Search PubMed⌕ Search

Biomedical subjects

D S Martin

Publications and source records attributed to D S Martin.

At least 91 records · Page 5Linked to original sources

Comparison of DNA fragmentation and color thresholding for objective quantitation of apoptotic cells.

Apoptosis is a process of cell death characterized by distinctive morphological changes and fragmentation of cellular DNA. Using video imaging and color thresholding techniques, we objectively quantitated the number of cultured CD4+ T-lymphoblastoid cells (HUT78 cells, RH9 subclone) displaying morphological signs of apoptosis before and after exposure to gamma-irradiation. The numbers of apoptotic cells measured by objective video imaging techniques were compared to numbers of apoptotic cells measured in the same samples by sensitive apoptotic assays that quantitate DNA fragmentation. DNA fragmentation assays gave consistently higher values compared with the video imaging assays that measured morphological changes associated with apoptosis. These results suggest that substantial DNA fragmentation can precede or occur in the absence of the morphological changes which are associated with apoptosis in gamma-irradiated RH9 cells.

Apoptosis↗

The glycan keratan sulfate in inner ear crystals.

The otoconial matrix (OM) of chicks (Gallus domesticus) inner ear was analyzed. Histochemically the OM was reacted with phosphotungstic acid (PTA) and immunohistochemically with the monoclonal antibody antikeratan sulfate (antiKS). The OM was digested with the enzyme endo-beta-galactosidase (E beta Galase) or separated by 1D and 2D gel electrophoresis. PTA which reacts with glycoproteins precipitated the OM, suggesting that the OM contains glycoproteins. A central core in each crystal had no PTA staining, suggesting that the core lacked glycoproteins. Anti KS antibody stained the OM with increased density in older embryos as determined by color thresholding. E beta Galase, which cleaves the lactosamine repeating units in KS, decreased the immunostain by 30% in the OM and by 20% in the cartilage. The OM from the utricle, saccule and macula lagena contained similar molecular weight bands. Five dense bands in the OM were less dense in tissue and blood controls, suggesting that such bands are enriched in the OM. Isoelectric focusing of the OM showed a negatively charged high molecular weight smear not present in blood and faint in tissue controls. The high affinity of the OM for the cationic PTA stain, the strong immunohistochemical reaction of the OM with anti KS antibody and high molecular weight negative smear in 2D gels taken together suggest that: a) the OM contains large amounts of glycoproteins and glycans, one of which is keratan sulfate, because its immuno stain with antiKS antibody was decreased by the enzyme E beta Galase, b) the utricle, saccule and macula lagena may have similar composition, and c) the concentration of KS may increase gradually until complete mineralization of the OM is reached.

Animals↗

Comparison of a screening coronal CT versus a contiguous coronal CT for the evaluation of patients with presumptive sinusitis.

BACKGROUND: Computed tomography has greatly improved the accuracy of sinus imaging. While contiguous coronal computed tomography scanning of the sinuses provides detailed imaging as compared with plain sinus radiography, this modality is significantly more expensive and involves exposure of the patient to a higher dose of radiation. It has become increasingly common to obtain screening, or non-contiguous, CT scans of the sinuses when screening for the presence of sinusitis. OBJECTIVE: To calculate the sensitivity and specificity of the screening coronal CT scan of the sinuses in screening for inflammatory disease using the contiguous coronal CT examination of the sinuses as the standard. METHODS: From contiguous coronal computed tomograms of the paranasal sinuses, screening coronal computed tomographic examinations were created for 44 patients. Patients were being screened for the presence of sinusitis in the Comprehensive Sinus Clinic at St. Louis University. The two examinations were reviewed independently and in random order by two neuroradiologists. Using the original examinations as the standard, the sensitivity and specificity of the screening studies were calculated for various situations. RESULTS: Overall, a sensitivity of 93.3% and a specificity of 89.3% for the detection of inflammatory disease of the sinuses by the screening examination was observed. CONCLUSIONS: The screening coronal computed tomogram of the paranasal sinuses may be useful in the evaluation of the patient with possible sinusitis.

Costs and Cost Analysis↗

The life history, ultrastructure, and experimental transmission of Hepatozoon catesbianae n. comb., an apicomplexan parasite of the bullfrog, Rana catesbeiana and the mosquito, Culex territans in Algonquin Park, Ontario.

