Low seroprevalence of Toxoplasma gondii in feral pigs from a remote island lacking cats

Serum samples from 1,264 feral pigs from Ossabaw Island, Georgia were initially screened for antibodies to Toxoplasma gondii by the modified agglutination test (MAT) using whole-formalinized tachyzoites and mercaptoethanol. Seropositive samples were also tested by the Sabin-Feldman dye test, the latex agglutination test (LAT), and the indirect hemagglutination test (IHAT). Ossabaw Island is a remote, barrier island located southeast of Savannah, Georgia. Antibodies to T. gondii were found in 11 (0.9%) of 1,264 pigs. The antibody titers were 1:20 (1 pig), 1:80 (2 pigs), 1:160 (2 pigs), 1:320 (4 pigs), and 1:640 (2 pigs) by the MAT, and 1:8 (2 pigs), 1:16 (3 pigs), 1:32 (1 pig), 1:64 (2 pigs), 1:128 (1 pig), and > or = 1:256 (2 pigs) by the Sabin-Feldman dye test. By the LAT, 5 pigs had a titer of > or = 1:64 and by the IHAT all 11 pigs had a titer of < 1:64. Antibodies (MAT titer, > or = 1:25) were found in 31 (18.2%) of 170 feral pigs from mainland Georgia. This seroprevalence on the mainland was significantly higher (P < 0.0001) as compared on Ossabaw Island. The markedly low prevalence of T. gondii on Ossabaw Island was attributed to the virtual absence of cats on the Island; only 1 domestic cat was known to be present.     

Mapping of the sites for ligand binding and receptor dimerization at the extracellular domain of the vascular endothelial growth factor receptor FLT-1

The vascular endothelial growth factor (VEGF) receptor FLT-1 has been shown to be involved in vasculogenesis and angiogenesis. The receptor is characterized by seven Ig-like loops within the extracellular domain. Upon VEGF binding FLT-1 becomes phosphorylated, which has been thought to be preceded by receptor dimerization. To further investigate high affinity binding of VEGF to FLT-1 and ligand-induced receptor dimerization, we expressed in Sf9 cells the entire extracellular domain comprising all seven Ig-like loops: sFLT-1(7) and several truncated mutants consisting of loop one, one and two, one to three, one to four, and one to five. The corresponding proteins, named sFLT-1(1), (2), (3), (4), and (5) were purified. Only mutants sFLT-1(3) to (7) were able to bind 125I-VEGF with high affinity. No binding of VEGF was observed with sFLT-1(1) and sFLT-1(2), indicating that the first three Ig-like loops are involved in high affinity binding of VEGF. The binding of VEGF to sFLT-1(3) could be competed with placenta growth factor (PlGF), a VEGF-related ligand, suggesting that high affinity binding of VEGF and PlGF is mediated by the same or closely related contact sites on sFLT-1. Deglycosylation of the sFLT-1(3), (4), (5), and (7) did not abolish VEGF binding. Furthermore, unglycosylated sFLT-1(3), expressed in Escherichia coli, was able to bind VEGF with similar affinity as sFLT-1(3) or sFLT-1(7), both expressed in Sf9 cells. This indicates that receptor glycosylation is not essential for high affinity binding. Dimerization of the extracellular domains of FLT-1 upon addition of VEGF was detected with all mutants containing the Ig-like loop four. Although sFLT-1(3) was able to bind VEGF, dimerization of this mutant was inefficient, indicating that sites on Ig-like loop four are essential to stabilize receptor dimers.     

Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent

Early diagnosis of kidney and urothelial cancer requires some new sensitive and specific methods. In this study the diagnostic use of serum alpha 1-acid glycoprotein (alpha 1-AG), coeruloplasmin, alpha 1-antitrypsin (alpha 1-AT), alpha 2-macroglobulin (alpha 2-MG) and albumin in patients with kidney, urinary bladder and upper tract urothelial cancer was evaluated. In kidney cancer patients the serum levels of alpha 1-AG, coeruloplasmin and alpha 1-AT were significantly increased over the controls (p < 0.001), however, albumin was decreased (p < 0.005). Sensitivity was relatively high for alpha 1-AG (85%), albumin (85%) and alpha 1-AT (77%). In patients with urinary tract urothelial cancer alpha 1-AG, alpha 1-AT and coeruloplasmin were also increased but not as much as in kidney cancer. Sensitivity of alpha 1-AG (63%), albumin (75%) and alpha 1-AT (66%) was also lower than in kidney cancer. This study has established the relative importance of alpha 1-AT and albumin determination in patients with kidney as well as with urothelial cancer.     

