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Biomedical subjects

D Ma

Publications and source records attributed to D Ma.

At least 163 records · Page 9Linked to original sources
PubMed1998

The effect of sevoflurane on spontaneous sympathetic activity, A delta and C somatosympathetic reflexes, and associated hemodynamic changes in dogs.

UNLABELLED: This study examined the effect of sevoflurane on spontaneous renal sympathetic nerve activity (RSNA), A delta- and C-fiber-mediated somatosympathetic reflexes, and hemodynamic changes in anesthetized dogs. RSNA, and A delta and C reflexes evoked by electrical stimulation of the radial nerve were observed in multifiber recordings of efferent activity in renal sympathetic nerves. Sevoflurane was administered at 1%, 2%, 3%, and 4% end-tidal concentrations for periods of 20 min. The mean A delta reflexes decreased by 20%, 39%, and 54% (P < 0.05 to < 0.01), and the C reflexes decreased by 38%, 62%, and 74% (P < 0.05 to < 0.01) at concentrations of 2%, 3%, and 4%, respectively. The relatively greater effect on C reflexes was significant (P < 0.05) and comparable with the effect of mu-opioids. There was no change in mean RSNA, heart rate (HR), and cardiac output (CO) up to 3% sevoflurane, but these decreased by 36%, 24%, and 13% (P < 0.05), respectively, at 4% sevoflurane. Sevoflurane 1%-4% caused a virtually linear reduction in systemic vascular resistance (SVR) from 7% (P < 0.05) to 44% (P < 0.05), together with a reduction in mean arterial pressure (MAP) that was significant for concentrations greater than 2%. The results indicate that sevoflurane causes a greater depression of C compared with A delta reflexes, and that the reduction in MAP was entirely due to a decrease in SVR up to 3%, whereas at 4% sevoflurane, reductions in sympathetic activity, HR, and CO also contributed its depressor effect. IMPLICATIONS: The relatively greater depressant effect of sevoflurane on C compared with A delta nociceptive somatosympathetic reflexes is similar to mu-opioids. The hypotensive effect of sevoflurane was significant at 2% concentration, whereas heart rate, cardiac output and sympathetic activity were reduced only at concentrations greater than 3%.

Anesthetics, Inhalation↗
PubMed1998

Role of epidermal growth factor receptor in the metastasis of intraocular melanomas.

PURPOSE: To explore the expression and function of epidermal growth factor receptor (EGFR) expression on human uveal melanoma cells. METHODS: Five human uveal melanoma cell lines were examined by flow cytometry for the expression of EGFR. The correlation between EGFR expression and metastasis of uveal melanoma cells was tested in a nude mouse model of intraocular melanoma. The effect of EGFR on liver homing of blood-borne uveal melanoma cells was tested by tracing the fate of radiolabeled cells treated with anti-EGFR monoclonal antibody. The capacity of EGFR to inhibit the cytotoxic effects of tumor necrosis factor-alpha (TNF-alpha) was determined in vitro. The role of EGFR in promoting metastatic disease was studied by infusing intraocular melanoma-bearing mice using a neutralizing antibody against EGFR. RESULTS: EGFR was expressed to varying degrees on all eight human uveal melanoma cell lines. Expression of EGFR correlated with metastatic potential and capacity of blood-borne uveal melanoma cells to localize in the liver. EGFR rendered uveal melanoma cells resistant to the cytolytic effects of TNF-alpha. Blocking EGFR with a neutralizing monoclonal antibody increased the susceptibility of uveal melanoma cells to TNF-mediated cytolysis, inhibited metastases, and prolonged host survival. CONCLUSIONS: The expression of EGFR on five human uveal melanoma cell lines is correlated with an increased capacity to localize in the liver, an increased resistance to TNF-mediated lysis, and decreased survival. Targeting EGFR expression and function may be a fruitful strategy for managing patients with uveal melanoma.

Animals↗
PubMed1998

Synergism between sevoflurane and intravenous fentanyl on A delta and C somatosympathetic reflexes in dogs.

