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Biomedical subjects

J S Hyams

Publications and source records attributed to J S Hyams.

At least 19 recordsLinked to original sources
PubMed1992

Relationship of common laboratory parameters to the activity of Crohn's disease in children.

The Pediatric Crohn's Disease Activity Index (PCDAI) has been proposed as a simple instrument to aid in the classification of patients by disease severity. The PCDAI includes subjective patient reporting of symptoms, physical examination, nutritional parameters, and several common laboratory tests (hematocrit, erythrocyte sedimentation rate, albumin). In this report we examine the relationship of each of the laboratory parameters to the PCDAI, as well as to a modified Harvey-Bradshaw Index score and physician global assessment of disease activity. Data were gathered from the clinical and laboratory observations from 133 children and adolescents at 12 pediatric gastroenterology centers in North America. A statistically significant relationship (p less than 0.05) was noted between each of the laboratory tests and the PCDAI for patients with either disease limited to the small bowel or in those with colonic involvement. For patients with disease limited to the small bowel, a statistically significant (p less than 0.05) relationship was also noted between the three laboratory parameters and the modified Harvey-Bradshaw Index and global assessment. For patients with large-bowel involvement, the erythrocyte sedimentation rate was statistically related to the modified Harvey-Bradshaw Index and global assessment (p less than 0.01), as was hematocrit to global assessment (p less than 0.01). Although the laboratory parameters used in the PCDAI appear to generally reflect disease activity in most patients, no single laboratory test is adequate to reflect disease activity in all patients. Future work will need to identify additional laboratory measures to reflect the inflammatory process and serve as important adjuncts in the assessment of disease activity.

Adolescent↗
PubMed1992

Cytokeratin immunohistochemical examination of liver biopsies in infants with Alagille syndrome and biliary atresia.

Identifying bile duct epithelium is sometimes difficult with standard histologic techniques. The availability of antibodies to specific cytokeratin (CK) intermediate filaments has allowed identification of CK expressed by bile duct epithelium. Formalin-fixed, paraffin-embedded liver tissue from five infants (aged 1-12 months) with Alagille syndrome and five infants with biliary atresia (aged 1.5-11 months) were pepsin digested then reacted with a combination of anti-cytokeratin monoclonal antibodies using an avidin-biotin immunoperoxidase technique. Liver tissue obtained at autopsy from infants without primary liver disease (aged 22 weeks gestation to 24 months) was treated similarly for comparison. Control specimens showed progression from prominent immunoreactivity of the ductal plate cells at the rim of the portal tract (22-24 weeks gestation) to incorporation of tubular ductal structures into portal tract mesenchymal tissue (26-34 weeks gestation) and formation of intensely immunoreactive mature discrete interlobular ducts with progressive loss of cytokeratin immunoreactivity of the ductal plate cells (1-24 months). In contrast, biopsies from infants with Alagille syndrome showed few immunoreactive interlobular ducts. Biopsies from infants with Alagille syndrome less than 2 months old showed only immunoreactivity of single ductal plate cells or small ductules at the periphery of the portal tracts. Biopsies from some infants greater than 3 months old showed increased numbers of immunoreactive cells in groups and anastomosing bands lacking true lumens and extending into the fibrous bridges between adjacent portal areas (neoductular proliferation).(ABSTRACT TRUNCATED AT 250 WORDS)

Alagille Syndrome↗
PubMed1991

Use of a heat-stable microtubule-associated protein class-specific antibody to investigate the mechanism of microtubule binding.

Members of the heat-stable family of microtubule-associated proteins (MAPs), MAP 2, tau, and MAP 4, contain three or four tandem imperfect repeated sequences close to their carboxyl termini. These sequences lie within the microtubule-binding domains of the MAPs; they have been proposed to be responsible for microtubule binding and the ability of these MAPs to lower the critical concentration for microtubule assembly. Their spacing may reflect that of the regularly arrayed tubulin subunits on the microtubule surface. We here characterize the 32- and 34-kDa chymotryptic microtubule-binding fragments of MAP 2 identified in earlier work. We identify the primary chymotryptic cleavage site in high molecular weight MAP 2 as between Phe1525 and Lys1526, within 13 amino acids of the known MAP 2 splice junction. We have raised a monoclonal antibody to the 32- and 34-kDa fragments and find that it reacts with all members of the heat-stable MAPs class. To determine where it reacts, we sequenced immunoreactive subfragments of the 32- and 34-kDa fragments, selected several cDNA clones with the antibody, and tested for antibody reactivity against a series of synthetic MAP 2 and tau peptides. We identify the epitope sequence as HHVPGGG (His-His-Val-Pro-Gly-Gly-Gly). The antibody also recognized several other MAP 2 and tau repeats. Despite reacting with this highly conserved element, we find that the antibody does not block microtubule binding, but binds to the MAPs and co-sediments with microtubules. These results suggest that there are other regions besides the repeated elements which are essential for microtubule binding.

