Search PubMed⌕ Search

Biomedical subjects

R J Levin

Publications and source records attributed to R J Levin.

At least 37 records · Page 2Linked to original sources

Sex and the human female reproductive tract--what really happens during and after coitus.

The scientific study of the interaction of human genitals during coitus and after ejaculation with and without female orgasm has always been difficult and controversial with ethical, technical and social problems. The present brief review examines critically the results from these studies. Early observations utilised changes induced in sexually self-aroused subjects or by coitus with artificial (transparent) penes with few objective measurements. These culminated in the synthesis of the useful unitary descriptive, EPOR (excitation, plateau, orgasm, resolution)-model by Masters and Johnson (1966). Later investigations by other workers developed or employed instrumentation to record objectively the changes induced in the motility and pressures of genital muscles, in genital blood flow, in the ion and fluid movements creating the neurogenic transudate of vaginal lubrication, in its pH and pO2 and in the disposition of the ordered spurting ejaculate with subsequent sperm transport. More recently, studies have begun to use endoscopy and ultrasound imaging to picture what really happens especially during penile thrusting. While the newer techniques have often confirmed selected features of the original EPOR model they have also shown that the characterisation of the coital changes just by a unitary model is inappropriate. New observations suggest a plurality in the changes that can occur. Coital mechanisms are dynamic and our investigations and descriptions of them should match their dynamism. The knowledge gained will be more than helpful in the treatment of infertility, genital dysfunctions and disease transmission.

Cervix Uteri↗

Relationship between National Institutes of Health research awards to US medical schools and managed care market penetration.

CONTEXT: Medical research conducted in academic medical centers is often dependent on support from clinical revenues generated in these institutions. Anecdotal evidence suggests that managed care has the potential to affect research conducted in academic medical centers by challenging these clinical revenues. OBJECTIVE: To examine whether empirical evidence supports a relationship between managed care and the ability of US medical schools to sustain biomedical research. DESIGN: Data on annual extramural research grants awarded to US medical schools by the National Institutes of Health (NIH) from fiscal years 1986 to 1995 were obtained, and each medical school was matched to a market for which information about health maintenance organization (HMO) penetration in 1995 was available. MAIN OUTCOME MEASURES: Growth in total NIH awards, traditional research project (R01) awards, R01 awards to clinical and basic science departments, and changes in institutional ranking by NIH awards were compared among schools located in markets with low, medium, and high managed care penetration. RESULTS: Medical schools in all markets had comparable rates of growth in NIH awards from 1986 to 1990. Thereafter, medical schools in markets with high managed care penetration had slower growth in the dollar amounts and numbers of NIH awards compared with schools in markets with low or medium managed care penetration. This slower growth for schools in high managed care markets was associated with loss of share of NIH awards, equal to $98 million in 1995, and lower institutional ranking by NIH awards. Much of this revenue loss can be explained by the slower growth of R01 awards to clinical departments in medical schools in high managed care markets. CONCLUSIONS: These findings provide evidence of an inverse relationship between growth in NIH awards during the past decade and managed care penetration among US medical schools. Whether this association is causal remains to be determined.

Academic Medical Centers↗

An immortalized cell culture from a malignant mixed tumor of the lacrimal gland.

Tumor cells from a malignant mixed tumor of the lacrimal gland were maintained in tissue culture for more than 55 generations. Comparative immunohistochemical analysis was performed on whole tumor sections and on the tumor cell culture to define the origin of the cells in culture. The cultured cells expressed cytokeratin, smooth-muscle actin, S-100 protein, and vimentin and were negative for glial fibrillary acidic protein. Tumor sections expressed cytokeratin but were negative for muscle-specific actin, vimentin, and glial fibrillary acidic protein. Through tissue culture studies of salivary gland epithelial neoplasias, which are very similar to lacrimal gland epithelial neoplasias, pluripotential stem cells have been identified. Similar tissue culture analysis of lacrimal gland epithelial neoplasms can be a valuable tool for studying the origin of these uncommon tumors.

