings would provide improvements in weight, height, body composition, immune parameters, morbidity, and mortality. METHODS: We collected clinical data on 23 HIV-infected children who were fed chronically by gastrostomy tube. The main outcome measures included weight, height, triceps skinfold thickness (TSF), arm-muscle circumference (AMC), hospital days, caloric intake, and CD4-positive T-lymphocyte count. Each of these parameters was measured or evaluated at four points: 6 months before nasogastric tube feeding, at the time nasogastric tube feeding was initiated, at the time gastrostomy tube feeding was initiated, and 6 months after gastrostomy tube feedings began. RESULTS: Weight z score [-2.1 (0.14) to -1.58 (0.14)] and weight-for-height z score [-0.98 (0.16) to -0.15 (0.17)] improved with gastrostomy tube feedings. There was a trend toward improvement in weight z score with nasogastric tube feedings. Caloric intakes increased progressively with nasogastric and gastrostomy tube feedings. No improvement in height, TSF, AMC, hospital days, or CD4 counts was seen in the follow-up period. However, children who had the greatest increase in weight had the most improvement in fat stores (TSF) (r = .65, P = .002) and a decrease in hospital days after the gastrostomy tube was placed (r = -.48, P = .025). Higher age-adjusted CD4 counts and lower weight-for-height z scores at the time of enteral supplementation were significant predictors of a positive response to gastrostomy tube feedings (r = .85, P = .0001). Children who responded favorably had a 2.8-fold reduction in the risk of dying for every positive unit change in weight z score (P = .005). CONCLUSION: Gastrostomy tube supplementation for HIV-infected children can improve weight and fat mass when other oral methods fail. Weight gain is coincident with greater caloric intakes. HIV-infected children with higher CD4 counts and lower weight-for-height z scores are likely to respond favorably to gastrostomy tube feedings. Early nutritional intervention is indicated for HIV-infected children.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Protein phosphatase activity against protein kinase C-phosphorylated substrates in human placenta.

The presence of endogenous modulators of protein kinase C (PKC) in human placenta has not been reported. The specific activity of PKC in human placental cytosol was 20.52 +/- 1.8 pmol/min x mg protein. Partial purification of placental cytosol on diethylaminoethyl cellulose (DEAE) resulted in recovery of 145 per cent of original enzyme activity. Placental cytosol mixed with a control preparation of PKC significantly inhibited the control enzyme activity (control 42.42 +/- 2.8 pmol/min; control+placental cytosol 27.44 +/- 2.8 pmol/min, P < 0.05). The PKC-inhibitory activity was abolished by the addition of phosphatase inhibitors calyculin A (0.09 nM), microcystin LR (0.8 nM), and okadaic acid (0.4 nM). Protein substrates phosphorylated by PKC were rapidly dephosphorylated upon the addition of placental cytosol; this dephosphorylation was prevented by the presence of calyculin A and was removed by fractionation of placental cytosol on DEAE. Protein but not peptide substrate supported both the PKC-inhibitory activity and the dephosphorylation of PKC-phosphorylated substrates. The placental serine-threonine protein phosphatase was active against phosphorylase a, but not against substrate phosphorylated by cAMP-dependent protein kinase. These data indicate that the human placenta contains an endogenous inhibitor of PKC which interacts with substrate rather than with the PKC and that the inhibitor is a protein phosphatase.

Calcium↗
PubMed1993

The endogenous inhibitor of protein kinase-C in the rat ovary is a protein phosphatase.