Amino Acid Sequence↗
PubMed1991

Microtubules in the fission yeast Schizosaccharomyces pombe contain only the tyrosinated form of alpha-tubulin.

The state of tubulin tyrosination in the fission yeast Schizosaccharomyces pombe was investigated using a combination of indirect immunofluorescence microscopy and Western blotting. Antibodies specific for the tyrosinated form of alpha-tubulin stained all microtubule arrays in wild type cells and recognised the two alpha-tubulin polypeptides in Western blots of cell extracts enriched for tubulin by DEAE-Sephadex chromatography. Antisera that specifically recognised the detyrosinated, glu, form, on the other hand, gave consistently negative results, both in cells undergoing rapid exponential growth and in those allowed to accumulate in stationary phase. Neither the "ageing" of microtubules, by arresting cells at different points (late G1 or G2/M) in the cell division cycle, nor stabilising them, using D2O, lead to any detectable tubulin detryrosination. These results suggest that S. pombe lacks the carboxypeptidase that carries out the tubulin detyrosination reaction. This is the first report of an organism that possesses the correct C-terminal alpha-tubulin sequence yet fails to carry out this post-translational modification. The implication of this novel finding for the biological role of these events is discussed.

Amino Acid Sequence↗
PubMed1991

Comparison of collagen propeptides as growth markers in children with inflammatory bowel disease.

The serum concentrations of the carboxy-terminal propeptide of type I procollagen and the amino-terminal propeptide of type III procollagen as biochemical markers of growth activity were compared in 46 children and adolescents with inflammatory bowel disease. Significant correlations were noted between growth velocity and type I procollagen (r = 0.65; P less than 0.001) and type III procollagen concentrations (r = 0.64; P less than 0.001). Although the serum concentration of type I procollagen was generally about 15 times greater than that of type III, the respective serum concentrations were highly correlated (r = 0.66; P less than 0.001) at all growth velocities. The use of daily corticosteroid therapy was associated with significantly lower concentrations of both propeptides (P less than 0.01) than was alternate-day or no corticosteroid therapy, respectively. Children with growth arrest (0.0 cm/mo) had type I and type III procollagen concentrations similar to those found in adults. These observations indicate that the serum concentrations of both collagen propeptides reflect growth activity in children with inflammatory bowel disease and suggest that routine measurement of collagen propeptides may have clinical value in monitoring normal and abnormal growth. The data suggest that the measurement of one propeptide does not offer an advantage over the other.

Adolescent↗
PubMed1991

Suppression of gastric acid secretion by intravenous administration of famotidine in children.

This study was designed to establish appropriate dosing requirements for intravenous use of famotidine, a new H2-receptor antagonist, in pediatric patients. Eighteen children, 2 to 69 months of age (mean +/- SD: 31 +/- 23 months), were treated with intravenously administered famotidine to prevent bleeding of the upper gastrointestinal tract. Continuous intragastric pH monitoring was carried out to ascertain the effectiveness of various intravenous doses. An initial dose of 0.4 mg/kg was given and repeated only after the intragastric pH had dropped to less than 4.0 for 2 hours. Increased doses were given (0.8, 1.2, and 1.6 mg/kg) if the previous dose did not raise the intragastric pH to greater than 4.0 for greater than or equal to 6 hours. Sixteen patients achieved an intragastric pH greater than or equal to 4.0 for greater than or equal to 6 hours, 13 with a dose of 0.4 mg/kg, and three with a dose of 0.8 mg/kg. The mean duration of continuous pH greater than 4.0 per dose was 9.0 +/- 7.5 hours. Ten patients received two or more intravenous doses of famotidine; the mean duration of pH greater than 4.0 after the second dose was less than that after the first (14.9 +/- 8.0 hours vs 6.9 +/- 3.2 hours, p less than 0.01). We conclude that intravenous famotidine therapy raises gastric pH to greater than 4.0 for approximately 9 hours in most children. Prolonged intravenous use of famotidine rapidly leads to a decreased duration of efficacy, necessitating intragastric pH monitoring to assess the effectiveness of treatment.