Germ cell tumors of the mediastinum and testis: a comparative immunohistochemical study of 120 cases

REPORT: A retrospective review of major league baseball records was conducted for players' cause of death. Any death attributed to a toxic exposure was analyzed for causal agent, reason for exposure, age at time of death, location, time of year, team, and dominant position played while active. RESULTS: Twenty-eight poisoning deaths were identified between 1889-1995. The most common agent was carbon monoxide (8), followed by methane gas asphyxiation (4), opiate overdose (4), ethanol (3), and phenol (3). Fourteen (50%) were unintentional deaths, 13 (46%) were suicidal in nature, and 1 (4%) homicidal. The majority of deaths (75%) occurred after the players had retired from the game. The leading position was pitcher (13), followed by catcher (5), outfield (4), second base (2), first (1), shortstop (1), third (1), and umpire (1). CONCLUSIONS: With society's increased illicit drug use, better drug detection, escalating salaries, and increased public pressures placed on present-day players, more poisonings may likely occur.     

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP-27, but not PACAP-38) degradation by the neutral endopeptidase EC 3.4.24.11

VIP (vasoactive intestinal polypeptide) and PACAP (pituitary adenylate cyclase-activating polypeptide), which are potent relaxing agents in the airways, were submitted to in vitro degradation by the neutral endopeptidase EC 3.4.24.11 (NEP), one of the most active peptidase in the lung, to test their relative resistance to proteolysis. Both VIP and PACAP(1-27) were cleaved by NEP, but PACAP(1-38) was not. The main fragments produced were VIP(1-22) and VIP(1-25), and PACAP(1-22) and PACAP(1-25), respectively. The degradation of VIP(1-27), PACAP(6-27), and PACAP(13-27) was also hindered by extending their C-terminal ends with the (28-38) sequence of PACAP(1-38). The sensitivity to enzyme degradation was gradually reduced when the C-terminal extension was increased from PACAP(1-27) to PACAP(1-29), PACAP(1-32) and PACAP(1-38). The biological activities of the degradation products were evaluated on the three classes of PACAP/VIP receptors, with VIP(1-25) and PACAP(1-25) retaining an important part of their activities on the VIP1 receptor. Thus, the degradation of VIP and PACAP(1-27) by the neutral endopeptidase 24.11 might produce a VIP1 receptor-selective active metabolite, provided that very high VIP or PACAP(1-27) concentrations are achieved in the receptor vicinity.     

Stereoselective pharmacokinetics of bisoprolol after intravenous and oral administration in beagle dogs

We report 81 of 107 cases of hemolytic uremic syndrome (HUS), admitted between July 1994 and February 1996, following an outbreak of Shigella dysenteriae type 1 dysentery in Kwazulu/Natal. All patients, excluding 1, were black with a mean age of 38 months (range 1-121); 50 (61.7%) were males. The mean duration of dysentery was 11.3 days (range 1-41) and HUS 15 days (range 1-91). Most patients had acute oliguric renal failure (90.1%), 42 (51.6%) required peritoneal dialysis. Complications included encephalopathy 30 (37.0%), convulsions 12 (14.8%) and hemiplegia 2 (2.3%), gastrointestinal perforation 8 (9.9%), protein losing enteropathy 26 (32.1%), toxic megacolon 4 (4.9%), rectal prolapse 5 (6.2%), hepatitis 11 (13.6%), myocarditis 5 (6.2%), congestive cardiac failure 3 (3.7%), cardiomyopathy 3 (3.7%), infective endocarditis 1 (1.2%), septicemia 15 (18.5%), disseminated intravascular coagulation 17 (21%). Leukemoid reactions were found in 74 (91.3%) patients, hyponatremia in 56 (69.1%), and hypoalbuminemia in 67 (82.7%). Stool culture for Shigella dysenteriae type I was positive in only 7 (8.6%) patients; Shiga toxin assays were not performed. Outcome was as follows: recovery 32 (39.5%), impaired renal function 8 (9.9%), chronic renal failure 26 (32.1%), end-stage renal disease 1 (1.2%), and death 14 (17.3%) patients.     

