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Biomedical subjects

M J Fisher

Publications and source records attributed to M J Fisher.

At least 19 recordsLinked to original sources
PubMed1992

The effect of vanadate upon the expression of phenylalanine hydroxylase in streptozotocin-diabetic rat liver.

Induction of diabetes in rats is associated with a significant elevation in the phenylalanine hydroxylating capacity of the liver. This phenomenon reflects an increase in the abundance of both phenylalanine hydroxylase protein and phenylalanine hydroxylase-specific mRNA. These changes can be abolished by insulin-dependent control of diabetes. We show here that the control of diabetes by oral administration of sodium orthovanadate will also nullify the diabetes-related alterations in phenylalanine hydroxylase expression. In addition, diabetes-induced changes in the extent of phosphorylation of phenylalanine hydroxylase are reversed by either insulin or vanadate treatment in vivo. These treatments also abolished the diabetes-related, approx. 30-fold, decrease in glucagon sensitivity of phenylalanine hydroxylation in isolated liver cells.

Animals↗
PubMed1991

Sleep and nocturnal acid reflux in normal subjects and patients with reflux oesophagitis.

Nocturnal gastro-oesophageal reflux may be important in the pathogenesis of reflux oesophagitis. This study aimed to determine whether: (1) gastro-oesophageal reflux occurs during sleep in patients with reflux oesophagitis and, if so, to explore the mechanism, and (2) the sleep pattern of patients with oesophagitis is different from that of control subjects. After a standard evening meal, simultaneous manometric, oesophageal pH, and polysomnographic recordings were obtained in 11 patients with endoscopic oesophagitis and 11 control subjects. Patients with gastrooesophageal reflux disease had significantly more total reflux episodes throughout the nocturnal monitoring period than control subjects (105 v 6). Ninety two of 105 episodes of gastro-oesophageal reflux in patients occurred during the awake state and 10 during sleep stage II. A number of reflux episodes occurred during brief periods of arousal from the various sleep stages. Of the 105 reflux events recorded in patients, 42 were induced by transient lower oesophageal sphincter relaxation, 20 by stress reflux, 22 by free reflux mechanisms, and in 21 the mechanism was unclear. The sleep pattern and the time spent in each sleep stage was not different between the two groups. It is concluded that the awake state is crucial for the occurrence of nocturnal reflux episodes in normal subjects as well as in patients with reflux oesophagitis and that the difference between the frequency of gastro-oesophageal reflux between normal subjects and patients cannot be explained by different sleep patterns.

Adult↗
PubMed1991

Effect of decreased pH on force and phosphocreatine in mammalian skeletal muscle.

Phosphocreatine (PCr) and intracellular pH changes were monitored by 31P-NMR spectroscopy in isolated, arterially perfused cat biceps and soleus muscles, while the pH of the CO2-bicarbonate buffered perfusate was decreased from 7.1-7.4 to 6.4-6.7 by increasing the CO2 in the equilibrating gas from 5 to up to 70%. In biceps (fast twitch) muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force decreased by 8%, but the rise and relaxation times of tetanic were not significantly changed. In soleus muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force was unchanged, but the rise and relaxation times of tetani were increased by 27 and 112%, respectively. In both muscles greater decreases in tetanic force were observed during repetitive or ischemic stimulation, which resulted in intracellular pH similar to that produced by hypercapnia. Contrary to previous reports, there was no significant decrease in PCr level in either muscle type with decreased intracellular pH. In the soleus at 30 degrees C there was a significant increase in PCr level with decreased pH.

Animals↗
PubMed1991

Hypercapnic acidosis and increased H2PO4- concentration do not decrease force in cat skeletal muscle.