Gametogenesis and sporogonic development of a haemogregarine parasite of bullfrogs (Rana catesbeiana) was observed in cells of the Malpighian tubules of laboratory-reared Culex territans that had fed on naturally infected bullfrogs. Mature oocysts, which varied considerably in size, were multisporocystic with ellipsoidal sporocysts that contained 4 sporozoites. Sporogonic development was completed in about 20 days. Mature meronts were observed in the liver and merozoites in erythrocytes of laboratory-reared bullfrogs that had been fed sporocysts 19 days previously. Similar attempts to infect laboratory-reared green and northern leopard frogs experimentally were unsuccessful, suggesting rather narrow specificity for this parasite in ranids. Gametogenesis and sporogonic stages of this parasite were ultrastructurally similar to those described for Hepatozoon species. The parasite appears to be transmitted directly between bullfrogs and mosquitoes in the study area where Cx. territans feeds avidly on bullfrogs, which in turn were observed to naturally ingest these mosquitoes. Based on data presented in this study and the earlier description by Stebbins in 1903, the haemogregarine parasite of bullfrogs was designated as a new combination, Hepatozoon catesbianae.

Animals↗

Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear.

We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.

Animals↗

MR in neurofibromatosis of the larynx.

We report the MR results of four patients with plexiform neurofibromas of the larynx. Three had irregular margins and were circumferential around the airway. The distinction between regularly and irregularly shaped neurofibromas may have implications for symptom onset.

Biopsy↗

The demise of a phylum of protists: phylogeny of Myxozoa and other parasitic cnidaria.

The notion that members of the phylum Myxozoa Grassé, 1970 do not properly belong in classifications of protists has frequently been suggested because the infective spores of these parasites are not unicellular. Systematists have failed to be decisive about myxozoan phylogenetic affinities, either finding the suggestion of a cnidarian connection to be preposterous or considering the recent suggestion of a relationship with nematodes to be an obvious failure of molecular phylogenetics. Thus, the group has remained in classifications as a protistan phylum in its own right. The ultrastructure of the development of myxozoans was critically re-examined in order to more fully explore the possibility of morphological synapomorphies with metazoan taxa. These morphological characters, in combination with small ribosomal subunit gene sequences, were used in a phylogenetic analysis in order to assess myxozoan origins. The results unequivocally support the inclusion of myxozoans as a clade of highly derived parasitic cnidarians, and as sister taxon to the narcomedusan Polypodium hydriforme. Reassessment of myxozoans as metazoans reveals terminal differentiation, typical metazoan cellular junctions, and collagen production. Their "polar capsules" are redescribed as typical nematocysts bearing atrichous isorhiza. Insofar as taxa cannot be contained within other taxa of equal rank, the phylum Myxozoa is abandoned and it is recommended that the group as a whole be removed from all protistan classifications and placed in a more comprehensive cnidarian system.

Animals↗

Elliptical-P cells in the avian perilymphatic interface of the Tegmentum vasculosum.

Elliptical cells (E-P) are present at the perilymphatic interface lumen (PIL) of the lagena. The E-P cells often separate from the tegmentum vasculosum (TV) and have touching processes that form a monolayer between the K+ rich perilymph and the Na+ rich endolymph, similar to the mammalian Reissner's membrane. We examined the TV of chicks (Gallus domesticus) and quantitated the expression of anti-S100 alphaalphabetabeta and S100 beta. There was a 30% increase of S100 beta saturation in the light cells facing the PIL when compared to other TV light cells. We show that: (1) the dimer anti- S100 alphaalphabetabeta and the monomer anti-S100 beta are expressed preferentially in the light cells and the E-P cells of TV; (2) expression of S100 beta is higher in light cells facing the PIL than in adjacent cells; (3) the expression of the dimer S100 alphaalphabetabeta and monomer S100 beta overlaps in most inner ear cell types, including the cells of the TV, most S100 alphaalphabetabeta positive cells express S 100 beta, but S100 beta positive cells do not always express S100 alphaalphabetabeta; and (4) the S100 beta expression in light cells, the abundant Na+-K+ ATPase on dark cells of the TV, and previously demonstrated co-localization of S100 beta/GABA in sensory cells suggest that S100 beta could have, in the inner ear, a dual neurotrophic-ionic modulating function.

Animals↗

The development of Hepatozoon sipedon sp. nov. (Apicomplexa: Adeleina: Hepatozoidae) in its natural host, the Northern water snake (Nerodia sipedon sipedon), in the culicine vectors Culex pipiens and C. territans, and in an intermediate host, the Northern leopard frog (Rana pipiens).

