Search PubMed⌕ Search

Biomedical subjects

J Wallace

Publications and source records attributed to J Wallace.

At least 127 records · Page 7Linked to original sources

Similarities of Li+ and low Ca2+ in the modulation of secretion by parathyroid cells in vitro.

Parathyroid hormone (PTH) release from parathyroid cells in vitro was found to be stimulated by the presence of extracellular lithium ions through a specific secretory response which was comparable to that elicited by low extracellular Ca2+. Li+ (5-40 mM) caused a dramatic increase in the basal PTH secretory rate (up to 2.5-fold), as well as a further enhancement of the low Ca2+-stimulated PTH secretory rate (up to 0.5-fold). Cellular mediators commonly implicated in hormone release from endocrine cells, such as Ca2+ influx, cAMP, and changes in the activity of (Na+, K+) ATPase, were not involved in Li+-stimulated PTH release. The PTH secretory response induced by Li+ was fully maintained in the virtual absence of external Ca2+. Parathyroid cellular cAMP levels were unchanged in buffers varied with respect to both Li+ and Ca2+ and remained constant throughout the time course of Li+ uptake. Ouabain, in concentrations sufficient to block Na+, K+ activity, was also without effect on PTH release elicited by Li+. To identify the site and possible effectors of this stimulatory effect, experimental protocols were devised to modulate the level of intracellular Li+ at constant external Li+ concentrations. These results showed that the enhancement of PTH secretion by Li+ was independent of a 3-fold variation in intracellular Li+, but was directly related to the external Li+ concentration. This and previous evidence suggest that the regulation of PTH secretion by both lithium and calcium ions does not require their transmembrane influx but occurs instead in the parathyroid plasma membrane.

Animals↗

Parathyroid hormone secretion in the absence of extracellular free Ca2+ and transmembrane Ca2+ influx.

The involvement of extracellular Ca2+ and Ca2+ influx across the plasma membrane in parathyroid hormone (PTH) secretion was investigated in vitro using a new preparation of bovine parathyroid cells. Incubation of these cells in the presence of 25 microM or 2.5 microM free ambient Ca2+ induced a maximal rate of PTH secretion. Low free Ca2+ secretion is not associated with changes in membrane permeability, requires metabolic energy, and is reversible. The Ca2+ channel blocker D600 had no effect on either 45Ca-influx or PTH secretion in these cells. These results, showing that extracellular Ca2+ and Ca2+ influx across the plasma membrane are not required for PTH secretion by parathyroid cells, emphasize the differences in the cellular mechanisms underlying the secretion of PTH vs that of other secretory cells.

Animals↗

Insulin immunogenicity in pregnancy: maternal and fetal studies.

Antibodies to insulin were found in 92% of the 138 insulin-treated pregnant diabetic patients studied. No effect of pregnancy was shown on insulin antibody levels. Higher insulin antibody levels were significantly associated with the previous use of conventional insulins. Change from conventional to highly purified porcine insulin during pregnancy produced a significant reduction in insulin antibody levels. The combination of protamine zinc and soluble insulin used before pregnancy was found to be the most immunogenic. Insulin antibodies were freely transferred to the fetus but not detectable after the first 8 months of life. No insulin antibodies were found in the cord blood or during the next few weeks in the infants of mothers who had no antibodies to their injected insulin. There was a tendency for higher insulin antibody levels to be associated with indices of neonatal morbidity but not with percentile birth weights and C-peptide levels in cord sera.

Animals↗

Failure of oral 4',6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. Dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. A total of 63 volunteers were included in the analysis for efficacy. Dichloroflavan did not produce any consistent or significant reduction in quantitative clinical or laboratory evidence of infection, and there was no apparent negative correlation of such data with drug concentrations in plasma. It is concluded that administration of dichloroflavan in the oral formulation tested is not of value in the treatment of human rhinovirus infection.

Adolescent↗

An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-alpha 2.

Before the prophylactic effect of human interferon alpha 2 (HuIFN-alpha 2) can be tested against naturally acquired rhinovirus infection in a large-scale field trial, it is desirable to show that self-administration of the drug is practical, and to determine the smallest well-tolerated dose likely to produce a worthwhile effect. Here we report that self-administered intranasal interferon can be effective, and show how prophylaxis against rhinovirus infection is affected by both the quantity of interferon, and the interval between a dose and virus challenge. Finally, the medication regimen suggested for use in field trials (3.85 MU 3 times/day) was tested in a double-blind, placebo-controlled trial in volunteers. Although virus challenge was at a time when those being treated with interferon would be most susceptible, a substantial protective effect was still demonstrated.

Administration, Intranasal↗

Therapeutic activity of enviroxime against rhinovirus infection in volunteers.