Calcium- and lipid-dependent protein kinase (PKC) activity in the ovary of the pseudopregnant rat is masked by an endogenous inhibitor of PKC. These studies were undertaken to examine the mechanism of action of the endogenous inhibitor of PKC in the rat ovary. The addition of the phosphatase inhibitors calyculin-A (0.09 nM), microcystin-LR (6.4 nM), and okadaic acid (10 nM) resulted in the loss of PKC inhibitory activity and an increase in basal PKC activity in rat ovarian cytosol. In phosphatase assays, significant dephosphorylation of histone-III-S or myelin basic protein that had been phosphorylated by PKC occurred within 4 min after the addition of ovarian cytosol from the pseudopregnant rat. This dephosphorylation was prevented from the pseudopregnant rat. This dephosphorylation was prevented by the addition of calyculin-A (0.73 nM) and was removed by fractionation of ovarian cytosol on diethylaminoethyl cellulose. No inhibition of PKC activity was observed when the PKC-specific peptides AcMBP-(4-14) and [Ser25]PKC-(19-31) were used as the substrate for phosphorylation. In addition, rat ovarian cytosol did not exhibit phosphatase activity when the peptide AcMBP-(4-14) was used as the substrate. Addition of ovarian cytosol resulted in dephosphorylation of phosphorylase-alpha phosphorylated by phosphorylase kinase, but not dephosphorylation of histone-II-A or histone-VIII-S phosphorylated by PKA. The data suggest that the endogenous inhibitor of PKC in the rat ovary is a protein phosphatase.

Animals↗
PubMed1992

Pancreatitis in pediatric human immunodeficiency virus infection.

Because pancreatitis has been reported frequently in adults with human immunodeficiency virus infection, we sought to determine the incidence of pancreatitis in children with acquired immunodeficiency syndrome by reviewing all records of children with AIDS, their serum amylase and lipase levels, and the factors associated with pancreatitis through a case-control analysis. During a 6-year period pancreatitis developed in 9 (17%) of 53 pediatric patients with AIDS. Six children had vertical transmission of infection and three patients had acquired HIV infection through contaminated blood products. Pancreatitis developed at a median age of 5.2 years (range 1.2 to 20 years). All patients had vomiting and abdominal pain. When the patients were first seen, lipase values were elevated more than amylase values (p = 0.028). Amylase and lipase levels declined at comparable rates. In the case-control analysis, pentamidine isethionate was significantly associated with pancreatitis (p = 0.02); the risk was greater in patients who received pentamidine isethionate and had absolute CD4 T-lymphocyte counts less than 100 cells/mm3 (p = 0.001). Infections associated with the onset of pancreatitis included cytomegalovirus (4), Cryptosporidium (1), Pneumocystis carinii pneumonia (3), and Mycobacterium avium intracellulare (1). Coinfection with cytomegalovirus was associated with a protracted course in four children. Ultrasonographic examination demonstrated biliary ductal dilatation 6 months after the onset of pancreatitis in one child. Seven children have died at a mean of 8 months after the initial onset of pancreatitis; the one living child has survived 5 months from the onset of pancreatitis. We conclude that pancreatitis is common in pediatric patients with AIDS and may be related to pentamidine isethionate exposure, especially when absolute CD4 T-lymphocyte counts are less than 100 cells/mm3. Serum amylase levels do not always accurately predict the onset of pancreatitis; serum lipase levels should be measured in children with symptoms. The onset of pancreatitis in an HIV-infected child is a poor prognostic indicator.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Cornstarch fermentation by the colonic microbial community yields more butyrate than does cabbage fiber fermentation; cornstarch fermentation rates correlate negatively with methanogenesis.

Fermentations of cornstarch and a cabbage-fiber preparation by human fecal suspensions were studied. The molar percent of butyrate of total short-chain fatty acid products was significantly higher when cornstarch was the substrate. Higher molar percents of butyrate were also produced from cornstarch as compared with endogenous substrate when rat fecal suspensions were used. A range of cornstarch fermentation rates was found with suspensions from 20 human subjects. Rapid fermentaion was associated with the absence of methane production. Methane-negative rat fecal suspensions also fermented cornstarch more rapidly than did methane-positive suspensions. High butyrate production may be important because butyrate provides energy to colonocytes and it regulates differentiation of cultured cells.

Analysis of Variance↗
PubMed1991

Large-scale purification of gp70 from Moloney murine leukemia virus.