Peak tetanic tension was measured during acidosis resulting from either hypercapnia or repetitive tetanic stimulation in isolated, arterially perfused cat biceps brachii (predominantly fast twitch) or soleus (slow twitch) muscles. Phosphocreatine (PCr), Pi, intracellular pH (pHi), and extracellular pH (pHo) were monitored by 31P-nuclear magnetic resonance spectroscopy. During repetitive stimulation under normocapnic conditions (5% CO2, pHo 7.4) Pi increased, pHi decreased from 7.1 to 6.3, and there were significant correlations between both pHi and calculated [H2PO4-] vs. peak tetanic force in both muscle types. However, hypercapnic perfusion (70% CO2, pHo, 6.7, pHi 6.4-6.5) had no effect on peak tetanic force, and there was no significant correlation between pHi or [H2PO4-] during hypercapnia in either muscle. The results indicate that decreased peak tetanic force during repetitive stimulation is not directly due to changes in pHi or diprotonated phosphate.

Acidosis↗
PubMed1991

Cognitive factors influencing women to seek care during pregnancy.

To assess the relationship of cognitive factors to a pregnant woman's decision to seek prenatal care, a semi-structured interview instrument was administered to 30 women soon after they were seen for care. A content analysis of interview transcripts was performed to identify variables affecting the decision to seek care. Variables were coded numerically, and those correlated with number of weeks gestation at first visit for pregnancy care were entered into a stepwise linear multiple regression model. Three variables accounted for 74% of the variance in the week of gestation at which pregnancy care began. Women who desired the pregnancy, wished confirmation of the pregnancy, and experienced pregnancy-related symptoms tended to seek care earlier. Results were discussed in terms of the usefulness of this integration of quantitative and qualitative methods for the study of factors related to seeking pregnancy care and the need to consider cognitive factors when designing programs to improve the delivery of prenatal care.

Adolescent↗
PubMed1990

Experimental determination of the phosphorylation state of phenylalanine hydroxylase.

A monoclonal antibody (PH 7), which recognizes the phosphorylated form of phenylalanine hydroxylase from human liver, has been used for the analysis of the enzyme in crude cell extracts from rat. In immunoblot analyses of rat liver cell extracts, the extent of binding of PH 7 closely correlates with the phosphorylation state of phenylalanine hydroxylase, as judged by [32P]Pi incorporation. These observations have made possible the rapid non-radioactive quantification of hormonal effects on phenylalanine hydroxylase phosphorylation state. In particular, the glucagon-dependent phosphorylation of phenylalanine hydroxylase in liver cells was investigated. Epidermal growth factor was shown to modulate this process. In addition, this technique was used to demonstrate, for the first time, that dibutyryl cyclic AMP, unlike the Ca2+ ionophore A23187, stimulates the phosphorylation of phenylalanine hydroxylase in isolated kidney tubules from rat.

Animals↗
PubMed1990

The myocotoxin ochratoxin A is a substrate for phenylalanine hydroxylase in isolated rat hepatocytes and in vivo.

Ochratoxin A (OTA), is a myocotoxin contaminating food and feed stuffs, consisting of a chlorinated dihydroisocoumarin linked through a 7-carboxyl group to L-phenylalanine by an amide bond. When OTA (0.12-1.4 mM) is incubated with freshly isolated rat hepatocytes, it inhibits both the hydroxylation of phenylalanine (0.05 mM) to tyrosine, catalyzed by phenylalanine hydroxylase and the subsequent metabolism of tyrosine as measured by homogentisate oxidation. The IC50 of OTA for phenylalanine hydroxylation is 0.43 mM. OT alpha, (0.5-1.0 mM), the dihydroisocoumarin moiety of OTA, does not inhibit phenylalanine hydroxylase activity under these conditions. During incubations of hepatocytes with uniformly labelled [3H]-OTA and unlabelled phenylalanine, tyrosine-ochratoxin A is formed (up to 6% of the total mycotoxin added), indicating that ochratoxin can act as a substrate for phenylalanine hydroxylase. In vivo tyrosine-OTA is also found in liver of poisoned animals.

Adenosine Triphosphate↗
PubMed1990

Electrical and mechanical inhibition of the crural diaphragm during transient relaxation of the lower esophageal sphincter.

