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Biomedical subjects

R W Newcomb

Publications and source records attributed to R W Newcomb.

At least 19 recordsLinked to original sources
PubMed1990

Regulated release of multiple peptides from the bag cell neurons of Aplysia californica.

The bag cell neurons of Aplysia californica synthesize and store large amounts of peptides derived from the egg-laying-hormone (ELH) neuropeptide precursor. Different sets of peptides derived from the amino- and carboxyl-terminal regions of the prohormone possess unique biological activities, and are packaged in distinct sets of secretory granules. We report here quantitative measurements of the amounts of the peptide products stored in and released from the bag cell neurons using high pressure liquid chromatography (HPLC) and amino acid composition analysis. These studies demonstrate that both the autocrine acting bag cell peptides (BCPs) and ELH are released coincident with electrical activity in the bag cell cluster. The composition of the released peptide mixture is similar to that stored in the bag cells. ELH and other carboxy-terminal derived peptides are most often present at 5-fold greater levels than the BCPs. These results provide further insight into the use of multiple chemical messengers by the bag cell neurons.

Animals↗
PubMed1989

Use of adrenergic bronchodilators by pediatric allergists and pulmonologists.

Twenty-one pediatricians specializing in allergy, pulmonology, or both were questioned about their use of adrenergic bronchodilators for treating children of different ages at home, in the emergency department, and in the hospital. Most would use inhaled medications in all settings and for all ages. Few expressed strong preference for one drug over another, but only 2 would regularly use nebulized isoproterenol hydrochloride or isoetharine hydrochloride. Dosing frequency of inhaled medication at home was usually limited to every 4 hours, but in the emergency department or hospital, intervals between doses of 20 minutes or less were common. If this treatment failed, 9 physicians would use intravenous isoproterenol, but 4 strongly opposed its use. These results indicate that substantial variation exists in current expert practice, but that inhaled albuterol, metaproterenol, or terbutaline sulfate are most often preferred for treating asthma, bronchopulmonary dysplasia, and bronchiolitis in children of all ages, and that doses and dosing intervals are frequently altered to meet patient needs.

Adolescent↗
PubMed1989

Persistent peripheral airway obstruction in children with severe asthma.

We reviewed pulmonary function data on 447 children with the diagnosis of asthma, who were studied in our laboratory over a 6-year interval. We found 19 with evidence of consistent airway obstruction. Two patients who had obvious causes for persistent obstruction were excluded. Seven of the remaining 17 patients consented to further studies. In six of the seven patients studied, flow rates at low lung volumes were severely depressed and remained unchanged after 2 weeks of vigorous "inpatient" therapy. No clinical benefit was apparent. One patient had relentlessly worse disease and died of his asthma. The autopsy revealed changes characteristic of asthma. We conclude that some children with severe asthma have persistent and severe peripheral airway obstruction. These findings challenge the current paradigm that asthma in children is a completely "reversible" illness. Long-term follow-up of children with persistent chronic obstruction may clarify the question of childhood origin of adult lung disease.

Adolescent↗
PubMed1988

Respiratory failure from asthma. A marker for children with high morbidity and mortality.

During a seven-year interval, 78 children had documented episodes of respiratory failure from asthma, defined as arterial hypoxemia, hypercapnia, or use of mechanical ventilatory support or intravenous isoproterenol hydrochloride. During 407 patient-years of follow-up (5.2 years per patient), these 78 children had 227 episodes of respiratory failure (2.9 episodes per patient). Fifty-three patients (68%) have had two or more of such episodes. Second episodes usually followed the initial episodes within two years, but some were delayed for over six years. Seven of the 78 children died, and two others have incurred hypoxic brain damage, compared with two deaths among 2892 children with asthma--seen at this hospital during that interval--but without a documented previous episode of respiratory failure. We conclude that children whose asthma has caused even one episode of respiratory failure constitute a special group of asthmatic patients, members of which are at high risk for repeated episodes of respiratory failure and its catastrophic complications. This recognition allows special attention to be focused on them in designing both clinical and research strategies.