The life cycle of Hepatozoon sipedon sp. nov. was studied in two snake species, the Northern water snake and the Eastern garter snake, in its mosquito hosts Culex pipiens and C. territans, and in the Northern leopard frog. Gametogenesis, fertilization and sporogony occurred within fat body cells in the haemocoel of mosquitoes that had fed on infected water snakes. Mature oocysts averaging 263 microns in diameter and containing more than 500 sporocysts were observed in mosquitoes 28 days post-feeding. Each sporocyst enclosed eight sporozoites. Dizoic cysts were found in the liver of frogs that had been fed infected mosquitoes seven days previously. Two rounds of merogony in various internal organs and intraerythrocytic gamonts were observed in snakes that had been fed frogs which had been orally inoculated with infected mosquitoes. Developmental stages were not seen in snakes that were fed infected mosquitoes directly. A comparison of this life cycle with those described for other Hepatozoon species infecting snakes is presented with reference to the different modes of transmission featured by these parasites.

Animals↗

Non-Hodgkin's lymphomas of the nose and paranasal sinuses in the pediatric population.

Paranasal and nasal neoplasms often elude early diagnosis in the pediatric population. This report examines 3 cases of nasal and paranasal sinus lymphomas out of 29 lymphomas and lymphoproliferative disorders seen from 1983 to 1990. Diagnostic delays are common. The development of orbital signs and symptoms often leads to diagnosis. Computed tomography and magnetic resonance imaging are important in delineating the extent of disease and allow appropriate staging. Transnasal biopsy yields the definitive diagnosis, with low associated morbidity. Aggressive chemotherapy and irradiation prolongs survival; with this regimen all of our patients have remained alive, although 1 has residual disease. B-cell lymphomas are more common than T-cell varieties in children. One patient demonstrated B-cell immunodeficiency and preleukemia prior to developing primary paranasal sinus non-Hodgkin's lymphoma; this case reiterates the systemic nature of lymphoma, Key differences between children and adults in the manifestations of nasal and sinus lymphomas are emphasized.

Child, Preschool↗

Biochemical modulation of tumor cell energy in vivo: II. A lower dose of adriamycin is required and a greater antitumor activity is induced when cellular energy is depressed.

A quadruple drug combination--consisting of a triple-drug combination of N-(phosphonacetyl)-L-aspartate (PALA) + 6-methylmercaptopurine riboside (MMPR) + 6-amino-nicotinamide (6-AN), designed to primarily deplete cellular energy in tumor cells, + Adriamycin (Adria)--yielded significantly enhanced anticancer activity (i.e., tumor regressions) over that produced by either Adria alone at maximum tolerated dose (MTD) or by the triple-drug combination, against large, spontaneous, autochthonous murine breast tumors. The adenosine triphosphate (ATP)-depleting triple-drug combination administered prior to Adria resulted in a 100% tumor regression rate (12% complete regression; 88% partial regression) of spontaneous tumors. Histological examination of treated tumors demonstrated that the treatment-induced mechanism of cancer cell death was by apoptosis. The augmented therapeutic results (100% tumor regressions) were obtained with approximately one-half the MTD of Adria as a single agent and suggest the potential clinical benefit of longer, more effective, and safer treatment by low doses of Adria when combined with the triple-drug combination. Two likely mechanisms of action are discussed: (1) prevention of DNA repair; (2) complementary disruption of biochemical pathways by both the triple-drug combination and the biochemical cascade of apoptosis that is induced by a DNA-damaging anticancer agents such as Adria.

6-Aminonicotinamide↗

Potentiation of a three drug chemotherapy regimen by radiation.

The combination of N-(phosphonacetyl)-L-aspartate, 6-methylmercaptopurine, and 6-aminonicotinamide has been shown to be an effective antineoplastic regimen and also to enhance the effects of other chemotherapeutic agents. The mechanism of action of this combination of drugs is not known definitively, but one possible mechanism is biochemical modulation of energy metabolism and inhibition of production of tumor ATP. Tumor-bearing mice were treated with N-(phosphonacetyl)-L-aspartate, followed 17 h later by 6-methylmercaptopurine and 6-aminonicotinamide. 31P nuclear magnetic resonance spectroscopic studies demonstrated a significant depletion of high energy phosphates at 10 h post-6-methylmercaptopurine and 6-aminonicotinamide. The addition of radiation at this time was shown to induce a significantly longer tumor growth delay and a greater number of regressions (including durable complete regressions) than either chemotherapy or radiation alone. The combination of chemotherapy and radiation was found to be supra-additive compared to the antineoplastic effects of either modality administered separately, without a measurable increase in host toxicity.

