Biomedical subjects

B Alexander

Publications and source records attributed to B Alexander.

At least 37 records · Page 2Linked to original sources

PubMed1999

Paradoxical cholinergic and purinergic vascular reactivity of rabbit thoracic aorta cold-stored in University of Wisconsin solution.

Endothelial dysfunction has been reported in donor blood vessels destined for organ transplantation following cold-storage preservation with University of Wisconsin solution (UW). This was investigated in the present work. Segments of rabbit thoracic aorta were mounted on isometric fine-wire myographs at 37 degrees C and gassed with 95% O2/5% CO2. Concentration-dependent vasodilatations to acetylcholine and adenosine-5'-triphosphate (ATP) were obtained in freshly-harvested rabbit aortic rings, with and without the endothelium, and after 8 days of cold-storage, at 4 degrees C, in either UW, Krebs-Bülbring buffer (KBB) or saline. The action of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (100 microM) was evaluated upon the concentration-response curves to determine whether nitric oxide (NO) exerted any modulatory actions. Endothelium-dependent, NO-mediated responses to acetylcholine were unaltered after eight days of storage in UW, reduced after storage in KBB and absent after removal of the vascular endothelium, saline storage or after testing in the presence of L-NAME, suggesting improved NO-mediated endothelial function with the use of UW. Structural preservation was also confirmed using scanning electron microscopy. In contrast, endothelium-dependent responses to ATP were unchanged after eight days of storage in KBB but were reduced after storage in UW and saline, suggesting purinergic (ATP) endothelial dysfunction after storage in UW. L-NAME markedly reduced vasodilatation to ATP in freshly harvested rings and after eight days of storage in KBB. This reduction was statistically significant (P < 0.05, Student's two tailed, unpaired t-test) at -log (M) ATP concentrations of 5.5, 5.0, 4.5, 4.0 and 3.5. NO-dependent vasodilatation to ATP was not attenuated by L-NAME in UW-stored rings. Eight days' UW-storage of rabbit thoracic aortic rings appeared to have differential and paradoxical effects upon NO-dependent vasodilatation to acetylcholine and ATP. Morphological observations using electron microscopy suggested that UW preserved the vascular endothelium and this was verified by retained vascular reactivity of endothelium-dependent vasodilatations to acetylcholine. UW-storage however, significantly reduced endothelium-dependent relaxation to ATP thereby suggesting that P2Y-purinoceptors, which are located on the vascular endothelium, may be more susceptible to biodegradation than cholinergic receptors and may be responsible for endothelial dysfunction following transplantation.

Acetylcholine↗

PubMed1999

An investigation of shame and guilt in a depressed sample.

A self-report measure of proneness to shame and guilt was administered to 86 patients with moderate to severe depression, with the prediction that there would be a positive correlation of shame with severity of depression. Contrary to other, non-clinical studies, we found that guilt but not shame was associated with levels of depression. Shame-proneness demonstrated a unique association with a stable attributional style for negative outcomes, global negative self-evaluation, submissive behaviour and internalized anger. Contrary to prediction, no relationship was found between shame- or guilt-proneness and a reported history of childhood sexual abuse.

Adult↗

PubMed1999

Breeding structure of the sand fly Lutzomyia longipalpis (Lutz & Neiva) in Brazil.

Eleven populations of Lutzomyia longipalpis (Lutz & Neiva), the sand fly vector of Leishmania chagasi, from different areas of Brazil were analyzed for genetic variation at 16 enzyme loci. In this region, the prevalence of visceral leishmaniasis (VL) caused by L. chagasi is spotty and reproductive isolation among populations of Lu. longipalpis has been reported. It is thought that morphologically similar cryptic species with varying vectorial capacity may be responsible for the discontinuous distribution of VL. The aim was to study the genetic structure of populations within this region and to identify demes that may represent sibling species. Genotypic frequencies within populations were in close compliance to Hardy-Weinberg expectations, suggesting there are no sympatric species among these 11 populations. Levels of genetic distance between pairs of populations were very low (< 0.03), consistent with local populations within a single sand fly species. When genotypic frequency data for all populations were pooled, 9 of the 13 polymorphic loci deviated from Hardy-Weinberg expectations, indicating some degree of genetic substructuring. Estimates of effective migration rates (N(e)m) among all populations were low, 2.73, suggesting that gene flow is restricted among populations, which is probably the reason for the observed genetic substructuring.

