PubMed HealthSearch

Biomedical subjects

R J Levin

Publications and source records attributed to R J Levin.

At least 19 recordsLinked to original sources

Neuroectodermal antigens persist in benign and malignant salivary gland tumor cultures.

OBJECTIVE: To determine whether a heterogeneous collection of salivary gland tumors shared common antigenic characteristics and growth patterns in tissue culture. DESIGN: Cell cultures were derived from benign and malignant salivary gland neoplasms, cultured conservatively, and serially analyzed for epithelial, myoepithelial, and neuroectodermal antigens. SUBJECTS: Nineteen samples reflecting the spectrum of salivary tumor pathologic characteristics were established in tissue culture. Most were derived from benign pleomorphic adenomas, and several were from carcinomas, including carcinoma ex pleomorphic adenoma, and mucoepidermoid and adenoid cystic carcinoma. RESULTS: All cultures were epithelial as determined by morphologic and antigenic examination, using antibodies for cytokeratin. The phenotype of cells derived from benign tumors, especially the pleomorphic adenomas, resembled those in the original neoplasm. Those from carcinomas were similar, with less differentiated characteristics. Manipulation of growth conditions altered the phenotypes shown in culture. Some cultures contained cells expressing vascular smooth-muscle actin and glial fibrillary acidic protein or nestin. CONCLUSIONS: This model cell system containing proliferative cells from several tumor types is consistent with a stem-cell theory of salivary gland tumor origin. Our data were not consistent with the bicellular or multicellular theory. We hypothesize a neuroectodermal origin for this group of apparently heterogeneous tumors. These cultured cells will be valuable for in-depth investigation of the loss of proliferation controls in benign and malignant tumors of the salivary gland.

Antibodies, Monoclonal

Aggressive papillary tumors of the temporal bone: an immunohistochemical analysis in tissue culture.

Aggressive papillary tumors of the temporal bone are neoplasms that are locally invasive and destructive. Previously classified on histologic study as middle ear adenomas or adenocarcinomas, observational evidence suggested that they arose from endolymphatic sac. To evaluate this hypothesis, we established a tissue culture from cells derived from such a papillary tumor and compared immunohistochemical stains of the original tumor with stains on endolymphatic epithelium. Similarities in expression of neuroectodermal antigens were observed. Similar staining antigens in cells derived from tumor and the endolymphatic sac provide evidence that epithelium from endolymphatic sac is the site of origin for these aggressive neoplasms. In tissue culture the cells remain contact inhibited and dependent on serum or growth factors with survival beyond the expected senescence at 30 to 50 generations. Therefore the cell culture technique provides a model for study of the disruption of growth control and invasive properties of this tumor.

Adenocarcinoma, Papillary

Luminal capsaicin inhibits fluid secretion induced by enterotoxin E. coli STa, but not by carbachol, in vivo in rat small and large intestine.

The enterotoxin E. coli STa induced fluid secretion in the rat jejunum, ileum and proximal colon in vivo that was greatly inhibited by the co-presence of luminal capsaicin, which is a specific neural toxin of afferent C fibres. The same dose of capsaicin had no effect on the fluid secretion activated by carbachol in the jejunum, ileum and proximal colon. Afferent C fibres appear to be involved in the activation by STa of fluid secretion in the rat intestine in vivo.

Afferent Pathways

Human immunodeficiency virus--associated non-Hodgkin's lymphoma presenting as an auricular perichondritis.

AIDS-related NHL is an aggressive neoplasm, usually of high or intermediate grade, frequently extranodal at initial treatment, and often the first manifestation of AIDS. Although complete remissions have been reported, they occur in only a minority of patients. We describe a patient with NHL of the external ear that masqueraded as an auricular perichondritis. This is the first case reported in which AIDS-related NHL first appeared in the ear, and this should alert physicians who treat patient with AIDS to be aware of the protean manifestations of this disease.

Adult

Aggressive papillary tumors of the endolymphatic sac: clinical and tissue culture characteristics.

Aggressive papillary tumors of the temporal bone are neoplasms that were recently re-classified as tumors of the endolymphatic sac. They typically invade the mastoid bone and otic capsule and can grow into the petrous apex. The authors have treated three patients with this rare neoplasm and grown one of the tumors in tissue culture. This report reviews the clinical presentation in the three patients and the immunohistochemical staining characteristics of the tumor and tumor culture as compared to those of the endolymphatic sac. Findings support the hypothesis that aggressive papillary lesions of the temporal bone arise from the endolymphatic sac. Additionally, it is noted that the tumor culture maintains the characteristics of the original tumor and thus provides an exciting laboratory model for further study of this rare neoplasm.