Child, Preschool↗
PubMed1991

Evaluation of the effect of a fiber-enriched formula on infant colic.

Because infants with colic appear to have abdominal pain similar to that of adults with irritable bowel syndrome, who may benefit from the addition of fiber to their diet, we tested whether fiber added to infant formula would alleviate colic. Twenty-seven normal, term infants (aged 2 to 8 weeks; 14 girls) with colic, defined as crying plus fussing for more than 3 hours a day for at least 3 days of a 6-day baseline period, were enrolled. Infants were randomly assigned in 9-day periods to a sequence of placebo (Isomil formula) followed by fiber-supplemented formula (Isomil plus soy polysaccharide) (n = 12) or the reverse (n = 15). Daily diaries of crying, fussing, sleeping, formula, intake, and stooling were kept. Twenty-two infants completed three lactulose breath hydrogen tests at the end of the baseline period and after each study period. The crossover trial was followed by 30 to 35 days of use of the study formula chosen by the parents as most beneficial but unknown to the investigators. Growth was monitored throughout. Serum cholesterol, calcium, phosphate, albumin, iron, and zinc concentrations were measured at the conclusion. There were no significant differences in average daily time spent by the infants in fussing and crying during ingestion of the fiber-supplemented formula. However, parents of 18 of 27 infants chose fiber-supplemented formula as most beneficial in ameliorating symptoms of colic. While the infants were consuming fiber-supplemented formula, stool frequency increased, and breath hydrogen excretion increased significantly, in response to lactulose. Growth and serum biochemical measurements were normal in all infants. Supplementation of infant formula with the level of soy polysaccharide used in this study may have reduced crying and fussing in some infants but did not affect colicky behavior in the majority of infants, who continued to cry and fuss excessively.

Breath Tests↗
PubMed1991

Tumor necrosis factor-alpha is not elevated in children with inflammatory bowel disease.

Chronic undernutrition and high-dose daily corticosteroid therapy are well-accepted causes of growth failure in children with inflammatory bowel disease. Occasionally, children are seen with minimal gastrointestinal symptoms but in whom severe anorexia and profound growth impairment are evident. Recent observations that elevated serum levels of tumor necrosis factor-alpha (TNF) in cachexia associated with a number of disease states have suggested a similar possible role in inflammatory bowel disease. Accordingly, we determined TNF levels in 45 children and adolescents with inflammatory bowel disease (18 ulcerative colitis, 27 Crohn's disease) at varying times during their clinical course and compared them to values obtained from a group of 25 children with functional bowel disease. No differences were noted in serum TNF levels between the children with inflammatory bowel disease and the control population. Values were generally within the range of the lower limit of detection of the assay. In the children with inflammatory bowel disease, there was no significant correlation between TNF levels and disease activity or growth parameters. Our observations suggest that elevated TNF levels are not associated with inflammatory bowel disease in children.

Adolescent↗
PubMed1991

Spontaneous rupture of a choledochal cyst: clues to diagnosis and etiology.

A healthy 3-year-old black girl had acute onset of abdominal pain, vomiting, and elevated aminotransferase, amylase, and lipase levels. Sonographic evaluation suggested a choledochal cyst, but hepatobiliary scintigraphy clearly showed an extrahepatic biliary leak. Exploratory laparotomy confirmed bile peritonitis and a ruptured choledochal cyst. Other cases with this unusual presentation is reviewed in the literature. An anomalous insertion of the pancreatic duct into the common duct appears to facilitate reflux of pancreatic secretions into the biliary tree and may contribute to formation and even perforation of a choledochal cyst.

Child, Preschool↗
PubMed1991

Gastroesophageal reflux in the older child: presentation, response to treatment and long-term follow-up.