Adolescent↗
PubMed1987

Purification and amino acid composition of a peptide with molt-inhibiting activity from the lobster, Homarus americanus.

A peptide was isolated and purified from sinus glands of the lobster, Homarus americanus, that was able to decrease circulating titers of ecdysteroids and increase the molt interval of eyestalk-ablated juvenile lobsters. This molt-inhibiting activity was demonstrated to consist of two very closely related peptides by means of high-performance liquid chromatography and gel electrophoresis. By means of amino acid analyses, a molecular weight of approximately 8700 was obtained.

Amino Acids↗
PubMed1987

Amino acid sequences of neuropeptides in the sinus gland of the land crab Cardisoma carnifex: a novel neuropeptide proteolysis site.

The sinus gland is a major neurosecretory structure in Crustacea. Five peptides, labeled C, D, E, F, and I, isolated from the sinus gland of the land crab have been hypothesized to arise from the incomplete proteolysis at two internal sites on a single biosynthetic intermediate peptide "H", based on amino acid composition additivities and pulse-chase radiolabeling studies. The presence of only a single major precursor for the sinus gland peptides implies that peptide H may be synthesized on a common precursor with crustacean hyperglycemic hormone forms, "J" and "L," and a peptide, "K," similar to peptides with molt inhibiting activity. Here I report amino acid sequences of these peptides. The amino terminal sequence of the parent peptide, H, (and the homologous fragments) proved refractory to Edman degradation. Data from amino acid analysis and carboxypeptidase digestion of the naturally occurring fragments and of fragments produced by endopeptidase digestion were used together with Edman degradation to obtain the sequences. Amino acid analysis of fragments of the naturally occurring "overlap" peptides (those produced by internal cleavage at one site on H) was used to obtain the sequences across the cleavage sites. The amino acid sequence of the land crab peptide H is Arg-Ser-Ala-Asp-Gly-Phe-Gly-Arg-Met-Glu-Ser-Leu-Leu-Thr-Ser-Leu-Arg-Gly- Ser-Ala-Glu- Ser-Pro-Ala-Ala-Leu-Gly-Glu-Ala-Ser-Ala-Ala-His-Pro-Leu-Glu. In vivo cleavage at one site involves excision of arginine from the sequence Leu-Arg-Gly, whereas cleavage at the other site involves excision of serine from the sequence Glu-Ser-Leu. Proteolysis at the latter sequence has not been previously reported in intact secretory granules. The aspartate at position 4 is possibly covalently modified.

Amino Acid Sequence↗
PubMed1986

Pulmonary assessment of children after chlamydial pneumonia of infancy.

We evaluated the pulmonary status of 18 children 7 to 8 years after their hospitalization for chlamydial pneumonia of infancy. Pulmonary function tests (PFTs) and respiratory questionnaire results in this group were compared with those in a control group of 19 comparable children from the same community, and with values that other investigators have reported for normal children. Significant limitations of expiratory airflow were found (FEV1, FEV1/FVC, PEF, and FEF 25%-75%), as well as signs of abnormally elevated volumes of trapped air (FRC and RV/TLC ratios). These obstructive patterns were responsive to inhalation of isoproterenol. Moreover, a significantly greater number of patients had physician-diagnosed asthma than in the control group. The obstructive PFT abnormalities could not be accounted for by recognized risk factors, such as exposure to smoking at home or family history of atopy. Our results show that chlamydial pneumonia of infancy is associated with PFT abnormalities and respiratory symptoms 7 to 8 years after recovery from the acute illness.

Child↗
PubMed1986

Outcomes of emergency room visits for asthma. I. Patient determinants.