Adenocarcinoma, Papillary

Neurally maintained hypersecretion in undernourished rat intestine activated by E. coli STa enterotoxin and cyclic nucleotides in vitro.

1. The electrogenic secretory responses of stripped jejuna and ilea from chronically undernourished rats (50% control diet for 21 days) to the bacterial enterotoxin Escherichia coli STa, measured as the short-circuit current in vitro, show an enhanced maximum secretion (ISC, max) with a prolonged duration compared with fed intestine. 2. The ISC, max is unaffected by pretreatment of the intestine in vitro with hexamethonium, atropine, procaine or indomethacin, or by desensitization to 5-hydroxytryptamine (5-HT), while the prolonged duration is unaffected by atropine, indomethacin or 5-HT desensitization but is reduced by hexamethonium and procaine. 3. Both 8-bromo-cyclic GMP and dibutyryl cyclic AMP added serosally activate the enhanced ISC, max and its maintenance. Pretreatment with tetrodotoxin had no effect on the initial ISC, max but prevented its maintenance. 4. Bethanechol, dimethyl phenyl piperazinium, vasoactive intestinal polypeptide, 5-HT and luminal propionate all induced the characteristic hypersecretory activity in the undernourished intestine compared with the fed state, but none could activate the maintenance circuit to prolong their transient responses. 5. Maintenance of the induced hypersecretory activity is the first example of induction of the neural control of intestinal secretion by the dietary intake level and illustrates the plasticity of the enteric nervous system.

Animals

Enterotoxin Escherichia coli STa activates a nitric oxide-dependent myenteric plexus secretory reflex in the rat ileum.

1. Mucosally added enterotoxin Escherichia coli STa increased the electrogenic Cl- secretion measured as the short-circuit current (Isc) across isolated muscle-stripped and muscle-unstripped rat mid-ilea incubated in vitro. 2. Pretreatment with serosal L-NAME (N omega-nitro-L-arginine methyl ester) or tetrodotoxin (TTX) significantly reduced the maximum Isc and the duration of action of STa in the unstripped but not stripped ilea. D-NAME (serosal), indomethacin or 5-hydroxy-tryptamine-desensitization was ineffective on STa-induced Isc in either stripped or unstripped ilea. 3. Serosal capsaicin reduced the maximum Isc of STa and its duration of action in unstripped ilea. 4. L-Arginine induced a significantly larger increase in the Isc across unstripped ilea than across stripped ilea; this could be significantly reduced by serosal L-NAME or TTX, although these were ineffective in stripped ilea. 5. Pretreatment of anaesthetized rats with I.P. L-NAME suppressed the fluid secretion induced by luminal STa in ilea in vivo but had no effect on that induced by luminal carbachol. 6. Mucosal STa increased electrogenic Cl- secretion across intact rat ileum in vitro by activating a capsaicin-sensitive, nitric oxide-dependent myenteric plexus-mediated secretory reflex. The suppression by L-NAME of STa induced ileal fluid secretion in vivo probably involves the inhibition of this reflex.

Animals

Digestion and absorption of carbohydrates--from molecules and membranes to humans.

Hydrolysis in the luminal bulk fluid by secreted enzymes is the major pathway for the breakdown of polysaccharides to oligosaccharides, and further hydrolysis is accomplished by a battery of carbohydrates in the brush border of the mature enterocytes. The glucose, galactose, and fructose produced are absorbed across the enterocytes of the upper half of the villus. Glucose and galactose (and other glucalogues) are actively transported into the enterocyte by the Na(+)-glucose cotransporter SGLT1 (gene on chromosome 22) via the transmembrane electrochemical Na+ gradient, and exit across the basolateral membrane by the glucose transporter GLUT2 (gene on chromosome 3). The critical importance of the correct expression of SGLT1 for human sugar absorption is shown by the rare genetic disease of glucose-galactose malabsorption. People with this disease cannot absorb hexoses and have severe watery diarrhea, which, if untreated, is terminal. Fructose absorption is by an Na(+)-independent transport system that has not been fully characterized (possibly GLUT5). Despite many kinetic and other studies in animals, and some in humans, that suggest multiple Na(+)-glucose transporters, only SGLT1 is expressed in enterocytes. Absorption of monosaccharides from disaccharides appears to have a kinetic advantage (disaccharide-related transport system). Hexose absorption is enhanced by dietary intake of hexoses by increased activity of SGLT1 and GLUT2 and by increased enterocyte numbers.

