Biomedical subjects
Publications and source records attributed to J C Allen.
A 13-year-old boy with Down syndrome (DS) had a brainstem glioma confirmed at autopsy, 10 years after receiving prophylactic cranial irradiation for acute myeloblastic leukemia. There is no clear association of brain tumors with DS; despite a reported link between leukemia and glioma, a causal association with radiation therapy is more likely.
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The incidence of post-operative wound infections in Belize in 1986 and 1987 was studied. Both military practice in the military hospital and civilian practice in the rural hospitals of the local towns were included. Despite previous misgivings and sub-optimal conditions in the rural hospitals an acceptably low incidence was found in both areas of work.
Serotonin (5-HT) and other contractile agonists stimulate Na(+)-H+ exchange in vascular smooth muscle. Since intracellular alkalinization, per se, stimulates contraction, we tested whether 5-HT-induced contraction was associated with an increased pHi. In HCO3(-)-free buffer (pHo 7.4), 5-HT (10(-5) M) increased pHi, as measured by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein fluorescence, from 7.10 +/- 0.03 to 7.34 +/- 0.03 (p < 0.01) in primary cultures of canine femoral artery vascular smooth muscle cells grown to confluence in the presence of 10% fetal calf serum. In HCO3- buffer (24 mM, pHo 7.4), resting pHi was 7.26 +/- 0.04 (p < 0.01 versus HCO3(-)-free buffer) but was not altered by 5-HT. In both types of buffer, 5-HT stimulated 5-(N-ethyl-N-isopropyl)amiloride-sensitive 22Na+ uptake (Na(+)-H+ exchange). In HCO3- buffer and in Na(+)- and HCO3(-)-free buffer, 5-HT increased 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive 36Cl- uptake, suggesting that 5-HT stimulated Na(+)-independent Cl(-)-HCO3- and Cl(-)-Cl- exchange activities, respectively. Individual vascular smooth muscle cells were then cultured on rat tail tendon collagen gels in the presence of 0.5% fetal calf serum, and cell length and pHi were measured by video and epifluorescence microscopy. 5-HT contracted cells in a dose-dependent, reversible, and ketanserin-inhibitable manner. These cells, like cells grown in 10% fetal calf serum, exhibited Na(+)-H+ and Na(+)-independent Cl(-)-HCO3- exchange. In HCO3- buffer, 5-HT contracted cells without an associated change in pHi. We concluded the following: 1) 5-HT stimulated both Na(+)-H+ and Na(+)-independent Cl(-)-HCO3- exchange activities in cultured vascular smooth muscle cells in parallel. 2) As a result of enhanced H+ and HCO3- efflux, pHi was not altered. 3) In the presence of HCO3-, 5-HT-induced contraction was not associated with a change in pHi.
By regulating transmembrane Na+ and K+ concentrations and membrane potential, the Na+,K(+)-ATPase plays an important role in regulating cardiac, skeletal, and smooth muscle function. A high degree of amino acid sequence and structural identity characterizes the three Mr 100,000 Na+,K(+)-ATPase alpha subunit isoforms expressed in cardiac and skeletal muscle. Strikingly, vascular smooth muscle utilizes alternative RNA processing of the alpha-1 gene to express a structurally distinct Mr approximately 65,000 isoform, alpha 1-T (truncated). Analysis of both its mRNA and protein structure reveals that alpha-1-T represents a major, evolutionarily conserved, truncated Na+,K(+)-ATPase isoform expressed in vascular smooth muscle. This demonstrates an unexpected complexity in the regulation of vascular smooth muscle Na+,K(+)-ATPase gene expression and suggests that a structurally novel, truncated alpha subunit may play a role in vascular smooth muscle active ion transport.
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Colostrum Zn concentrations were measured in eight randomly selected Holstein dairy cows. Overall mean Zn concentrations were highest within 12 h postpartum (257 +/- 14 microM, mean +/- SEM), fell to 141 +/- 8 microM by 24 h, and then declined at a linear rate of 30 microM/d during the following 48 h. Zn concentrations at 3 d (82 +/- 5 microM) were not different from 150-d milk samples (72 +/- microM). In a second experiment, 32 early-gestation cows were blocked by stage of lactation into four groups in a randomized block design and injected with 0, 15, 30, or 45 mg of dexamethasone. Milk and blood samples were collected at 0, 12, and 24 h after injection and analyzed for Zn, and for fat, protein, and lactose in milk. Cows administered 0 and 15 mg of dexamethasone showed no difference in milk Zn concentrations compared to pretreatment measurements; however, milk Zn concentrations in cows administered 30- and 45-mg doses increased significantly. Plasma cortisol decreased in the dexamethasone-treated cows. Plasma Zn and milk fat, protein, and lactose did not change. These data indicate that glucocorticoids can mediate Zn uptake and transport by the mammary glands of lactating cows and suggest that the high Zn concentration in colostrum could be a result of the preparturient surge of cortisol.
