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Biomedical subjects

R Fogel

Publications and source records attributed to R Fogel.

At least 37 records · Page 2Linked to original sources

The gliding nucleus.

The lens glide is a disposable sterile plastic piece designed to achieve smooth, easy, safe expression of the nucleus in planned extracapsular cataract extraction. The advantages of the technique include prevention of iris prolapse or iris trauma, controlled nucleus extraction without sudden nucleus expulsion, direction of the nucleus toward the external opening, and prevention of malengagement of the nucleus to the anterior chamber angle or vitreous cavity. Using the glide facilitates extraction of a nucleus through a small limbal or scleral incision. Combining the glide with other modern surgical techniques, such as scleral tunnel small incision, capsulorhexis, and hydrodissection, results in a no-stitch low astigmatic wound and stable intraocular lens fixation in the capsular bag.

Cataract Extraction↗

Intestinal distension alters vagal efferent activity and small intestinal transport in vivo.

We investigated whether intestinal distension altered net water absorption by an adjacent noncontiguous segment of intestine and the mechanism for this effect. Influx and efflux catheters were placed in two intestinal loops, after which the bowel was transected between the loops. During perfusion with Ringers-HCO3-, the proximal loop efflux catheter was elevated 5, 10, or 15 cm above the plane of the rat. Net water absorption was measured in the nondistended caudal (control) loop. Elevation of the proximal loop efflux catheter caused distension and increased intraluminal pressure in this loop but did not alter the circumference or intraluminal pressure of the caudal loop. Distension increased net water absorption by the caudal loop if the vagi were intact and the splanchnic nerves transected. Afferent vagotomy prevented the distension effect. Using the intracellular recording technique, we were able to show that the increase in absorption resulted from a reduction in the activity of vagal neurons innervating the gastrointestinal tract. Intestinal distension reduced the neural activity of 24 of 26 vagal efferent neurons. Our results demonstrate that after splanchnectomy intestinal distension activates a neural circuit that includes afferent and efferent vagal fibers, resulting in increased water absorption.

Absorption↗

Physiology and morphology of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract that are sensitive to distension of the small intestine.

We have recently shown that distension-sensitive vagal afferents are part of a neural circuit affecting absorption of water in the rat small intestine. Our results indicated that vagal afferent activity directly or indirectly influences the activity of neurons in the dorsal motor nucleus of the vagus (DMNV). In the present study we pursued this interaction by examining the structure and function of neurons in the DMNV and nucleus of the solitary tract (NST) that responded to moderate distension of the small intestine. Distension-sensitive cells were filled by intracellular iontophoretic injection of horseradish peroxidase. A total of 43 distension-sensitive brainstem neurons were successfully characterized and labeled. Sixteen of the 17 NST neurons were excited by distension of the small intestine. Ten of the seventeen were restricted to the ipsilateral NST. Only two NST neurons possessed axons that terminated in the subjacent DMNV. In contrast to the response profile of the NST neurons, 24 of 26 DMNV neurons were inhibited by intestinal distension. Fourteen of the DMNV neurons appeared to contribute to the vagus nerve and 15 extended dendrites into the overlying NST. We propose that distension-induced inhibition of DMNV activity is accomplished by inhibitory NST neurons, which synapse on the dendrites of DMNV neurons in the NST.

Afferent Pathways↗

The target specificity of the extrinsic innervation of the rat small intestine.

The target specificity of the extrinsic innervation of the rat small intestine was examined by simultaneously injecting the proximal and distal small intestine with either wheat germ agglutinin-horseradish peroxidase (HRP) or fast blue. The number of single- and double-labeled cells in the nodose, dorsal root and coeliac-superior mesenteric ganglia and the dorsal motor nucleus of the vagus were counted and expressed as percentages of total labeled cells. Cells containing both HRP and Fast blue projected to both regions of the intestine. We found that the nodose and mesenteric ganglia contained significantly fewer double-labeled neurons (approximately 3 and 9% respectively) than the dorsal motor nucleus (19%) or dorsal root ganglion (20%). Presumably, a large number of double-labeled afferent or efferent neurons would limit the ability of a given component of the extrinsic innervation to control the activity of restricted regions of the small intestine (but might be important in overall regulation of intestinal function). In a separate series of experiments we examined the topography of neurons in the dorsal motor nucleus of the vagus labeled with HRP injection into either the proximal or distal small intestine. Both of these injections labeled neurons in the entire rostro-caudal extent of the nucleus, though approximately 75% of the cells were located between 720 microns caudal and 720 microns rostral to the obex. Cells in the rostral regions were found primarily in the lateral pole of the nucleus, whereas caudal regions contained labeled cells in both the medial and lateral poles.

