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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 271 records · Page 15Linked to original sources

Tuftsin and tuftsin conjugates potentiate immunogenic processes: effects and possible mechanisms.

The immunoglobulin heavy chain associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity was found to augment the antigen presenting capacity of macrophages in culture when applied simultaneously with the antigen. To study the immunogenic effect of tuftsin in vivo the peptide was coupled covalently to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) antigens to form stable entities. Tuftsin-antigen conjugates were found to be very potent immunogens as tested by their capacity to increase antigen presentation in culture in primary and secondary responses. Thus, monolayers of macrophages pulsed in vitro with KLH-tuftsin conjugates exerted a stronger immunogenic effect than KLH alone. BSA, which by itself was not immunogenic, when applied to macrophages as tuftsin conjugate evoked a high lymphoproliferative immune response. In vivo, BSA conjugated to tuftsin, when injected in aqueous solutions, augmented significantly antibody production, whereas administration of BSA alone or BSA admixed with tuftsin had no immunogenic effect. Studies conducted to elucidate the mechanisms underlying the activation of the immunogenic function of macrophages by the peptide revealed that treatment of cells with antigen and tuftsin increases secretion of interleukin-1 and expression of cell surface Ia encoded antigens. The effect of tuftsin on increasing the immunogenic capacity of antigens may at least partly be attributed to these effects.

Adjuvants, Immunologic↗

Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS.

Long-term cultures were established of HTLV-III-infected T4 cells from patients with the acquired immune deficiency syndrome (AIDS) and of T4 cells from normal donors after infection of the cells in vitro. By initially reducing the number of cells per milliliter of culture medium it was possible to grow the infected cells for 50 to 60 days. As with uninfected T cells, immunologic activation of the HTLV-III-infected cells with phytohemagglutinin led to patterns of gene expression typical of T-cell differentiation, such as production of interleukin-2 and expression of interleukin-2 receptors, but in the infected cells immunologic activation also led to expression of HTLV-III, which was followed by cell death. The results revealed a cytopathogenic mechanism that may account for T4 cell depletion in AIDS patients and suggest how repeated antigenic stimulation by infectious agents, such as malaria in Africa, or by allogeneic blood or semen, may be important determinants of the latency period in AIDS.

Acquired Immunodeficiency Syndrome↗

Life events stress and psychosocial factors in men with peptic ulcer disease. A multidimensional case-controlled study.

We carried out a case-controlled study of multiple psychological and social factors in 49 men with complicated or uncomplicated peptic ulcer disease. Thirty-two men with renal stones or gallstones and 20 healthy men served as controls. Ulcer patients and controls experienced a similar number of potentially stressful life events. However, ulcer patients perceived their events more negatively (p less than 0.05). Ulcer patients also had significantly more personality disturbances than controls, although no one type of "ulcer personality" was found consistently. Some ulcer patients tended to be hypochondriacal complainers, overly pessimistic, and excessively dependent. Other personality disturbances were also more common in ulcer patients (e.g., immaturity, impulsivity, and feelings of social isolation and alienation). Ulcer patients had significantly lower ego strength and they had fewer friends and relatives whom they felt they could call upon in times of crisis. Finally, ulcer patients exhibited significantly more emotional distress in the form of depression and anxiety. Hypochondriasis, a negative perception of their life events, dependency, and lowered ego strength were the four variables that best discriminated ulcer patients from controls. This controlled study demonstrates a strong association between life events stress, psychosocial factors, and peptic ulcer disease.

Adaptation, Psychological↗

Influence of food and marker length on gastric emptying of indigestible radiopaque markers in healthy humans.

A simple, noninvasive radiographic method was used to investigate the influence of food and of marker length on gastric emptying of indigestible solids. Ten healthy human subjects who had fasted for 12 h exhibited more rapid emptying when solid radiopaque markers were ingested with water than they did when markers were ingested with a 400-kcal solid and liquid meal. Mean (+/- SE) emptying of markers that were 10 mm in length averaged 55% +/- 15%, 97% +/- 3%, and 100% 1, 2, and 4 h after ingestion of the markers with water, compared with 4% +/- 2%, 32% +/- 11%, and 64% +/- 12% emptying 1, 2, and 4 h after ingestion of markers with the meal (p less than 0.05). Ingestion of a second and third test meal significantly prolonged gastric emptying of indigestible markers (p less than 0.05). No significant difference in emptying of the 10- and 2-mm markers from the stomach was detected. These experiments indicate that gastric emptying of indigestible solids in humans is strongly influenced by food intake, but not by the particle lengths studied.

Adult↗

Lack of specific binding of prostaglandin E2, prostaglandin F2 alpha, and 6-keto prostaglandin F1 alpha to serum in patients with peptic ulcer disease and in healthy subjects.

