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Biomedical subjects

J G Moore

Publications and source records attributed to J G Moore.

At least 19 recordsLinked to original sources
PubMed1995

A multimerizing transcription factor of sea urchin embryos capable of looping DNA.

SpGCF1 is a recently cloned sea urchin transcription factor that recognizes target sites in several different sea urchin genes. We find that in gel-shift experiments this factor is able to multimerize. A quantitative simulation of the gel-shift results suggests that SpGCF1 molecules that are bound to DNA target sites may also bind to one another, thus associating several DNA probe molecules. SpGCF1 might therefore be able to loop DNA molecules bearing its target sites at distant locations. We demonstrate this prediction by electron microscopy, and using the well-characterized cis-regulatory domain of the CyIIIa cytoskeletal actin gene, we show that the loop conformations predicted from the known SpGCF1 target site locations are actually formed in vitro. We speculate that the multimerization of this factor in vivo may function to bring distant regions of extended regulatory domains into immediate proximity so that they can interact with one another.

Actins↗
PubMed1995

Gastric emptying response to variable oral erythromycin dosing in diabetic gastroparesis.

Intravenous erythromycin has been shown to improve gastric emptying in diabetic gastroparesis. Oral erythromycin also accelerates gastric emptying, but to a lesser degree. To determine if this is a dose-dependent phenomenon, gastric emptying was measured in 10 insulin-requiring diabetic patients with gastroparesis after administration of either 250 mg or 1000 mg of erythromycin or placebo. The drugs were orally administered in a randomized, double-blind fashion 30 min prior to ingestion of a meal containing [99mTc]-sulfur colloid-labeled beef stew and [111In]DTPA-labeled orange juice. Anterior and posterior gastric images were recorded for 3 hr at 15-min intervals using an externally positioned gamma camera. The results demonstrated that both doses of oral erythromycin significantly improved solid-phase gastric emptying. The mean half-emptying time of solids was decreased from 151 +/- 40 min with placebo to 58 +/- 10 min and 40 +/- 9 min with 250 mg and 1000 mg of erythromycin, respectively. However, a dose-dependent relationship was not demonstrated with the two doses of erythromycin employed. These results suggest that for most patients with diabetic gastroparesis, a single 250-mg dose of erythromycin will significantly improve gastric emptying. It is possible that a dose-dependent relationship will be demonstrated with doses of erythromycin less than 250 mg.

Administration, Oral↗
PubMed1995

Circannual rhythm in DNA synthesis (S-phase) in healthy human bone marrow and rectal mucosa.

Cytotoxic anti-cancer drugs are meant to interact with tumor cells to impair the replicative and/or transcriptional functions of DNA in order to reduce proliferative rate and cause cell death. These drugs also affect rapidly proliferating healthy tissues such as the bone marrow and the gastrointestinal tract, thereby resulting in toxicity-related dose reductions and/or delays in treatment. We previously demonstrated a circadian rhythm in DNA synthesis (S-phase) of total bone marrow (BM) nucleated cells in 16 healthy, diurnally active men sampled every 4 h for 24 h (19 series). Highest values determined by flow cytometry were found near midday. We also reported a circadian rhythm in DNA synthesis of the rectal mucosa (RM) in 16 healthy men sampled every 2-3 h for 24 h under fed and fasting conditions (24 series). Highest proliferative activity as reflected by in vitro [3H]Tdr uptake, was found near the time of awakening. Circannual (about yearly) rhythmicity in cell division rates may also influence treatment effects. Our BM and RM DNA data, which were collected over several years, were reanalyzed for seasonality by ANOVA and for circannual rhythm by the least-squares fit of a 1 year cosine. Characteristics of circadian amplitudes and acrophases were also compared between seasons. In addition to a significant circadian rhythm, a significant circannual rhythm in cell proliferation in healthy BM (P = 0.008) and RM (P < 0.001) could be established on the basis of these serially independent data. The range between the lowest and highest points of the fitted 1 year cosine (circannual double amplitude) was comparable to the circadian range for BM (25%); it was at least doubled for RM (70%). Highest values occurred in the late summer for BM and mid-fall for RM. Based on limited data in some seasons, the circadian patterns were more prominent in the fall and winter, with larger amplitudes and later acrophases, when compared with summer for BM and spring and summer for RM. Thus, in addition to time of day, time of year may influence chemo- and immunotherapeutic strategies and should be considered in the design of preclinical and clinical treatment regimens and other procedures.