The external envelope glycoprotein, gp70, of the Moloney murine leukemia virus was extracted from NIH 3T3 cells utilizing the detergent n-octyl-beta-D-glycopyranoside. The extracted gp70 was sequentially purified utilizing lectin-affinity, anion-exchange, and molecular-exclusion chromatography techniques. Approximately 10 mg of gp70 was purified by this method and shown to be 95% homogeneous, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of purified gp70 from Moloney murine leukemia virus was confirmed by amino acid analysis, amino-terminal sequencing, and immunoreactivity with a monoclonal antibody raised against gp70. The procedure is rapid, utilizes commercially available media, and can be used to purify large amounts of retroviral envelope glycoprotein from virus.

Amino Acid Sequence↗
PubMed1991

Malnutrition and carbohydrate malabsorption in children with vertically transmitted human immunodeficiency virus 1 infection.

The nutritional needs of children with human immunodeficiency virus infection are poorly understood. Twenty-eight children with vertically transmitted human immunodeficiency virus infection were evaluated for carbohydrate malabsorption using lactose hydrogen breath tests and d-xylose absorption studies. Lactose malabsorption was a common finding in human immunodeficiency virus-infected children and occurred in 8 of 20 patients who had no identifiable enteric pathogen. Lactose malabsorption occurred at an earlier age in human immunodeficiency virus-infected children than in an age-matched group of 45 symptomatic control children (P = 0.02). However, lactose malabsorption was not associated with higher rates of diarrhea or growth failure. Abnormalities in d-xylose absorption were not significantly associated with either diarrhea or growth failure. However, 39% of d-xylose studies (9 of 23) showed abnormal results and were significantly associated with enteric infections (P = 0.004). Abnormalities in small-bowel morphology were found in 4 of 9 children with growth failure, 3 of whom had an enteric infection and low d-xylose absorption. Lactose hydrogen breath testing and d-xylose testing showed carbohydrate malabsorption in 61% of children (17 of 28). This study demonstrates that human immunodeficiency virus-infected children are at risk for malabsorptive disorders, which are not always related to clinical symptoms. We speculate that human immunodeficiency virus may be directly involved in the development of lactose malabsorption. Carbohydrate malabsorption in human immunodeficiency virus-infected children may not be the only factor responsible for growth failure.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Chlordecone impairs Na(+)-stimulated L-[3H]glutamate transport and mobility of 16-doxyl stearate in rat liver plasma membrane vesicles.

Chlordecone (CD) treatment of rat liver plasma membranes (LPM) provided in vitro evidence for mechanisms of in vivo liver dysfunction caused by CD. LPM preparations enriched 14- to 19-fold in the bile canalicular markers gamma-glutamyl transpeptidase, alkaline phosphatase, and leucine aminopeptidase were isolated from male Sprague-Dawley rats. CD inhibited the bile canalicular-specific active transport of Na(+)-stimulated L-[3H]glutamate in LPM vesicles. CD (0.08 and 0.5 mumol/mg protein) reduced both the initial velocity and the maximum level of Na(+)-stimulated L-[3H]glutamate uptake without significantly reducing Na(+)-independent uptake. In vitro treatment of LPM with CD (0.2-1.0 mumols/mg protein) also reduced the mobility of a 16-doxyl stearate spin label probe in a concentration-dependent manner. No change in mobility was apparent at CD concentrations below 0.2 mumol/mg protein. These results demonstrated that CD impaired a bile canalicular-specific transport system and induced liver plasma membrane perturbation. Na(+)-stimulated L-[3H]glutamate uptake was more sensitive to CD than was detectable immobilization of the spin label probe.

Animals↗
PubMed1990

Urgent care center pediatric telephone advice.

Pediatric telephone advice is sought frequently by members of the community. This study was undertaken to evaluate the quality and accuracy of pediatric telephone advice given by free-standing urgent care centers. One hundred such facilities were telephoned and advice was requested by a research assistant. A case was presented that could have represented a pediatric medical emergency. Overall only 17 centers gave adequate advice. The data suggest that under some circumstances free-standing urgent care center pediatric telephone advice may be inaccurate and inappropriate. Workable policies and protocols for pediatric telephone advice should be instituted by these facilities.

Algorithms↗
PubMed1989

Increase in colonic methanogens and total anaerobes in aging rats.

