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Biomedical subjects

J D Welsh

Publications and source records attributed to J D Welsh.

At least 19 recordsLinked to original sources

A solution to the rheumatoid factor paradox: pathologic rheumatoid factors can be tolerized by competition with natural rheumatoid factors.

Rheumatoid factors (RF) associated with arthritic joint erosion are only seen transiently, if at all, in nondiseased individuals. Therefore, a tolerance mechanism must exist that prevents pathologic RF B cells from expressing Abs. Surprisingly, it has been shown that pathologic RF B cells are not tolerized by any previously established tolerance mechanism such as deletion, receptor editing, anergy, or prevention of memory establishment. How are pathologic RF cells tolerized? By simulating the RF response with a cellular automaton model immune system, we demonstrate that pathologic RFs can be tolerized by the novel mechanism of "competitive tolerance" with natural, nonpathologic RFs. We then demonstrate that competitive tolerance can be broken when a sequestered pool of expanding B cells are inappropriately subjected to chronic stimulation (as appears to occur in MRL/lpr mice and in patients with rheumatoid arthritis).

Animals↗

Individual differences in emotion regulation and behavior problems in preschool children.

Emotion regulation (ER) was assessed during a negative mood induction in 79 preschoolers who varied in degree of behavior problems. Facial expressivity during the induction was used to identify 3 ER groups: inexpressive, modulated expressive, and highly expressive. Group differences in ER were significantly related to heart rate and skin conductance. Inexpressive preschoolers had the highest heart rate, lowest vagal tone, and smallest autonomic nervous system (ANS) change during the induction. Highly expressive preschoolers had the slowest heart rate, highest vagal tone, and largest ANS change. The inexpressive and highly expressive groups had more externalizing symptoms than the modulated group at preschool age and at follow-up at the end of 1st grade. Inexpressive preschoolers appeared to have more depressed and anxious symptoms at follow-up.

Adaptation, Psychological↗

Affective interactions of depressed and nondepressed mothers and their children.

The expressed affect of clinically depressed and nondepressed mothers as measured by the Schedule for Affective Disorders and Schizophrenia: Lifetime Version (SADS-L) and their children (1 1/2 to 3 1/2 years) was observed in seminatural situations. The objectives were to investigate how maternal depression enters into affective interactions between mother and child and how the affect patterns of mother and child are related. Forty-nine unipolar and 24 bipolar depressed mothers and 45 nondepressed mothers were observed on 2 days, 2 weeks apart, for a total of 5 h. Each minute was coded for the predominant affect of mother and child. Affects relevant to depression (anxious--said, irritable--angry, downcast, pleasant, tender-affectionate) were coded. Depressed mothers expressed significantly more negative affect than did control mothers. Mothers' expressed affect and their self-reports of affect on days of observation were unrelated. Mother's and child's affects, measured on different days, were significantly correlated. Unipolar mothers and mothers severely depressed spent significantly more time in prolonged bouts of negative affect. There was significant synchrony between their bouts and the negative bouts of their daughters. Gender of child was related to mother's and child's affect, and to relations between mother's and child's affect.

Affect↗

Recovery of phenytoin suspension after in vitro administration through percutaneous endoscopic gastrostomy Pezzer catheters.

Various methods of administering phenytoin suspension through a percutaneous endoscopic gastrostomy (PEG) Pezzer catheter were evaluated in vitro to determine which method resulted in the most complete recovery of phenytoin. To determine the effect of temperature on phenytoin recovery, 12 mL of phenytoin suspension (Dilantin-125, 125 mg/5 mL) was administered through three separate 35.5-cm 20 French latex PEG Pezzer catheters under each of three temperature conditions (suspension 11.8 degrees C and catheter 22 degrees C, suspension and catheter 22 degrees C, and suspension 22 degrees C and catheter 37 degrees C). To determine the effect of the administration method, 12-mL aliquots of phenytoin suspension were injected into the catheter by seven methods that varied with respect to catheter temperature, dilution of suspension, and irrigation of catheter. Each method was tested in triplicate, and samples were assayed by high-performance liquid chromatography. Varying the temperature of the catheter or suspension had little effect on the recovery of phenytoin. There was no appreciable loss of phenytoin when the suspension was undiluted, regardless of whether the catheter was irrigated. The greatest losses were seen when the suspension was diluted before administration. Irrigation also caused a decrease in recovery, but to a lesser extent than dilution. Until the effects of administering multiple doses of phenytoin through PEG Pezzer catheters are investigated, phenytoin suspension should not be diluted before administration because of decreased recovery and increased administration time.