Adult↗
PubMed1994

Effect of constant light on rhythmic gastric functions in fasting rats.

The effects of four weeks of continuous illumination (LL), a subacute stress, on gastric mucosal endogenous aggressive and defensive factors were studied. Young male Sprague-Dawley rats were used with two different illumination regimens: LL and 12 hr light/12 hr dark (LD). At the end of three to four weeks of either regimen of illumination, gastric acid secretion, pepsin secretion, mucus secretion, and potential difference (PD) were studied. All gastric parameters, except mucus secretion, were significantly reduced by LL. The reduction in acid secretion (13.3%) was not significant after Bonferroni correction for the four t tests Pepsin secretion and PD were 27.9% and 24.6% less, respectively. These differences were significant after Bonferroni correction. The LD rats showed significant circadian rhythms for acid, mucus, and pepsin secretion. The LL rats showed significant rhythmicity for these same parameters with period lengths different from 24 hr. Gross inspection of the gastric mucosa indicated that 69.8% of the LL rats had lesion scores of 1.0 or higher, while none of the LD rats had scores above 0.5.

Action Potentials↗
PubMed1994

Asynchrony in circadian rhythms of gastric function in the rat. A model for gastric mucosal injury.

A model for gastric mucosal injury is proposed in which a key pathogenetic event is the disruption in the normal relationships among several circadian rhythms of gastric function. In the rat a circadian rhythm in acid secretion was found to be out of phase with a circadian rhythm in gastric pepsin secretion, another aggressive factor, and several mucosal defensive factors (mucus and bicarbonate efflux and tissue prostacyclin content). Gastric corpus mucosal blood flow circadian patterns paralleled the the rhythmicity in acid secretion and, therefore, was out of phase with the other measured mucosal defensive factors. Thus, gastric mucosal defense was maintained by different mechanisms over the 24-hr cycle. During the dark phase, when this species was active and when acid secretion was highest, enhanced damage by topical acidified aspirin was documented, despite increased mucosal blood flow. Natural asynchrony in circadian rhythms of gastric function can be protective of gastric mucosal integrity but disruption of this circadian interplay of gastric aggressive and defensive factors could theoretically lead to greater vulnerability to damage. In the human, a circadian rhythm in basal gastric acidity has been described but no information exists as to the possibility of similar rhythmic variation in other gastric factors (aggressive and defensive) and possible disruption of these rhythms in disease.

Animals↗
PubMed1993

Circadian rhythm in aspirin (ASA)-induced injury to the stomach of the fasted rat.

Circadian rhythms exist in several gastric parameters affecting ulcerogenesis. This study investigated possible circadian rhythmicity in observed aspirin (ASA)-induced gastric lesions in the rat. In five experiments 183 rats were studied at 14 time points over a 24-hr period. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18 hr, then given oral acidified ASA. One hour later, the rats were sacrificed, the stomachs were removed, stretched flat, photographed, scanned, and measured for percent area of gross lesions in the gastric corpus by computer planimetry. Cosinor rhythmometric analysis showed a significant (P < 0.001) rhythm. Mean of rhythm (MESOR) was 5.60 +/- 0.25% of total corpus. Amplitude was 25.89 +/- 6.07% of MESOR. Peak time (acrophase) was 1909 +/- 0101 hr after lights on. Thus, gastric vulnerability to ASA injury exhibited circadian rhythmicity with peak injury during the dark period in this species.

Animals↗
PubMed1993

Circadian rhythm of pepsin efflux in the fasting rat stomach.