Experimental infection of domestic cats with Bartonella henselae by inoculation of Ctenocephalides felis (Siphonaptera: Pulicidae) feces

Aqueous methanol extracts from the bulbs of Hyacinthusorientalis were subjected to various ion-exchange column chromatographic steps to give 2(R),5(R)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (1), 2,5-dideoxy-2,5-imino-dl-glycero-d-manno-heptitol (homoDMDP) (2), 2,5-imino-2,5,6-trideoxy-d-manno-heptitol (6-deoxy-homoDMDP) (3), 2,5-imino-2,5,6-trideoxy-d-gulo-heptitol (4), 1-deoxynojirimycin (5), 1-deoxymannojirimycin (6), alpha-homonojirimycin (7), beta-homonojirimycin (8), alpha-homomannojirimycin (9), beta-homomannojirimycin (10), and 7-O-beta-d-glucopyranosyl-alpha-homonojirimycin (MDL 25,637) (11). The structures of the new natural products 3 and 4 were determined by spectroscopic analysis, including extensive 1D and 2D NMR studies. Compound 2 was found to be a potent inhibitor of bacterial beta-glucosidase, mammalian beta-galactosidases, and mammalian trehalases, while 3 was a potent inhibitor of rice alpha-glucosidase and rat intestinal maltase. Compound 4 was observed to be a good inhibitor of alpha-l-fucosidase.     

Cytomegalovirus-induced interstitial pneumonitis in a patient with systemic lupus erythematosus

BACKGROUND: Antibodies of the Knops system have been referred to as nonneutralizable because they cannot be inhibited with serum, saliva, or urine. Because the Knops system antigens have been located on complement receptor 1 (CR1), the question of whether the antibodies could be neutralized with soluble CR1 (sCR1) produced by recombinant DNA techniques was studied. STUDY DESIGN AND METHODS: First, radiolabeled immunoprecipitation techniques were used to test sCR1 for the expression of the high-incidence Knops system antigens. Then, a total of 45 antibodies were neutralized with sCR1, including the following: one each of anti-Cr(a), -Dr(a), -Do(b), -Hy, -Ge, -Jr(a), -Sc1, -Jk(a), -Cs(a), and -Kp(b); two each of anti-Lu(b), -Yt(a), and -JMH; three each of anti-McC(a), -Rg, and -Sl(a); and four each of anti-Ch, -Kn(a), -Yk(a), -Kn/McC. In addition, two examples of anti-Kn(a) + K, one example of anti-Sl(a) + K + Fy(a), and one example of anti-Yk(a) + E were tested. The sCR1 was added to each test serum and 6-percent albumin was added to the control; this was followed by neutralization incubation for 5 minutes at 25 degrees C. The antibody samples were then tested by a low-ionic-strength solution, anti-human globulin technique. RESULTS: The sCR1 expressed Kn(a), McC(a), Sl,a and Yk(a). All Knops system antibodies (n = 22) were neutralized by the sCR1, but none of the other 23 alloantibodies decreased in reactivity. The samples containing antibodies of two specificities showed inhibition of the Knops system antibody but not of the second antibody. CONCLUSION: This neutralization method, in which recombinant protein is used, provides an expedient and definitive method of identifying Knops system antibodies.     

The role of a bidirectional cavopulmonary anastomosis in the correction and palliation of complex congenital cardiopathies

Between May 1990 and January 1998, 68 patients underwent bidirectional cavo-pulmonary anastomosis. We evaluated all patients in whom the bidirectional cavo-pulmonary anastomosis was associated with additional pulmonary flow (group A) and those in whom it was associated with biventricular repair (group B). Group A included 23 patients (33.8%), 14 males and 9 females, mean age 25 years and 6 months (range 4 months-16 years). Diagnoses were double outlet right ventricle (6), univentricular heart (6), tricuspid atresia (5), congenitally-corrected transposition of the great arteries with ventricular septal defect and pulmonary stenosis (3), right isomerism (2) and pulmonary atresia with atrioventricular canal (1). Group B included 13 patients (19.1%), 6 males and 7 females, mean age 13 years and 7 months (range 1 year-37 years). Diagnoses were pulmonary atresia with intact ventricular septum (4), Ebstein's anomaly (3), tetralogy of Fallot (3), atrioventricular canal (1), hypoplastic right ventricle (1), and pulmonary and tricuspid insufficiency (1). Four patients (17.3%) in group A died in the postoperative period, whereas there was no postoperative mortality in group B. Follow-up data were available in 31 patients (19 from group A, 13 from group B). Mean follow-up was 1 year and 6 months (range 30 days to 6 years). Evaluation was done by NYHA class functional status. In group A, 14 patients are doing well (NYHA I or II), while five patients (26.3%) underwent Fontan operation with one death. All group B patients are currently doing well (NYHA class I or II). In group A, complications were pericardial effusion (7), transient superior vena cava syndrome (5), pleural effusion (4), chylothorax (1) and rhythm disturbance (1). Complications in group B involved neurological events (2), pleural effusion (1) and rhythm disturbance (1). Bidirectional cavo-pulmonary anastomosis can be associated with additional pulmonary flow with good short- and intermediate-term outcome. Concern remains for the ability to properly regulate the amount of effective pulmonary blood flow. Bidirectional cavo-pulmonary anastomosis can be associated with biventricular repair in patients with diminutive right ventricles, amenable to anatomic complete correction, with good clinical outcome.     