Methanogens are present in the colons of our local Wistar rat colony. We studied the changes in concentrations of their fecal methanogenic and nonmethanogenic bacteria with age as a model of the development of these communities in humans. We found that the predominant methanogen in the rats is a Methanobrevibacter species. The log of the concentration of total anaerobes increased from 9.8/g (dry weight) at 3.0 weeks of age (shortly after weaning) to 10.7/g (dry weight) at 96 weeks (shortly before the end of the life span). In contrast, the log concentration of methanogens increased from 5.5 to 9/g (dry weight) during the same time period. Therefore, methanogens increased as a percentage of the total anaerobes from 0.005% at 3.0 weeks to 2.0% at 96 weeks. About 12 doublings of the methanogenic population and 3.3 doublings of the nonmethanogenic population took place from weaning until death. The slow increase in the ratio of methanogens to total anaerobes with age followed the same pattern in cecal contents as found in feces. There were no relationships between animal weights or fecal outputs and the increase in total anaerobe and methanogen concentrations in feces. A possible explanation for the slow increase in the Methanobrevibacter species in Wistar rats with age is a gradual shifting of the use of electrons from the reduction of CO2 to acetate by acetogens to the reduction of CO2 to CH4. The results provide the first evidence for an age-related change in the nonmethanogenic bacteria of the colon and supporting microbiological evidence for physiological studies that have shown age-related increases in colonic methane production in humans.

Aging↗
PubMed1989

Constancy of glucose and starch fermentations by two different human faecal microbial communities.

The fermentation of glucose and corn starch by faecal suspensions from two subjects was examined over a three and a half year period. The substrate specificity and products of the faecal fermentations of each subject were relatively stable during this period and were significantly different between subjects. The major soluble end products of fermentation of glucose or starch were acetate, propionate, and butyrate. Hydrogen temporarily accumulated and was subsequently used in fermentations by both subjects. Hydrogen was used without methane production in fermentations of subject 1, but was used for methane formation in fermentations of subject 2. Although the rates of glucose fermentation were similar between both subjects; subject 1 produced a significantly greater molar ratio of propionate than did subject 2. The rate of fermentation of starch by faecal suspensions from subject 1 was faster than that of subject 2. The molar ratio of butyrate was greater for starch fermentations by subject 2, while the molar ratio of propionate was greater with subject 1. Significant differences were found between subjects in molar ratios and concentration of acetate and propionate and concentrations of butyrate in faeces.

Acetates↗
PubMed1988

Activity of the anion exchange protein (band 3) of human erythrocytes as affected by hydroxychloroaromatic chemicals.

The membranous segment of the anion transport protein (band 3) of the human erythrocyte membrane has been shown [T.L. Miller and R.J. Smith, Archs Biochem. Biophys. 250, 128 (1986)] to be destabilized by relatively low concentrations of many hydroxychloroaromatic compounds (HO-Cl chi-Ar), including hydroxychlorodiphenyl ethers (HO-Cl chi-DPE), major contaminants of technical grade pentachlorophenol (PCP). In the present study, HO-Cl chi-DPE also caused a concentration-dependent inhibition of the rate of sulfate exchange mediated by band 3 in human erythrocytes. The most active compound studied, 2-HO-Cl9-DPE, was about nine times more potent in inhibiting sulfate exchange than 2-HO-2',4,4'-Cl3-DPE, the least active compound studied. The potency of HO-Cl chi-DPE as inhibitors of anion exchange generally increased with the degree of chlorination. The concentration-dependent decreases in the sulfate exchange rate elicited by 2-HO-Cl9-DPE and 2-HO-2',4,4'-Cl3-DPE paralleled the effects of these compounds on the stability of band 3.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1988

Acetate production from hydrogen and [13C]carbon dioxide by the microflora of human feces.