Abdomen↗

Regulation of rat ileal water absorption by central alpha 2 adrenergic receptors.

This study examined the role of central adrenergic receptors in the regulation of water absorption by the rat ileum. Clonidine, an alpha 2-adrenergic receptor agonist, increased water absorption in vivo following intracerebroventricular but not intravenous injection. Intracerebroventricular injection of prazosin, an alpha 1-adrenergic receptor antagonist, did not alter basal water absorption. Prazosin did not prevent the clonidine effect. In contrast, the alpha 2-adrenergic receptor antagonist, yohimbine, reduced basal absorption and prevented the intracerebroventricular clonidine effect. Treatment with reserpine reduced ileal norepinephrine content by 98%, reduced basal water absorption consistent with a loss of sympathetic outflow to the mucosa, but did not prevent the increase in water absorption due to intracerebroventricular clonidine. These results suggest that central alpha 2 receptors regulate water absorption by the rat ileum. The clonidine-induced increase in water absorption is not mediated by the sympathetic nerves innervating the intestine.

Absorption↗

Accelerated evolution of a false-truffle from a mushroom ancestor.

THE false-truffles (Hymenogastrales) are a group of basidomycetous fungi that produce underground truffle-like basidiocarps. They are generally believed to be independently derived from several mushroom lineages, but extensive morphological divergence often obscures recognition of these phylogenetic connections. Comparisons of mitochondrial DNA now demonstrate a surprisingly close relationship between species of false-truffles in the genus Rhizopogon (Hymenogastraceae) and the mushroom genus Suillus (Boletaceae). The striking morphological differences separating all Suillus species from Rhizopogon imply an acceleration in the rate of morphological change relative to molecular change during the evolution of these false-truffles from their mushroom ancestors. This acceleration can best be explained by rapid morphological divergence resulting from selective pressures which may have acted on a small number of developmental genes.

Base Sequence↗

Identification and function of brain stem neurons regulating rat ileal water absorption.

The central nervous system (CNS) regions regulating ileal water and ion absorption are unknown. We determined 1) the CNS origin of brain stem neurons that directly innervate the rat ileum, and 2) that these neurons influence intestinal water absorption. Horseradish peroxidase (HRP) was injected into the muscle layer of the rat ileum. The brains were examined for HRP reaction product (HRPRP) 3, 5, or 7 days later. Only cell bodies of the dorsal motor nucleus of the vagus (DMNV) were labeled. Unilateral cervical vagotomy prevented deposition in the ipsilateral DMNV. To determine whether the DMNV regulates ileal water absorption, electrical and chemical stimulation (30 microA, 4 Hz, 0.2 ms, and 300 pmol L-glutamate every 5 min, respectively) were used. Both the DMNV and the adjacent nucleus tractus solitarius (NTS) were stimulated, causing a reduction in water absorption. Bilateral vagotomy prevented the effect of bilateral electrical stimulation, but unilateral vagotomy did not prevent the decrease due to ipsilateral stimulation. These studies show that 1) the DMNV innervates the ileum, and 2) alteration of vagal efferent activity by stimulation of the DMNV and NTS reduces ileal water absorption.

Animals↗

Central administration of benzodiazepines alters water absorption by the rat ileum in vivo.

Two types of benzodiazepine receptors have been identified in the central nervous system. The aim of these experiments was to determine if ligands for these receptors alter basal water absorption by rat ileum in vivo after central administration. Specifically, the effects on net water flux of the systemic and central administration of diazepam and the central administration of RO 5-4864, a "peripheral" receptor agonist, and of the "central" receptor agonists clonazepam and lorazepam were determined. Diazepam increased absorption at 4.3 mg/250 g body wt i.p. but not at 430 micrograms/250 g body wt. Intracerebroventricular diazepam (28 micrograms) increased water absorption. Larger doses had a greater effect. Intracerebroventricular RO 5-4864 (100 micrograms) increased net water absorption; intracerebroventricular lorazepam (50 or 100 micrograms) or clonazepam (100 micrograms) reduced basal water absorption. Systemic atropine (2 mg/kg i.v.) abolished the effect of lorazepam (100 micrograms i.c.v.). To evaluate the possibility that diazepam and RO 5-4864 have effects similar to those of calcium channel antagonists, nifedipine, nitrendipine, and diltiazem were administered intracerebroventricularly. The dihydropyridine calcium channel antagonists nifedipine and nitrendipine increased basal water absorption. Diltiazem, a benzothiazepine compound, did not alter basal water absorption. We conclude that the binding of benzodiazepine agonists to receptors located in the central nervous system alters net water absorption by the rat ileum. Agonists of the central benzodiazepine receptor reduce basal water absorption via a cholinergic neural pathway. Peripheral agonists increase net water absorption. In this model, diazepam behaves as a peripheral receptor agonist. This study provides further evidence of a role for the central nervous system in the regulation of intestinal absorption of water and ions.