Electrical and mechanical correlates of crural diaphragm activity during swallow-induced and transient lower esophageal sphincter relaxation were monitored in 12 healthy subjects. Simultaneous esophageal manometric, pH, and crural diaphragm electromyogram recordings were performed for 1 hour in the postprandial period. Swallow-induced lower esophageal sphincter relaxation was associated with minimal inhibition of the crural diaphragm, but transient lower esophageal sphincter relaxation was accompanied by marked inhibition of the crural diaphragm. The degree of lower esophageal sphincter relaxation appeared to correlate with the degree of crural diaphragm inhibition during transient lower esophageal sphincter relaxation. Inhibition of crural diaphragm during transient lower esophageal sphincter relaxation may play an important role in facilitating flow across the gastroesophageal junction.

Deglutition↗
PubMed1990

Phenylalanine hydroxylation in isolated rat kidney tubules.

1. Phenylalanine hydroxylation has been demonstrated to occur in isolated rat kidney tubules under physiological conditions. 2. The hydroxylation flux response is hyperbolic with apparent Km and Vmax values of ca 85 microM phenylalanine and 49 nmol tyrosine formed/mg dry wt per hr respectively. 3. Hydroxylation in kidney tubules is substantially less sensitive to effectors of cyclic AMP turnover and Ca2+ mobilization than phenylalanine hydroxylation in isolated liver cells.

Animals↗
PubMed1990

Direct relationship between proton T2 and exercise intensity in skeletal muscle MR images.

Exercise selectively increases the signal intensities (SI) of active muscles in T2-weighted magnetic resonance (MR) images. If these SI increases are graded with exercise intensity, the identification of muscle recruitment patterns may be possible using MR imaging. The purpose of this study was to determine the effect of force generation during exercise on muscle T2 values. Also, we examined the effects of extracellular fluid volume (ECV) expansion on muscle T2 values. Transaxial midcalf images were collected before and after exercise on eight volunteers in a 1.5T GE magnet using a standard spin echo sequence. Exercise consisted of three consecutive bouts of ankle dorsiflexion against graded loads. Three subjects also underwent brief bouts of lower leg venous occlusion (ECV expansion) during and in addition to the exercise protocol. T2 values for the dorsiflexors significantly increased after exercise. Greater mean force produced during exercise caused greater increases in T2 after exercise (T2 = 29.6 +/- 0.9 X Force). Exercise and venous occlusion caused equivalent increases in muscle cross-sectional area. These equivalent increases in ECV were not accompanied by equivalent increases in muscle T2; venous occlusion alone caused less than a 5% increase in T2 while exercise caused a 14% to 25% increase. Consequently, a direct relationship between increases in T2 and in ECV after exercise was not established. Venous occlusion during exercise, however, did significantly augment the increase in T2 and ECV of the anterior compartment muscles. Contrast enhancement among muscles after exercise in T2-weighted MR images is dependent on generated force during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Comparative analysis of the proliferative response of the rat urinary bladder to sodium saccharin by light and scanning electron microscopy and autoradiography.

Three methods used to detect proliferative changes in the rat urothelium, light microscopy, scanning electron microscopy, and autoradiography, were compared for their sensitivity in detecting changes produced by administration of sodium saccharin. Weanling male F344 rats were fed sodium saccharin as 0, 3, 5, or 7.5% of the diet, and the bladders were evaluated after 4, 7, and 10 wks of feeding. Light microscopic changes and an increase in labeling index were seen at all time points in rats fed 7.5% sodium saccharin, but not at the lower doses. A slight increase in labeling index was also observed at 10 wks in the 5.0% group. Scanning electron microscopic changes were evident as early as 4 wks with increasing severity at the 3, 5, and 7.5% doses. This study demonstrates that the hyperplastic response of the urothelium to sodium saccharin administration varies with dose and time, and that observation by scanning electron microscopy is the most sensitive of the three methods evaluated for detecting these changes.

Animals↗
PubMed1989

The effect of streptozotocin-induced diabetes on phenylalanine hydroxylase expression in rat liver.

