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Biomedical subjects

B Harvey

Publications and source records attributed to B Harvey.

At least 19 recordsLinked to original sources

Ethanol and mitotic inhibitors promote differentiation of trophoblastic cells.

Chronic ethanol abuse during pregnancy can cause fetal injury. A contributing factor in this fetal injury may be the effect of ethanol on the placenta. Ethanol treatment increases human chorionic gonadotropin (hCG) production by cultured human placental trophoblasts. In this study, we show that ethanol treatment reduces total DNA and total protein while stimulating hCG production in term trophoblasts. Ethanol treatment inhibits growth in rapidly proliferating trophoblastic cells from a first trimester placenta and JEG-3 choriocarcinoma cells. In both cell types, the normal increases in total DNA were inhibited in an ethanol dose-dependent manner. Normal increases in total protein were inhibited as well. In contrast, hCG production, an indicator of differentiation, was stimulated by ethanol treatment. Treatment of JEG-3 cells with antimitogenic agents, methotrexate (MTX) or cytosine arabinoside (Ara-C), inhibited cell growth as indicated by decreased total DNA and total protein accumulation. Similar to that with ethanol treatment, inhibition of cell proliferation was accompanied by increases in hCG production. Taken together, these data suggest that one mechanism by which ethanol increases hCG production in human placental trophoblasts may involve alterations in cellular growth and/or differentiation; such alterations may also occur in other proliferating cells in the growing fetus.

Cell Differentiation

The stimulatory effect of chronic lithium treatment on basal thyrotropin secretion in rats: in vivo antagonism by methylparaben.

Chronic treatment of rats with lithium chloride was examined in order to determine its effects on hypothalamic monoamine and metabolite content, basal thyrotropin (TSH) secretion and thyroid function. The hypothalamic concentrations of noradrenaline (NA), dopamine (DA) and its metabolites, dihydroxyphenylacetic acid. (DOPAC) and homovanillic acid (HVA) in the lithium treated rats remained unaltered when compared to control levels. NA turnover and the NA metabolite, 3-methoxy-4-hydroxyphenylglycol (total MHPG), were significantly lower (p < 0.01), whereas both serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were significantly higher (p < 0.01 and p < 0.02, respectively) in the lithium treated rat hypothalami than in controls. Chronic lithium treatment significantly elevated basal TSH levels (p < 0.05). This effect was antagonized by methyl p-hydroxybenzoate (methylparaben, p < 0.01), which did not itself affect basal TSH levels. Free serum T3 and T4 levels were not significantly affected by chronic lithium treatment, although T4 tended to be slightly lower than control levels. The monoamine changes observed in the hypothalamus of lithium treated rats did not appear to account for the elevated TSH levels observed in these rats since NA activity which is generally regarded as stimulatory was decreased and 5-HT which has an inhibitory effect on TSH secretion, was increased. The elevated TSH levels may have been due to a reduced negative feedback inhibition of TSH release by the mildly reduced circulating T4 levels caused by chronic lithium treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Absence of an effect of the lithium-induced increase in cyclic GMP on the cyclic GMP-stimulated phosphodiesterase (PDE II). Evidence for cyclic AMP-specific hydrolysis.

Chronic treatment of rats with LiCl is known to induce a decrease in cAMP, while this decrease has also been found to occur together with both a simultaneous increase in total cortical phosphodiesterase (PDE; EC 3.1.4.17) activity and a concomitant increase in cGMP. These studies have implicated an involvement of PDE in lithium (Li+) action and it has been suggested that cGMP and the cGMP-stimulated PDE may be instrumental in the observed effects of Li+ on cAMP. In this study, three isozymes of PDE were isolated and identified from rat cortex and their activity determined, together with simultaneous measurement of cAMP and cGMP, after chronic treatment with oral LiCl (0.35% m/m). Li+ treatment exerted profound effects on cyclic nucleotides in the cortex, inducing significant suppression of cAMP while increasing cGMP levels. However, the ion only induced a slight but insignificant increase in the activities of the three PDE isozymes. To confirm these observations, methylparaben (MPB), a drug demonstrating both an ability to induce a selective stimulation of cAMP-specific PDE and also to lower intracellular levels of cGMP, was co-administration orally (0.4% m/m) with Li+ over the same period. This combination emphasized certain actions of Li+ not noted with Li+ alone. MPB inhibited the Li(+)-induced increase in cGMP, yet did not prevent the ion from decreasing cAMP. However, the combination of Li+ and MPB engendered a synergistic 100% increase in the activity of the membrane-bound, cAMP-specific PDE, PDE IV. This combination also produced a significant suppression of cAMP, while no reduction in cGMP was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases

Bereavement support: evaluation of a palliative care memorial service.