Alleles↗

PubMed1998

IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma.

In many different murine models, the immunogenicity of tumor cells can be increased by transduction with a range of immunostimulatory genes, inducing an immune response that causes regression of pre-existing unmodified tumor cells. To investigate the relevance of these animal models to pediatric malignancy, we used autologous unirradiated tumor cells transduced with an adenovirus-IL-2 to immunize 10 children with advanced neuroblastoma. In a dose-escalation study, we found that this tumor immunogen induced a moderate local inflammatory response consisting predominantly of CD4(+) T lymphocytes, and a systemic response, with a rise in circulating CD25(+) and DR+ CD3(+) T cells. Patients also made a specific antitumor response, manifest by an IgG antitumor antibody and increased cytotoxic T-cell killing of autologous tumor cells. Clinically, five patients had tumor responses after the tumor immunogen alone (one complete tumor response, one partial response, and three with stable disease). Four of these five patients were shown to have coexisting antitumor cytotoxic activity, as opposed to only one of the patients with nonresponsive disease. These results show a promising correlation between preclinical observations and clinical outcome in this disease, and support further exploration of the approach for malignant diseases of children.

Adenoviridae↗

PubMed1998

Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed neuroblastoma.

Tumor cells that have been genetically modified to express immunostimulatory genes will induce effective antitumor responses in a range of syngeneic animal models. For human applications, transduced autologous tumor cell lines are often difficult or impossible to prepare, so that there are strong incentives for substituting a standardized allogeneic tumor cell line. However, such lines may be inferior immunogens if they differ from host tumors in the antigens they express. We have evaluated the safety, immunostimulatory, and antitumor activity of an interleukin-2-secreting allogeneic neuroblastoma cell line in 12 children with relapsed stage IV neuroblastoma. They received two to four subcutaneous injections of cells in a dose-escalating schedule, up to a maximum of 10(8) cells per injection. There was induration and pruritus at the injection site, and skin biopsies revealed mild panniculitis with CD3+ cells surrounding scanty residual tumor cells. There was a limited but significant peripheral monocytosis. No patient showed any increase in direct cytotoxic effector function against the immunizing cell line, but 3 patients had a rise in the frequency of neuroblastoma-reactive cytotoxic T lymphocyte precursor cells. One child had > 90% tumor response (PR), 7 had stable disease, and 4 had progressive disease in response to vaccine alone. Although these results offer some encouragement for the continued pursuit of allogeneic vaccine strategies in human cancer, the antitumor immune responses we observed are inferior to those obtained in an earlier immunization study using autologous neuroblastoma cells. Hence, we suggest that this earlier approach remains preferable, its difficulties notwithstanding.

Cancer Vaccines↗

PubMed1998

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens.

OBJECTIVE: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. METHODS: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl). RESULTS: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. CONCLUSION: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

Adult↗

PubMed1998

Detection of Leishmania (Viannia) braziliensis complex in wild mammals from Colombian coffee plantations by PCR and DNA hybridization.

The small mammal fauna of coffee plantations in SW Colombia was surveyed to determine which of the species present were infected with parasites of the Leishmania (Viannia) braziliensis complex and might therefore act as reservoirs of human cutaneous leishmaniasis. Fifty animals of seven different species were captured. Tissue samples were taken from the ears of specimens from each of the seven species. Thirty three samples were analysed by polymerase chain reaction (PCR) using oligonucleotide primers directed against conserved regions of L. (V) braziliensis complex kinetoplast DNA. Three of the samples (two from mouse opossums Micoureus demerarae, and one from a pygmy rice at Microryzomys minutus) gave positive results based on PCR analysis. When the samples were subjected to DNA hybridization (dot blot) analysis using the B18 (L. (V.) braziliensis complex-specific) probe, a total of ten specimens belonging to six species (the opossums M. demerarae and Didelphis marsupilalis, the rodents Melanomys caliginosus, Mi. minutus and Rattus rattus, and a rabbit Sylvilagus brasiliensis) gave positive results, indicating that all these animals had flies of species occurring in the same habitat by allowing them to feed on infected animals.

