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Biomedical subjects

I Ramirez

Publications and source records attributed to I Ramirez.

At least 55 records · Page 3Linked to original sources

High-fat diets stimulate transient hyperphagia whereas wet diets stimulate prolonged hyperphagia in Fischer rats.

The effectiveness of several different kinds of diets in stimulating hyperphagia in Fischer strain rats was compared. Of three different high-fat diets examined, only one stimulated significant hyperphagia and stimulated weight gain; this diet was high in both fat and carbohydrate. However, this hyperphagia and increased weight gain was transient, lasting less than four weeks. A high-sucrose diet stimulated energy intake for only one week. In contrast, adding water to a high-starch diet or adding saccharin to a wet diet stimulated energy intake and weight gain for at least ten weeks. Once water or saccharin were removed from these diets, hyperphagia subsided or even turned into hypophagia, until body weights approached control levels. The degree of hyperphagia during the first week did not correlate with subsequent hyperphagia or weight gain. These results suggest that wet diets act by different mechanisms than do dry high-fat and high-sucrose diets.

Animals↗

Starch flavor: apparent discrimination between amylopectin and amylose by rats.

Rats given a choice between dilute suspensions of corn amylopectin and corn amylose generally preferred amylopectin. The preference threshold for amylopectin was lower than the preference threshold for amylose (0.1% and 0.5%, respectively). Two sources of evidence indicate that the difference in preference for these two types of starch is due to an off-taste component in corn amylose rather than to an ability to discriminate between amylopectin and amylose per se: 1) rats given a choice of purified amylopectin and amylose from potato did not show a significant preference, and 2) aqueous extracts of amylose reduce preference for water and amylopectin, respectively. Extensive washing of corn amylose with ammonia-methanol, water and methanol did not completely remove the off-taste of corn amylose. Despite the difference in off-taste, rats trained to avoid amylopectin also avoided amylose. It is proposed that starch has two flavor components: a component due to starch itself that induces preference, and a component due to impurities that reduces preference.

Amylopectin↗

High-dose cyclophosphamide-high-dose methotrexate with coordinated intrathecal therapy for advanced nonlymphoblastic lymphoma of childhood: results of a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) investigated a high-dose cyclophosphamide (CPM) high-dose methotrexate (MTX) regimen to determine therapeutic efficacy in confirmed advanced nonlymphoblastic non-Hodgkin's lymphoma (NHL) (stages III and IV) and B-cell acute lymphatic leukemia (B-ALL) in children. Another goal was to determine the comparative effectiveness of shortened maintenance treatment (2 versus 6 courses) in the study population. Systemic induction therapy included vincristine, prednisone, cyclophosphamide, and intermediate-dose MTX with leucovorin rescue. Superimposed intrathecal (IT) therapy included cytosine arabinoside for 2 successive days followed on day 3 by MTX. Intrathecal MTX was given 3 times during induction. At the end of induction, 2 days of triple (hydrocortisone, MTX, and cytosine arabinoside) therapy were given intrathecally (TIT). All patients then received a consolidation course of 4 doses of TIT, 2 doses of cyclophosphamide, and 4 more courses of vincristine and MTX with leucovorin rescue. Patients were then randomized to receive either 2 or 6 cycles of vincristine plus MTX with leucovorin rescue. The TIT was given with each cycle. Complete response rates by histology and Murphy stage (1) were as follows: undifferentiated lymphoma (DUL) stage III, 84/105 (80%): stage IV, 5/12 (42%); and other NHL [primarily large cell lymphoma (LCL)] stage III, 21/28 (75%); stage IV, 2/3 (67%). Event-free survival (EFS) at greater than 2 years was similar for patients with DUL and LCL, i.e., 65 and 61%, respectively. No significant difference in outcome was noted between patient groups receiving 2 or 6 maintenance treatments (p = .76). Treatment was notable for its modest toxicity following the early change to single-dose CPM therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Chemoreception for an insoluble nonvolatile substance: starch taste?

Substances that are insoluble in both water and lipids, such as starch, are commonly assumed to be tasteless. Starch was suspended in water with a viscous gum. Rats given a choice of fluid containing starch and the same fluid without starch consistently preferred fluids containing starch. Rats were able to detect as little as 0.5% starch from several species of plants (corn, rice, wheat, and potato). In contrast, rats ignored comparable concentrations of cellulose suspended in water. Rats were also capable of choosing the fluid containing higher levels of starch when given a choice of 1 vs. 2% starch or 0.5 vs. 1% starch. This ability to detect starch did not appear to be mediated by salivary alpha-amylase because 1) raw starch is highly resistant to hydrolysis by salivary amylase, 2) starch preference was not correlated with the susceptibility of the starch to hydrolysis by salivary amylase, and 3) starch preference was not blocked by partial or extensive desalivation. Attempts to extract impurities with either organic solvents or water did not provide any evidence that such impurities contribute to starch preference. These experiments point to a seemingly novel form of chemoreception that could be useful to animals that need to identify starch-rich foods.