Characterization of SFO-1, a plasmid-mediated inducible class A beta-lactamase from Enterobacter cloacae

Enterobacter cloacae 8009 produced an inducible class A beta-lactamase which hydrolyzed cefotaxime efficiently. It also hydrolyzed other beta-lactams except cephamycins and carbapenems. The activity was inhibited by clavulanic acid and imipenem. The bla gene was transferable to Escherichia coli by electroporation of plasmid DNA. The molecular mass of the beta-lactamase was 29 kDa and its pI was 7.3. All of these phenotypic characteristics of the enzyme except for inducible production resemble those of some extended-spectrum class A beta-lactamases like FEC-1. The gene encoding this beta-lactamase was cloned and sequenced. The deduced amino acid sequence of the beta-lactamase was homologous to the AmpA sequences of the Serratia fonticola chromosomal enzyme (96%), MEN-1 (78%), Klebsiella oxytoca chromosomal enzymes (77%), TOHO-1 (75%), and FEC-1 (72%). The conserved sequences of class A beta-lactamases, including the S-X(T)-X(S)-K motif, in the active site were all conserved in this enzyme. On the basis of the high degree of homology to the beta-lactamase of S. fonticola, the enzyme was named SFO-1. The ampR gene was located upstream of the ampA gene, and the AmpR sequence of SFO-1 had homology with the AmpR sequences of the chromosomal beta-lactamases from Citrobacter diversus (80%), Proteus vulgaris (68%), and Pseudomonas aeruginosa (60%). SFO-1 was also inducible in E. coli. However, a transformant harboring plasmid without intact ampR produced a small amount of beta-lactamase constitutively, suggesting that AmpR works as an activator of ampA of SFO-1. This is the first report from Japan describing an inducible plasmid-mediated class A beta-lactamase in gram-negative bacteria.     

Breast masses in childhood and adolescence. A presentation of 17 cases and a review of the literature

Breast masses are uncommon in the first two decades of life. 17 girls aged between 2 and 15 years who presented over a 5-year period are reviewed retrospectively. The cases comprised inflammation (11), asymmetrical gynaecomastia (1), precocious puberty (1), giant juvenile fibroadenoma (1), primary rhabdomyosarcoma (1), lymphoma (1), and metastatic neuroblastoma (1). Ultrasound was useful in all cases in identifying the abnormality and guiding any further investigation.     

Hemodynamic follow-up of cardiac allografts from poisoned donors

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.     