Animals↗

PubMed1998

The role of nitric oxide in hepatic metabolism.

Nitric oxide (NO) may regulate hepatic metabolism directly by causing alterations in hepatocellular (hepatocyte and Kupffer cell) metabolism and function or indirectly as a result of its vasodilator properties. Its release from the endothelium can be elicited by numerous autacoids such as histamine, vasoactive intestinal peptide, adenosine, ATP, 5-HT, substance P, bradykinin, and calcitonin gene-related peptide. In addition, NO may be released from the hepatic vascular endothelium, platelets, nerve endings, mast cells, and Kupffer cells as a response to various stimuli such as endotoxemia, ischemia-reperfusion injury, and circulatory shock. It is synthesized by nitric oxide synthase (NOS), which has three distinguishable isoforms: NOS-1 (ncNOS), a constitutive isoform originally isolated from neuronal sources; NOS-2 (iNOS), an inducible isoform that may generate large quantities of NO and may be induced in a variety of cell types throughout the body by the action of inflammatory stimuli such as tumor necrosis factor and interleukin (IL)-1 and -6; and NOS-3 (ecNOS), a constitutive isoform originally located in endothelial cells. Another basis for differentiation between the constitutive and inducible enzymes is the requirement for calcium binding to calmodulin in the former. NO is vulnerable to a plethora of biologic reactions, the most important being those involving higher nitrogen oxides (NO2-), nitrosothiol, and nitrosyl iron-cysteine complexes, the products of which (for example, peroxynitrite), are believed to be highly cytotoxic. The ability of NO to react with iron complexes renders the cytochrome P450 series of microsomal enzymes natural targets for inhibition by NO. It is believed that this mechanism provides negative feedback control of NO synthesis. In addition, NO may regulate prostaglandin synthesis because the cyclooxygenases are other hem-containing enzymes. It may also be possible that NO-induced release of IL-1 inhibits cytochrome P450 production, which ultimately renders the liver less resistant to trauma. It is believed that Kupffer cells are the main source of NO during endotoxemic shock and that selective inhibition of this stimulation may have future beneficial therapeutic implications. NO release in small quantities may be beneficial because it has been shown to decrease tumor cell growth and levels of prostaglandin E2 and F2 alpha (proinflammatory products) and to increase protein synthesis and DNA-repair enzymes in isolated hepatocytes. NO may possess both cytoprotective and cytotoxic properties depending on the amount and the isoform of NOS by which it is produced. The mechanisms by which these properties are regulated are important in the maintenance of whole body homeostasis and remain to be elucidated.

Animals↗

PubMed1998

The dependence of hepatic function upon sufficient oxygen supply during prolonged isolated rat liver perfusion.