Amylases↗

Establishment and characterization of human B-cell lymphoma cell lines using B-cell growth factor.

B-cell non-Hodgkin's lymphomas (NHL-B) have been difficult to establish in long-term cell culture using standard techniques. We report the establishment of five representative cell lines from high grade NHL-B using B-cell growth factor (BCGF). The five NHL-B cell lines display the morphologic, immunophenotypic, genotypic, and biologic characteristics of the lymphoma cells present in the original diagnostic specimen. The cell lines showed at least a sevenfold dose-dependent increase in proliferation in vitro over background in the presence of BCGF. Other putative B-cell growth-stimulating cytokines showed no significant proliferative activity or were inhibitory in some cases. NHL-B cell lines secreted growth factor(s) into culture supernatants that mediated at least a fivefold dose-dependent increase in cell proliferation in autochthonous lymphoma cells and a 10-fold or greater stimulation in growth factor-dependent normal B cell lines in vitro. The cell lines show monoclonal rearrangements of IgH genes and nonrandom chromosomal abnormalities characteristic of NHL-B, while the expression of Epstein-Barr virus associated antigen (EBNA-I) is present in two of the five cell lines. The studies show that lineage-specific growth factors may be used to establish neoplastic B cell lines in vitro, which are important experimental systems for cellular and molecular studies in the NHL-B.

Adolescent↗

Dietary hyperphagia in rats: role of fat, carbohydrate, and energy content.

Dietary energy, fat and carbohydrate content were varied to determine the nutritional factors responsible for hyperphagia induced by feeding rats high-fat diets. In the first experiment, rats were fed isoenergetic high-fat or high-carbohydrate diets for 2 weeks. Weight gain and energy intake were lower in rats given the high-fat diet. When some of the rats were switched to a diet that was high in fat, carbohydrate and energy, gram food intake was initially unchanged, resulting in a substantial increase in energy intake and weight gain. Energy intake gradually declined over the 4 weeks following the switch to the high-energy diet. In the second experiment, rats were fed high-fat diets that were either high or low in carbohydrate content and either high or low in energy content (kcal/g). Rats fed a high-fat diet that was high in energy and carbohydrate ate the most energy and gained the most body weight and carcass fat. In the third experiment, rats were fed high-carbohydrate diets varying in fat and cellulose content. Energy intake and body weight gain varied directly as a function of caloric density regardless of the fat or cellulose content of the diets. It is concluded that hyperphagia induced by feeding high-fat diets is not due to the high dietary fat content alone. Rather, high levels of fat, carbohydrate, and energy interact to produce overeating and obesity in rats fed high-fat diets.

Animals↗

What do we mean when we say "palatable food"?

The word palatability and related words have not been used in a consistent way. Palatability may be a property of a food, of the organism eating the food, or both. Investigators have failed to distinguish different possible meanings of the statement: "palatable foods increase intake". This may indicate: (1) a simple observation that some foods stimulate more intake than others, (2) an innate response to the taste of foods that alters appetite, (3) a correlate of food intake that does not itself affect intake, and (4) a link in a causal chain involving prior associations between foods and their postingestive consequences.

Appetite↗

Does dietary hyperphagia contradict the lipostatic theory?

It has frequently been suggested that body weight or fat somehow exerts an inhibitory influence on food intake in a way that acts to maintain a stable body weight or fat. The principal evidence supporting this idea is that animals that have been induced to overeat and become overweight by various means, eat less than control rats when they are permitted to eat freely. If the degree of suppression of appetite by overweight is as large as several experiments suggest, then dietary hyperphagia should be self-limiting. Any overeating induced by dietary treatments should disappear after animals become moderately overweight. Animals fed some kinds of hyperhagia-promoting diets do show this pattern. However, animals fed other kinds of diets do not show this pattern, and with most diets, dietary hyperphagia continues for extended periods. This implies that either 1) overweight does not suppress appetite as much as suggested by various authorities, 2) dietary manipulations can override normal regulatory mechanisms, or 3) certain diets induce irreversible changes in body fat that are not evident from changes in body weight.

Adipose Tissue↗

Why do sugars taste good?