Animals

Fluid hypersecretion induced by enterotoxin STa in nutritionally deprived rats: jejunal and ileal dynamics in vivo.

The effect of luminal enterotoxin Escherichia coliSTa on fluid transport across the jejunum and ileum of fed, starved (72 h) and chronically undernourished (50% control food intake for 21 days) rats was assessed in vivo using a gravimetric technique. Dose-response curves for net fluid secretion (stimulated-basal (30 min)-1) activated by 5,50 and 500 ng ml-1 STa were obtained for jejuna and ilea from fed, starved and chronically undernourished rats. Compared to the fed rats, both dietary deprivations showed enhanced net fluid secretion at 500 ng ml-1, but only the jejunum from chronically undernourished rats showed significantly enhanced secretion at 5 and 50 ng ml-1. Net fluid secretory responses to a standard dose of STa (500 ng ml-1) were monitored in the jejuna and ilea of fed, starved and chronically undernourished rats at 30, 60, 90 and 120 min. The pattern in jejuna and ilea from fed rats was very different; the jejunal secretion over 30 min was transient, but ileal secretion increased continuously to a maximum at 120 min. In both jejunum and ileum from starved rats, the secretory response to STa at 30 min was significantly greater than that in fed rats and subsequently remained near this level. In the jejunum from chronically undernourished rats, the net fluid secreted in response to STa was greatly enhanced at 30 and 60 min, but not at 90 min. The ileal response was significantly greater than that in the fed rats at 30 and 120 min. Luminal procaine (10 mM) selectively increased fluid absorptive tone in the jejunum from fed rats, reduced STa-induced fluid secretion in the ileum from undernourished rats, but had no effect on STa in the jejunum from undernourished rats or in the jejunum or ileum from starved rats. Luminal 8-bromo-cyclic GMP (1 mM) had no effect on basal absorptive tone in the jejunum of fed or chronically undernourished rats, but enhanced the secretory tone of jejunum from starved rats. In the ileum, however, while 8-bromo-cyclic GMP enhanced secretory tone in the fed and starved conditions, it still had no action in the chronically undernourished state. The enhanced fluid secretion observed in the jejunum and ileum of the starved and undernourished rats compared to the fed rats supports previous in vitro findings of an increased electrogenic secretion induced by STa in these dietary deprivations. The fluid hypersecretion could be a cause of the increased severity of diarrhoea often observed in undernourished and starved humans.

Animals

Role of the enteric nervous system in the maintained hypersecretion induced by enterotoxin STa in the nutritionally deprived intestine.

Electrogenic (Cl-) secretion was measured as the short circuit current (Isc, microA/cm2) across muscle-stripped sheets of jejunum and ileum incubated in vitro after removal from fed rats, rats starved for three days, and chronically undernourished rats (50% of fed control intake for 21 days). Concentration and Isc response curves for serially-added mucosal Escherichia coli STa enterotoxin showed that the rats which had undergone dietary deprivation had a larger secretory Isc maximum but the ED50 values were unchanged compared with fed animals. In fed intestine the action of STa was transient, with an Isc peak and subsequent decay to the baseline over 60 minutes but in the undernourished intestine the response consisted of a significantly greater peak than that of the fed state (jejunum = 94%; ileum = 168%) and the Isc was maintained at or near the peak for at least 60 minutes. The starved intestine had a less well developed maintenance of its enhanced peak Isc. Serosal tetrodotoxin (1 microM) had no effect on the initial peak Isc values but caused a decay of the maintained Isc down to the basal or fed levels in the starved and, especially, in the undernourished intestines. Thus, dietary deprivation, especially chronic undernutrition, enhances the maximum electrogenic secretion due to STa and creates a new neural path in the submucosal plexus that, when activated by STa, maintains its enhanced secretory action. Its putative role in exacerbating secretory diarrhoea in malnourished human subjects could be an important component underlying the known relation between malnourishment and the increased severity of diarrhoea.

Animals

Evaluation of vaginal and perineal area during the use of external sanitary protection throughout the menstrual cycle.

A clinical study evaluated potential external genital effects associated with the use of sanitary protection. The subjects used either a pad with traditional cellulose absorbent core or one containing cellulose and absorbent gelling material. Assessments included objective (transepidermal water loss, vaginal pH) and semi-quantitative subjective--methods (skin irritation grading, gynaecological inspection). No statistical or clinical significant differences for any of the parameters evaluated between the groups using the two pads, or compared to the non-pad control period, were found. The parameters used to study the effects on the genital area of an external sanitary product appear appropriate. No significant changes were observed for either of the two pads during daily use for two menstrual cycles.