It is unclear how the omission of a perfusate oxygen carrier may influence data derived from prolonged in vitro liver perfusions. The effects of reduced perfusate oxygen content upon liver function tests conducted in livers from male Sprague-Dawley rats perfused for 6 h, were studied using diluted rat blood (PCV = 10%) (group 1) and compared to lines perfused with Krebs' buffer (group 2). Perfusate and bile samples were withdrawn at the start and at hourly intervals following the commencement of perfusion for biochemical analysis of aspartate-serine transaminase, alkaline phosphatase, bilirubin, urea and potassium concentrations, and also for perfusate gas measurements for calculations of hepatic oxygen uptake. There were no significant differences between the initial perfusion pressures of 11.4+/-1.6 and 15.7+/-2.4 mm Hg at the start of perfusion (group 1 versus group 2, respectively). Maintenance of comparable perfusion pressures at the start of perfusion, however, resulted in a significant difference in the fixed flow rate between the two groups of 1.9+/-0.1 and 2.6+/-0.2* ml/min/g liver and resulted in significantly higher perfusion pressures in group 2 than in group 1 after 6 h of perfusion (18.2+/-2.0 versus 8.7+/-1.7 mmHg, respectively). Bile volume production was significantly greater in group 1 than in group 2, at 784+/-84 vs 458+/-75 microl/h** respectively. Hepatic oxygen uptake (HOU) was significantly greater in group 1 than in group 2, and maximal at 0.93+/-0.13 vs 0.32+/-0.08** micromol/min/g, respectively. Bile concentrations of bilirubin and potassium were significantly greater in group 1 than in group 2, 23.0+/-0.6 vs 4.9+/-0.4 micromol/l*** and 4.7+/-0.5 vs 1.1+/-0.2 mmol/l**, respectively. Perfusate concentrations of urea, bilirubin, and glucose were significantly higher in group 1 than group 2, 5.7+/-0.5 versus 1.4+/-0.2 micromol/l**; 2.4+/-0.5 versus 0.7+/-0.1 micromol/l** and 22.1+/-1.4 versus 17.8+/-0.9 micromol/l***. It is concluded that in vitro perfusion of the rat liver with Krebs'-Henseleit buffer (KHB) via the portal vein alone may be insufficient to maintain optimum liver function as assessed by the tests used. Inclusion of a perfusate oxygen carrier is optimal if livers are to be perfused at physiological pressures. *p < 0.05; **p < 0.01; ***p < 0.001; group 1 versus group 2, Student's unpaired t test.

Alkaline Phosphatase↗

PubMed1998

Correlation of endothelium-dependent and -independent vasodilatation with liver function tests during prolonged perfusion of the rat liver.

Twelve male Wistar rats were anaesthetized with pentobarbitone (3 mg 100g(-1) i.p.), the livers were excised and perfused in vitro through the hepatic artery and portal vein at constant flow rates of 0.32+/-0.01 (mean+/-S.E.) and 0.98+/-0.03 ml min(-1) g liver(-1), respectively. The tone of the preparation was raised by methoxamine (7.5 x 10(-6) M). Responses to mid-range doses of acetylcholine (-11 log mol) and sodium nitroprusside (-9 log mol) produced submaximal degrees of vasodilatation (-log mol ED50 = 12.18+/-0.08) and (-log mol ED50 = 9.95+/-0.23), respectively, which did not subside until 5.5 h of perfusion. These did not coincide with the increase in activities of lactic acid dehydrogenase (LDH) and aspartate serine transaminase (AST) activity at 2.5 h, which were indicative of hepatocellular mitochondrial and cytoplasmic damage, respectively. Vascular responses suggested that there was little deterioration in endothelial or smooth muscle function in the hepatic artery up to 5 h perfusion. This model can be reliably used to investigate endothelium-dependent and -independent vasodilators in vascular pharmacological studies of the rat liver although some minimal increases may occur in AST and LDH activity before hemodynamic changes appear at 5.5 h.

Acetylcholine↗

PubMed1998

Differentiation between the effects of unprocessed portal blood and reduced liver function on brain indole amine metabolism in the portacaval shunted rat.