Gastric pepsin efflux, a putative aggressive factor because of its proteolytic activity, was examined to determine if it displays circadian rhythmicity as has been shown for other factors such as acid, bicarbonate, mucus, blood flow, potential difference, and tissue prostacyclin activity. Ninety-six fasted Sprague-Dawley male rats, 6-7 weeks of age were acclimated in sound-attenuating, light-proof chambers on a 12/12 light/dark schedule. They were studied in groups of 12 at 3-h intervals. After anesthesia and minor surgery, the stomach was cannulated and filled with 2 ml of saline for two sequential periods of 30 min. The samples were tested for pepsin according to the modified hemoglobin substrate colorimetric method. The data were analyzed with cosinor rhythmometric techniques. Pepsin efflux displayed significant (p < 0.05) circadian rhythmicity with an acrophase value or peak time at 06:49 h after lights on, during the lights-on resting phase. In contrast, the acrophase for acid secretion in the same model occurs during the dark period, when the rats are normally active. We postulate that differences in the circadian patterns of acid and pepsin may be protective.

Acclimatization↗
PubMed1993

Gastric potential difference in fasted rats: circadian studies.

The pathophysiology of gastroduodenal ulcer disease remains the subject of intense research and controversy. One model of gastric ulcerogenesis implicates a disruption of complementary circadian rhythms between protective and destructive factors. Parallel circadian rhythms have been reported between acid secretion and gastric potential difference (PD) in in vitro models. The purpose of this study was to investigate the circadian measurements of PD, a parameter of intact gastric mucosal function and thus a putative parameter of gastric protection, in intact, fasted, anesthetized rats. Sixty-four male Sprague-Dawley rats were acclimatized in sound-attenuating, lightproof chambers for 3 weeks on a 12:12-h light-dark schedule. Eight rats were fasted 18 h before being sampled at each of eight times on the circadian clock (01:00, 04:00, 07:00, 10:00, 13:00, 16:00, 19:00, and 22:00 hours after lights on) (HALO). In each rat, after anesthesia (ketamine/acepromazine) and laparotomy, the tip of a catheter (pre-filled with KCl agar) was passed into the gastric corpus through the duodenum. The tip of a second KCl-agar catheter was placed within the peritoneal cavity. The position of the intragastric catheter was gently adjusted for obtaining the highest stable PD reading. The data showed significantly higher values at 07:00 and 10:00 HALO. The lowest value was at 13:00 HALO. The difference between high (10:00 HALO) and low (13:00 HALO) values was 4.5 mV or 13% of the mean. This difference was highly significant (p = 0.003) Analysis of variance showed that the values at 07:00 and 10:00 HALO were significantly higher than the values at 01:00, 13:00, and 16:00 HALO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Twenty-four-hour intragastric pH patterns in ICU patients on ranitidine.

Thirty critically ill patients with mixed diagnoses underwent continuous intragastric pH monitoring for 72 hr while confined to a shock/trauma intensive care unit. The first 24 hr were monitored under no specific acid-suppressing therapy (placebo control). During the second and third consecutive 24-hr periods, patients received continuous infusion of intravenous ranitidine in the dose of 6.25 mg/hr and 12.5 mg/hr, respectively. Results of the placebo-control 24-hr study revealed that one third (N = 10) of the patients were gastric acid hyposecretors (24-hr median intragastric pH values above pH 4.0). In the normosecreting group (N = 20), both ranitidine schedules significantly elevated 24-hr median pH values, when compared to placebo (placebo 24-hr median intragastric pH 1.75; ranitidine 6.25 mg/hr 24-hr median intragastric pH 4.625, P < 0.0001; ranitidine 12.5 mg/hr 24-hr median intragastric pH 6.29, P = 0.0099). Five patients (18%) failed to adequately respond to the ranitidine 12.5 mg/hr dose (24-hr median intragastric pH < 4.0). These findings suggest that a significant percentage of intensive care unit patients are not in need of acid-suppressing therapy as prophylaxis against stress-induced ulceration. Conversely, other patients may require more intensive acid-suppressing regimens because of failure to respond to high dose H2-antagonist therapy.

Adolescent↗
PubMed1992

Circadian rhythm in prostacyclin activity in gastric tissue of the fasting rat.