Adult

Increased vaginal blood flow induced by implant electrical stimulation of sacral anterior roots in the conscious woman: a case study.

The sacral anterior nerve roots were stimulated in a conscious female paraplegic by means of an intradural implanted Finetech/Brindley stimulator activated by inductive radio signals. Changes in vaginal blood flow were monitored by a photoplethysmograph. Stimulating S2 and S3 (but not S4) caused significant increases in vaginal pulse amplitude indicating genital vasodilation and increased blood flow.

Adult

Electrogenic ion secretion in proximal, mid and distal colon from fed and starved mice.

1. Electrogenic ion transport was monitored in vitro as the short-circuit current (Isc in microA/cm2) across proximal, mid and distal colon removed from fed and 48 hr-starved Swiss albino mice (Mus muscaris). 2. Electrogenic secretion was induced either with serosal bethanechol (muscarinic agonist), DMPP (nicotinic agonist) or dibutyryl-cyclic AMP (DbcAMP). Proximal and distal colon from starved mice showed greater electrogenic secretion in response to bethanechol than those the fed controls while DMPP and DbcAMP did not activate the hypersecretion. 3. In the distal colon, starvation induced a large increase in the basal Isc that was unaffected by mucosal amiloride but was inhibited by tetrodotoxin (TTX) and by diphenylamine-2-carboxylic acid (DPC) unlike the fed basal Isc. Bethanechol activated a biphasic response consisting of a transient decrease in the Isc followed by a sustained increase both of which were significantly greater in the starved than the fed tissue and were inhibited by TTX, DPC and atropine but not hexamethonium. 4. Starvation enhances the secretory response to muscarinic activation in proximal and distal colon and induces an increased basal electrogenic (Cl-) secretion in the distal colon stimulated by an augmented neural tone.

Animals

Enterocytes on rat jejunal villi but not in the crypts posses m3 mRNA for the M3 muscarinic receptor localized by in situ hybridization.

Localization of m3 mRNA, for the expression of the M3 muscarinic receptor, along the crypt-villus axis, was undertaken in rat jejunum by in situ hybridization. While enterocytes on the lower two-thirds of the villi showed the presence of m3 mRNA it was absent in the crypt enterocytes. This indicates that the final locus of muscarinically activated jejunal secretion is mediated by the M3 receptor on the enterocytes of the villi and not via the crypt cells.

Animals

Enhanced electrogenic secretion in vitro by small intestine from glucagon-treated rats: implications for the diarrhoea of starvation.

Glucagon treatment of fed rats (50 micrograms I.P. every 6 h for 3 days) induces significant increases in vitro of the basal short-circuit currents of the jejunum (52%) and proximal ileum (81%) and in their electrogenic secretory responses to stimulation by bethanechol, a muscarinic agonist. The results support a role for glucagon in the intestinal hypersecretion observed in starvation and nutrient deprivation.

Animals

Dietary restriction sensitizes the rat distal colon to aldosterone.

1. The effects of starvation and undernutrition were assessed on rat colonic electrogenic Na+ absorption in fed controls, 72 h starved and acute undernourished (fed one-third of the control group's daily food intake for up to 9 days). The basal short-circuit currents (Isc) of three segments of rat colon (proximal, mid- and distal), stripped of their external muscle layers were monitored before and during addition of 0.1 mM-mucosal amiloride. The decrease in Isc was used as the measure of the electrogenic Na+ absorption. 2. Acute undernutrition and to a lesser extent 72 h starvation elevated the basal Isc only in the distal colon. The increase was inhibited by amiloride (0.1 mM, mucosal) indicating that it was due to electrogenic Na+ transport. 3. Allowing the 9 days acute undernourished rats to drink 0.9% NaCl failed to prevent the increase in the basal Isc in the distal colon but it was reduced by administration of spironolactone. 4. Adrenalectomy completely abolished the increased basal Isc in the distal colon induced by the 9 day undernutrition. However, the plasma aldosterone levels in the fed and 9 day undernutrition groups were not significantly different. 5. Injection of aldosterone into adrenalectomized rats drinking 0.9% NaCl and which were undernourished for 9 days induced a large increase in their distal colonic Isc which was inhibited by mucosal amiloride. Similar treatment of sham-operated rats on 0.9% NaCl or adrenalectomized control fed rats on 0.9% NaCl had no effect on the distal colonic Isc. 6. The results indicate that acute undernutrition for 9 days makes the distal colonic epithelium more sensitive to the prevailing plasma aldosterone level allowing an enhanced electrogenic Na+ absorptive capacity to be induced.

Adrenalectomy