UNLABELLED: In this study, we defined the nature of the interactions between sevoflurane and fentanyl on spontaneous and reflex-evoked sympathetic activity, resting heart rate (HR), and mean arterial pressure (MAP). Spontaneous renal sympathetic nerve activity (RSNA) and A delta- and C-fiber-mediated somatosympathetic reflexes, evoked by electrical stimulation of radial nerves, and HR and MAP were recorded in anesthetized dogs. In one group, the effects of incremental doses of 2-64 micrograms/kg fentanyl i.v. were observed. It had a greater inhibitory effect on C than on A delta reflexes, which were abolished by mean cumulative doses of 64 micrograms/kg and approximately 128 micrograms/kg, respectively. Although 1.5% sevoflurane reduced C reflexes by 28% and A delta reflexes by only 12%, it reduced the total doses of fentanyl required for their abolition to 32 micrograms/kg and 64 micrograms/kg, respectively. Mean RSNA, HR, and MAP values were reduced by 46%, 54%, and 30%, respectively, by fentanyl alone and by 23%, 11%, and 17%, respectively, in response to 1.5% sevoflurane. The combination of fentanyl and sevoflurane caused reductions of 44%, 54%, and 41%, respectively, which indicates a less than additive effect. These results indicate that sevoflurane interacts synergistically with fentanyl to depress A delta and C somatosympathetic reflexes, whereas for RSNA, HR, and MAP, their effects were less than the additive. IMPLICATIONS: Although fentanyl caused a greater depression of C than of A delta reflexes to the point of abolition, the maximal depression of spontaneous sympathetic activity, heart rate, and arterial pressure occurred at smaller doses. The combined depressant effects of sevoflurane and fentanyl were synergistic on somatosympathetic reflexes but were less than additive on spontaneous sympathetic activity, heart rate, and arterial pressure.

Analgesics, Opioid↗
PubMed1998

Conditions affecting enhanced corneal allograft survival by oral immunization.

PURPOSE: To determine the optimal conditions for enhancing corneal allograft survival by oral immunization with donor-specific alloantigens. METHODS: CB6F1 mice were orally immunized with various doses of C3H/Hej corneal epithelial and endothelial cells before receiving orthotopic C3H/Hej corneal allografts. Paraformaldehyde-fixed corneal cells were compared with viable corneal cells for their capacity to promote corneal allograft survival. The mucosal adjuvant, cholera toxin B (CTB), was examined for its capacity to enhance corneal graft survival when given separately or conjugated to corneal cells used for oral immunization. Oral immunization was also evaluated for its capacity to prevent immunologic rejection in three high-risk settings: preimmunized hosts, hosts with prevascularized graft beds, and grafts that contain donor-specific Langerhans' cells. RESULTS: Optimal graft survival occurred when 2 x 10(6) corneal cells were administered orally 10 days before orthotopic corneal transplantation. Paraformaldehyde-fixed corneal cells were as effective as viable cells in preventing corneal graft rejection. Cholera toxin B enhanced the efficacy of oral immunization when conjugated with the orally administered corneal cells but was ineffectual when administered separately. Oral immunization with donor corneal cells enhanced corneal graft survival in all three high-risk settings. CONCLUSIONS: Oral immunization with donor cells is an effective strategy for enhancing corneal graft survival and preventing graft rejection in high-risk settings. Graft enhancement is optimized when the orally administered cells are conjugated with CTB and administered before corneal transplantation. Because fixed cells retain their capacity to enhance corneal graft survival, it may be possible to store donor cells for long-term use in high-risk hosts.

Administration, Oral↗
PubMed1998

Extensive phosphorylation and axonal transport of triton-soluble neurofilament subunits.

The low abundance of soluble neurofilament (NF) subunits in mature axons has suggested that newly synthesized NF proteins rapidly assemble into highly stable polymers and associate with the Triton X-100-insoluble cytoskeleton. Here we present evidence for multiple populations of NFs and NF subunits, distinguished by differential solubility in Triton, within perikarya and axons of neurons in situ and in culture. We further demonstrate, using microinjection of "tagged" NF subunits and by pulse-chase radiolabeling of endogenous NF subunits, that these soluble NF populations represent precursors for incorporation into the axonal cytoskeleton.

Animals↗
PubMed1997

Inhibition of metastasis of intraocular melanomas by adenovirus-mediated gene transfer of plasminogen activator inhibitor type 1 (PAI-1) in an athymic mouse model.

Uveal melanoma is the most common intraocular malignancy in adults and results in the death of 50% of the patients. Plasminogen activators (PA) are believed to facilitate tumor metastasis by promoting invasion of tissue barriers. The present study explored the possibility of preventing the metastasis of intraocular melanomas by disrupting plasminogen activator function through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of plasminogen activator inhibitor type 1 (PAI-1) cDNA. Intraocular injection of an adenovirus vector (AdCMV-PAI-1) expressing plasminogen activator inhibitor-1 resulted in: (1) the transduction of more than 95% of human and murine uveal melanoma cells in the eyes of nude mice; (2) a 50% reduction in the number of animals developing liver metastases; and (3) a 78% reduction in the metastatic tumor burden in animals that eventually developed metastases. In other experiments intravenous injections of AdCMV-PAI-1 resulted in transduction of normal liver cells and culminated in a sharp reduction in the incidence of metastases and a significant prolongation of host survival. The results support the feasibility of disruption of PA function through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival.

Adenoviruses, Human↗
PubMed1997

Differential regulation of microtubule-associated protein 1B (MAP1B) in rat CNS and PNS during development.

