Octahedral Coordination of an Iodide Ion in an Electrophilic Sandwich.
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Journal Article↗
Biomedical subjects
M Diaz
Publications and source records attributed to M Diaz.
Mercuracarborand "anti-crown ether"-based chloride-sensitive liquid/polymeric membrane electrodes.
Highly sensitive and selective chloride liquid/polymeric membrane electrodes are described that employ [9]-mercuracarborand-3 (MC3), a neutral preorganized macrocyclic Lewis acid, as the anion carrier. MC3-based chloride-sensitive membrane electrodes, doped with different mole percentages of cationic additives (5, 10, and 60 mol % tridodecylmethylammonium chloride) relative to the amount of the carrier, exhibit enhanced potentiometric selectivity for chloride over other anions, including more lipophilic anions such as perchlorate, nitrate, and thiocyanate. In addition, the selectivity coefficients obtained are shown to meet the requirement for clinical applications. The obtained selectivity pattern is shown to correlate very well with 199Hg NMR titrations of MC3 with various anions, performed in organic solvents. Optimized membrane electrodes show a near-Nernstian response toward chloride over a wide concentration range and have micromolar detection limits. MC3-based chloride sensors show a fast response time (in the order of few seconds), as well as short recovery time. The developed mercuracarborand-based sensors do not practically respond to pH changes over the pH range of 2.5-7.0. Response characteristics (e.g., detection limit, linear range, response slope, and selectivity) of the [9]mercuracarborand-3 based chloride sensors remain essentially the same over a period of approximately 2 months, reflecting remarkable stability and well-defined chemistry of the macrocyclic Lewis acid ionophore.
Chlorides↗
Supraceliac aortic clamping during the anhepatic phase of experimental orthotopic liver transplantation.
BACKGROUND: The pig tolerates simultaneous clamping of the liver pedicle and inferior vena cava poorly, so venovenous bypass has to be used during the anhepatic phase of experimental orthotopic liver transplantation (OLT). The aim of this work is to assess whether clamping of the supracoeliac aorta during the anhepatic phase (AP) of experimental OLT in pigs allows transplantation in stable hemodynamic conditions. METHODS: Fourteen pigs (weight, 16 to 18 kg) received whole liver grafts from 14 age-matched donors and were subsequently divided into two groups: group I, OLT without venovenous bypass during the AP, group II, OLT with supracoeliac aortic clamping during the AP. Variables analyzed were cardiac output (CO) and related variables, mean systemic arterial pressure (MAP), mixed venous oxygen saturation (SvO2), hepatic artery and portal vein blood flow, systemic and hepatic O2 supply and uptake (SDO2, SVO2, HDO2, HVO2, respectively), liver enzymes, glucose, creatinine, and electrolytes. RESULTS: In group I, CO, MAP, and SvO2, decreased during the AP (anhepatic) in comparison with baseline (preanhepatic) values (CO, 3.60+/-0.74, preanhepatic, v. 1.21+/-0.25 L x min(-1), anhepatic; P<.05. MAP, 97+/-12, preanhepatic, v. 43+/-17 mm Hg, anhepatic; P<.05. SvO2, 91.6+/-5.6, preanhepatic v. 70.0+/-12.5%, anhepatic; P<.05), and SDO2/SVO2 increased by 16% (preanhepatic) to 33% (anhepatic; P<.05). In group II, CO decreased during the anhepatic phase by only 21% (3.82+/-0.81, preanhepatic, v. 3.07+/-0.99 L x min(-1), anhepatic; not significant), the MAP increased significantly (100+/-8, preanhepatic, v. 135+/-4 mm Hg, anhepatic; P<.05), and SVO2, SDO2, SVO2, and SDO2/SVO2 remained unchanged. After revascularization, none of these variables differed significantly between groups, and levels of liver enzymes, glucose, creatinine, urea, and electrolytes were similar in both groups, both before and aftertransplantation. CONCLUSIONS: Experimental OLT can be carried out in pigs without venovenous bypass, but it leads to severe hemodynamic disturbances. Clamping of the supraceliac artery during the AP is well tolerated and results in excellent hemodynamic stability, so it may prove to be a useful technique in liver transplantation in animals, such as dogs or pigs, that do not tolerate simultaneous clamping of the liver pedicle and inferior vena cava as well as human beings.
Animals↗
Late biliary complications in pediatric liver transplantation.
