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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 415 records · Page 23Linked to original sources

Enrichment of suppressor cell activity by hydrocortisone: suppression of in vitro activation of splenocytes from mice bearing Lewis lung carcinoma.

Suppressor cells in spleens of mice bearing the Lewis lung carcinoma (3LL) suppressed the anti-tumor immune response in vivo but not in vitro. The hydrocortisone (HC)-resistant fraction of spleen cells from tumor-bearing mice (TBM) was, on the other hand, suppressive in vitro, due to enrichment for HC-resistant suppressor cells. This cellular fraction suppressed the tumor-induced differentiation of memory cells as well as the tumor-independent in vitro activation of TBM spleen cells. The in vitro lymphoproliferative response of TBM spleen cells to mitogens was also subjected to suppression: these cells showed a lower response to a mitogen such as Concanavalin A (Con A) and were capable of suppressing the response of normal spleen cells to this mitogen. HC treatment of TBM 2 days prior to spleen harvest enriched the splenic population for suppressor cells that suppressed Con A-induced activation.

Animals↗

Host's immune state and kinetics of local tumor growth control--progression of postoperative lung metastasis.

In a study of the progression of lung metastases in tumor-bearing and tumor-excised mice as a function of the host's immune status and of the rate of local 3LL tumor development, the following observations were noted. 1) The total metastatic volume was larger in mice transplanted intrafootpad with the lower doses of 3LL tumor cells (1 x 10(5)--3 x 10(4)) than in mice inoculated with high doses of tumor cells (5 x 10(-6)--1 x 10(6)). 2) A dramatic acceleration of metastatic development followed surgical removal of the local tumor which developed following inoculation of low, but not high doses of 3LL tumor cells. 3) In immunoimpaired mice, growth of the local tumor induced by inoculation of 3 x 10(6) or 1 x 10(5) 3LL tumor cells was enhanced in cyclophosphamide-treated (200 mg/kg) mice and retarded in B mice, yet metastasis development was accelerated in both types of immunosuppressed tumor-bearing mice. Tumor excision was an additional stimulus for metastatic growth. In immunosuppressed animals, the growth of postoperative pulmonary metastases accelerated to the same degree, independent of whether local tumors had been produced by high or by low doses of 3LL tumor cells.

Animals↗

Arrangement of chromosomes in the interphase nucleus of plants.

Chromosomal arrangement in the interphase nucleus has two main aspects: (1) arrangement of chromosomes with respect to nuclear polarity and to other nuclear components, and (2) arrangement of chromosomes with respect to one another. The latter aspect consists of two main types of spatial relationships; (1) relationships between different members of one chromosomal set, (b) relationships between different chromosomal sets. Data concerning various aspects of chromosomal arrangement in the interphase nucleus are presented and discussed and the genetic control as well as subcellular mechanisms which are involved in nuclear organization, are elucidated. Evidence is presented indicating that, in common wheat, the gene system that determines the specific pattern of chromosomal arrangement in the nucleus is operating via the microtubular elements of the spindle system. The significance of ordered arrangement of chromosomes in the nucleus for the regularity of genetic activity and chromosomal behavior, is pointed out.

Cell Nucleus↗

Serum gastrin response to secretin after vagotomy.

It is unknown whether the gastrin response to secretin (secretin test) can distinguish hypergastrinemia due to vagotomy from hypergastrinemia due to Zollinger-Ellison syndrome (ZES). Therefore, we measured serum gastrin concentrations basally and in response to intravenous secretin in 13 vagotomized duodenal ulcer patients without preoperative evidence evidence of ZES and in 5 vagotomized patients with ZES. Following secretin, serum gastrin concentrations increased 40 pg/ml or less [mean (+/- SE) rise 23 +/- 3 pg/ml] in the vagotomized patients without ZES. On the other hand, in the patients with ZES serum gastrin increments after secretin ranged from 105 to 1224 pg/ml. Thus, a large (> 100 pg/ml) rise in serum gastrin concentrations following secretin in a vagotomized patient should suggest Zollinger-Ellison syndrome and not be attributed to vagotomy per se.

