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J G Fitz

Publications and source records attributed to J G Fitz.

83 records · Page 5Linked to original sources

Sex differences in membrane potential in the intact perfused rat liver.

The electrical potential difference across the plasma membrane was compared in paired livers from male and female rats perfused single-pass with Krebs-bicarbonate buffer. Variability in the membrane potential measured for different cells within the same liver was small (SD = 1.3 mV). The mean membrane potential was 5.1 mV more negative for male livers than for female livers (-30.3 +/- 0.6 vs. -25.2 +/- 1.0 mV, P less than 0.001), and the male liver had a more negative membrane potential than the female liver in all nine pairs studied. No correlation between membrane potential and perfusion rate was seen. Variability among female livers was more than twice as great (range -19.6 to -30.0 mV) as for male livers (range -26.7 to -31.9 mV). These results suggest that hepatic membrane potential may be modulated by sex hormone levels, which are more variable in female animals. Because the hepatic uptake of bile acids such as taurocholate and organic anions such as bilirubin may involve net movement of electrical charge across the plasma membrane, the current results may explain previously reported sex differences in the uptake of these and other electrogenically transported molecules.

Animals↗

Patient and house officer attitudes on physician attire and etiquette.

To study patient preferences on physician attire and etiquette, we interviewed 200 patients on the general medical services of teaching hospitals in Boston and San Francisco. Of these 200 patients, 65% believed physicians should wear a white coat, 27% believed physicians should not wear tennis shoes, 52% believed physicians should not wear blue jeans, 37% believed male physicians should wear neckties, and 34% believed female physicians should wear dresses or skirts. Forty percent of patients wanted physicians to address them by first name, but only 10% of patients wanted to address their physicians by first name. A concurrent mailed survey of 74 medical house staff members at the two hospitals revealed wide variability in physicians' attire and in how patients were addressed at each institution. Thus, many house officers had habits that were less formal than a substantial portion of their patients preferred.

Adult↗

Regulation of transmembrane electrical potential gradient in rat hepatocytes in situ.

The transmembrane electrical potential gradient (Em) has been measured in hepatocytes from intact anesthetized rats using conventional intracellular microelectrodes under a variety of conditions. Em measurements in control animals were normally distributed around a mean of -35.5 +/- 4.6 mV (SD) with a coefficient of variation (CV) of 13.1% and a range of -26 to -54 mV. In individual livers, however, measurements of Em at a given point in time exhibited little cell-to-cell variation (cv of 4.5%). The Em was noted to fluctuate spontaneously over time and to change consistently in response to a variety of physiological stimuli including fasting (depolarization to -28.5 +/- 3.8 mV) and infusion of glucagon in physiological amounts (hyperpolarization to -45.0 +/- 1.8 mV). Hepatocyte Em abruptly depolarized (2-5 mV) after an intravenous bolus of taurocholate (3 mumol) or alanine (45 mumol), suggesting that both solutes exhibit electrogenic uptake. The Em returned to or below preinfusion values within 5 min. Continued infusion of alanine (10.8 mumol/min), but not taurocholate (810 nmol/min), caused a sustained and unexpected hyperpolarization of Em of 8.2 +/- 3.1 mV that lasted at least 60 min. In separate studies, alanine administration did not alter the biliary excretion of a taurocholate load. Taken together, these observations demonstrate that rat hepatocytes in situ are tightly coupled electrically and that physiological stimuli, including fasting, glucagon, and sodium-coupled solute uptake can change Em considerably over time. The late hyperpolarization of Em caused by alanine appears to offset the rise in intracellular Na+ associated with alanine uptake and preserve the Na+ electrochemical gradient such that Na+-coupled taurocholate transport is maintained.

Alanine↗

Intracellular chloride activity in intact rat liver: relationship to membrane potential and bile flow.