PURPOSE: The aim of this study was to review the biliary complications occurring in late follow-up after liver transplantation in children. METHODS: The medical records of 135 children who received orthotopic liver transplantations (OLT) and had graft survival of more than 1 year were reviewed. Technical variants using a reduced-size graft were applied in 32 (23.7%). For biliary reconstruction, 15 patients had choledochocholedochostomy and 120 a Roux-en-Y loop. Biliary reoperation in the early post-OLT period was needed in 24 patients (17.7%). Routine checking of liver function and duplex Doppler ultrasonography (DDS) were performed during the follow-up period, which averaged 58 months. Late biliary complication was defined as that occurring after the first hospital discharge. RESULTS: Late biliary complications occurred in 18 children (13.3%); 16 showed symptoms or analytical disturbances in liver function tests. The Diagnoses included uncomplicated cholangitis (n = 6), anastomotic biliary stricture (n = 7), ischaemic damage of the biliary tree (n = 3) including one late (28 months) hepatic artery thrombosis leading to an intrahepatic biloma. and bile leak after T-tube removal (n = 2). The six children with uncomplicated cholangitis had no repeat episodes in follow-up despite persistent aerobilia. Six patients affected by anastomotic strictures were treated successfully with percutaneous dilatation and, if present, stone removal. Persisting dysfunction and cholangitis occurred in one case affected by ischaemic biliary disease. Biliary leaks after T tube removal settled spontaneously. Risk factors for late biliary complications were determined. There was no relation to the cold ischaemia time, type of graft or biliary reconstruction, or previous early post-OLT biliary reoperation. Aerobilia (affecting 21.5% of OLT patients) was related to cholangitis (P = .001). CONCLUSIONS: Anastomotic strictures, reflux of intestinal contents via the Roux-en-Y loop, and residual ischaemic damage led to late biliary complications in 12% of paediatric OLT patients. Evidence of biliary dilatation on DDS may be delayed in anastomotic strictures; in these cases the results of percutaneous treatment were excellent. Children with aerobilia have and increased risk of cholangitis.
Analysis of Variance↗
Comparison of Bacillus subtilis and Serratia marcescens as protease producers under different operating conditions.
Two microorganisms, Bacillus subtilis and Serratia marcescens, have been selected in order to assess their ability to produce proteases. First, their performances have been studied using three media providing different levels of the main nutrients (complex, semi-defined and defined). The optimal absolute production was obtained in the complex media, while maximum protease activity per cell weight appeared in defined medium for Bacillus and in semi-defined and complex media for Serratia. Then, the effects of applying different environmental conditions to the cells were studied. The two microorganisms were immobilised in calcium alginate beads, protease production by these systems was assessed in the previously tested culture media, and the performances in free and immobilized operating conditions were compared. The richest medium seemed to be the best one in terms of absolute protease production, although the use of semi-defined or defined media could be considered more appropriate, in order to minimise growth of cells leaked from the support, and therefore downstream processing cost. Productivity was slightly higher in free cultures than in immobilized cultures, and retention of enzyme within the alginate beads was detected in the latter, indicating the occurrence of diffusional limitations. In all the cases studied, Serratia marcescens appeared as a better protease producer than B. subtilis, in terms of absolute production. This fact could be related to the different cell growth levels observed for the two microorganisms.
Journal Article↗
Mutational pattern of the nurse shark antigen receptor gene (NAR) is similar to that of mammalian Ig genes and to spontaneous mutations in evolution: the translesion synthesis model of somatic hypermutation.
The pattern of somatic mutations of shark and frog Ig is distinct from somatic hypermutation of Ig in mammals in that there is a bias to mutate GC base pairs and a low frequency of mutations. Previous analysis of the new antigen receptor gene in nurse sharks (NAR), however, revealed no bias to mutate GC base pairs and the frequency of mutation was comparable to that of mammalian IgG. Here, we analyzed 1023 mutations in NAR and found no targeting of the mechanism to any particular nucleotide but did obtain strong evidence for a transition bias and for strand polarity. As seen for all species studied to date, the serine codon AGC/T in NAR was a mutational hotspot. The NAR mutational pattern is most similar to that of mammalian IgG and furthermore both are strikingly akin to mutations acquired during the neutral evolution of nuclear pseudogenes, suggesting that a similar mechanism is at work for both processes. In yeast, most spontaneous mutations are introduced by the translesion synthesis DNA polymerase zeta (REV3) and in various DNA repair-deficient backgrounds transitions were more often REV3-dependent than were transversions. Therefore, we propose a model of somatic hypermutation where DNA polymerase zeta is recruited to the Ig locus. An excess of DNA glycosylases in germinal center reactions may further enhance the mutation frequency by a REV3-dependent mutagenic process known as imbalanced base excision repair.
Amino Acid Sequence↗
Nitric oxide participates in the immune response against Neisseria meningitidis serogroup B.
The present report explores the role of nitric oxide into the immune response against Neisseria meningitidis serogroup B. Here we show that NO mediates the alphaTNF increase induced by N. meningitidis derived lipopolysaccharides (LPS), at the same time that participates in the bactericidal activity of resting or gammaIFN activated macrophages and plays a role in the specific DTH and IgG response induced by a commercial anti-meningococcal vaccine. Our findings suggest a positive role for NO at the final effector mechanisms and in the early events driving the immunity against N. meningitidis, suggesting also an insight into its role in endotoxic shock.
Animals↗
Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers.