Fecal suspensions from humans were incubated with 13CO2 and H2. The suspensions were from subjects who harbored 10(8) and 10(10) methanogens per g (dry weight) of feces, respectively, and from a subject who did not harbor methanogens. Quantitative nuclear magnetic resonance spectroscopy showed that acetate labeled in both the methyl and carboxyl groups was formed by suspensions from the subject without methanogens and the subject with the lower concentrations of methanogens. The amounts of labeled acetate formed were in agreement with the amounts expected based on measurements of H2 utilization. No labeled acetate was formed by suspensions from the subject with the higher concentrations of methanogens, and essentially all of the H2 used was accounted for by CH4 production. Suspensions from the subject with lower concentrations of methanogens produced both methane and acetate from H2 and CO2. The results indicate that reduction of CO2 to acetate may be a major pathway for microbial production of acetate in the human colon except when very high concentrations of methanogens (ca. 10(10) per g [dry weight] of feces) are present. Double-labeled acetate was also formed from H2 and 13CO2 by fecal suspensions from nonmethanogenic and moderately methanogenic rats.

Acetates↗
PubMed1988

Short chain fatty acid distributions of enema samples from a sigmoidoscopy population: an association of high acetate and low butyrate ratios with adenomatous polyps and colon cancer.

We investigated the distribution of short chain fatty acids (SCFA) in enema samples taken from subjects before sigmoidoscopy as an indicator of possible microbial community differences between subjects subsequently diagnosed as normal or having colonic disorders. The major SCFA in all groups were acetic, propionic, and butyric acids. A significantly higher ratio of acetate to total SCFA and lower ratio of butyrate to total SCFA was found for polyp-colon cancer subjects than for normal subjects. There were no significant differences in the ratios of acetate, propionate, or butyrate between the diverticulosis or inflammatory bowel groups and the normal group. There were no significant sex differences nor were there correlations with the ratios of acetate, propionate or butyrate and age, subject weight, or dry weights of samples. Significant differences in concentrations of individual acids were found between normal and certain diagnostic groups. The difference in proportions of individual SCFA between groups suggest differences in fermentation patterns of the colonic microflora.

Acetates↗
PubMed1987

Bowel cancer characteristics in patients with regional enteritis.

We report 10 carcinomas in 8 patients with regional enteritis. Five of the cancers were in the ileum, 4 in the right colon, and 1 in the rectum. The visualized small bowel cancers appeared as benign strictures in small bowel involved by regional enteritis. Most were poorly differentiated. The colon cancers had a more typical radiographic appearance of malignancy. In some patients with small bowel cancer the malignancy was discovered only on histologic evaluation; the malignant nature of the lesion was not appreciated by radiography or gross examination at surgery.

Adenocarcinoma↗
PubMed1986

Liquid chromatographic assay for cerebrospinal fluid serotonin.

A novel liquid chromatographic method was developed for accurate and precise routine quantification of serotonin in human cerebrospinal fluid. Serotonin is derivatized with an amine-specific reagent leaving its hydroxy group free for electrochemical detection and making it lipophilic enough for efficient extraction into organic solvents. The method is reproducible, linear and free of interferences by endogenous amines other than serotonin. The limit of sensitivity is 100 fmol/ml CSF or 20 parts per trillion. Serotonin concentrations in lumbar cerebrospinal fluid from drug free, depressed patients were in the low nanomolar range.

Chromatography, Liquid↗
PubMed1986

Thermotropic properties of human erythrocyte membrane proteins as affected by hydroxychloroaromatic compounds.

The thermal stability of the anion transport protein (band 3) and other proteins of the human erythrocyte membrane, as influenced by hydroxychloroaromatic (HO-Cl2-Ar) compounds, was studied by differential scanning calorimetry. Various hydroxychlorodiphenyl ethers (HO-Clx-DPEs) and hexachlorophene, but not pentachlorophenol, caused a marked decrease in the thermal stability of band 3. Most of the other calorimetric transitions of the erythrocyte membrane were only slightly affected. The activity of HO-Clx-DPEs toward lowering the transition temperature of band 3 generally increased with the degree of chlorination, and was somewhat dependent on the position of hydroxyl substitution. At higher concentrations of HO-Clx-DPEs, there was a decrease in the enthalpy change and a broadening of the endothermic transition of band 3. The order of effectiveness of these compounds, as determined from band 3 denaturation temperatures, was similar to the order of potency previously observed for hemolysis of human erythrocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