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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 721 records · Page 40Linked to original sources

Lack of interaction between acid and pepsinogen secretion in isolated gastric glands.

Gastric glands isolated from rabbit stomach were employed to study the relation between acid and pepsinogen secretion. The effects of adenosine and guanosine nucleotides were examined for both secretory processes. cAMP, dibutyryl cAMP (DBcAMP), and 8-bromo-cAMP (8BrcAMP) were found to stimulate both acid and pepsinogen secretion with a potency sequence of 8BrcAMP greater than DBcAMP greater than cAMP. Adenosine, ATP, and AMP were ineffective, indicating that the responses to adenosine cyclic nucleotides do not involve an adenosine receptor. 8BrcGMP was found to produce a weak stimulation of both acid and pepsinogen secretions, while GMP, cGMP, and DBcGMP were ineffective. DBcGMP was found to inhibit competitively the stimulation of pepsinogen secretion by cholecystokinin (CCK)-like peptides. No inhibition was found with cGMP or 8BrcGMP. Stimulation of pepsinogen secretion by carbachol or isoproterenol was not inhibited by DBcGMP nor was the stimulation of acid formation by CCK-like peptides. Thiocyanate inhibited acid formation but did not affect pepsinogen secretion stimulated by 8BrcAMP or carbachol, indicating that stimulation of pepsinogen secretion does not require simultaneous acid formation. Costimulation of acid formation by histamine and pepsinogen secretion by isoproterenol showed no interaction between the two secretory processes. The results are interpreted to suggest that correlations between acid and pepsinogen secretion observed in vivo do not result from direct interactions between parietal and chief cells.

Adenosine↗

Gastric perforation: a late complication of abdominal radiation for para-aortic lymph node metastasis from cervical squamous carcinoma.

Gastric perforation was found at laparotomy for acute abdominal pain in a woman treated with pelvic and abdominal radiation for squamous cell carcinoma of the uterine cervix metastatic to the para-aortic nodes. This case may provide additional evidence suggesting that risks involved in para-aortic radiation may outweigh the benefits.

Carcinoma, Squamous Cell↗

Role of glucose metabolism in acid formation by isolated gastric glands.

The role placed by glucose in providing energy for acid formation was studied in isolated gastric glands from rabbit. The widely-used inhibitors of glycolysis, iodoacetic acid and iodoacetamide were found to inhibit glucose oxidation as well as the indicators of acid formation, respiration and accumulation of aminopyrine. However, the potent inhibitor of acid formation was found to involve a nonspecific mechanism other than the simple inhibition of glycolysis. An alternative approach involved use of the glucose transport inhibitor, phloretin. Phloretin blocked glucose oxidation and also inhibited functional responses. Acid formation was restored easily by the addition of pyruvate or various other oxidizable substrates. Measurement of lactate formation in the absence of exogenous glucose showed that the gastric glands contain very little glycogen. Addition of external glucose resulted in a 10-fold increase in lactate formation and this rate was stimulated further by histamine and rotenone. Rotenone also inhibited both respiration and aminopyrine accumulation; however, the inhibition was not complete. Phloretin treatment resulted in total inhibition of the residual aminopyrine accumulation after rotenone treatment. The results are interpreted to indicate that gastric glands are dependent almost totally on external substrate supply to support acid formation; and, that while anaerobic glucose metabolism can sustain a very low level of acid formation, the major role of glucose is to yield pyruvate equivalents for subsequent oxidation.

Animals↗

The development of hyponatremia following combination chemotherapy for metastatic germ cell tumors.