Rabbits immunized against prostaglandins develop antibodies to prostaglandins and peptic ulcer disease (duodenal and gastric ulcers). We have evaluated the hypothesis that idiopathic gastric or duodenal ulcer disease in humans may be associated with the spontaneous occurrence of serum antibodies directed against endogenous prostaglandins. We found that serum from 45 ulcer patients (34 duodenal, 11 gastric) had a low degree of binding of radiolabeled prostaglandin E2, prostaglandin F2 alpha, or 6-keto prostaglandin F1 alpha. The extent to which prostaglandins were bound to serum of ulcer patients was not statistically different from prostaglandin binding to serum from 25 normal subjects. Therefore, we conclude that spontaneous occurrence of circulating antibodies against endogenous prostaglandins is an unlikely cause of gastroduodenal ulceration in humans.

6-Ketoprostaglandin F1 alpha↗

Effect of parietal cell vagotomy on acid secretory responsiveness to circulating gastrin in humans. Relationship to postprandial serum gastrin concentration.

To study the relationship between gastric acid secretion and serum gastrin concentration after vagotomy, gastric acid output and serum gastrin concentration were measured simultaneously during intravenous infusion of graded doses of human gastrin heptadecapeptide (G-17) in duodenal ulcer patients with parietal cell vagotomy and in unoperated patients with duodenal ulcer disease (controls). The curve relating serum gastrin concentration to gastric acid output was shifted downward and to the right after vagotomy; the peak acid output to G-17 was reduced by 50% (p less than 0.001). The serum gastrin concentration that produced half of peak acid output (EC50%) averaged 185.5 pg/ml after vagotomy and 74.1 pg/ml in controls (p less than 0.01). Mean basal and postprandial serum gastrin concentrations were twofold to threefold higher in vagotomy patients than in controls (p less than 0.005). However, when peak postprandial serum gastrin concentrations were used to predict acid secretion from curves relating serum gastrin to acid output, predicted acid secretion was only 12.6 mmol/h in vagotomy patients compared to 24.4 mmol/h in controls. Parietal cell vagotomy decreases "functional" parietal cell mass, as reflected by a 50% decrease in peak acid output, and also reduces the responsiveness of "functional" parietal cells to gastrin to such an extent that acid secretion is reduced after vagotomy despite basal and postprandial hypergastrinemia.

Duodenal Ulcer↗

Role of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion in humans.

The relative importance of thought, sight, smell, and taste of food in the cephalic phase of gastric acid secretion has not been studied systematically. We found that discussing appetizing food for 30 min (without sight, smell, or taste) increased acid secretion from 4 to 13 mmol/h in healthy human subjects (p less than 0.001) and also increased serum gastrin concentrations significantly (p less than 0.02). Discussing food resulted in an acid secretory response that averaged 66% +/- 10% of the response to modified sham feeding, which activates thought, sight, smell, and taste. Discussing topics other than food (e.g., current events, sports) did not increase acid secretion significantly. The sight of appetizing food (without smell or taste), the smell of appetizing food (without sight or taste), or the combination of sight and smell (without taste) also increased acid secretion and serum gastrin concentrations significantly. However, sight and smell were significantly less potent stimulants of acid secretion than sham feeding, with responses averaging only 23%-46% of the response to sham feeding. These studies indicate that thinking about food is a potent stimulant of gastric secretion in healthy humans. Moreover, the sight and smell of food increase gastric acid secretion and serum gastrin concentrations, probably by provoking thoughts related to food.

Adult↗

Total 24-hour gastric acid secretion in patients with duodenal ulcer. Comparison with normal subjects and effects of cimetidine and parietal cell vagotomy.

The purposes of these studies were as follows: (a) to compare gastric acid secretion throughout an entire 24-h period in 8 patients with duodenal ulcer disease and in 7 normal subjects, and (b) to determine in duodenal ulcer patients to what extent total, 24-h acid secretion was reduced by oral cimetidine (n = 7) or parietal cell vagotomy (n = 7). Basal, interprandial, and nocturnal acid secretion were measured by gastric aspiration, whereas acid secretion in response to breakfast, lunch, and dinner was measured by in vivo intragastric titration. Total, 24-h acid secretion averaged 408.3 +/- 61.7 mmol in duodenal ulcer patients and 208.3 +/- 18.5 mmol in normal subjects (p less than 0.02). Acid secretion was higher in duodenal ulcer patients than in normal subjects during both day (p less than 0.01) and night (p less than 0.05). Cimetidine (400 mg twice daily) significantly (p less than 0.001) reduced total, 24-h acid secretion in duodenal ulcer patients to 235.3 +/- 58.6 mmol, a rate that was not significantly different from 24-h acid secretion in normal subjects. On the other hand, total, 24-h acid secretion averaged only 86.7 +/- 20.7 mmol after parietal cell vagotomy, a rate that was significantly lower than 24-h acid secretion in normal subjects (p less than 0.001) and in duodenal ulcer patients receiving cimetidine (p less than 0.05). These studies indicate that patients with duodenal ulcer disease secrete excessive amounts of gastric acid during the day and night and throughout an entire 24-h period. A twice-daily 400-mg dose of cimetidine reduces 24-h acid secretion in duodenal ulcer patients to nearly normal rates, whereas parietal cell vagotomy reduces acid secretion to well below normal rates.