Time-dependent changes in milk composition and secretion from pregnancy through greater than or equal to 6 mo of exclusive breast-feeding were studied in 13 multiparous women. Concentrations and secretion rates of lipid, lactose, protein, sodium, chloride, potassium, total calcium, ionized calcium, magnesium, glucose, citrate, inorganic phosphate, creatinine, and urea and pH were analyzed longitudinally from day 6 until weaning commenced. The composition of the antepartum secretion was related to the permeability of the junctional complexes between mammary cells. Significant increases in lactose, glucose, pH, and ionized calcium and significant decreases in protein, sodium, potassium, chloride, and calcium concentrations were observed between 1 and 6 mo. Significant differences among individuals, which persisted through lactation, were observed for the concentrations of sodium, potassium, chloride, and inorganic phosphate. The amount of lactose, ionized calcium, and magnesium transferred to the infant was also characteristic of each mother-infant pair. Our data imply that lactation performance is determined in the first month postpartum.
Concentrations and secretion rates of macronutrients and major ions in human milk during lactogenesis (birth to 8 d) and late lactation (greater than 6 mo postpartum) are reported. Postpartum changes in lactose, sodium, and chloride concentrations signalled closure of the paracellular pathway during days 1-2. From days 2 to 4 postpartum, initiation of copious milk secretion was accompanied by significant increases in citrate, free phosphate, glucose, and calcium concentrations and a decrease in pH. During weaning, significant changes in milk protein, lactose, chloride, and sodium concentrations were observed only when milk volume fell below 400 mL/d; more than one feed per day was necessary to maintain milk secretion. Temporal changes in the concentration of other milk components, except glucose and magnesium, were not different in weaning and non-weaning women. Differences between the relation of milk volume and composition during lactogenesis and weaning suggest that volume is differently regulated in the two periods.
The mechanisms that control intracellular pH (pHi) in vascular smooth muscle are not fully understood. We reported that pHi in primary cultured vascular smooth muscle cells from canine femoral artery is 7.26, a value maintained via HCO3- influx by the Na(+)-dependent C1(-)-HCO3-exchanger but not via H+ efflux by the Na(+)-H+ exchanger [A. M. Kahn, E. J. Cragoe, Jr., J. C. Allen, R. D. Halligan, and H. Shelat. Am. J. Physiol 259 (Cell Physiol. 28): C134-C143, 1990]. To explain these findings, in the present study, we determined the pHi activity profile of these two transport systems. Although both were active at acidic pHi, Na(+)-H+ exchange activity was very low at and above pHi 7.0, while Na(+)-dependent C1(-)-HCO3-exchange activity maintained near-maximal activity up to pHi 7.26 but fell to undetectable levels by pHi 7.4. A Na(+)-independent C1(-)-HCO3-exchanger was present, which mediated HCO3-efflux after an acute alkaline load. The activity of this system was negligible at pHi 7.2 and was stimulated at alkaline pHi. In conclusion, the pHi of these vascular smooth muscle cells at rest is maintained via HCO3-influx by the Na(+)-dependent C1(-)-HCO3-exchanger. After acute acidic or alkaline loads, correction of pHi is mediated by activation of the normally quiescent Na(+)-H+ and Na(+)-independent C1(-)-HCO3-exchangers, respectively. All three acid-base transport systems have pHi set points that protect the cell from overcorrecting pHi after a disturbance in either direction.
Total RNA isolated from canine saphenous vein smooth muscle cells was examined for Na+ pump alpha- and beta-mRNA content by three increasingly sensitive methods: Northern analysis, RNase protection assay, and polymerase chain reaction. Northern analysis clearly showed the presence of beta-mRNA. An alpha 1 signal was not demonstrable using either Northern analysis with a 1.5-kb cDNA probe or RNase protection. However, an "alpha 1-like" transcript was detected using polymerase chain reaction with two sets of primers constructed to selected areas of the rat alpha 1-cDNA. These data suggest that beta-mRNA in canine blood vessels is in large excess of the alpha 1-mRNA. This discrepancy may be reflected in the relatively low number of Na+ pump sites in this tissue.
Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.