A memorial service providing bereavement support in a palliative care unit is evaluated. Results indicate that respondents found it to be a positive experience, particularly in relation to its formality and content. One-fifth of respondents experienced distress during the service, but this was evaluated as appropriate, being related to personal thoughts, feelings of loss and sadness, and remembrance.

Bereavement

Common channels for water and protons at apical and basolateral cell membranes of frog skin and urinary bladder epithelia. Effects of oxytocin, heavy metals, and inhibitors of H(+)-adenosine triphosphatase.

We have compared the response of proton and water transport to oxytocin treatment in isolated frog skin and urinary bladder epithelia to provide further insights into the nature of water flow and H+ flux across individual apical and basolateral cell membranes. In isolated spontaneous sodium-transporting frog skin epithelia, lowering the pH of the apical solution from 7.4 to 6.4, 5.5, or 4.5 produced a fall in pHi in principal cells which was completely blocked by amiloride (50 microM), indicating that apical Na+ channels are permeable to protons. When sodium transport was blocked by amiloride, the H+ permeability of the apical membranes of principal cells was negligible but increased dramatically after treatment with antidiuretic hormone (ADH). In the latter condition, lowering the pH of the apical solution caused a voltage-dependent intracellular acidification, accompanied by membrane depolarization, and an increase in membrane conductance and transepithelial current. These effects were inhibited by adding Hg2+ (100 microM) or dicyclohexylcarbodiimide (DCCD, 10(-5) M) to the apical bath. Net titratable H+ flux across frog skin was increased from 30 +/- 8 to 115 +/- 18 neq.h-1.cm-2 (n = 8) after oxytocin treatment (at apical pH 5.5 and serosal pH 7.4) and was completely inhibited by DCCD (10(-5) M). The basolateral membranes of the principal cells in frog skin epithelium were found to be spontaneously permeable to H+ and passive electrogenic H+ transport across this membrane was not affected by oxytocin. Lowering the pH of the basolateral bathing solution (pHb) produced an intracellular acidification and membrane depolarization (and an increase in conductance when the normal dominant K+ conductance of this membrane was abolished by Ba2+ 1 mM). These effects of low pHb were blocked by micromolar concentrations of heavy metals (Zn2+, Ni2+, Co2+, Cd2+, and Hg2+). Lowering pHb in the presence of oxytocin (50 mU/ml) produced a transepithelial current (3 microA.cm-2 at pHb 5.5) which was blocked by 100 microM of Hg2+, Zn2+, or Ni2+ at the basolateral side, and by DCCD (10(-5) M) or Hg2+ (100 microM) from the apical side. The net hydroosmotic water flux (JH2O) induced by oxytocin in frog bladder sacs was blocked by inhibitors of H(+)-adenosine triphosphatase (ATPase). Diethylstilbestrol (DES 10(-5) M), oligomycin (10(-8) M), and DCCD (10(-5) M) prevented JH2O when present in the lumen. These effects cannot be attributed to inhibition of metabolism since cyanide (10(-4) M), or 2-deoxyglucose (10(-3) M) had no effect on JH2O.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Why we need a national child health policy.

Although the federal government has long had an interest in the health of children, action in support of this interest has been limited, fragmented, and inequitable. While health problems are increasing and becoming more complex and while policy leaders, business groups, and the public recognize that action is necessary, no response has been forthcoming. Development of a policy with measurable goals is needed. Resources must be allocated and data collected to periodically evaluate progress toward goals and to appropriately redirect resources.

Child

Effect of mucosal H+ and chemical modification on transcellular K+ current in frog skin.