The preference humans and animals show for sweet solutions has been the subject of hundreds of publications. Nevertheless, the evolutionary origin of sweet preference remains enigmatic because of the relatively low nutritional value of sugars and the absence of specific tastes for other, more essential, nutrients. Moderate concentrations of sugars are found in most plant foods because sugars play an important role in plant physiology. Widespread occurrence of sugars in plants is paralleled by widespread preference for sugar solutions in mammals. These observations suggest that preference for sugars evolved because they are common in plants and easy to detect rather than because of any special nutritional merits they offer. Perception of sweetness cannot be used to accurately meter the metabolizable energy or nutritive value of a food.

Animals↗

Stimulation of energy intake and growth by saccharin in rats.

Rats fed wet diets containing saccharin consumed 12-14% more energy and gained 24-55% more weight than rats fed the same diets without saccharin. Saccharin-induced stimulation of intake was usually not so pronounced during the first week as during subsequent weeks of each experiment. Similar results were obtained using diets high in starch and fat. However, these effects could be obliterated by simply exposing the rats to unsweetened (plain) diet or to saccharin in water for several days before the sweetened diets were introduced. Furthermore, although stimulation of intake by saccharin was observed with diets containing 80% water, no such effect was observed with a diet containing 60% water. Rats given low-energy sweetened water in addition to their 80% water diet consumed substantially more fluid but not more or less energy than rats given unsweetened water. Preference tests suggest that saccharin increases diet palatability only very slightly; this finding is one of several observations suggesting that stimulation of intake by saccharin cannot be interpreted in terms of increased diet palatability. These results suggest that dietary hyperphagia results from the interaction between innate and learned responses to the taste of foods. Osmotic factors did not seem to exert a major influence in these experiments.

Analysis of Variance↗

Fuel partitioning and food intake: role for mitochondrial fatty acid transport.

Administration of methyl palmoxirate (MP; 10 mg/kg po), an inhibitor of carnitine palmitoyltransferase I (CPT I), increased the food intake of rats maintained on a diet high in triglycerides comprised of long-chain fatty acids, which require CPT I for mitochondrial uptake and oxidation. MP did not affect food intake in rats fed a comparable diet high in medium-chain fatty acids, which do not require CPT I for mitochondrial uptake and oxidation. The feeding response to MP was reduced more effectively by an intragastric preload of medium-chain triglyceride (MCT) oil than a preload of a long-chain triglyceride (LCT) oil. Food intake of MCT- and LCT-fed rats differed under control conditions (no MP), and this appeared to reflect differences in the diurnal distribution of feeding. Measurement of plasma ketone body concentrations indicated that the dietary manipulations and MP had their intended metabolic effects. The results strongly suggest that mitochondrial transport of fatty acids plays a role in the control of food intake. CPT I participates in that control by regulating the partitioning of long-chain fatty acids between pathways of storage and intramitochondrial oxidation.

Adipose Tissue↗

Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials.

Thirty-two children or adolescents had B cell acute lymphocytic leukemia (ALL) diagnosed by demonstration of surface immunoglobulin expression on greater than 10% of their bone marrow blasts. All patients had greater than 25% bone marrow lymphoblasts. Only five of 32 patients (16%) presented with an abdominal mass; however, 24 cases (75%) had FAB L3 morphology. By comparison with findings in common ALL, these 32 children were older (median age, 8 years) and had a higher incidence of central nervous system disease at presentation (22%); all but one were white, and 24 were males. Blast cells from individual cases expressed mu kappa (n = 13), mu lambda (n = 9), gamma kappa (n = 1), alpha kappa (n = 1), or mu with an undetermined light chain (n = 8). The most frequently identified cytogenetic abnormality was the classic B cell-associated t(8;14)(q23;q24) (n = 4); the t(1;19)(q23;p13.3), t(9;22)(q23;q11), and t(1;22) were observed in single cases. Twenty patients were treated uniformly on a single protocol designed for children with advanced B cell malignancy; therapy for the other 12 children varied. Nine children (28%) are surviving event-free; all but one for 3 years or more. We conclude that approximately 25% of children with B cell ALL are curable with intensive multiagent chemotherapy and that classification by immunophenotyping is superior to use of clinical and/or lymphoblast morphologic features.

Adolescent↗

Hepatic endothelial lipase activity in neonatal rat liver.