Changes in brain 5-HT turnover which have been associated with portal-systemic encephalopathy (PSE) in man were studied in rats with experimental PSE for intervals up to 15 weeks following the surgical construction of end-to-side portacaval shunts (PCS). These were compared to changes measured in portacaval transposed rats (PCT) which, show little hepatic dysfunction or cerebral abnormalities but, in common with the PCS rat, sustain total portal-systemic diversion. Thus any differences between these two groups were indicative of hepatic dysfunction and not the systemic diversion of portal blood. After 15 weeks, sustained increases were measured in brainstem and cerebral concentrations of the catabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), from 0.25+/-0.01 to 0.68+/-0.01*** microg g(-1) brain and from 0.18+/-0.01 to 0.31+/-0.03*** microg g(-1) brain respectively in PCS rats and were statistically greater to those measured in the brainstem and cerebrum of PCT and control rats. Sustained increases in cerebral concentrations alone of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, from 0.17+/-0.01 to 0.23+/-0.02 microg g(-1) brain were measured in PCS rats and were significantly*** greater than in PCT control rats after 15 weeks. Some early increases in 5-HTP were measured in PCS above control rats but these were not significant after 15 weeks. No sustained significant differences between the 3 groups were measured in 5-HT after 15 weeks. These data confirm previous evidence that the elevations in 5-HTP and 5-HIAA concentrations observed in experimental chronic liver failure and PSE are due to liver dysfunction and not portal-systemic diversion and may contribute additional information regarding the role of derangements in central 5-HT turnover as one of the causes of PSE. ***p<0.001, Newman-Keuls ANOVAR followed by Student's unpaired t-test for individual comparisons, (data shown are mean +/- SEM).

Animals↗

PubMed1998

Evidence that S-adenosyl-L-methionine diastereoisomers may reduce ischaemia-reperfusion injury by interacting with purinoceptors in isolated rat liver.

1. Mechanisms underlying the haemodynamic activity of diastereoisomers of S-adenosyl-L-methionine (SAM) were investigated using inhibitors of purinoceptors and nitric oxide (NO) synthase in perfused rat livers damaged by sequential 24 h cold and 20 min rewarming ischaemia + reperfusion. 2. Stored livers were flushed with 10 ml saline alone (control) or with added (R,S) or (S,S) SAM (100 microM) and reperfused in the absence (control) or presence of 10 microM 8-phenyltheophylline (8-PT) or 100 microM L-N-monomethylarginine (L-NMMA). 3. Both SAM diastereoisomers rapidly increased blood flow and bile production versus controls (P<0.001) but the (R,S) isomer induced greater increases in blood flow and the (S,S) isomer greater increases in bile production: 625 versus 596 versus 518 ml blood flow and 100 versus 119 versus 56 mg bile production per g liver over 3 h in (R,S), (S,S) and control, respectively. 4. 8-PT prevented the enhancement of blood flow by (S,S) SAM (529 versus 596 ml g(-1) liver over 3 h for (S,S) SAM alone, P<0.001), but was without effect in control livers. 8-PT also reduced SAM-enhanced bile production: 51 versus 119 mg g(-1) liver over 3 h, P<0.001. L-NMMA reduced blood flow and bile production similarly in the absence or presence of (S,S) SAM. 5. Thus, SAM may improve liver perfusion after ischaemia-reperfusion injury via stimulation of P, (A2) purinoceptors at which SAM shows activity. The choleretic activity of (S,S) SAM is disproportionately greater than enhanced blood flow and may occur independently of a NO-dependent component of bile production.

Animals↗

PubMed1998

The relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver.

BACKGROUND: Portal hypertension is associated with gross haemodynamic disturbances characterised by high cardiac output, low peripheral vascular resistance, increased splanchnic blood flow, and portal systemic shunting. AIMS: To study the relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver. METHODS: Different sized microspheres were sequentially injected into the portal vein of male Wistar rats. RESULTS: Steady state portal venous pressure was increased by 102.2 (35.6)% (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure following sequential injections of 15 and 80 microns diameter microspheres, respectively. Sequential injection of 15, 40, and 80 microns diameter microspheres in either ascending or descending order of size did not generate further increases in portal venous pressure. A single injection of 1.8 x 10(5) 80 microns microspheres consistently produced a steady state portal venous pressure of 19.0 (1.3) mm Hg but did not approach the much higher value of 36.6 (43.2) mm Hg measured during clamping of the portal vein. These data indicate that the opening of patent intrahepatic shunts was responsible for the reduced pressures observed during microsphere injections and further evidence for this was provided by the location of microspheres in the pulmonary vascular bed. The elevation in portal venous pressure achieved by microsphere injections was not significantly different to that produced in rats subjected to partial portal vein ligation (20.7 (0.5) mm Hg, p > 0.05). Wedged hepatic venous pressure decreased from 6.7 (0.7) to 3.0 (0.6) mm Hg following injection of 80 microns microspheres, suggesting a decrease in total hepatic blood flow. Conversely, injection of 15 microns microspheres induced an increase in wedged hepatic venous pressure from 7.0 (1.0) mm Hg to 12.4 (1.8) mm Hg, indicating a localised redistribution of blood flow at the presinusoidal level of the portal venous vascular network and increased intrahepatic shunt flow. CONCLUSION: It is suggested that there may be a protective pathophysiological role for these shunts when the liver is subjected to changes which induce acute portal hypertension.