6-Aminonicotinamide↗

Stimulation of the hypothalamic paraventricular nucleus causes systemic venoconstriction.

Venous capacitance plays an important role in cardiovascular homeostasis. The anatomical loci within the central nervous system involved in modulating venous function remain to be elucidated. Stimulation of the hypothalamic paraventricular nucleus is known to increase sympathoadrenal outflow and arterial blood pressure. The present study was undertaken to determine whether electrical stimulation of the paraventricular nucleus can also affect the venous circulation. Mean circulatory filling pressure (MCFP) was used as an index of venous tone. Male Long Evans rats were initially anesthetized with pentobarbital (i.p.; 60 mg/kg) and subsequently maintained with urethane (i.v.; 600 mg/kg). Blood pressure and systemic venous pressure were monitored via catheters in the femoral artery and vein and heart rate was derived from the pulsatile blood pressure signal. A latex tipped balloon was placed in the right atrium via the right jugular vein. Mean circulatory filling pressure was calculated from the arterial and venous plateau pressures recorded during five second balloon inflations. Arterial pressure, systemic venous pressure, heart rate and mean circulatory filling pressure were monitored before and during unilateral monopolar electrical stimulation (0.5 ms pulses at 50 Hz for a train duration of 10 s with constant current intensities of 100, 150, 200, and 300 microA) of the paraventricular nucleus. Increased graded stimulation of the paraventricular nucleus increased blood pressure by 6 +/- 2, 8 +/- 1, 13 +/- 2 and 26 +/- 5 mm Hg while heart rate changed by -22 +/- 6, -18 +/- 6 and -15 +/- 9 bpm and +10 +/- 10 bpm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enhancement of thymidylate synthase inhibition.

Molecular modeling techniques and a knowledge of thymidylate synthase protein structure have assisted in the development of several potent new inhibitors of thymidylate synthase, the enzyme mediating de novo formation of thymidylate for use in DNA synthesis. Information on several new and specific thymidylate synthase inhibitors, including ICI-D1694, 1843U89, AG-331, and AG-337, is presented. The effects of thymidylate synthase inhibition on the induction of thymidylate synthase protein synthesis have raised the question of whether thymidylate synthase inhibition alone will be sufficient to provide a desirable clinical effect. Formation of a thymidylate synthase-inhibitor complex prevents posttranscriptional regulation of thymidylate synthase synthesis, allowing for increased thymidylate synthase synthesis and the possibility of drug resistance. Therefore, recent efforts have also focused on characterizing this increase in thymidylate synthase protein induced by inhibitors of thymidylate synthase and on devising combination drug strategies that may prevent the induction of thymidylate synthase protein synthesis in addition to inhibiting thymidylate synthase activity.

Animals↗

Hemodynamic responses to paraventricular nucleus disinhibition with bicuculline in conscious rats.

The present study was undertaken to determine the hemodynamic responses associated with stimulation of the hypothalamic paraventricular nucleus (PVN). Male Sprague-Dawley rats (n = 21) were instrumented with guide cannulas directed bilaterally at the PVN, with an electromagnetic flow probe placed on the ascending aorta and with femoral venous and arterial catheters. Bicuculline methiodide (BMI, 2 mM) was infused bilaterally (100 nl/20 min) into the PVN region before and after treatment with the beta 1-adrenergic antagonist, metoprolol bitartrate (2 mg/kg iv) or the alpha 1-adrenergic receptor antagonist, prazosin hydrochloride (2 mg/kg iv). Infusion of BMI into the PVN increased mean arterial pressure by 17 +/- 2 mmHg, and heart rate rose by 91 +/- 8 beats/min. Cardiac index increased 17 +/- 3%, whereas total peripheral resistance index was not altered significantly. After metoprolol treatment, the mean arterial pressure response to BMI was similar to control (16 +/- 2 mmHg), but the tachycardia was reduced significantly (10 +/- 4 beats/min). In addition, the blood flow response was changed qualitatively. Total peripheral resistance increased 13 +/- 3%, whereas the cardiac index response was abolished (1 +/- 2%). After prazosin treatment, BMI administration into the PVN failed to increase arterial pressure (-1 +/- 4 mmHg). Nevertheless, the BMI infusion was associated with significant hemodynamic effects. Total peripheral resistance index decreased (-24 +/- 6%), whereas cardiac index and stroke volume index increased 34 +/- 8 and 17 +/- 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