Animals↗

Central action of gamma-aminobutyric acid ligands to alter basal water and electrolyte absorption in the rat ileum.

The gamma-aminobutyric acid agonist muscimol and the gamma-aminobutyric acid antagonist bicuculline were studied to determine their effects on basal net water and electrolyte transport in the rat ileum. Whereas the intraperitoneal injection of muscimol caused a reversible, dose-dependent decrease in net water absorption, bicuculline produced a reversible, dose-dependent increase in net water and ion absorption. The threshold doses of muscimol and bicuculline were greater than 2.1 and 2.2 micrograms/kg, respectively. Lower doses of muscimol (0.1 microgram) or bicuculline (0.3 microgram) administered into the cerebrospinal fluid had the same effect as higher doses given systemically. Vagotomy prevented the effect of intracerebroventricular muscimol. Atropine (6 micrograms intracerebroventricularly) alone did not alter basal water absorption but abolished the muscimol effect, suggesting that muscimol promoted the release of acetylcholine from central cholinergic neurons. Atropine did not prevent the bicuculline effect. We conclude that (a) muscimol decreases ileal water absorption and bicuculline enhances ileal water absorption by an action at a gamma-aminobutyric acid receptor in the central nervous system, (b) the muscimol effect is due to an alteration in parasympathetic vagal outflow to the intestine, (c) the muscimol effect is mediated by a central cholinergic interneuron, and (d) the bicuculline effect is not mediated by the release of acetylcholine from central cholinergic neurons.

Animals↗

Role of enkephalins in regulation of basal intestinal water and ion absorption in the rat.

Intraluminal administration of naloxone (10(-4) M), a mu-opiate receptor antagonist, or diprenorphine (10(-6) M), an opiate receptor antagonist with high affinity for both delta- and mu-receptors, decreased basal in vivo water and electrolyte absorption in the jejunum and ileum but not the colon of the rat. Diprenorphine (10(-5) M) decreased basal colonic water transport. These changes were not due to a reduction in mucosal Na-K-ATPase activity. Intravenous atropine prevented as well as abolished the changes in water transport due to naloxone. The diprenorphine-induced changes were not altered by atropine. Naloxone and diprenorphine acted by different receptors. Pretreatment with naloxone (10(-4) M) prevented the increase in water transport due to morphine, a mu-agonist, whereas a higher concentration of naloxone (10(-3) M) was required to inhibit the increase due to D-Ala-methionine-enkephalinamide, a delta-receptor agonist. In contrast, diprenorphine (10(-6) M) abolished the absorption caused by morphine and D-Ala-methionine-enkephalinamide. Diprenorphine (3 X 10(-7) M) partially prevented the morphine-induced increase in water absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of dopamine and bromocriptine on rat ileal and colonic transport. Stimulation of absorption and reversal of cholera toxin-induced secretion.

Water and electrolyte transport were determined in rat ileum and colon using the single-pass perfusion technique. Intraperitoneal dopamine caused prompt stimulation of both ileal and colonic water absorption. The dopamine effect was mediated by both specific dopamine and alpha 2-adrenergic receptors. Haloperidol, a specific dopamine antagonist, and yohimbine, an alpha 2-adrenergic antagonist, inhibited the effect of dopamine in ileal absorption; both antagonists alone had no effect on basal water transport. Bromocriptine (intravenous and intraluminal) stimulated ileal and colonic water absorption, which was inhibited by haloperidol and yohimbine, and reversed cholera toxin-induced ileal secretion. Magnitude and time-courses of the increased water absorption in ileal loops, inoculated with saline, were the same as in loops, inoculated with saline, suggesting that bromocriptine acted to reverse cholera toxin-induced secretion by stimulating absorption. Bromocriptine had no effect on the cyclic adenosine monophosphate increase caused by cholera toxin. We conclude (a) dopamine stimulates water absorption in vivo in rat ileum and colon; (b) this dopamine effect is via specific dopamine and alpha 2-receptors; (c) bromocriptine stimulates water absorption in ileum and colon and also acts by dopamine and alpha 2-receptors; and (d) bromocriptine reverses cholera toxin-induced secretion.

Animals↗

Chloroquine stimulates absorption and inhibits secretion of ileal water and electrolytes.