MAP1B is a major cytoskeletal protein in growing axons and is strongly regulated during brain development. The present studies compare the expression of MAP1B mRNA, the protein, and its phosphorylated isoform in spinal cord and dorsal root ganglia (DRGs) with brain. In spinal cord and brain, MAP1B mRNA levels were highest in early stages of development, decreased several fold during postnatal development, and remained low in adults. In contrast, there were no significant changes of MAP1B mRNA levels during development of DRG and they remained high in adults. The levels of MAP1B protein decreased in brain and spinal cord in parallel with the changes of their mRNA. The protein levels in DRG remained relatively high but declined in the sciatic nerve. Phosphorylated MAP1B was expressed in high levels during the early stages of development in brain, spinal cord, and sciatic nerve and decreased rapidly to undetectable levels postnatally except for sciatic nerve where it remained detectable. Immunohistochemical analysis showed that phosphorylated MAP1B was absent from DRG cell bodies at all stages but was present in axons of DRG and motor neurons in both spinal cord and sciatic nerve. Immunostaining also confirmed Western blot analysis indicating that MAP1B was initially abundant within the spinal cord but was at later stages present only in motor neurons and the central processes of DRG neurons. These results reflect differential distribution of MAP1B isoforms at different stages of development and in different regions of the nervous system.

Animals↗
PubMed1997

Modeling, chemistry, and biology of the benzolactam analogues of indolactam V (ILV). 2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKCdelta and discovery of an ILV analogue of improved isozyme selectivity.

Protein kinase C (PKC) is a complex enzyme system comprised of at least 11 isozymes that serves to mediate numerous extracellular signals which generate lipid second messengers. The discovery of isozyme-selective activators and inhibitors (modulators) of PKC is crucial to ascertaining the role of the individual isozymes in physiological and pathophysiological processes and to manipulating their function. The discovery of such small molecule modulators of PKC is at present a largely unmet pharmacological need. Herein we detail our modeling studies which reveal how the natural product indolactam V (ILV) and its 8-membered ring analogue, the benzolactam 15, bind to the CRD2 activator domain of PKC. These modeling studies reveal that not all PKC ligands possess a common pharmacophore, and further suggest an important role of specific hydrophobic contacts in the PKC-ligand interaction. The modeling studies find strong experimental support from mutagenesis studies on PKC alpha that reveal the crucial role played by the residues proline 11, leucine 20, leucine 24, and glycine 27. Next, we describe the synthesis of two 8-substituted benzolactams starting from L-phenylalanine and characterize their isozyme selectivity; one of the two benzolactams exhibits improved isozyme selectivity relative to the n-octyl-ILV. Lastly, we report inhibition of cellular proliferation of two different breast carcinoma cell lines by the benzolactam 5 and show that the compound preferentially down-regulates PKCbeta in both cell lines.

Antineoplastic Agents↗
PubMed1997

Oxidation of 4-methoxymandelic acid by lignin peroxidase. Mediation by veratryl alcohol.

The mechanism of veratryl alcohol-mediated oxidation of 4-methoxymandelic acid by lignin peroxidase was studied by kinetic methods. For monomethoxylated substrates not directly oxidized by lignin peroxidase, veratryl alcohol has been proposed to act as a redox mediator. Our previous study showed that stimulation of anisyl alcohol oxidation by veratryl alcohol was not due to mediation but rather due to the requirement of veratryl alcohol to complete the catalytic cycle. Anisyl alcohol can react with compound I but not with compound II. In contrast, veratryl alcohol readily reduces compound II. We demonstrate in the present report that the oxidation of 4-methoxy mandelic acid is mediated by veratryl alcohol. Increasing veratryl alcohol concentration in the presence of 2 mM 4-methoxymandelic acid resulted in increased oxidation of 4-methoxymandelic acid yielding anisaldehyde. This is in contrast to results obtained with anisyl alcohol where increased concentrations of veratryl alcohol caused a decrease in product formation. ESR spectroscopy demonstrated that 4-methoxymandelic acid caused a decrease in the enzyme-bound veratryl alcohol cation radical signal, which is consistent with its reaction at the active site of the enzyme.

Benzyl Alcohols↗
PubMed1997

Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic family of putative nucleotide-sugar transporters.