The therapeutic effect of intranasal 2-amino-1-(isopropylsulphonyl)-6-benzimidazole phenyl ketone oxime (enviroxime) against human rhinovirus type 9 was evaluated in a double-blind, placebo-controlled volunteer trial. Enviroxime given 6 times a day was well tolerated, producing a reduction in clinical evidence of infection which coincided with the start of medication (44 h after virus challenge). Although there was a statistically significant reduction in clinical score in the enviroxime group on day 5 after virus challenge, reductions in total clinical score accumulated during the trial and reductions in the quantity of nasal secretions were not significant. A separate analysis was performed on data from volunteers who did not have symptoms when medication began (and who might have been expected to benefit more from enviroxime therapy). No apparent enhancement of the effects of enviroxime could be demonstrated in this group.

Adult↗

Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.

In a double-blind, placebo-controlled study, self-administered intranasal human interferon alpha A produced by recombinant DNA technology was given both before and after virus challenge with a respiratory coronavirus. The incidence of colds, the severity of symptoms and signs, and virus replication were all reduced in subjects receiving interferon as compared with those given placebo.

Administration, Intranasal↗

Tumors: the Cancer Information System (CIS) of the Minneapolis-West Metropolitan CHCP.

The Cancer Information System of the Minneapolis-West Metropolitan Community Hospital Cancer Program, using the Upper Midwest Oncology Registry System, avoids duplication of effort, is cost effective, has means of quality control, abstracts clinically useful data, provides a case summary, the data is immediately available, has a protocol system to assist the site committees, and provides both structured reports and a Query System for analysis of the data.

Hospitals, Community↗

Regulation of parathyroid hormone secretion in vitro by divalent cations and cellular metabolism.

Parathyroid hormone (PTH) secretion was investigated in intact cells isolated in vitro. Parathyroid cells from bovine parathyroid glands were obtained through tissue dispersion and cell purification through isotonic Percoll gradients, a newly developed protocol enhancing cell homogeneity and viability. Isolated cells maintained both metabolic viability and plasma membrane intactness for over 3 h at 37 degrees C, as shown by the large ATP/ADP ratios and the high intracellular K+ content (ouabain-sensitive) measured. The rate of PTH secretion was inversely related to the Ca2+ concentrations in the medium; secretion was 54 and 18 ng PTH/mg of protein/min when free Ca2+ in the buffer was 0.8 and 2 mM, respectively. At either Ca2+ concentration, PTH secretion was strongly dependent on cell metabolism; it was inhibited by 80-85% within 10 min when cells were suspended in glucose-free buffer containing either cyanide or oxidative phosphorylation uncoupler. Under these conditions, both cellular ATP production and calcium-dependent PTH release could be partially restored by addition of 5 mM glucose. La3+, Mn2+, Sr2+, Ba2+, and Mg2+ were each tested in a range of 0.5-2.5 mM for their effects in suppressing low calcium-stimulated secretion. La3+ and Mn2+ were about twice as effective as Ca2+ on a molar basis, Sr2+ was similar to Ca2+, Mg2+ was about half as effective, and Ba2+ had almost no effect. These results suggest that the Ca2+-dependent stimulus-secretion coupling of these cells is largely different from that established in other secretory cells and provide an in vitro system to further investigate the regulation of PTH secretion.

Adenosine Diphosphate↗

Purified interferon as protection against rhinovirus infection.

In a double-blind placebo-controlled study a preparation of human leucocyte interferon purified by affinity chromatography using a monoclonal antibody and applied by repeated nasal sprays reduced the incidence and severity of colds in volunteers challenged with human rhinovirus 9. Although interferon itself caused some symptoms, these were minor compared with the clinical colds. Interferon activity was still detectable in nasal washings as long as 26 hours after the last dose in about half the volunteers on active treatment.

Administration, Intranasal↗

Lead poisoning in an art conservator.

A case of lead poisoning in a female art conservator is reported. The patient had experienced excessive lead exposure while restoring an antique Peruvian tapestry from the Chancay period (1000 to 1500 AD) using a powdered pigment (cinnabar), which had been recovered from the same tomb in which the tapestry was found. Over two months, prominent neurological, gastrointestinal, and diffuse muscular symptoms developed. Severe anemia accompanied by basophilic stippling of RBCs led to the diagnosis of lead poisoning, which was confirmed by markedly elevated blood lead levels (up to 130 micrograms/dL) and impairment of heme synthetic enzymes. The severity of the intoxication necessitated chelation therapy. Chemical analysis of the antique powdered pigment showed it to be the source of lead exposure, in that it contained about 1% lead.

Adult↗