To learn how differences among individual patients influence the outcomes of their emergency room (ER) visits for asthma, we matched the results of 1209 sequential ER visits with the records of the 464 children and young adults who visited during a 37-week interval. Most patients visited the ER only once and were unlikely to be admitted. Those patients admitted once were unlikely to be admitted a second time. Only 119 patients (25.6%) made 54.7% of all ER visits and were responsible for 68.5% of admissions; they also accounted for all but eight of 92 relapses. Patients were accordingly stratified into group F, frequent visitors, and group I, infrequent visitors. A separate high-risk category (group HR) was composed of 50 other patients who received especially conservative treatment in the ER owing to prior episodes of severe asthma. HR patients included both frequent and infrequent visitors and had a very high probability of being admitted on any given visit. The patients of group F, each of whom visited the ER at least four times during the 37 weeks initially studied, were also consistently frequent visitors for comparable periods before and after the initial period. Their rate of ER relapses for exceeded their visiting rate, at least in part because some patients tended to relapse on repeated occasions. Patterns of ER use allow differentiation among groups of patients with distinctly different prognoses. These groups are similar to prognostic categories reported by previous authors. Such differences among individual patients must be taken into account when management systems are evaluated or clinical strategies are organized.

Adolescent↗
PubMed1986

Outcomes of emergency room visits for asthma. II. Relationship to admission criteria.

To learn how the outcomes of emergency room (ER) care relate to the decision-making process, criteria for the disposition of asthma in the ER were incorporated into a formal protocol in the form of an algorithm for use by pediatric resident physicians. We compared the application of those criteria with the consequences of 199 decisions to admit patients to the hospital for asthma and of 293 decisions to discharge patients from the ER. For most patients the chance of relapse was significantly raised if they were discharged from the ER when the protocol had specified admission. This was not true, however, for a group of "frequent visitors" (12.7% of all patients) who accounted for 66.3% of all relapses. This finding offers an explanation for previous difficulties in identifying characteristics of visits destined to be followed by relapse. Patients were placed in jeopardy by inappropriate ER discharges only if they were high-risk patients who had experienced prior episodes of respiratory failure. Nearly all admissions involving severe episodes of asthma were also limited to high-risk patients. A variety of criteria supported such admissions. At the other extreme, "avoidable" admissions, in which obstruction resolved within a few hours of admission, occurred equally among all patient strata, and no particular admission criterion could be held at fault for admission of such rapidly remitting cases. The results support the use of explicit, quantitative criteria for guiding ER disposition of asthma, especially specific arrangements for management of ER visits by high-risk patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1977

Aminophylline therapy in children: guidelines for dosage.

The oral dosage of aminophylline required for therapeutic "trough" serum theophylline levels was studied in 150 children, 16 months to 19 years old (mean 8.28 years). Dosage requirements tended to be higher for children under 10 years, but marked person-to-person variability in the relation of dose to serum level was seen at all ages. Individual patients generally maintained consistent serum levels when receiving unchanging doses, although intercurrent disease sometimes disrupted this relationship. Individualization of oral dosage based on frequent serum measurements is necessary to maintain theophylline levels in the therapeutic range and to avoid toxicity.

Administration, Oral↗
PubMed1975

Influence of IgG antibody and glycopeptide allergens on the correlation between the radioallergosorbent test (RAST) and skin testing or bronchial challenge with alternaria.

The radioallergosorbent test (RAST) for alternaria was compared to skin tests and bronchial challenges in children suffering from chronic intractable asthma. In contrast to when such children were tested with a timothy grass pollen extract, the bronchial challenge and skin test results against alternaria did not correlate significantly. When alternaria allergens were coupled to cyanogen bromide-activated microcrystalline cellulose, the RAST correlated with the results of skin testing but not bronchial challenge. It was demonstrated by column immunabsorption that some allergic sera contained sufficient IgG antibody against alternaria to competitively inhibit the RAST. When Sepharose 2B was substituted for cellulose as the insoluble support, the inhibition by IgG antibody was largely overcome and then the RAST correlated with both skin test and bronchial challenge results. Glycopeptides contribute significantly to the allergenicity of alternaria, and when these materials were coupled to a Sepharose 2B conjugate by mild oxidation, the RAST correlated with bronchial challenge, but not skin test, results. It was concluded that in this group of steroid-dependent asthmatic children, the correlation of the RAST with the in vivo challenges was strongly influenced by the presence of IgG antibody in the allergic sera and the chemical nature of the mould allergens investigated.

Absorption↗