Diagnosis, Differential↗

Digital infrared fundus reflectance.

An infrared sensor was inserted at the film plane of a fundus camera. The signal was visualized on an oscilloscope. In this manner we measured infrared reflectance from the surface of the fundus. The purpose was to characterize choroidal malignant melanomas more reliably than is done with infrared color translation photography. Control lesions were choroidal nevi, metastatic tumors, and disciform macular degenerations. Correlations were made with radioactive phosphorus (32P) uptake, fluorescein angiography, and histopathologic findings. Several cases are presented, one in which this new method of infrared detection was the first diagnostic test to detect the spread of a choroidal melanoma. The simplicity of this technique and its increased accuracy justify the needed further refinements.

Adult↗

Localization of androgen-binding protein in proliferating Sertoli cells in culture.

The peroxidase and immunofluorescent localization patterns of androgen-binding protein (ABP), a biological marker of Sertoli cell function, have been examined in cultured Sertoli cells isolated from 20- to 22-day-old rats. ABP immunoreactivity in the form of cytoplasmic granules of variable diameter was observed in Sertoli cells with characteristic lipid droplets and a colony-forming, epithelial-like growth pattern. Incubation of cultures with [3H]thymidine demonstrated that Sertoli cells continue to produce ABP while retaining their capability for synthesizing DNA and undergoing mitosis. A variable number of cultured Sertoli cells became morphologically transformed after exposure to follitropin (follicle-stimulating hormone) and pharmacological agents acting on cyclic nucleotide metabolism. The induced change in Sertoli cell shape coincided with a disappearance of ABP-containing granules from the cytoplasm. These observations demonstrate that localization of ABP by immunological techniques is a valuable tool for the characterization of structural and functional properties of Sertoli cell in culture.

1-Methyl-3-isobutylxanthine↗

Acute meningoencephalitis after withdrawal of antibiotics in Whipple's disease.

A man with Whipple's disease was treated with oral penicillin (500 mg twice a day) for 2 years with eradication of bacillary organisms from the jejunum and a return of jejunal histologic findings to normal. While he was on this regimen, however, intermittent vertigo and tinnitus and decreased auditory acuity developed. Two days after penicillin was withdrawn, the patient developed acute meningoencephalitis that responded to parenteral penicillin and chloramphenicol therapy. Subsequently, central nervous system signs and symptoms and cerebrospinal fluid pleocytosis have been controlled with chronic chloramphenicol therapy. Penicillin may suppress, but not prevent, central nervous system disease in patients with otherwise successfully treated Whipple's disease.

Acute Disease↗

Control of lung metastasis progression in mice: role of growth kinetics of 3LL Lewis lung carcinoma and host immune reactivity.

Studies were made of the growth of metastases of the 3LL Lewis lung carcinoma in tumor-bearing and tumor-excised C57BL/6 mice after intrafootpad inoculation of different cell doses to the intact or immunosuppressed host. The total metastatic volume was higher in tumor-bearing mice given transplants of low doses of 3LL cells (3 X 10(4)- 1 X 10(5)) than in mice receiving high doses of cells (1 X 10(6)-5 X 10(6)). The growth of postoperative lung metastases depends on the size of the removal of local tumors and the rate of their development. Surgical removal of small, medium, or large local tumors, respectively, resulted in the development of smaller, similar, or larger volumes of pulmonary metastases compared to the metastases in tumor-bearing mice not having surgery. Accelerated growth of postoperative metastases in mice inoculated with low doses of 3LL cells was observed following removal of the local tumors of more than 310 mm3. The same effect was observed on mice given transplants of high doses of 3LL cells only when the removed local tumors had reached a volume of more than 550 mm3. In immunologically suppressed tumor-bearing mice, acceleration of the metastatic growth in the lungs was observed independently of the inoculum size. Even in the immunosuppressed mice, the growth of metastases was not optimal, and an additional stimulus for their growth was achieved following the removal of local tumors. This finding suggested that immunologic and nonimmunologic mechanisms were involved in the control of the metastatic growth of 3LL tumors in mice.

