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Biomedical subjects

J C Allen

Publications and source records attributed to J C Allen.

At least 127 records · Page 7Linked to original sources
PubMed1991

Studies in human lactation: milk composition and daily secretion rates of macronutrients in the first year of lactation.

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.

Breast Feeding↗
PubMed1991

Studies in human lactation: milk volume and nutrient composition during weaning and lactogenesis.

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.

Citrates↗
PubMed1991

Effects of pHi on Na(+)-H+, Na(+)-dependent, and Na(+)-independent C1(-)-HCO3-exchangers in vascular smooth muscle.

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.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Disproportionate alpha- and beta-mRNA sodium pump subunit content in canine vascular smooth muscle.

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.

Animals↗
PubMed1991

Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy.

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.

Adolescent↗
PubMed1991

Effects of ensiling on the digestibility and utilization of whole oilseeds by wethers.

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.

Animals↗
PubMed1991

Controversies in the management of intracranial germ cell tumors.

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.

Brain Neoplasms↗
PubMed1991

Serotonin-induced Na+/K+ pump stimulation in vascular smooth muscle cells. Evidence for coupling to multiple receptor mechanisms.

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)

Animals↗
PubMed1991

Glioneurofibroma: renaming the pediatric "gliofibroma": a neoplasm composed of Schwann cells and astrocytes.

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.

Astrocytes↗
PubMed1990

Hyperfractionated radiotherapy for children with brainstem gliomas: a pilot study using 7,200 cGy.

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)

Adolescent↗
PubMed1990

Sigmoid volvulus in pregnancy.

Sigmoid volvulus is uncommon in the U.K. and more so in pregnancy. A case of sigmoid volvulus in pregnancy with a rare successful conclusion by conservative management is described and discussed, with a review of the literature. Sigmoid volvulus in the U.K. accounts for only 0.9% of all cases of intestinal obstruction, with most cases occurring in the elderly. Intestinal obstruction in pregnancy is also uncommon, with a reported incidence varying between 1 in 3,600 maternities to 1 in 66,431 maternities. A case is reported which was successfully treated conservatively.

Adult↗
PubMed1990

Na(+)-H+ and Na(+)-dependent Cl(-)-HCO3- exchange control pHi in vascular smooth muscle.

The mechanisms that control intracellular pH (pHi) in vascular smooth muscle are not fully understood. These studies were performed to determine the identity and relative importance of the sarcolemmal transport systems that mediate net acid efflux in primary cultured vascular smooth muscle cells from canine femoral artery. In HEPES- or HCO3(-)-buffered physiological salt solution (HEPES-PSS, HCO3(-)-PSS), recovery from an acute acid load was totally dependent on external Na+. 5-[N-ethyl-N-isopropyl]amiloride (EIPA, 50 microM) inhibited pHi recovery 100 and 68% in HEPES-PSS and HCO3(-)-PSS, respectively. EIPA-insensitive pHi recovery in HCO3(-)-PSS was inhibited 48% by 4,4'-diisothyocyanostilbene-2,2'-disulfonic acid (DIDS). An outwardly directed H+ gradient stimulated amiloride-sensitive 22Na+ uptake, and an inwardly directed HCO3- gradient stimulated amiloride-insensitive 22Na+ uptake. The latter was inhibited by DIDS or prior depletion of cell Cl-. In HEPES-PSS, resting pHi was 7.17 +/- 0.03, was not affected by DIDS, but was lowered by EIPA or by removing extracellular Na+. In HCO3(-)-PSS, resting pHi was 7.25 +/- 0.02 (P less than 0.05) and was not affected by EIPA. Removing extracellular Na+ in the presence of EIPA decreased pHi in HCO3(-)-PSS but not in HEPES-PSS. DIDS lowered resting pHi in HCO3(-)-PSS, after which EIPA further lowered pHi. We conclude that acid efflux from these cells is mediated by a Na(+)-H+ exchanger and a Na(+)-dependent Cl(-)-HCO3- exchanger. In HEPES-PSS, acid efflux via the Na(+)-H+ exchanger maintains resting pHi. In HCO3(-)-PSS, additional acid efflux via the Na(+)-dependent Cl(-)-HCO3- exchanger results in a higher pHi. Although the Na(+)-H+ exchanger is primarily responsible for acid efflux after an acute acid load, the Na(+)-dependent Cl(-)-HCO3- exchanger is responsible for acid efflux under physiological conditions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

Milk synthesis and secretion rates in cows with milk composition changed by oxytocin.