Acute Disease↗

PubMed1997

The action of ATP on the hepatic arterial and portal venous vascular networks of the rabbit liver: the role of adenosine.

ATP is released from blood vessels during periods of hypoxia and may be responsible for hepatic arterial vasodilatation during instances of reduced hepatic portal venous flow. The role of adenosine in ATP-induced vasodilator and vasoconstrictor responses of the hepatic arterial and portal venous vascular networks respectively was studied in the isolated dual-perfused rabbit liver in vitro to ascertain whether ATP could be catabolised to adenosine during transit through the hepatic parenchyma. Intra-arterial and intra-portal injections of ATP (-10 to -4 log mol/100 g liver) resulted in dose-dependent vasodilatation in the hepatic artery and vasoconstriction in the portal vein. Addition of 8-phenyltheophylline (10 microM), a non-selective P1-purinoceptor antagonist, to the hepatic arterial and portal venous perfusate significantly inhibited the hepatic arterial ED50 for responses to intra-arterial injected ATP from -8.70 +/- 0.22 to -7.63 +/- 0.28 log mol/100 g liver (P < 0.001); it also inhibited hepatic arterial responses to, mid-range, portal venous injections of ATP. The data suggest that the hepatic arterial vasodliatation to ATP is partly mediated via catabolism to adenosine and may be an important mechanism during periods of relative hepatic hypoxia associated with portal flow reduction.

Adenosine↗

PubMed1997

Morphological changes during hepatocellular maturity in neonatal rats.

BACKGROUND: Hepatocellular maturation is characterised by the progressive transition from an architecture in which hepatocyte plates are at least two cells thick to the familiar adult pattern in which liver cell plates are predominantly single-cell in thickness. A similar process also has been noted during compensatory hyperplasia following damage, or destruction to the hepatic parenchyma. The pathological events that underlie these processes remain inadequately explained. A new morphological approach has been developed to study the maturity of rat neonatal livers in order to identify the factors which govern the structured morphogenesis of the liver in greater detail. METHODS: Sections of hepatic tissue obtained from the left lateral and right posterior lobes from neonatal rats were studied at 8, 10, 11, 13, 14, 18, 23, and 28 days postpartum. These were mounted, fixed, and stained with haematoxylin and eosin and analysed using a modified point-counting technique. Following validation of the technique, the proportion of single-cell plates to double-cell plates was then calculated at each time point. RESULTS: Liver sections from 8-day neonatal rats had the lowest percentage of single-cell thick plates of 16.9 +/- 4.6% and the lowest standard deviation (mean +/- SD). The hepatic architecture had fully matured by 28 days and was characterised by predominantly single-cell plates (84.6 +/- 4.6%) lining the hepatic sinusoids. During the intervening time, the standard deviations increased significantly, peaking between 18-23 days, and reflected the rapidly changing morphology of the liver during this maturation process of the conversion of double-cell plates to single-cell plates. CONCLUSIONS: It is concluded that the process of hepatocellular maturity in the neonatal Sprague-Dawley rat is reproducibly complete by 28 days and that further studies may now be conducted to determine the anatomical and pathophysiological changes that govern this important transition.

Age Factors↗

PubMed1997

Evaluation of the fungus Beauveria bassiana as a potential biological control agent against phlebotomine sand flies in Colombian coffee plantations.