Animals↗

Acid inhibition of sham feeding-stimulated gastrin release and gastric acid secretion: effect of atropine.

The effect of intraluminal pH on the gastrin response to sham feeding was studied in healthy subjects. Before, during, and after sham feeding, an acidified solution of saline (at either pH 5.0 or 2.5) was infused into the stomach continuously and intragastric pH was maintained at either 5.0 or 2.5 by in vivo intragastric titration. When intragastric pH was maintained at 5.0, vagal stimulation induced by sham feeding released statistically significant amounts of gastrin. Acidification to pH 2.5 abolished the gastrin response and also inhibited by approximately 50% the acid secretory response to sham feeding. A small dose of atropine (2.3 micrograms/kg) prevented the inhibition of gastrin release which had occurred at pH 2.5. Moreover, in the presence of atropine, acidification to pH 2.5 did not inhibit acid secretion stimulated by sham feeding. These findings suggest that acid inhibition of sham feeding-stimulated gastrin release and gastric acid secretion is mediated by an atropine-sensitive pathway.

Adult↗

The biological significance of estradiol receptor binding to DNA.

MTW9-D, a rat mammary tumor derived from MTW9 by chronic administration of the dopamine antagonist drug R33,812 shows ovariectomy-induced regression (OIR). MTW9-MtT is also a variant of MTW9, grown by coimplantation of a mammosomatotropic tumor MtTW10, but it does not show OIR. However, when the mammosomatotropic tumor (MtT) is resected, the tumor regresses and shows rapid OIR; implantation of MtT into animals bearing MTW9-D prevents OIR following drug withdrawal. The estradiol receptor (ER) from MTW9-D cytosol binds to DNA-cellulose significantly more than that from MTW9-MtT. After MtT resection, the mammary tumor ER binds to DNA-cellulose, as well as ER from MTW9-D, whereas implantation of MtT into animals bearing MTW9-D decreases ER binding to DNA-cellulose. The significance of these findings in relation to possible clinical application is discussed.

Animals↗

Effect of sham feeding on gastric emptying.

We studied the effect of vagal stimulation by sham feeding on gastric emptying in normal human subjects. When a saline test meal was infused into the stomach, simultaneous sham feeding did not alter the emptying of a nonabsorbable marker added to the meal or the volume of fluid emptied from the stomach. When a homogenized steak meal was infused, sham feeding caused a slight acceleration of emptying (47 +/- 2 vs. 53 +/- 2% marker recovered from the stomach 45 min after the meal, P less than 0.05). Gastric acid secretion in response to both meals was significantly augmented by sham feeding. Our results suggest that vagal stimulation by sham feeding has no effect on the emptying of isotonic saline and only a monor effect on gastric emptying of homogenized food in humans.

Adult↗

Distention-induced gastrin release: effects of luminal acidification and intravenous atropine.

We evaluated whether gastric distention with saline test meals could release gastrin in healthy subjects and whether luminal acidification or atropine would modify this response. Distention with 700 ml saline adjusted to pH 5.0 led to a significant gastrin response (averaging 9 +/- 3 pg/ml above basal levels during the first 15 min after distention, P less than 0.02), whereas distention with 25 ml saline led to no gastrin release. Distention with 700 ml saline adjusted to pH 2.5 also led to a significant gastrin rise, which was nearly identical to that seen at pH 5.0. A small dose of atropine (2.3 micrograms/kg i.v.) significantly enhanced the gastrin response to 700-ml distention at pH 5.0 (average gastrin rise 20 +/- 3 pg/ml, P less than 0.02 vs. 700 ml without atropine). This enhancement of gastrin release by atropine was not due to changes in intragastric pH, because pH was held constant at 5.0 by in vivo intragastric titration. Enhancement was also not due to greater gastric distention after atropine, because gastric volumes after the 700-ml test meal were similar with or without atropine. Although atropine enhanced distention-induced gastrin release, atropine reduced acid secretion by more than 50% (P less than 0.05). Our findings indicate (a) that gastric distention releases significant amounts of gastrin in healthy subjects; (b) this gastrin response is resistant to inhibition by luminal acidification to pH 2.5 and (c) the gastrin response to distention is enhanced by atropine, suggesting that distention may also activate cholinergic pathways that inhibit gastrin release.