Supraphysiological doses of oxytocin were used to investigate the association among milk composition, secretion rates, and cell electrolyte concentrations. Groups of 8 Holstein cows were injected i.v. with 1, 10, 100, or 1000 IU oxytocin after a normal milking. Milk yield over the following 12-h period declined 5.5, 8.1, 17.0, and 43.7% respectively. Milk Na increased in proportion to oxytocin dose. Yield and concentration of lactose and protein declined with increasing oxytocin doses, but milk fat yield remained unchanged. To determine whether the decreased milk lactose secretion was caused by a decline in synthesis or leakage into blood plasma and subsequent renal clearance, milk and urine were collected for 24-h periods before and after 100 IU oxytocin. Urinary lactose accounted for 2.7 +/- 3.19 and 12.9 +/- 8.9% of the total collected on the days before and after oxytocin. This increase (46.7 g/d) was only one-fifth of the 25% decline in total lactose recovery, suggesting that reduced mammary lactose synthesis is primarily responsible for lower milk yield. Measurement of Na and K in biopsied mammary tissue suggests that a high Na:K ratio in milk will increase that ratio in secretory cells, which may be part of the mechanism for lower milk yield under circumstances that increase permeability of mammary tight junctions.

Animals↗
PubMed1989

High-dose leucovorin reverses acute high-dose methotrexate neurotoxicity in the rat.

Intravenous high-dose methotrexate (HD-MTX) reduces cerebral glucose metabolism and produces behavioral abnormalities and electroencephalographic slowing in an animal model of acute HD-MTX neurotoxicity and in cancer patients undergoing HD-MTX chemotherapy. We used our model of HD-MTX neurotoxicity in the rat to determine if leucovorin (5-formyltetrahydrofolate) reduces this neurotoxicity, and extended our characterization of this model to identify regional as well as global HD-MTX treatment effects and to investigate HD-MTX-induced alterations in regional brain pH. Intravenous high-dose leucovorin reversed the HD-MTX-induced decrease in cerebral glucose metabolism and associated behavioral and electroencephalographic abnormalities in the rat, but low-dose leucovorin was ineffective. The major effect of HD-MTX on cerebral glucose metabolism was a global reduction; however, smaller region-specific treatment effects were identified in auditory, thalamic, and white matter structures. HD-MTX did not alter regional brain pH. These findings suggest a potential clinical role for high-dose leucovorin in severe or prolonged acute HD-MTX neurotoxicity and provide an important justification for the role of positron emission tomography in the early detection of clinical HD-MTX neurotoxicity.

Animals↗
PubMed1989

Intracellular Na+ regulation of Na+ pump sites in cultured vascular smooth muscle cells.

Enzymatically dispersed cells from canine saphenous vein and femoral artery were grown in fetal calf serum and studied at day 0 (freshly dispersed) through confluence in primary culture. Intracellular Na levels (Nai), but not intracellular K (Ki), were increased after 24 h in culture and then decreased to a steady state by 4 days. Na+ pump site number [( 3H] ouabain binding) increased through day 3 and remained elevated. Nai was still elevated at 2 days when the Na+ pump site number began to increase. Total pump turnover (maximum ouabain-inhibited 86Rb uptake) reflected the increase in Na+ pump site number. These key events precede the observed increases in both protein production and cellular proliferation. If the same cells are maintained in defined medium, without fetal calf serum, Nai, Ki, and the number of [3H]ouabain binding sites do not change with time. These data are consistent with the suggestion that the initial mitogenic response of vascular smooth muscle cells to fetal calf serum involves an increased Na+ influx, and a Nai accumulation, caused by low Na+ pump density. The synthesis of new pump sites effects a decrease in the accumulated Nai, which may be related to cell proliferation.

Animals↗