Active chloride transport has been described in a variety of epithelia, and intracellular chloride activity (aiCl) in these tissues is generally elevated twofold or more above the level predicted for passive diffusion. To determine whether active chloride transport might contribute to canalicular bile formation, we have used conventional and Cl- -selective microelectrodes to measure aiCl of rat hepatocytes in vivo under a variety of conditions. Under basal conditions, the membrane potential difference averaged -33.2 +/- 3.5 mV (means +/- SD) in 29 animals, and the ratio (R) of observed aiCl (24.8 mM) to that expected for passive distribution at this membrane potential (22.6 mM) was 1.10 +/- 0.08, a value slightly but significantly greater than that predicted for passive distribution. Infusion of alanine (45-mumol bolus, 10.8-mumol/min infusion) in 5 animals hyperpolarized the membrane potential to -43.6 +/- 4.0 mV over 10-15 min and resulted in a significant fall in aiCl to 15.1 +/- 4.8 mM but with no change in R. Infusion of theophylline (577 nmol/min), taurocholate (3-mumol bolus, 810-nmol/min infusion), and ursodeoxycholic acid (4-mumol bolus, 2.13-mumol/min infusion) into 5 animals each increased bile flow by 6.1, 34.1, and 96.8%, respectively, compared with saline-infused controls but did not alter membrane potential or chloride distribution. These observations indicate that aiCl is close to the level predicted for passive distribution under basal conditions, after hyperpolarization of the membrane potential by alanine, and after stimulation of bile flow by a variety of choleretics. By analogy with Cl- -secreting epithelia, it appears unlikely that active chloride transport across the basolateral membrane contributes significantly to canalicular bile formation by the hepatocyte.

Alanine↗

Chronic active hepatitis presenting with rheumatoid nodules and arthritis.

Chronic active hepatitis is often accompanied by extrahepatic rheumatic symptoms of mild or moderate severity. We report a 16-year-old girl with this disorder who presented with severe polyarthritis and rheumatoid nodules mimicking juvenile rheumatoid arthritis. Rheumatoid nodules have not previously been described in chronic active hepatitis, and the severity of the rheumatic symptoms in our patient led to a delay in the recognition of the underlying liver disease. Our report provides support for an autoimmune etiology in some patients with chronic active hepatitis, notes the occurrence of rheumatoid nodules in the disorder, and emphasizes that severe extrahepatic symptoms may obscure the diagnosis and institution of therapy in some individuals.

Adolescent↗

Muscarinic cholinergic regulation of epileptic spiking in kindling.

Electroencephalographic monitoring of spontaneous interictal spiking (SIS) following kindling demonstrated that SIS occurs in both amygdalas and that it declines sharply during the days following kindling. Systemically administered muscarinic antagonists which pass the blood-brain barrier (atropine and scopolamine) activated interictal spiking in kindled rats but not in controls. Interictal spiking activated by atropine was reversed by physostigmine. Both physostigmine and choline, agents which increase brain ACh concentration by different mechanisms, caused a reduction in spontaneous (not drug activated) interictal spiking. The results of these pharmacologic studies indicate that the interaction of endogenous ACh with central muscarinic receptors is capable of suppressing SIS in kindled rats. Whether cholinergic suppression of SIS represents a convulsant or an anticonvulsant action is presently unclear.

Amygdala↗

Spontaneous interictal spiking in the awake kindled rat.

The spontaneous interictal spike (SIS) noted in EEG recordings is a signal of the abnormally excitable behavior of neurons in an epileptic focus. This study provides a detailed, quantitative, temporal and spatial profile of SIS in the amygdaloid kindled rat. The reproducible nature of the development and decline of SIS in kindling provides a useful model for biochemical study of the mechanisms that initiate and regulate SIS.

Action Potentials↗

Modulation of colonic motility by substance P, cholecystokinin and neuropeptide Y.

The effects of substance P, cholecystokinin and neuropeptide Y were examined on rabbit distal colonic motility. All three agents produced increased contractile activity but the mechanisms responsible differed depending on the agent tested. In the intact animal, peptide effects were measured under basal conditions and following exposure to atropine, tetrodotoxin and the alpha-adrenergic antagonist phentolamine. Administration of all three peptides resulted in a stimulation of colonic motility. Phentolamine did not significantly effect substance P-, cholecystokinin- or neuropeptide Y-induced activity. By contrast, the in vivo activity induced by cholecystokinin and neuropeptide Y, but not substance P, was nearly eliminated by tetrodotoxin. Only the neuropeptide Y response was partially atropine sensitive. In isolated colonic strips, cholecystokinin-induced activity, but not that produced by neuropeptide Y or substance P, was blocked by tetrodotoxin. Atropine did not significantly inhibit any of the hormone-induced contractions.

Animals↗

Liver transplantation. Patient selection and organ allocation.

Liver transplantation represents a major advancement in treating selected patients with advanced liver disease. The keys to successful outcome include: 1) early evaluation and listing for transplantation before the patient develops severe complications of cirrhosis; 2) control of comorbid conditions; and 3) a cooperative and dynamic interchange between the transplant center and other physicians involved in the care of the patient.

Adult↗