Much attention has been focused on the natural history of gastroesophageal reflux (GER) in neurologically normal infants which generally resolves by two years of age. In contrast, little is known of the outcome of GER diagnosed in normal older children. The charts of 32 children (21 males) without neurologic or esophageal anatomic abnormalities, age 3.5 to 16 years (mean = 9.8) at the time of diagnosis, were reviewed. Diagnosis was based on suggestive presenting symptoms and evaluation of prolonged intraesophageal pH monitoring. Esophagitis was diagnosed by histologic criteria in 16 of the 32 patients. Medical treatment consisted of prokinetic agents (metoclopramide, bethanechol) and H2-receptor antagonists. After a one to eight year follow-up period (mean +/- SD - 3.4 +/- 2.1), the symptoms in 13 children had resolved or were sufficiently improved to discontinue medication. In 13 patients, symptoms were improved but medication was required for adequate control. Four children were symptomatic without improvement in spite of medical therapy and two others required fundoplication for continued severe symptoms and refractory esophagitis. In summary, less than 50% of otherwise normal older children with GER undergo spontaneous resolution of marked improvement in symptoms and the remainder require continued long-term medical and/or surgical management.

Adolescent↗
PubMed1991

Conserved structural motifs in cyclins identified by sequence analysis.

Cyclins, as regulatory subunits of the ubiquitous p34cdc2 protein kinase, act as key controlling elements of the eukaryotic cell cycle. We have examined published sequences of A- and B-type cyclins for both amino acid and secondary structure homologies. In particular, we sought regions of homology outside the recognised area of sequence conservation known as the "cyclin box', as well as conserved features predicted to lie at the protein surface. Our analysis demonstrates the existence of a number of islands of homology outside the cyclin box, and indicates candidate residues for phosphorylation. One of these, a motif containing the amino acids SPXXXE/D is also present in fission yeast p13suc1, another protein known to interact with p34cdc2. This motif may define a possible p34cdc2 binding or phosphorylation site. A database search revealed that the CDC25 and SCD25 genes of the budding yeast Saccharomyces cerevisiae also contain some of the newly identified motifs, perhaps indicating a common regulatory or degradation pathway.

Amino Acid Sequence↗
PubMed1991

Development and validation of a pediatric Crohn's disease activity index.

Clinical and laboratory observations of 133 children and adolescents with Crohn's disease were used to validate an index of severity of illness previously developed by a group of senior pediatric gastroenterologists at a research forum in April 1990. This pediatric Crohn's disease activity index (PCDAI) included (a) subjective reporting of the degree of abdominal pain, stool pattern, and general well-being; (b) presence of extraintestinal manifestations, such as fever, arthritis, rash, and uveitis; (c) physical examination findings; (d) weight and height; and (e) hematocrit, erythrocyte sedimentation rate, and serum albumin. Independent evaluation of each patient by two physician-observers was performed at the time of a visit, and each physician completed a PCDAI index and a modified Harvey-Bradshaw index and made a "global assessment" of disease activity as none, mild, moderate, or severe. Excellent interobserver agreement was noted for the PCDAI, modified Harvey-Bradshaw index, and global assessment. There was a strong correlation between global assessment and both the PCDAI or modified Harvey-Bradshaw. Increasing PCDAI scores were noted with increasing disease severity, and significant differences in scores were noted between the severity groups. We propose that the PCDAI could be used in multicenter projects to facilitate patient stratification by disease severity and that longitudinal PCDAI scores might provide a numerical measure of response to therapeutic regimens.

Adolescent↗
PubMed1991

Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of long-chain acyl-CoA dehydrogenase deficiency.

Inherited defects in fatty acid oxidation, which have been described and diagnosed with increasing frequency in the last decade, are most commonly attributed to a deficiency in the activity of medium-chain acyl-CoA dehydrogenase. Few cases of the related enzyme defect of long-chain acyl-CoA dehydrogenase activity have been reported. An infant with documented long-chain acyl-CoA dehydrogenase deficiency is described with a detailed metabolic profile, long-term clinical follow-up, and response to treatment. This patient is compared with the seven previously published cases of this disorder in order to stress the unique features of the initial presentation, more subtle late manifestations of the disease, and clinical and biochemical differentiation from the more common medium-chain acyl-CoA dehydrogenase deficiency. This report stresses the enlarging spectrum of the clinical presentation and natural history of this defect in fatty acid oxidation.

Acyl-CoA Dehydrogenase, Long-Chain↗