A transcellular K+ current (IK) was established across the skin of the frog Rana temporaria, whose apical K+ permeability had been previously stimulated by exposure to K(+)-rich media. Short-term (less than or equal to 15 s) mucosal pH-titration of IK indicated two titrated groups (A and B), with apparent pKA of 6 and pKB of 3. The height of the titration steps, A and B, varied from skin to skin. Intracellular (i) H(+)-sensitive microelectrode studies on Rana esculenta skin (which lacks apical PK) were conducted in order to assess possible changes in pHi and basolateral K+ conductance as a consequence of the rise in mucosal [H+]. Cell pH decreased only at mucosal pH lower than 5.4 which caused a drop in basolateral K+ conductance as estimated from I-V records of the serosal membranes. These effects were much too slow to account for the fast mucosal pH effects on IK (Rana temporaria). Thus, we conclude that the two-step titration curves reflect solely the interaction of external H+ with the mucosal side of apical membrane K+ channels. Exposure to the SH-reagent PCMB, and to the carboxy-modifying EEDQ markedly reduced total IK at neutral pH; however, PCMB seemed to preferentially affect titration step B while EEDQ virtually eliminated step A. When the saturating IK kinetics were studied at different mucosal pH, protons showed a 'mixed' type inhibition of K+ current in the range of titration step A; at pH values less than 5, protons blocked IK by competition with K+ ions. These results are compatible with the presence of two K+ channel populations in the apical membrane which are discernible by their different interactions with external protons and chemical modifiers.

Animals

Lithium modulation of cortical cyclic nucleotides: evidence for the Yin-Yang hypothesis.

Rats were subjected to chronic treatment with lithium chloride (0.2-0.3%) over a period of 3 weeks. The activity of cortical phosphodiesterase (EC 3.1.4.17) was determined simultaneously with cyclic AMP and cyclic GMP content and compared to control, untreated animals. Lithium, at therapeutic serum concentrations was found to suppress cyclic AMP levels with a concomitant increase in cyclic AMP-phosphodiesterase activity. A simultaneous two-fold increase in cyclic GMP was observed. Through the alteration of cortical cholinergic activity with physostigmine and the use of cyclic GMP as a cholinergic marker, we were able to demonstrate a novel cholinotropic property of lithium to stimulate synthesis of cyclic GMP. This effect appears to be linked, in a Yin-Yang mechanism, to the observed suppression of cyclic AMP induced by lithium through activation of cyclic AMP-phosphodiesterase.

Animals

Services and charges by PPO physicians for PPO and indemnity patients. An episode of care comparison.

Physicians who participate in preferred provider organizations (PPOs) usually agree to various types of utilization review and sometimes discount their charges or agree to accept lower fees. This study was performed to determine whether they provided more or fewer services to their PPO patients than to their indemnity patients and whether the discounting resulted in lower expenditures for each episode of illness. In 1984, Metropolitan Life offered PPO coverage to Dade County (Florida) school board employees and dependents but only a standard indemnity plan to Dade County government employees and dependents. Episodes of care were examined for patients with chest pain, hypertension, joint pain, gastrointestinal or liver disorders, and lower back pain cared for by physicians who treated patients in both the PPO and indemnity employee groups. For PPO patients, charges per physician service were the same or lower, but total physician charges during an episode were higher. For services such as laboratory tests, diagnostic x-rays, and room and board, PPO and indemnity patients' charges were not significantly different.

Fees, Medical

Surgery, sepsis, and nonspecific immune function in neonates.

An audit of 143 neonatal surgical operations identified low birth weight infants as being at particular risk of developing post-operative sepsis following major surgical trauma. Activity of the nonspecific immune system was examined pre- and post-operatively in order to elucidate the susceptibility to post-operative sepsis of these infants. A chemiluminescence micro-method was developed specifically for this purpose. Neonatal plasma was shown to have significantly impaired opsonising activity, and activity was further reduced in low birth weight infants. Levels of immunoglobulin and complement factors were also reduced, particularly in the low birth weight infant. Following major surgical trauma polymorph activity was significantly lower in low birth weight infants than in mature neonates.

Anti-Bacterial Agents