Antigens, Neoplasm↗

Expression of the opioid growth factor, [Met5]-enkephalin, and the zeta opioid receptor in head and neck squamous cell carcinoma.

Despite the prevalence of cancers of the head and neck, survival rates have not changed in the past few decades. Recent work has implicated peptide growth factors and their receptors in the genesis and progression of head and neck squamous cell carcinoma. Opioid growth factor (OGF, [Met5]-enkephalin) is a tonically active, autocrine and/or paracrine produced, inhibitory factor that influences the growth of normal and abnormal cells and tissues. This peptide interacts with the zeta (zeta) opioid receptor to modulate cellular proliferation, migration, and survival. Both OGF and the zeta receptor are present in mammalian tongue epithelium and skin, and modulate DNA synthesis. In the present study we examined the presence and distribution of OGF and the zeta opioid receptor in the head and neck squamous cell carcinomas from seven individuals. All specimens expressed this growth factor and its receptor regardless of tumor stage, location, and histologic grade. Immunoreactivity for both OGF and the zeta receptor were associated with the cytoplasm but not the nucleus in cells of each of these carcinomas. Our findings that a potent negative growth regulator and its receptor are present in head and neck squamous cell carcinoma lead us to suggest that OGF may modulate the growth of these types of cancers.

Aged↗

Actions of spermicidal and virucidal agents on electrogenic ion transfer across human vaginal epithelium in vitro.

Human ectocervical tissue was removed at operation over the menstrual cycle mounted as a sheet in vitro in an Ussing-style chamber and incubated in bicarbonate saline. The net electrogenic ion transport was measured as the short-circuit current (Isc in muamps/cm2) and was characterised as mainly (60-86%) an amiloride-sensitive electrogenic Na+ transport (lumen to serosa). Serosal application of amiloride had no effect. Serosal application of ouabain, a selective Na(+)-pump inhibitor, reduced the Isc to near zero but neither theophylline (10 mM) nor furosemide (1 mM) had any action. The data are compatible with a model ectocervical vaginal cell having an amiloride-sensitive Na+ entry mechanism at the lumenal membrane and a Na(+)-pump at the basolateral membrane removing the ion from the cell. The effects of the putative virucides, chlorhexidine and benzalkonium chloride, were tested on the preparation. Mucosally added chlorhexidine (2 mg/ml) had no effect on the Isc or tissue resistance but benzalkonium chloride, at concentrations between 0.06-1.2%, caused a rapid fall in the Isc. At the highest concentration this was only partly reversible even after two washes with fresh buffer. At the lowest concentration (0.03%) benzalkonium chloride sometimes caused an initial increase in the Isc which then fell to zero. In all the tissues even after the Isc was reduced to near zero, nigrosin left in contact with the tissue for 5 min. did not enter and stain the cells, indicating the detergent had a selective membrane action rather than causing a non-specific increase in permeability. The preparation allows objective measurements to be made of the initial acute membrane actions of putative spermicides and virucides on human vaginal ectocervical epithelial cells and offers a new approach of assessing their pharmacological/toxicological actions.

Adult↗

Cholinergic modulation of electrogenic ion transport in different regions of the rat small intestine.

Acetylcholine acting via muscarinic receptors located in the intestinal mucosa controls ion and fluid transport. This study examined the pathway(s) by which cholinergic receptors mediate secretion in rat isolated duodenum, jejunum and ileum using the short-circuit current (Isc) as an index of electrogenic CL- secretion. Carbachol and bethanechol induced electrogenic CL- transport which was insensitive to the neural blocker tetrodotoxin, indicating their direct action on the enterocytes. Functional characterization of electrogenic secretion activated via muscarinic receptors on jejunal and ileal enterocytes was achieved by use of selective muscarinic antagonists in the presence of tetrodotoxin. In both regions the rank order of potency of these compounds (atropine > 4-diphenylacetoxy-N-piperidine methiodide (4-DAMP) > hexahydro-sila-difenidol (HHSiD) > pirenzepine > methoctramine) indicated the M3 receptor subtype. Secretion activated by the muscarinic agonist 4-[[(3-chlorophenyl)amino]carbonyl]-N,N, N-trimethyl-2-butyn-1-ammonium chloride (McN-A-343) was sensitive to tetrodotoxin and pirenzepine but not to the ganglionic blocker, hexamethonium, indicating the M1 receptor subtype on post ganglionic neurons. Regional differences for bethanechol-activated secretion showed an increasing gradient in secretory capacity (Isc max) in a proximal-to-distal direction along the small intestine. Responses to McN-A-343 also showed regional differences but these were unlike those of bethanechol. These results show that cholinomimetic-induced electrogenic CL- secretion in rat isolated small intestine appears to be mediated by two dissimilar populations of muscarinic receptor: M3 muscarinic receptors positioned on enterocytes and M1 muscarinic receptors sited on submucosal neurons.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