Catheterization↗

Esophageal acid clearance during sleep in patients with Barrett's esophagus.

Sleep-related gastroesophageal reflux and esophageal acid clearance have been shown to be important components in the pathogenesis of reflux esophageal disease. Previous studies have suggested that patients with more severe esophagitis are distinguished by an accumulation of acid mucosal contact time during sleep. These data would suggest that patients with Barrett's esophagus should have particularly severe impairment of acid clearance, most notable during sleep. To address this issue, 16 asymptomatic healthy volunteers and 13 patients with Barrett's esophagus were studied. Acid clearance was assessed by timing the reestablishment of an esophageal pH of 4 following the infusion of 15 ml 0.1 N HCl. Sleep was polygraphically monitored in order to objectively determine sleep and waking. The results indicated that while patients with Barrett's esophagus had a marked increase in the frequency of spontaneous gastroesophageal reflux during sleep, they unexpectedly demonstrated faster acid clearance times during both waking and sleep. A greater percentage of arousal responses to acid infusion during sleep was noted in the Barrett's group. It is concluded from these results that patients with Barrett's esophagus can adequately clear acid from the distal esophagus but experience considerable acid mucosal contact through repeated episodes of spontaneous reflux during sleep.

Adult↗

Comparative sequence analysis of the 5' noncoding region of the enteroviruses and rhinoviruses.

A comparative sequence analysis of the 5' noncoding region of a subgroup of the picornaviruses, including the polioviruses, coxsackie B3, and the human rhinoviruses, reveals the conservation of certain features despite the divergence of sequence. In this subgroup, for which nine complete sequences are available, two long stretches of sequence, two pyrimidine-rich regions, and 22 hairpins are conserved. Based on these results, similar secondary structures encompassing the entire 5' noncoding regions of these viruses are predicted. The fact that sequence divergence occurred only in a manner that allowed conservation of these structures implicates a biologically functional role for this region. The possible roles it may have in the picornavirus life cycle are discussed.

Base Sequence↗

Resolutions of control episodes between well and affectively ill mothers and their young children.

Control interactions between 87 well and affectively ill mothers and their 15- to 51-month-old children were studied. Spontaneously occurring control interventions (conceptualized as episodes of interaction between mother and child) were coded from 90 minutes of videotaped interactions in a naturalistic laboratory apartment setting. The results suggest developmental changes in mother-child interaction in the 2nd to 4th years of life: the increase of the rate of immediate maternal success (p less than .05) and compromise (p less than .05), on the decrease in maternal use of power (ultimate success by enforcement, p less than .01). Well mothers achieved compromise with their children, particularly daughters, more often than did affectively ill mothers (p less than .05). Affectively ill mothers more often than well mothers avoided confrontation with their children (p less than .05). The impairments in control interventions of affectively ill mothers were exacerbated by the severity of the disorder.

Bipolar Disorder↗

A second domain of simian virus 40 T antigen in which mutations can alter the cellular localization of the antigen.

Previous studies have demonstrated that mutations at amino acid position 128 of the simian virus 40 large T antigen can alter the subcellular localization of the antigen. A second domain in which mutations can alter localization of the nuclear antigen has been identified by mutations at amino acid positions 185, 186, and 199. Mutations in this region cause the polypeptide to accumulate in both the nucleus and cytoplasm of monkey cells. These T-antigen variants accumulate to near normal levels, but they don't bind to the simian virus 40 origin of DNA replication and are unable to mediate DNA replication. Furthermore, the altered tumor antigens can no longer transform secondary rat cells at normal efficiency, but they retain the ability to transform established mouse and rat cell lines.

Animals↗

Intestinal alkaline phosphatase activity in relation to age in humans.

Early studies of a few subjects suggested that intestinal alkaline phosphatase (IAP) activities in children 5 years of age or less were higher than in older individuals. To further investigate this finding, the IAP and disaccharidase activities of 298 subjects (133 were 5 years of age or less) with normal intestinal histology were assayed. Ninety-five of the children had serum alkaline phosphatase determined. The youngest individual with a low lactase activity was 5 years of age, which supported the earlier findings. When the whole population was tested, there was no correlation between the intestinal and serum alkaline phosphatase values. The mean IAP activity of subjects 1 year old and less was greater than in older individuals, but there was greater statistical dispersion and the data were not normally distributed. When studying the natural logarithm of the data, a wide dispersion of values about the mean in the 0 to 3 year-old age group was observed. This qualitative behavior is characteristic of functions involving the base of the natural logarithm and of processes that "age" in a simple way.