The synthesis of glycoconjugates within the secretory pathway of eukaryotes requires the provision of lumenal nucleotide-sugar substrates. This is particularly important for eukaryotic microbes such as Leishmania because they must synthesize considerable amounts of extracellular and cell surface glycoconjugates that play significant roles in the infectious cycle. Here we used properly oriented sealed microsomes to characterize lumenal uptake of GDP-Man in Leishmania donovani. In this system, GDP-Man uptake was saturable with an apparent Km for GDP-Man of 0.3 microM and facilitated its use as a donor substrate for lipophosphoglycan (LPG) synthesis. A lpg2(-) deletion mutant showed loss of GDP-Man but not UDP-Gal uptake, which was restored by introduction of the gene LPG2. Immunoelectron microscopy localized an active, epitope-tagged LPG2 protein to the Golgi apparatus. Thus, LPG2 is required for nucleotide-sugar transport activity and probably encodes this Golgi transporter. LPG2 belongs to a large family of eukaryotic genes that potentially encode transporters with different substrate specificities and/or cellular locations. In the future, the amenability of the Leishmania system to biochemical and genetic manipulation will assist in functional characterization of nucleotide-sugar transports from this and other eukaryotes. Furthermore, since LPG2 plays an important role in the Leishmania infectious cycle and mammalian cells lack a Golgi GDP-Man transporter, this activity may offer a new target for chemotherapy.

Amino Acid Sequence↗
PubMed1997

A new nutritional assessment in patients with oral and maxillofacial malignancies.

Combined subjective and objective nutritional assessment was performed on admission in 127 patients with oral and maxillofacial malignancies. On the basis of the nutritional assessment result, three typical nutritional parameters-body weight (BW) (X1), mid-upper-arm circumference (MAC) (X2), and hand grip strength (HGS) (X3) were used to establish a new nutritional assessment method that was developed by a computer-based discriminant analysis. The established model was as follows: Y1 = -126 + 1.09X1 + 1.34X2 + 0.23X3; Y2 = -95.63 + 0.96X1 + 1.17X2 + 0.19X3. In the model Y1 was regarded as good nutrition and Y2 as malnutrition. The larger value of Y stood for the patient's nutritional status (i.e. Y1 > Y2, well nourished; Y1 < Y2 malnourished). The new nutritional assessment correlates well with the combined subjective and objective nutritional assessment with a total agreement rate of 88.2%. With its simplicity and accuracy, the new nutritional assessment deserves a wide application in clinical situation.

Adult↗
PubMed1997

Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands.

Ninety-one cases of adenoid cystic carcinoma (ACC) of the salivary glands with more than ten years' follow up were studied to investigate factors influencing the survival rate of patients, which vary according to site, histological type, clinical stage and nature of therapy. The data were statistically analysed for survival curves. Log rank tests were employed to assess the statistical significance of various groups. As a result, it may be concluded that tumour site, clinical stage and histological type are the important factors influencing the prognosis. ACC of the palate and parotid, early clinical stage, glandular/tubular histological type, and tumour without nerve involvement had the best prognosis. ACC in the submandibular gland, maxillary antrum and tongue, advanced clinical stage (stage III and IV), solid histological type, and tumour with nerve involvement had a poor prognosis.

Adult↗
PubMed1997

Tau-like proteins in the nervous system of goldfish.

This report describes the presence of a group of tau-like proteins (TLPs) in goldfish central nervous system. The TLPs were immunoreactive with antibodies that recognized the carboxy-terminal domain of mammalian tau, but not with antibodies that recognized the amino-terminus. The TLPs of goldfish exhibited the basic properties of tau proteins including neuronal specificity, structural heterogeneity, heat stability and the ability to co-assemble with tubulin. We propose that TLPs may represent a precursor of tau, that share the microtubule binding domain and the carboxy-terminal domain with mammalian tau proteins. In contrast the amino-terminus of the TLPs is much shorter and may represent a more variable domain of tau proteins.

Animals↗
PubMed1997

Mobilization of predominantly Philadelphia chromosome-negative blood progenitors using cyclophosphamide and rHUG-CSF in early chronic-phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control.

Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m2 and rHUG-CSF 150 microg/m2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 x 10(6)/kg CD34+ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score > or = 1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P = 0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.

Adult↗
PubMed1997

Response of substance P-immunoreactive nerve fibres in the anterior pituitary to plasma oestrogen levels in the rat.

The mammalian anterior pituitary has recently been shown to be innervated by substantial amounts of peptidergic nerve fibres. It has also been found that adrenalectomy increases the amount of calcitonin gene-related peptide-like immunoreactive nerve fibres in the anterior pituitary of the rat, and that stimulation of the nerve fibres in vitro can enhance release of ACTH. In the present study, the density of substance P-like immunoreactive nerve fibres in the anterior pituitary of the rat were examined in relation to variations in plasma oestrogen status. The amount of substance P-like immunoreactive nerve fibres increased significantly (P < 0.001) after ovariectomy, and decreased significantly (P < 0.01) under oestrogen replacement, in a dose-dependent manner. The results suggest the possibility of the direct neural involvement of oestrogen secretion in anterior pituitary regulation, which further substantiates the hypothesis of neural-humoral dual regulation of the mammalian anterior pituitary.

Animals↗