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↗

The volume and mix of inpatient services provided by academic medical centers.

This is the first in a series of AAMC Papers that analyze the clinical spectrum of patients treated in the nation's teaching hospitals. As stated in the separate Introduction, "The Transformation of Data into Knowledge," subsequent papers will examine trends in the provision of care to the indigent and make comparisons of quality of care among teaching and non-teaching hospitals. These analyses, carried out by the AAMC's Center for the Assessment and Management of Change in Academic Medicine (CAMCAM), are made possible by a reorganization of the AAMC's information infrastructure, in which many formerly separate databases have been linked. The Introduction concludes with a description of specific AAMC-CAMCAM initiatives that are being planned. This initial analysis examines the volume and mix of clinical services provided by AMCs, examines trends in these services over time, and compares services provided at different AMCs, in different markets, and between AMCs and non-teaching hospitals. Data from a variety of sources were used in these secondary analyses. The American Hospital Association's Annual Survey of Hospitals database was used to analyze volumes of inpatient services provided in AMCs and other hospitals. The AAMC's Clinical-Administrative Data Service database was used to analyze the volume and mix of clinical services provided in individual AMCs. The Agency for Health Care Policy and Research's Nationwide Inpatient Sample was used to compare the mix of clinical services provided in AMCs and other hospitals. Volumes of inpatient services in AMCs changed little between 1991 and 1994 and totaled six million hospitalizations, 41 million inpatient days, and two million inpatient surgeries in 1994. The mix of inpatient services in AMCs also showed little variation over time among individual AMCs, in markets with both high and low managed care penetrations, between public and private AMCs, or between AMCs and non-teaching hospitals, with the ten most frequent diagnoses accounting for significant proportions of total services. In contrast, several specialized services were much more likely to be offered and provided by AMCs. Despite rapid change in the health care environment, the volume and mix of clinical services provided by AMCs have been relatively stable. Implications for hospital planners, service chiefs and administrators, medical educators, clinical investigators, and health policymakers are discussed.

Academic Medical Centers↗

Academic medical centers and the care of underserved populations.

As the number of Americans at risk of being underserved continues to rise, a better understanding of safety-net providers of health care is needed to help ensure continuing care for the underserved. In this article, the authors have begun the process of defining the role of academic medical centers (AMCs) as a group in the care of those persons most at risk of being underserved--the medically indigent and members of minority and poor populations--by quantifying the amount of inpatient care that AMCs provide to these individuals. The study went beyond previous work by using nationally representative sources of data (from 1989 to 1994) and by examining more than one underserved population rather than only the medically indigent. The study focused on AMCs and other hospitals in urban areas and excluded hospitals in rural areas. The detailed findings confirm previous observations that urban AMCs of all types provide a large and disproportionate share of care for the medically indigent and the underserved members of minority and poor populations and that members of these populations constituted the majority of patients cared for in many AMCs in recent years. The findings show that the proportion of patients from underserved groups admitted to all urban hospitals is rising and that this growth is faster among AMCs than other hospitals. The authors comment that AMCs, because of their prominent and historical role in caring for the underserved, have the opportunity to lead efforts to continue such service through innovative approaches to health care and the prevention of illness. Whether AMCs can seize this opportunity when confronted by price competition and government policies that reduce AMCs' capacity to care for the underserved remains to be seen.

Academic Medical Centers↗

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↗