Adolescent↗

Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12.

The coding region for the structural and nonstructural polypeptides of the type A12 foot-and-mouth disease virus genome has been identified by nucleotide sequencing of cloned DNA derived from the viral RNA. In addition, 704 nucleotides in the 5' untranslated region between the polycytidylic acid tract and the probable initiation codon of the first translated gene, P16-L, have been sequenced. This region has several potential initiation codons, one of which appears to be a low-frequency alternate initiation site. The coding region encompasses 6,912 nucleotides and ends in a single termination codon, UAA, located 96 nucleotides upstream from a 3'-terminal polyadenylic acid tract. Microsequencing of radiolabeled in vivo and in vitro translation products identified the genome position of the major foot-and-mouth disease virus proteins and the cleavage sites recognized by the putative viral protease and an additional protease(s), probably of cellular origin, to generate primary and functional foot-and-mouth disease virus polypeptides.

Amino Acid Sequence↗

Concurrent Cushing's and Zollinger-Ellison syndromes in a patient with islet cell carcinoma. Case report and review of the literature.

This report documents the simultaneous occurrence of Cushing's and Zollinger-Ellison syndromes in a patient with islet cell carcinoma. The clinical concurrence of these two syndromes has been recorded in only three previous case studies, while three other case reports record evidence suggesting the presence of both gastrin and ACTH within the tumor but without clinical sequelae. In the present report, evidence based on multiple clinical and biochemical data supports the concept that both syndromes are a result of "ectopic" hormone production by the tumor.

ACTH Syndrome, Ectopic↗

Stricture location in Barrett's esophagus.

Twenty-eight patients with Barrett's esophagus were studied and strictures were present in 13. Two strictures were malignant. Of the 11 benign strictures, six were located at the squamocolumnar junction, while five were located below the squamocolumnar junction. Contrary to previous reports, benign esophageal strictures often occur below the squamocolumnar junction in patients with Barrett's esophagus.

Adenocarcinoma↗

Intestinal disaccharidase and alkaline phosphatase activity in giardiasis.

We report results on determinations of small intestinal brush-border enzyme activities in 22 children (aged 11 months to 14 years) with giardiasis. In particular, activities of disaccharidases (lactase, sucrase, maltase) and of alkaline phosphatase were investigated. Forty-one percent of the patients, irrespective of age, had a demonstrable depression of disaccharidase activities, usually in a combination involving two or more enzymes. A depression of intestinal alkaline phosphatase activity was present in 33% of patients, and only in those who demonstrated disaccharidase deficiencies. Mild villus atrophy was present in two mucosal specimens, whereas all others showed normal villus morphology by light microscopy. The results obtained in this study suggest that giardiasis in otherwise healthy children does not cause marked structural damage to the small bowel mucosa, as seen by the light microscope. However, some form of damage to the brush border does occur frequently, as evidenced by a depression of brush-border enzymes. This damage most likely contributes to the diarrhea and also to the carbohydrate intolerance in these patients.

Adolescent↗

Bacteremia associated with esophageal dilatation.

The present study was undertaken because the previously reported incidence of bacteremia associated with esophageal dilatation seemed high, and did not correlate well with clinical experience. Seventeen adult patients were dilated for benign esophageal strictures with one to three dilators on 41 occasions. Five blood cultures were taken over the 30-minute period after each dilatation. Either routinely sterilized dilators or dilators resterilized just before the procedure were used in a random fashion. On 22 of the occasions that routinely sterilized dilators were used in 17 patients, temperatures, white blood counts, and blood cultures were normal in each instance. Resterilized dilators were used on 19 occasions in 15 subjects, and postdilation temperatures and white blood counts were also normal. Two blood cultures from different patients grew Staphylococcus epidermidis, which were felt to be contaminants. On the basis of this and previous studies, extra precautions do not appear to be necessary for dilatation of routine benign strictures. In patients at risk for endocarditis, or those with cancer or tight strictures, it seems advisable to sterilize dilators just before use, and take extra precautions.

Adult↗