Adult↗

Stimulation of HCO3- secretion by the prostaglandin E2 analog enprostil: studies in human stomach and rat duodenum.

This study investigated the action of enprostil, a synthetic analog of PGE2, on gastric HCO3- secretion in humans and on duodenal HCO3- secretion in the anesthetized rat. A previously validated 2-component model was used to calculate gastric HCO3- and H+ secretion in 10 human subjects. Compared to placebo, a single 70 micrograms oral dose of enprostil increased basal gastric HCO3- secretion from 1810 +/- 340 to 3190 +/- 890 mumol/hr (P less than 0.05). In addition, enprostil reduced basal gastric H+ secretion from 5240 +/- 1140 to 1680 +/- 530 mumol/hr (P less than 0.02). Enprostil also increased HCO3- secretion and reduced H+ secretion during intravenous pentagastrin infusion. In the rat, duodenal HCO3- secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area and devoid of pancreatic and biliary secretions. Addition of enprostil (10 micrograms/ml) to the duodenal bathing solution increased duodenal HCO3- secretion from 6.3 +/- 1.3 to 15.1 +/- 2.0 mumol/cm X hr (P less than 0.01, n = 6). The stimulatory action of enprostil on duodenal HCO3- secretion at 10 micrograms/ml was comparable in magnitude and duration to that of 10 micrograms/ml natural PGE2. In summary, the PGE2 analog enprostil stimulated gastroduodenal HCO3- secretion, effects which may be beneficial in protection of the gastroduodenal mucosa against luminal acid.

Adult↗

Tuftsin analogues: synthesis, structure-function relationships, and implications for specificity of tuftsin's bioactivity.

Thirteen analogues of the natural macrophage activator peptide tuftsin, ten of which are novel, were synthesized with the aim of exploring the relation between their biological potency and their capacity to attach specifically to cellular tuftsin's receptors. The analogues representing modifications and chain extensions at various parts of the parent tuftsin molecule can be classified as N-terminal analogues, C-terminal analogues, "within-chain" derivatives, or dimers of tuftsin and retrotuftsin. The various synthetic routes employed to prepare the analogues are described. A direct correlation was found between the ability of analogues to inhibit [3H-Arg4]tuftsin specific binding to mice peritoneal macrophages and their capacity to enhance phagocytosis or to inhibit tuftsin-mediated phagocytosis by the cells and to potentiate the cell's immune response.

Animals↗

Gene-dosage compensation of endosperm proteins in hexaploid wheat Triticum aestivum.

Several aneuploid lines and one intervarietal substitution line of the hexaploid wheat Triticum aestivum (2n = 6x = 42; genomes AABBDD) cv. Chinese Spring were used to study the effects of different doses of chromosomes 1B, 1D, or 1A on the amount of the high molecular weight ("HMW") glutenins and gliadins of endosperm. These homeologous chromosomes carry HMW glutenin and gliadin gene clusters on their long and short arms, respectively. Increasing the dosage of chromosome 1B of Chinese Spring in plants having in their 3n endosperm zero or the normal three doses of the homeologue 1D, as well as in plants carrying in their endosperm one dose of 1B of the cultivar Timstein, had a dual effect: on one hand, a nonlinear increase in the amount of each subunit encoded by the chromosome whose dosage was elevated and, on the other hand, a compensating nonspecific decrease in the amount of other HMW glutenin and gliadin subunits encoded either by the homeoalleles on 1D or by the homoalleles on 1B of Timstein, respectively. Deletion of chromosome arm 1BL, which carries only a few HMW glutenin genes, had no significant effect on the amount of HMW glutenins encoded by 1DL and HMW gliadins encoded by 1DS and 1BS. However, deletion of 1BS or 1DS, each carrying many gliadin genes, caused a significant but nonspecific increase in the HMW glutenins and gliadins encoded by the remaining arms of 1B and 1D. The possible mechanism and evolutionary implications of gene-dosage compensation in polyploid wheat are discussed.

Journal Article↗

Dermatophytosis of camels.

A survey of ringworm in camels showed over 25% of young animals suffered from T. verrucosum infection, and fewer than 0.5% of the camels had T. mentagrophytes. Amino acid analyses of hair samples taken from human, camel and cow showed the compositions were similar to within 11%.

Amino Acids↗

Whipple's disease.