In Colombia, the entomopathogenic fungus Beauveria bassiana (Deuteromycotina: Hyphomycetes) is widely used to control the coffee berry borer Hypothenemus hampei (Coleoptera: Scolytidae) in coffee plantations. Recent studies suggested that this fungus is also pathogenic to several important vectors of disease, including Phlebotomus papatasi and Lutzomyia longipalpis (Diptera: Psychodidae). The present study evaluated the use of B. bassiana as a potential biological control agent against phlebotomine sand flies in Colombian coffee plantations. Histopathologic examination indicates that B. bassiana is unable to infect sand flies under natural conditions, although dead sand flies were shown to be readily infected. In addition, laboratory bioassays where flies were exposed to the fungus applied onto coffee plants (though not filter paper) showed lower mean survival times than the control.

Animals↗

PubMed1997

Retrospective study of selegiline-antidepressant drug interactions and a review of the literature.

Selegiline is a selective monoamine oxidase inhibitor used in the treatment of Parkinson's disease. It is estimated that approximately one-half of Parkinsonian patients will develop depression requiring antidepressant drug treatment. Recently, selegiline's package insert was revised to reflect the potential risk of adverse effects when it is used in combination with selective serotonin reuptake inhibitors and tricyclic antidepressants. The objective of our study is to assess the safety of combining selegiline with antidepressants. A retrospective chart review was performed on all 28 patients with Parkinson's disease receiving selegiline and antidepressants concurrently to identify possible drug interactions. Compliance was assessed according to prescription refill records. Suspected adverse reactions with combination therapy were documented. There was a total of 40 selegiline-antidepressant drug combinations involving tricyclic antidepressants (n = 25), selective serotonin reuptake inhibitors (n = 7), trazodone (n = 5), and bupropion (n = 3). One patient receiving fluoxetine developed a reaction consistent with the serotonin syndrome; however, it was never documented as such. No other selegiline drug interactions were found. Adverse effects noted were typical of antidepressant monotherapy. Although no selegiline drug interactions were documented in our study, the concurrent administration of selegiline and selective serotonin reuptake inhibitors should be avoided because of literature-reported interactions. We believe that bupropion, tricyclic antidepressants, and trazodone are reasonable choices in combination with selegiline, although tricyclic antidepressants and trazodone may be reserved as second-line treatments.

Antidepressive Agents, Second-Generation↗

PubMed1997

Establishment of multipotential and antigen presenting cell lines derived from myeloid leukemias in GM-CSF transgenic mice.

In this study neonatal mice expressing a GM-CSF transgene (GMT mice), and their normal littermate controls, were infected with Moloney murine leukemia virus (MoMLV) to examine in vivo tumorigenesis. By 200 days, all of the GMT mice had died whereas median survival had not been reached in the littermates (P < 0.0003). Thymomas developed in 32% of GMT mice and were more frequently CD4+CD8+ (83%) compared to the CD4+CD8- phenotype seen in 90% of thymomas developing in MoMLV-infected littermate mice. A primitive myeloid leukemia was induced in 21% of GMT mice, but none of the littermates. To characterize further the nature of the leukemic cells, a factor-dependent cell line (DGM36) was derived. DGM36 cells were tumorigenic, capable of differentiation to neutrophils, macrophages and eosinophils, and contained a partial deletion of chromosome 2. A subline arose spontaneously that was factor-independent and produced GM-CSF in an autocrine manner (IGM36 cells). Stimulation of the IGM36 cells with TNF alpha and IFNgamma resulted in increased expression of B7-1, class I MHC and class II MHC and consequent presentation of antigen in allogeneic MLRs. IGM36 cells thereby satisfy many of the criteria of dendritic cells and consequently may be used to examine antigen presentation by leukemic cells. This is the first report of primary myeloid leukemias arising in GMT mice and documents the derivation of a multipotential, autocrine leukemic cell line with dendritic cell characteristics.

Animals↗