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

1. The resuscitating activity of melanocortin peptides (MSH-ACTH peptides) was tested in an experimental model of prolonged respiratory arrest. 2. Anaesthetized, endotracheally intubated rats subjected to a 5 min period of ventilation interruption, invariably died from cardiac arrest within 6-9 min of resumption of ventilation. 3. When resumption of ventilation was associated with the simultaneous intravenous (i.v.) injection of a melanocortin peptide (alpha-MSH or ACTH-(1-24)) (160 microg kg(-1) there was an almost immediate (within 1 min), impressive increase in cardiac output, heart rate, mean arterial pressure (+ 560% of the before-treatment value) and pulse pressure (+356% of the before-treatment value), with full recovery of electroencephalogram after 30-45 min. Blood gases and pH were normalized within 15-60 min after treatment, and all treated animals eventually recovered completely and survived indefinitely (= more than 15 days). 4. The same response was observed in adrenalectomized animals, as well as in animals pretreated with a beta1-adrenoceptor blocking agent (atenolol, 3 mg kg(-1), i.v.), or with an alpha1-adrenoceptor blocking agent (prazosin, 0.1 mg kg(-1), i.v.), or with an adrenergic neurone blocking agent (guanethidine, 10 mg kg(-1), intraperitoneally). 5. An effect quite similar to that produced by melanocortins was obtained with ouabain (0.1 mg kg(-1), i.v.); the antioxidant drug, glutathione (75 mg kg(-1), i.v.) also produced 100% resuscitation, but the effect was slower in onset. On the other hand, adrenaline (0.005 mg kg(-1), i.v.) was able to resuscitate only 1 out of 8 rats and dobutamine (0.02 mg kg(-1), i.v.) resuscitated 4 out of 8 rats; moreover, the effect of both catecholamines was much slower in onset than that of melanocortins and the initial, impressive stimulation of cardiovascular function was absent. 6. These results show that melanocortin peptides have a resuscitating effect in a pre-terminal condition produced in rats by prolonged asphyxia. This effect seems primarily due to the restoration of cardiac function, not mediated by catecholamines. These data also suggest that these peptides may have potential therapeutic value in conditions of transient cardiac hypoxia and re-oxygenation such as occur in coronary artery disease.     

Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.     

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan

OBJECTIVE: To determine which types of kinin receptor are present in human bronchial epithelial cells we studied the capability of bradykinin to mobilize intracellular Ca2+ ([Ca2+]i) in a human bronchial epithelial cell line (16HBE cells). MATERIAL: Human bronchial epithelial cell line transformed with an original defective simian virus 40 (SV40). TREATMENT: Bradykinin (0.1 pM to 0.1 microM), des-Arg9 bradykinin (1 microM), des-Arg10) kallidin (1 microM), indomethacin (1 microM), phosphoramidon (1 microM), captopril (1 microM), des-Arg9-[Leu8]bradykinin (1 microM), HOE 140 (DArg-[Hyp3, Thi5, DTic , Oic8]-bradykinin) (1 microM), and NPC 16731 (DArg-[Hyp3, Thi5, DTic7, Tic8]-bradykinin) (1 microM). METHODS: The mobilization of [Ca2+]i was determined by the fura-2 method. Two sample Wilcoxon rank-sum (Mann-Whitney) test was used for statistical calculations. RESULTS: Bradykinin, but not the selective agonists for kinin B1 receptor des-Arg9 bradykinin and des-Arg10 kallidin, increased the mobilization of [Ca2+]i (EC50, 0.079+/-0.009nM) in 16HBE cells in a concentration-dependent manner. Pretreatment with the cyclooxygenase inhibitor indomethacin (1 microM) or the peptidase inhibitors, phosphoramidon (1 microM) or captopril (1 microM), did not affect the response to bradykinin. The kinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin (1 microM), was inactive. HOE 140 and NPC 16731, two selective antagonists of the kinin B2 receptor abolished the response to bradykinin (IC50 of HOE 140 and NPC 16731 were 0.52+/-0.037nM and 1.67 +/- 0.41 nM, respectively). CONCLUSIONS: The present data indicate the presence of kinin B2 receptors in the 16HBE cells.     

Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes

C receptor type 1 (CR1, CD35) is present in a soluble form in plasma (sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum concentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and was identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p < 0.0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p < 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/- 24.0 ng/ml (p < 0.001) in nine patients who underwent liver transplantation, and was 33.5 +/- 7.3 in 10 patients with functioning renal grafts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (> 47 ng/ml), which included B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and chronic myeloproliferative syndromes (4/5). By contrast, no increase was observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 decreased rapidly after chemotherapy. The mean concentration of sCR1 was not significantly modified in 181 HIV-infected patients at various stages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with active SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p < 0.0001, and r = 0.60, p < 0.03 respectively). In vitro, monocytes, lymphocytes, and neutrophils were found to release sCR1 into culture supernatants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCR1 levels correlated with those of human IgG (r = 0.97, p < 0.0001), suggesting synthesis of sCR1 by the transferred lymphocytes. The mechanisms underlining the increased levels of sCR1 and its biologic consequences remain to be defined.     

Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans

The effect of glucagon-like peptide-1 (GLP-1) on hepatic glucose production and peripheral glucose utilization was investigated with or without infusion of somatostatin to inhibit insulin and glucagon secretion in 13 healthy, non-diabetic women aged 59 years. After 120 min 3-(3)H-glucose infusion, GLP-1 was added (4.5 pmol kg(-1) bolus + 1.5 pmol kg(-1) min(-1)). Without somatostatin (n = 6), GLP-1 decreased plasma glucose (from 4.8 +/- 0.2 to 4.2 +/- 0.3 mmol L(-1), P = 0.007). Insulin levels were increased (48 +/- 3 vs. 243 +/- 67 pmol L(-1), P = 0.032), as was the insulin to glucagon ratio (P = 0.044). The rate of glucose appearance (Ra) was decreased (P = 0.003) and the metabolic clearance rate of glucose (MCR) was increased during the GLP-1 infusion (P = 0.024 vs. saline). Also, the rate of glucose disappearance (Rd) was reduced during the GLP-1 infusion (P = 0.004). Since Ra was reduced more than Rd, the net glucose flow was negative, which reduced plasma glucose. Somatostatin infusion (500 microg h(-1), n = 7) abolished the effects of GLP-1 on plasma glucose, serum insulin, insulin to glucagon ratio, Ra, Rd, MCR and net glucose flow. The results suggest that GLP-1 reduces plasma glucose levels mainly by reducing hepatic glucose production and increasing the metabolic clearance rate of glucose through indirectly increasing the insulin to glucagon ratio in healthy subjects.     

Glutathione S-transferase M1 and T1 and cytochrome P4501A1 polymorphisms in relation to the risk for benign and malignant head and neck lesions

BACKGROUND: Susceptibility to head and neck cancer in a particular individual may depend in part on the metabolic balance between Phase 1 enzymes, such as cytochromes P450 (CYPs), and Phase II enzymes, such as glutathione S-transferases (GSTs). Genetic variability in CYP and GST isoenzymes may contribute to individual differences in susceptibility to chemical carcinogenesis. GSTM1 and GSTT1 null genotypes as well as polymorphic variants in the CYP1A1 gene that may help determine the risk for head and neck cancer have been described in previous reports. METHODS: Polymorphisms of GSTM1, GSTT1, and CYP1A1 in whole blood were detected by polymerase chain reaction (PCR) in 185 patients with head and neck squamous cell carcinoma (HNSCC), 78 patients with benign head and neck lesions (BHNL), and 207 blood donors. RESULTS: GSTM1 null genotype was demonstrated to be equally frequent in patients with HNSCC (50.8%), patients with BHNL (47.4%), and blood donors (51.7%). GSTT1 null genotype occurred significantly more often in patients with BHNL (33.3%) as compared with blood donors (20.3%), demonstrating that lack of GSTT1 may be a risk factor for BHNL. Presence of the rare valine in the CYP1A1/Nco1 site was found in 33 patients with HNSCC (17.8%), in 20 patients with BHNL (25.6%), and in 34 blood donors (16.4%). The frequencies with which the presence of the rare cytosine nucleotide in the CYP1A1/Msp1 site was detected were 17.8%, 15.4%, and 15.9%, respectively. CONCLUSIONS: The occurrence of polymorphic variants in the GSTM1, GSTT1, and CYP1A1 genes did not differ between the groups investigated, therefore indicating no significant contribution to the development of head and neck cancer.     

Surgical management of dumbbell and paraspinal tumors of the thoracic and lumbar spine

The lateral extracavitary approach was used for single-staged tumor resection in 12 patients with complex dumbbell or paraspinal tumors of the thoracic and lumbar spine. Six women and six men (age, 28-72 yr) were treated between August 1990 and January 1994. The tumors included schwannoma (6 patients), malignant meningioma (1 patient), hemangioma (1 patient), chondrosarcoma (1 patient), osteocartilaginous exostosis (1 patient), radiation-induced osteogenic sarcoma (1 patient), and metastatic renal carcinoma (1 patient). Gross total resection was achieved in 11 patients. Radical subtotal removal was performed in the remaining patient, who had a malignant osteogenic sarcoma. Concomitant spinal stabilization with internal fixation and anterior interbody strut grafting was performed on two patients. No significant perioperative complications occurred. Ten patients were alive and clinically stable at follow-up visits ranging from 14 to 55 months. Two patients died from systemic tumor dissemination during the follow-up period. The lateral extracavitary approach is useful when extensive or difficult spinal and paraspinal exposure is required. The surgical aspects of these neoplasms and the technique of lateral extracavitary approach are described in detail.