The combination of high dose vinblastine, cisplatin, and bleomycin is an extremely effective, but potentially quite toxic, program for the treatment of metastatic germ cell tumors. In addition to the well-described toxicities, we have noted moderate to severe hyponatremia associated with these drugs. Twelve patients who were receiving this combination chemotherapy program had serum electrolyte levels, plasma osmolality, and creatinine clearance performed prior to and again 5 to 9 days after chemotherapy. Nine of the patients had standard water load tests prior to and again 6 to 15 days after chemotherapy. All 12 patients developed a fall in serum sodium concentrations following chemotherapy, and four patients had severe symptoms attributable to the hyponatremia. Eight patients also developed hypoosmolality suggesting that the hyponatremia was secondary to impaired water handling. In five patients further evidence of impaired water handling was documented by the development of an abnormal standard water load test following chemotherapy. The hyponatremia and impaired water handling may be due primarily to the high doses of vinblastine in the chemotherapeutic program. Patients who are receiving this combination chemotherapy program should be observed for the development of hyponatremia. The presence of severe, symptomatic hyponatremia and impaired water handling may require appropriate treatment including water restriction and hypertonic saline administration.

Adult↗

Overt and hidden forms of chronic malnutrition in the rat and their relevance to man.

We have examined the physiological weight changes seen in rat dams and their offspring as sequelae of either an overt or a hidden form of chronic protein malnutrition. In the overt model, which was produced by feeding dams a very low protein diet (6% casein) starting 5 weeks prior to conception and continued through lactation, the females showed significant weight losses at all ages compared to dams maintained on a normal diet (25% casein). This caused the malnourished 6% dams to have offspring that were categorized as small-for-date at birth in terms of their weight indices and peripheral metabolic profiles. Also, the inadequate milk production of these dams resulted in their pups displaying the almost total failure of growth (greater than 60% decreases in body weights) and peripheral imbalances characteristic of infantile marasmus by day 8 of lactation. Consequently, at all times examined the 6% dams and pups showed most of the typical responses seen in the more severe forms of in utero and lactational malnutrition of mankind. In contrast, the hidden form of malnutrition produced by feeding dams a somewhat higher protein diet (8% casein) throughout the same time periods caused no marked weight losses by these females during their pregnancy compared to the normal dams. Although the 8% pups had the same birth weight indices as the normal offspring, previous data from our group have indicated that the 8% progeny show many metabolic imbalances at birth which are indicators of severe gestational malnutrition in humans. Moreover, while the 8% dams displayed lactational insufficiencies as noted by their pups retarded postnatal growth, nursing of these offspring by 25% dams allowed them to maintain a normal lactational growth curve. However, not only was this cross-fostering unable to rehabilitate most of the prenatally determined biochemical alterations affecting the 8% pups but, additionally, this form of malnutrition will remain undetected if weight indices alone are used as assessors of normalcy. Thus, it appears that the 8% rats may serve as a useful model for the hidden forms of malnutrition in man.

Animals↗

Absence of learning and memory deficits in the vasopressin-deficient rat (Brattleboro strain).

Active and passive avoidance behavior was compared between vasopressin (ADH)-deficient rats of the Brattleboro strain and normal Long-Evans rats. In retention of a passive avoidance task across three levels of footshock (0.5, 1.0 and 1.5 mA) the ADH-deficient rats exhibited a slight but overall superior passive avoidance performance. In a one-way avoidance task, diabetes insipidus (D.I.) and normal rats had closely comparable performance; whereas, in a shuttle-box avoidance task the D.I. rats made significantly more avoidance response than the Long-Evans rats. Flinch-jump testing indicated that the D.I. rats had a small but statistically significant lowered jump threshold. These findings, which add to an increasingly conflicting literature regarding the role of ADH in learning and memory processes, indicated that ADH per se is not critical for normal learning and memory. Possibly, variations in breeding procedures for the D.I. rat have resulted in variations in behavioral reactivity with interact with learning tasks to enhance or impair performance.

Animals↗

Altered body composition and muscle protein degradation in nutritionally growth-retarded children with cystic fibrosis.