The impact of experimentally induced diabetes on the expression of rat liver phenylalanine hydroxylase has been investigated. A significant elevation in maximal enzymic activity was observed in diabetes. This was associated with significant increases in the amount of enzyme, the phenylalanine hydroxylase-specific translational activity of hepatic RNA and the abundance of phenylalanine hydroxylase-specific mRNA. These changes in phenylalanine hydroxylase expression were not observed when diabetes was controlled by daily injections of insulin. These results are discussed in relation to the hormonal control of phenylalanine hydroxylase gene expression.

Animals↗
PubMed1989

Influences of diet and strain on the proliferative effect on the rat urinary bladder induced by sodium saccharin.

Rats were fed sodium saccharin as 5 or 7.5% of the diet by weight, and proliferation of the bladder epithelium was assessed by autoradiography, histology, and scanning electron microscopy. In Experiment 1, male F344 rats, 5 weeks old, were placed on a diet of 0, 5, or 7.5% NaS mixed in Prolab 3200, NIH-07, or AIN-76A diet for 4 or 10 weeks. In Experiment 2, 5-week-old F344 rats or 4-week-old Sprague-Dawley rats were fed 0, 5, or 7.5% NaS in Prolab 3200 or Purina 5002 diet for 10 weeks. In Experiment 1, at both the 4- and 10-week intervals, NaS had a greater effect on the urothelium when administered in the Prolab diet compared to the NIH diet, and there was little response with the AIN diet. Eight of 10 rats fed 7.5% NaS in Prolab 3200 for 4 or 10 weeks had bladders with simple or nodular hyperplasia, and eight of nine bladders contained abnormal surface features visible by scanning electron microscopy. At 10 weeks for control animals, the average labeling index following [3H]thymidine incorporation into bladder epithelium was approximately 0.05%. For rats fed 7.5% NaS diets, the labeling index was 0.43% for Prolab, 0.14% for NIH-07, and 0.04% for AIN-76A. In Experiment 2, the response to NaS was considerably greater in F344 rats than in Sprague-Dawley rats fed the same diet, and for both strains, the response to NaS was greater in Prolab than in Purina diets. In conclusion, the proliferative effect of NaS on male rat urinary bladder depended on rat strain as well as on type of diet.

Animals↗
PubMed1989

31P NMR study of insulin effects on the isolated perfused rabbit urinary bladder.

Insulin stimulates hexose transport, intermediary metabolism, and cell growth and development. These effects are well-documented in skeletal but not smooth muscle. 31P NMR spectroscopy was performed on rabbit urinary bladders (n = 4) to characterize insulin's actions on smooth muscle. The bladder and its vasculature were surgically isolated from the animal and perfused with a PSS/red blood cell perfusate. After a control steady state was achieved (approx 1-2 h), insulin (0.100 mU/ml) was added to the perfusate. Relative levels of intracellular phosphorylated compounds, pH, and free Mg2+ were measured and compared to control values. Also, extracellular pH and fractional volume were assessed using phenylphosphonate, a 31P NMR extracellular pH and volume indicator. Insulin induced significant increases in PCr (16 +/- 9%) at the expense of Pi, intracellular pH (delta pH 0.24 +/- 0.07), and fractional extracellular volume (49 +/- 1%). Intracellular free Mg2+ and extracellular pH did not change. These results indicate that in situ smooth muscle is sensitive to physiological levels of insulin. In fact, insulin improves the energy state of smooth muscle cells and the overall tissue perfusion.

Adenosine Triphosphate↗
PubMed1989

Hiccups and gastroesophageal reflux: cause and effect?

Chronic hiccups may be a problem of great significance to the affected patient. A 62-year-old man with severe heartburn and persistent hiccups despite numerous diagnostic tests and therapeutic drug trials presented to our clinic. Esophageal motility and intraluminal pH studies demonstrated decreases in intraesophageal pressure during hiccups and acid exposure during 68% of the measured time. The patient underwent Nissen fundoplication, which improved his heartburn but not his hiccups. The association between gastroesophageal reflux and hiccups is discussed. Our experience suggests that the presence of hiccups and gastroesophageal reflux in the same patient may be coincidental rather than having a cause-and-effect relationship.

Chronic Disease↗