Hepatic endothelial lipase (HEL) activity is as high in the neonatal (1-day old) rat liver as in adults. Most of the HEL activity is located at the capillaries since 75% of the total activity is released by heparin or collagenase perfusion. The residual activity (non-releasable) is located in hepatocytes and not in hemopoietic cells, which are the major cell type in neonatal liver. Per mg of protein, the HEL activity is 50% higher in neonatal than in adult hepatocytes. We suggest that neonatal hepatocytes have an increased capacity to synthesize and secrete HEL activity, so maintaining a high activity in the whole organ. It might contribute to the hepatic uptake of cholesterol from circulating lipoproteins, in a period in which endogenous cholesterol synthesis is known to be inhibited in the liver.

Animals↗

Dietary hyperphagia and obesity: what causes them?

Diets that cause animals to overeat and become obese have been used in many investigations of obesity. Most of this research, however, has concentrated on the consequences rather than the causes of overeating. Furthermore, in most studies, several nutritional variables were manipulated simultaneously, making cause and effect relationship impossible to disentangle. Consequently, progress has been slow. Diets could alter energy intake by virtue of their effects on oral-sensory, gastrointestinal or postabsorptive effects. Palatability is the most popular oralsensory hypothesis but the empirical basis for this hypothesis is particularly weak. A substantial body of evidence is consistent with the possibility that the osmotic effects of diets in the gastrointestinal tract and metabolic postabsorptive factors may play a major role in dietary hyperphagia and obesity. Suggestions for future research directions are offered.

Animals↗

Resistance to dietary hyperphagia in juvenile rats.

Adult rats (12 wk of age) fed a wet, high starch diet consumed more energy, gained more weight, and had more carcass fat than rats fed the same diet in a dry form. In contrast, juvenile rats (3.5 wk of age) did not consume more energy, gain more weight, or become fatter when fed the wet, high starch diet than when fed the same diet in dry form. Although rats of both age groups fed high fat diets consumed more energy than rats fed high starch diets, the effect of the high fat diets was much smaller in juvenile than in adult rats. The level of dietary protein (20 vs. 8%) in the diets did not interact with diet type, but juvenile rats fed low protein diets gained less weight than juvenile rats fed standard protein diets. Additional experiments showed that juvenile rats fed a 20% protein diet were capable of increasing fluid intake and energy intake when given sweetened water or insulin, respectively. Thus, low susceptibility to dietary hyperphagia in juvenile rats cannot be explained by assuming that juvenile rats already eat as much as they can. These data are consistent with the possibility that developmental changes in taste responsiveness may contribute to this effect of age.

Aging↗

Overeating, overweight and obesity induced by an unpreferred diet.

Rats fed diets containing 50-71% added water (liquid diets) eat more energy and gain more weight than rats fed the same diets without added water (solid diets). The present experiments examined the effects of making a liquid diet less palatable. The first experiment examined the effects of sucrose octaacetate on diet preference. Rats, given a choice of a liquid diet containing 0.5% sucrose octaacetate and a plain solid diet, preferred the plain solid diet for three weeks. When the concentration of sucrose octaacetate was reduced to 0.05%, the rats did not show a reliable preference for either the sucrose octaacetate liquid or plain dry diet. In subsequent experiments, each rat was given only one diet at a time. In the second experiment, rats were fed 0.5% sucrose octaacetate liquid diet for three weeks followed by 0.05% sucrose octaacetate liquid diet for another four weeks. The rats fed the sucrose octaacetate liquid diet overate and became obese compared to the rats fed plain solid diet throughout. In the third experiment, rats fed 0.5% sucrose octaacetate liquid diet for six weeks became obese compared to rats fed plain solid diet throughout. Thus, the overeating and obesity induced by liquid diets cannot be attributed solely to their high palatability.

Animals↗

Insulin counteracts the satiating effect of a fat meal in rats.

The effects of insulin administration of the reduction on food intake which follows a meal of corn oil was examined in normal and streptozotocin-diabetic rats. In the first experiment, a single injection of long-acting, protamine zinc insulin (3 IU) curtailed the decrease in 24-hr food intake that occurred in normal and diabetic rats after ingestion of 2.0 ml of oil. In a second experiment, injection of short-acting, regular insulin (0.5 IU) prevented the depression of food intake which occurred 6-24 hr after ingestion of 1.5 ml of corn oil, but not at earlier time intervals. In a third experiment, the short-term suppression of food intake in diabetic rats that occurred within 6 hr after a 1.5 ml meal of oil was reduced by chronic administration of insulin (3 IU/day) via a subcutaneously implanted osmotic pump. The results indicate that a relatively long-lasting effect of insulin counteracts the satiation from ingested fat and suggest that insulin's role in the control of food intake may depend on the composition of the diet.

Animals↗