Two digestion and N metabolism trials were conducted with 35-kg wethers to assess the feeding value of whole cottonseed or soybeans ensiled with corn silage in 3.6-m3 concrete silos (1.8 x 1.4 m). Dietary treatments for the cottonseed trial were ensiled whole cottonseed, untreated whole cottonseed, and 21 or 13% cottonseed meal in a basal diet of corn silage. There were no differences among treatments for DM and ADF intakes. Including ensiled or whole cottonseed in rations decreased digestibility of DM and ADF. Digestibility of CP was similar for the 21% cottonseed meal and whole cottonseed treatments. Nitrogen retention was similar for all treatments. Treatments for the soybean trial were ensiled whole soybeans, untreated whole soybeans, and 4 or 14% soybean meal. Lambs fed 14% soybean meal consumed more DM and ADF than those fed whole soybeans. Dry matter and ADF digestibilities were similar for all diets. Lower CP intakes resulted in less retained N for lambs fed whole soybean diets compared with those fed 14% soybean meal. Ensiling soybeans did not affect digestibilities of DM, CP, or ADF, or N retention. Ensiled whole soybeans or whole cottonseed may be fed to wethers as an alternative to separate feeding of oilseed meals with little effect on intake, CP digestibility, or N retention.
The management of patients with primary intracranial germ cell tumors is evolving. There is attention to minimizing late effects of therapy and preserving curability in those patients with pure germinomas and in intensifying chemotherapy for patients with nongerminoma germ cell tumors in an attempt to prolong disease-free survival.
Exposure of cultured canine femoral artery vascular smooth muscle cells to serotonin (5-HT) caused a 3.6-fold stimulation of ouabain-sensitive 86Rb uptake. The 5-HT2 receptor antagonist, ketanserin, partly blocked the 5-HT-mediated Na+/K+ pump stimulation and the 5-HT1/5-HT2 receptor antagonist, methiothepin, completely blocked the response, suggesting that both 5-HT1 and 5-HT2 receptors play a role in the 5-HT-mediated Na+/K+ pump activation. Second messengers generated by 5-HT2 receptor-mediated phosphoinositide hydrolysis, Ins(1,4,5)P3 and diacylglycerol were implicated in the stimulatory action of 5-HT on the vascular Na+/K+ pump. Like some other contractile agonists, 5-HT activated a Na+ influx pathway which caused Na+/K+ pump stimulation by increasing the rate-limiting substrate. The maximum stimulation of Na+ influx by 5-HT was 2.5-fold. The 5-HT-stimulated Na+ influx was totally blocked by methiothepin but only 29% inhibited by ketanserin, indicating that most of the Na+ influx was mediated by the 5-HT1 receptor. The 5-HT-stimulated Na+ influx was substantially inhibited by 50 microM dimethylamiloride, suggesting that the Na+ influx pathway stimulated by 5-HT was Na+/H+ exchange. BAPTA/AM 1,2-[bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra (acetoxymethyl) ester], an intracellular Ca++ chelator, partly blocked 5-HT-stimulated Na+ influx and ouabain-sensitive 86Rb uptake, suggesting that Ca++ is an important mediator of these responses. These data suggest that: 1) 5-HT, in addition to its well known activity as a contractile agonist, can stimulate the electrogenic Na+/K+ pump which, in theory, would tend to oppose contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Three children had central nervous system tumors with histologic and ultrastructural features corresponding to those of tumors previously described as "gliofibromas." These features, which include a composite appearance with glial and mesenchymal elements, with glial fibrillary acidic protein (GFAP)-containing and GFAP-immunonegative cells, diffuse S-100 immunoreactivity, and basal lamina wrapping processes of both cell types, suggest that the "mesenchymal" cells are Schwann cells, not fibroblasts. We therefore propose to rename this entity "glioneurofibroma." The clinical behavior of these lesions is uncertain but is more often indolent or benign.
Brainstem gliomas, constituting approximately 10% of all childhood central nervous system tumors, remain the most resistant of all brain tumors to therapy. A subgroup of high-risk patients with tumors that diffusely involve the brainstem or that microscopically demonstrate foci of anaplasia on biopsy specimens rarely survive after treatment. Conventional doses of radiotherapy result in temporary clinical improvement in the majority of these high-risk patients; however, few if any remain alive 18 months after treatment. Hyperfractionated radiotherapy, with delivery of larger numbers of smaller fractions of radiotherapy, is a possible way to increase tumor control without increasing neurological toxicity. In 1985, a multiinstitutional phase I/phase II trial, using 100 cGy of radiation therapy twice daily to a total dose of 7,200 cGy, was undertaken for patients with high-risk brainstem gliomas. At the time of writing, 24 (69%) had developed progressive disease and 11 remained in continuous progression-free remission. Actuarial progression-free survival at 20 months is approximately 30%. Twenty-three of 31 evaluable patients had an objective radiographic response to therapy. In comparison to both historical control patients and patients treated in a previous trial using 6,480 cGy of hyperfractionated radiation therapy, there was a statistically significant improvement in progression-free survival rate for patients treated with 7,200 cGy of hyperfractionated radiation therapy (p less than 0.01). To date no patient has died as a result of treatment. Six patients developed transient neurological deterioration or cystic intralesional changes, as demonstrated on magnetic resonance imaging, within 6 weeks of the completion of radiotherapy. Postmortem examination performed in 7 patients did not disclose significant radiation necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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