Gastroduodenal ulcer disease may result from the desynchronization of the circadian rhythms of gastric protective and destructive factors. The purpose of this study was to evaluate whether gastric tissue 6-keto prostaglandin F1 alpha (PGF1 alpha), a catabolic derivative of the putative protective factor prostacyclin, is produced in a circadian fashion in the rat model. Forty-eight male Sprague-Dawley rats were acclimatized in sound-attenuated, lightproof chambers for 3 weeks on a 12:12 hour light/dark entrainment schedule. After an 18-hour fast, six rats were killed at each of eight sampling times. The stomachs were exposed, removed, and assayed for total 6-keto PGF1 alpha content by radioimmunoassay. Cosinor analysis of the data showed significant (p = 0.0262) circadian rhythmicity in 6-keto PGF1 alpha content with an acrophase (peak time) value of 0503 HALO (hours after lights on) or in the middle of the lights-on inactive period for the rats. Hypothetically, the circadian rhythm in some gastric protective factors may render the gastric mucosa vulnerable to injury in a circadian fashion.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Gastrointestinal chronopharmacology: physiology, pharmacology and therapeutic implications.

This chapter discusses the influence of ultradian and circadian rhythms of gastrointestinal motor and secretory function on the action of orally administered drugs. Most drugs exhibit more rapid absorption in the morning compared to the evening due, in part, the circadian alterations in gastric emptying. Gastric acid secretion and gastrointestinal toxicity to oral drugs also display circadian rhythmicity. These observations provide a rationale for use or avoidance of drugs based on time-of-day dosing considerations. The chronopharmacological behavior of a drug may thus play an important role in the effectiveness of any oral medication treatment schedule.

Animals↗
PubMed1992

Circadian differences in pharmacological blockade of meal-stimulated gastric acid secretion.

The effects of identical morning (08.05 hours) and evening (20.05 hours) meals on intragastric pH were compared in 12 healthy volunteers receiving gastric antisecretory medication. Dosing included continuous intravenous infusion ranitidine (50 mg bolus followed by 12.5 mg/h) or a matching placebo which were randomly administered prior to and following 7 days of treatment with oral omeprazole (40 mg mane). Intragastric pH was monitored continuously using a tethered indwelling pH probe. Subjects were divided into groups, one of which began the pH monitoring session in the morning, the other in the evening. The median 24-h intragastric pH was significantly increased by all active dosing regimens (P less than 0.05). Combined omeprazole and ranitidine produced the highest median pH, 5.92. However, a breakthrough drop in intragastric pH occurred during the evening after all active dosing. Intragastric pH fell prior to and after consumption of the evening meal with median pH values less than 4 during all sessions. The evening meal led to significantly lower intragastric pH compared to the morning meal for omeprazole and the combined omeprazole and ranitidine dosing periods (P less than 0.05). There was no difference between morning and evening pH during the placebo or ranitidine periods. Ranitidine and omeprazole, either alone or in combination, were unable to prevent the meal-stimulated decline in intragastric pH during the evening time period.

Adult↗
PubMed1992

Automated sequential affinity chromatography of sea urchin embryo DNA binding proteins.

An automated method of running a tandem sequence of oligonucleotide affinity columns was used to purify factors that interact specifically with cis-regulatory sites of the CyIIIa cytoskeletal actin gene of the sea urchin embryo (Strongylocentrotus purpuratus). The method allows quantitative enrichment in a single chromatographic run of up to 12 different sequence-specific DNA binding proteins, each of which may then be readily purified to homogeneity by methods such as preparative gel electrophoresis. The affinity chromatography and identification of six different CyIIIa-regulatory factors is described, and the general utility of the method is discussed.

Actins↗
PubMed1991

Circadian rhythms of gastric mucus efflux and residual mucus gel in the fasting rat stomach.

We hypothesized that two putative gastric protective factors, mucus efflux and residual mucus gel content, would manifest circadian rhythms, as reported in several other gastric functions. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18-hr and studied at 3-hr intervals. Under anesthesia, the stomachs were cannulated and filled with test solution. Thirty minutes later, they were drained and the luminal fluid was analyzed for mucus content by Alcian blue binding. Residual mucus gel was determined by direct injection of dye into the lumen. Alcian blue binding of rat mucus was expressed as equivalent milligrams of porcine mucin. Both parameters showed a significant (P less than 0.001) circadian rhythm. Mucus efflux peaked at 5:03 +/- 0:52 HALO (hours after lights on), and residual mucus at 6:00 +/- 0.46 HALO. Thus, the interplay of circadian rhythms in aggressive and defensive gastric mucosal functions is supported.