Adult↗

Effect of naloxone and morphine on gastric acid secretion and on serum gastrin and pancreatic polypeptide concentrations in humans.

To evaluate the role of endogenous opiates on gastric acid secretion, we infused naloxone, a pure opiate antagonist drug, into 8 healthy subjects in the basal state and then after an amino acid meal. Naloxone significantly reduced basal acid secretion and the gastric acid secretory response to the meal. Maximum inhibition averaged 65% for basal acid secretion and 35% for meal-stimulated secretion. Naloxone had no effect on serum gastrin concentraitons or on the rate of gastric emptying of the meal. In the same subjects morphine also significantly reduced meal-stimulated acid secretion. In contrast to naloxone, morphine delayed gastric emptying and also enhanced the gastrin response to the meal. Morphine also abolished the pancreatic polypeptide response to the meal. Our studies with naloxone suggest that endogenous opiates may augment gastric acid secretion in humans. Failure of exogenous opitates to increase acid secretion suggests that actions other than opiate receptor stimulation (such as anticholinergic effects) may have come into play during morphine infusion.

Adolescent↗

Experience with sham feeding as a test for vagotomy.

Sham feeding is thought to stimulate gastric acid secretion solely via vagal pathways. We evaluated whether sham feeding can be used as a test for vagotomy. From results in 50 nonvagotomized subjects (28 unoperated duodenal ulcer patients and 22 healthy controls), a ratio of sham feeding-stimulated acid output to peak acid output of 0.10 or less was defined as abnormally low (with 95% confidence). The ratio of sham feeding to peak acid output was abnormally low in 28 of 41 (68%) vagotomized duodenal ulcer patients without clinical evidence of recurrent ulcer, suggesting that most of these patients had indeed had an effective reduction in vagal innervation of the stomach. On the other hand, 11 of 15 (73%) vagotomized duodenal ulcer patients with symptomatic, recurrent ulcers had normal ratios of sham feeding to peak acid secretion. That a normal ratio represented an incomplete vagotomy was independently suggested in 5 of these patients; in 1 an intact vagal trunk was confirmed at a second operation; in the other 4, acid secretion fell strikingly after transthoracic vagotomy, which would not have been expected to happen if vagotomy had initially been complete. In 5 vagotomized patients tested on two occasions, the ratio was reasonably reproducible. We conclude that a ratio of sham feeding-stimulated to peak acid output greater than 0.10 after an attempted vagotomy suggests persistent vagal innervation, whereas a ratio of 0.10 or less suggests, with at least 95% confidence, that vagotomy has been successful.

Adult↗

Effect of sham feeding on gastric acid secretion in healthy subjects and duodenal ulcer patients: evidence for increased basal vagal tone in some ulcer patients.

Sham feeding augments gastric acid secretion by activating efferent vagal pathways to the stomach. If increased vagal activity in the basal state were the cause of increased basal acid secretion in some patients with duodenal ulcer, these patients might be expected to secrete little or no additional acid in response to sham feeding. To test this, we measured basal and sham feeding-stimulated acid secretion (as well as peak pentagastrin-stimulated acid output) in 29 duodenal ulcer patients and 22 healthy subjects. Four ulcer patients who had markedly increased basal acid secretion (basal/peak acid output > 0.30) and normal basal serum gastrin concentrations failed to augment acid secretion in response to sham feeding. On the other hand, patients with marked basal acid hypersection owing to hypergastrinemia (Zollinger-Ellison syndrome) responded to sham feeding with a large increase in acid secretion above basal rates. Every normal subject responded to sham feeding with an increase in acid secretion above basal rates, even when acid secretion had been stimulated by an intravenous pentagastrin infusion before beginning sham feeding. These findings suggest that in some patients with duodenal ulcer (4 of 29 in this study) increased basal acid secretion is caused by increased vagal tone.

Adult↗