The effects of chloroquine diphosphate, a drug with "'membrane-stabilizing" properties, were studied on basal ileal absorption and on ileal secretion induced by increased intracellular cAMP levels and calcium (serotonin). The studies were performed on rat (in vivo) and rabbit ileum (in vitro). Intraluminal chloroquine (10(-4) M) reversed cholera toxin- and theophylline-induced secretion in rat ileum but did not alter the cholera toxin- and theophylline-induced increases in cAMP content. Addition of chloroquine (10(-4) M) to the mucosal surface of rabbit ileum did not alter basal active electrolyte transport or the serotonin-induced decreased Na and Cl absorption but inhibited the theophylline-induced C1 secretion. Addition of chloroquine (10(-4)) M) to the serosal surface stimulated net Na and Cl absorption. This effect may involve intracellular calcium. Chloroquine increased the rabbit ileal calcium content and decreased 45Ca2+ influx from the serosal surface. Both the mucosal and serosal effects of chloroquine described led to a net increase in absorptive function of the intestine and should prove useful in developing treatment of diarrheal diseases.

Absorption↗

Dopamine stimulation of active Na and Cl absorption in rabbit ileum: interaction with alpha 2-adrenergic and specific dopamine receptors.

The effects of dopamine on active intestinal ion transport have been evaluated. An epithelial sheet preparation of rabbit ileum was used in vitro with the Ussing chamber-voltage clamp technique. Dopamine, in the presence of 1 mM ascorbic acid, added to the serosal bathing solution caused a dose-dependent decrease in short-circuit current, with a half-maximal effect at 1.2 muM and maximal effect of -50 muA/cm(2) at 50 muM; dopamine decreased the potential difference, and increased the conductance and net Na and net Cl absorption. There was no effect on the residual ion flux. Dopamine did not alter the change in short-circuit current caused by mucosal glucose (10 mM) or serosal theophylline (10 mM). Mucosal dopamine had no effect. The effect of dopamine on short-circuit current was inhibited by the dopamine antagonists haloperidol and domperidone and the alpha(2)-adrenergic antagonist yohimbine; there was no effect of the alpha(1)-antagonist prazosin and the beta-antagonist propranolol. In addition, the alpha(2)-adrenergic agonist clonidine, but not the alpha(1)-agonist methoxamine caused a dose-dependent decrease in short-circuit current. The ileal effects of dopamine did not occur via conversion into norepinephrine or release of norepinephrine from the peripheral nerves since "peripheral sympathectomy" with 6-hydroxydopamine did not alter the dopamine-induced change in ileal short-circuit current. The dopamine effects were not associated with a change in basal ileal cyclic AMP content but were associated with a decrease in total ileal calcium content as measured by atomic absorption spectrometry and as estimated by (45)Ca(++) uptake. The decrease in calcium content could be attributed to a dopamine-induced decrease in (45)Ca(++) influx from the serosal surface. Because of the presence of dopamine in ileal mucosa and these effects on ileal electrolyte transport, it is possible that dopamine may be involved in the physiologic regulation of active intestinal electrolyte absorption.

Animals↗

Suppressor mononuclear cells in giant lymph node hyperplasia and thymoma.

The existence of suppressor mononuclear cells were demonstrated in two lymphoproliferative disorders: giant lymph node hyperplasia and thymona. The three patients tested also showed cell-mediated immunodeficiency as expressed in the low number of T cells, negative graft versus host reactions and negative skin tests; the one patient tested with phytohemagglutinin (PHA) and concavalin A (Con A) showed a low response. Suppressor activity was tested with a new experimental model, the local xenogeneic graft versus host reaction. It is proposed that this model be used for testing suppressor activities in other human disorders as well.

Adolescent↗

Combined valve and coronary artery surgery.

From 1970 to 1978, 79 patients (Group 1) underwent combined valve replacement and coronary bypass operation. They were compared with 79 consecutive subsequent patients (Group 2) undergoing similar valve replacement. In Group 1, 73% were men compared with 48% in Group 2. The average age in Group 1 was 60 years (range, 42 to 84 years) and in Group 2, 57 years (range, 29 to 74 years). When the patients were first seen, angina was present in 49% in Group 1 and only 24% in Group 2. More than 95% of the patients in both groups were in New York Heart Association Functional Class III or IV. Areas of abnormal contraction were twice as frequent in the angiograms of patients in Group 1 (43%). Thirty-three mitral, 44 aortic, and 2 aortic plus mitral valve replacements were performed in each group. One to 4 grafts were placed in each patient group. One to 4 grafts were placed in each patient in Group 1, and most had single or double grafts. Early morbidity was more frequent in Group 1. Early mortality was 5 to 6% in each group. Late mortality (average, 3.5 years after operation) was 16 to 17% in each group. The working status and Functional Classification at follow-up were similar for patients in both groups. Combined valve and coronary operation carried a similar operation risk and had similar late results as valve replacement alone.

Adult↗