Animals↗
PubMed1991

Circadian rhythm of cellular proliferation in the human rectal mucosa.

Circadian rhythms of DNA synthesis and cellular proliferation in the gastrointestinal mucosa have been well documented in animal models. This investigation was designed to determine whether similar rhythms could be demonstrated in the human rectal epithelium: 24 studies were performed in 16 healthy men under fasting (n = 14) and fed (n = 10) conditions. Rectal mucosal biopsy specimens were obtained through a proctoscope every 2 or 3 hours for a 24-hour span. Ex vivo measurements of tritiated thymidine incorporation into DNA were made on the mucosal samples. Feeding and time of day were each found to have an effect on the rate of thymidine incorporation into the DNA of rectal mucosal cells. Both fasted and fed subjects showed significant circadian rhythms in thymidine incorporation, which peaked at about 7 AM. Fasting lowered the overall mean thymidine uptake without altering the rhythm. Thymidine uptake generally reflects the amount of DNA synthesis in the sampled tissue. Therefore, these data may be important in the design of cancer chemotherapeutic regimens that use drugs specifically active during DNA synthesis.

Adult↗
PubMed1991

Age does not influence acute aspirin-induced gastric mucosal damage.

Gastroduodenal ulceration and complications occur more commonly in elderly patients consuming aspirin and other nonsteroidal antiinflammatory drugs than in younger cohorts. To test the hypothesis that the gastroduodenal mucosa of the elderly is more sensitive to nonsteroidal antiinflammatory drug damage, acetylsalicylic acid in low (325 mg) and high (1300 mg) doses was administered on separate days to 10 elderly (median age, 67.5; range, 60-74 years) and 10 young (median age, 24.5; range, 19-30 years) healthy, male volunteer subjects. Gastroduodenal mucosal damage was assessed 2 hours after aspirin dosage by video-endoscopic techniques. At the conclusion of the study, the videotapes of all procedures were randomly evaluated by two endoscopists blinded to subject identification or study sequence. Endoscopically observed lesions were counted in the duodenum, gastric antrum, and gastric body. Aspirin damage was dose-related and more severe in the stomach than in the duodenum. There were no significant differences in total gastroduodenal lesion counts between age groups. In addition, no differences in median gastric pH or tissue 6-ketoprostaglandin F1 alpha content were observed between age groups. These data suggest that age is not a significant factor in determining the extent of acutely administered aspirin-induced damage.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Circadian rhythm in gastric mucosal blood flow in fasting rat stomach.

Circadian rhythms are present in several gastric functions including acid secretion and emptying rates. We hypothesize that aggressive and defensive factors in the gastric mucosa follow similar circadian rhythms. The purpose of this study was to determine if gastric mucosal blood flow, a known defensive factor, manifests a circadian rhythm in fasting rats. Ninety-six male Sprague-Dawley rats were light-adapted in isolation chambers for 3 weeks prior to the study. Half the rats experienced light from 6:00 AM to 6:00 PM, the other half from 6:00 PM to 6:00 AM. After an 18-hr fast, 12 rats were studied at each of eight sampling times: 0100, 0400, 0700, 1000, 1300, 1600, 1900, and 2200 hr after lights on (HALO). After anesthesia and laparotomy, the stomachs were opened along the anterior surface, gently stretched with mucosal surface upmost, and trapped between two lucite rings, with blood supply intact. Mucosal blood flow (ml/min/100 g) was measured in the forestomach, corpus, and antrum with a laser Doppler flowmeter (TSI Laserflo BPM 403). Cosinor analysis showed a significant (P less than 0.01) circadian rhythm in gastric mucosal blood flow within the corpus and antrum, but not in the forestomach. Peak time for corpus blood flow was 21:45 +/- 0:56 HALO (3:45 AM). In the antrum it was 0:51 +/- 1:08 HALO (6:51 AM). These results support the hypothesis that circadian rhythms in mucosal defensive functions are an integral part of normal gastric physiology.

Animals↗