To investigate nutritional growth retardation and the adaptive response to malnutrition in cystic fibrosis (CF), body composition and muscle protein catabolism were studied in nine malnourished CF children and eight healthy controls by anthropometry, measurement of whole body potassium, urinary creatinine excretion, creatinine height index, and urinary 3-methylhistidine excretion, an index of myofibrillar protein catabolism. CF children had a significant deficit of body mass (p less than 0.001), derived from both the body fat and the fat-free compartments, including a deficit in muscle mass (p less than 0.005). A deficit of muscle mass in CF was also reflected by a lower creatinine height index (mean +/- 1 SEM = 0.66 +/- 0.04 in CF, versus 0.85 +/- 0.5 in controls, p less than 0.02). Urinary 3-methylhistidine excretion was elevated in CF children and the mean (+/- 1 SEM) rate of muscle protein catabolism was 0.82 +/- 0.06 versus 0.53 +/- 0.04 kg-1 24 h-1 in CF and controls, respectively (p less than 0.01). 3-Methylhistidine excretion rates did not correlate with severity of disease as assessed by clinical score. We conclude that nutritional growth retardation in CF is characterized by a protein energy deficit resembling that of protein-energy malnutrition, but that in contrast to the normal adaptive response to protein-energy malnutrition, muscle protein catabolism is markedly increased. These data may have important implications regarding the clinical course and prognosis of CF and the design of optimal therapy.

Adipose Tissue↗

Radiation and risk for thyroid cancer: atypical findings of a community thyroid recall program.

Screening of 553 persons for thyroid disease by scan and physical exam was performed. Group I (245) had documented irradiation, with most (85%) receiving 300 R for lymphoid hyperplasia. Group II (308) had only a history of prior irradiation. Abnormal glands were found in 17 of 245 (7%) of Group I with 7 of 245 (3%) having nodular disease. No cancers were found in six of eight (75%) persons with nodular disease having surgery. Abnormal glands were found in 45/308 (14.6%) of Group II with 16/308 (5.2%) having nodular disease. Twelve of 16 (75%) with nodular disease from Group II had surgery and three thyroid cancers were found; in addition, one person from this group had a history of prior surgery for thyroid cancer. The incidence of thyroid cancer in Group I was 0%, Group II was 1.3%, and the combined incidence was 0.7%. The relatively low incidence of thyroid cancer observed is attributed to the relatively late average age at time of irradiation; 22 years for Group 1, 13 years for Group II.

Acne Vulgaris↗

Anxiety and mood fluctuation during the normal menstrual cycle.

Eleven women with an average age of 23 were evaluated daily for pregnanediol excretion, mood, and behavioral fluctuations during the menstrual cycle. Subjects carefully screened for present and preexisting psychopathology experienced only minor fluctuations in rating on the Moos Menstrual Distress questionnaire (MDQ), only the water retention achieving significance. The other scales on the MDQ and the Spielberger State Anxiety Scale had nonsignificant premenstrual elevations.

Adult↗

Increased secretion of vasopressin and adenosine 3',5'-monophosphate from hypothalamic-posterior pituitary units of spontaneously hypertensive rats.

To determine if the increased vasopressin (AVP) levels observed in the blood and urine of spontaneously hypertensive rats (SHR) are a response to peripheral factors that may influence AVP release or are a consequence of altered hypothalamic-neurohypophysial activity, AVP release from hypothalamic-neurohypophysial units was studied using an in vitro perifusion system. Spontaneous and 30 mM K+-stimulated AVP release was significantly greater from tissue of SHR rats than from those of WKYN. Adenosine (10(-5) M) added to the perifusion medium increased AVP release into the perifusate in both strains, even through AVP release into the perifusate was greater in tissue of SHR rats. Measurement of AVP content revealed that hypothalamic AVP was lower in SHR rats, whereas the neural lobes of the SHR contained a significantly higher concentration of AVP compared to the tissue of WKYN rats. In addition, exposing tissue from SHR rats to 30 mM K+ stimulated an increase in cAMP release into the perifusate, whereas tissue from WKYN rats did not increase cAMP release above basal level. These data suggest that central nervous system-mediated hyperresponsiveness is the basis for the increased AVP secretion that occurs in the SHR rat and are consistent with reports of a hypersensitive hypothalamic-anterior pituitary axis in these animals.

Animals↗