Whipple's disease is a systemic bacterial infection that once was uniformly fatal and now is treatable with several different antibiotics in most cases. The exact nature of the Whipple's bacillus is unknown, since the organism cannot consistently be cultured. There is also controversy concerning the role of immunologic dysfunction in patients with Whipple's disease. In addition to the small intestine, Whipple's disease can involve the remainder of the gastrointestinal tract, as well as the lymph nodes, joints, nervous system, heart, eyes, hematopoietic system, lungs, liver, and other organs. The clinical manifestations, diagnosis, and treatment of this rare but fascinating disease will be reviewed in this article.

Bacterial Infections↗

Transtelephonic monitoring of 25,919 implanted pacemakers.

In order to evaluate the behavior of lithium-powered cardiac pacemakers, a database of 25,919 lithium-powered pacing systems including 23,517 single and 2,402 dual chambered pacemaker generators were followed in 21,750 patients. Of this group, 11,319 were currently active in addition to 7,560 who died, as well as 2,871 patients who terminated their follow-up service prior to the end-of-life of the pacemaker system. A total of 23,517 single chambered pacemakers were followed for 719,173 months of pacing. The mean time to explant for generator malfunctions was 42 months and for all pacing system malfunctions it was 38 months compared to 31.9 months and 28.6 months, respectively, for the 2,402 dual chambered units that were observed for 38,718 months. In the single chambered units, the most frequent reason for explant was battery exhaustion (37% of explants) followed by lead problems (26%) compared to 49% and 12%, respectively, for the dual chambered units. The incidence rates, defined as a transtelephonic test result, required physician decision for action or clarification of the pacing mode or program parameters and showed a high incidence rate immediately post-implant; thereafter, there was a relatively trouble-free period until the 36th month when capture, sensing, and battery problems began to occur at a steady rate reaching 4% at the end of 48 months. Similarly, for dual chambered units, an 8% incidence rate was seen within the first 3 months, followed by a quiescent period until the 28th month when the incidence rate jumped to 16%.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗

Effects of transdermal scopolamine, alone or in combination with cimetidine, on total 24 hour gastric acid secretion in patients with duodenal ulcer.

Transdermal scopolamine is an antimuscarinic preparation approved for use in the United States for prevention of motion sickness. A recent study using this drug (0.5 mg/patch) suggested that enough scopolamine was absorbed through the skin to reduce basal gastric acid secretion in patients with duodenal ulcer. We have compared the effect of transdermal scopolamine and oral cimetidine (400 mg twice daily) in seven men with chronic duodenal ulcer, both alone and in combination, on acid secretion throughout an entire 24 hour period in a placebo-controlled, randomised, double blinded cross over study. The effect of these drugs on basal, interprandial, and nocturnal gastric juice volume and hydrogen ion concentration also was measured. Transdermal scopolamine had no significant effect on mean 24 hour acid secretion (placebo, 409.4 mmol/day; scopolamine, 364.0 mmol/day) nor did it have a significant effect on gastric juice volume or hydrogen ion concentration. The combination of transdermal scopolamine plus cimetidine was not more effective than cimetidine alone in reducing total 24 hour acid secretion (mean, 231.8 versus 235.3 mmol/day) nor in reducing gastric juice volume or hydrogen ion concentration.

Administration, Cutaneous↗

Salivary response to food in humans and its effect on gastric acid secretion.

The purpose of these studies was to determine the amount of saliva secreted in response to food in humans and to evaluate the effect of saliva on postprandial gastric acid secretion. Subjects chewed and spat out an appetizing steak and french-fried potato meal (modified sham feeding), with the increase in the weight of the meal during sham feeding taken to represent salivary secretion. Mean salivary flow rose from basal rates of 37.1 ml/h to 167.3 ml/h during modified sham feeding (P less than 0.001). Chewing gum increased salivary secretion to approximately the same extent as modified sham feeding, whereas chewing on plastic tubing caused a much smaller increase in salivary flow. Intravenous infusion of bethanechol (50 micrograms . kg-1 . h-1) was approximately half as potent as modified sham feeding or gum chewing in stimulating salivary flow. The salivary response to sham feeding was completely blocked by 15 micrograms/kg intravenous atropine. Salivary secretion increased approximately 20 ml/h when a 700-ml amino acid meal was infused directly into the stomach (P less than 0.01), whereas gastric distension with 700 ml saline had no effect. These findings suggested that food in the stomach or upper small intestine may activate a reflex or release a hormone into the circulation that augments salivary flow. Although intravenous gastrin-17 infusion had no effect on salivary flow, somatostatin-14 infusion increased salivary flow 15 ml/h (P less than 0.02). Saliva contained approximately 2,000 pg/ml immunoreactive urogastrone, an inhibitor of acid secretion when administered parenterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