The new antigen receptor (NAR) gene in the nurse shark diversifies extensively by somatic hypermutation. It is not known, however, whether NAR somatic hypermutation generates the primary repertoire (like in the sheep) or rather is used in antigen-driven immune responses. To address this issue, the sequences of NAR transmembrane (Tm) and secretory (Sec) forms, presumed to represent the primary and secondary repertoires, respectively, were examined from the peripheral blood lymphocytes of three adult nurse sharks. More than 40% of the Sec clones but fewer than 11% of Tm clones contained five mutations or more. Furthermore, more than 75% of the Tm clones had few or no mutations. Mutations in the Sec clones occurred mostly in the complementarity-determining regions (CDR) with a significant bias toward replacement substitutions in CDR1; in Tm clones there was no significant bias toward replacements and only a low level of targeting to the CDRs. Unlike the Tm clones where the replacement mutational pattern was similar to that seen for synonymous changes, Sec replacements displayed a distinct pattern of mutations. The types of mutations in NAR were similar to those found in mouse Ig genes rather than to the unusual pattern reported for shark and Xenopus Ig. Finally, an oligoclonal family of Sec clones revealed a striking trend toward acquisition of glutamic/aspartic acid, suggesting some degree of selection. These data strongly suggest that hypermutation of NAR does not generate the repertoire, but instead is involved in antigen-driven immune responses.
Amino Acid Sequence↗
Long-term follow-up of patients with biliary atresia successfully treated with hepatic portoenterostomy. The importance of sequential treatment.
The outcome of 18 biliary atresia (BA) patients (5 male, 13 female; age range 10.7-22.5 years; mean 15.4+/-0.7 years) treated with hepatic portoenterostomy (HPE) and jaundice-free for more than 10 years without liver transplantation (LT) is analyzed retrospectively. Eight of these patients subsequently required LT (age at LT 12. 8+/-0.5 years, range 10.5-15.2 years); 3 children (aged 11.6, 13.2 and 14.1 years, respectively) had episodes of gastrointestinal variceal bleeding associated with other signs of severe disease and are now candidates for LT; and among the 7 asymptomatic patients (age range 11.2-22.5 years; mean 15.9+/-2.1 years), 5 had sonographic and biochemical signs of moderate portal hypertension (PH). In order to analyze whether the age at transplantation influences the survival of children transplanted for BA, we also reviewed the outcome of 71 BA patients transplanted at our hospital between 1986 and 1996. All the children older than 10 years at the time of LT were alive; only patients younger than 10 years died following LT (n = 15). We conclude that the natural outcome of extrahepatic BA is toward PH, fibrosis, and cirrhosis, even in those cases successfully treated with HPE. In our experience, the results of sequential treatment with HPE and LT were excellent.
Adolescent↗
Functional results of laparoscopic fundoplication in children.
BACKGROUND: There is no evidence that the results of laparoscopic fundoplication in children match those of the open procedure. In the current report, pre- and postoperative function of the antireflux barrier is examined in children having laparoscopic fundoplication for gastroesophageal reflux. METHODS: Twenty-seven patients with gastroesophageal reflux, aged 7.2+/-4.5 years, were operated on for unremitting gastrointestinal symptoms (n = 24), with respiratory tract disease (n = 11), cystic fibrosis (n = 2), or brain damage (n = 11). Gastrostomy was added in 5 cases. Barium contrast study, pH-metering, endoscopic examination, and biopsy were performed before and after a median of 19 months (range, 8 to 46) after operation. RESULTS: At diagnosis, 15 of 21 patients had esophagitis that was moderate or severe in 11 (1 with Barrett's esophagus). Symptoms disappeared after fundoplication in all but 2 patients, in whom they became milder. The reflux index decreased from 20.2+/-20% to 4.9+/-9% and became normal in all except 4 children (2 with brain damage and 1 with cystic fibrosis). Open repair of the failed wrap was considered necessary in only 1 of them. CONCLUSIONS: Laparoscopic fundoplication is as effective as the open procedure (14% overall failure rate). However, the failure rate in neurologic patients (18%) suggests that before reaching conclusions on the benefits of this approach, careful long-term assessment of the functional results is necessary.
Biopsy↗
Evolution of somatic hypermutation and gene conversion in adaptive immunity.
Examples of somatic hypermutation of antigen receptor genes can be seen in most lineages of vertebrates, including the cartilaginous fish. Analysis of the phylogenetic data reveals that two distinctive features of the mechanism are shared by most species studied: the mutation hot spot sequence AGY, and a preponderance of point mutations. These data suggest that some of the components of the machinery are shared between ectotherms and mammals. However, unique characters in particular species may have occurred by independent recruitment of novel factors onto the mechanism. A spotty phylogenetic distribution of gene conversion has also been revealed and can be explained if the two mechanisms share some characteristics. Both mutation and conversion require transcription-related sequences and/or factors. We theorized that targeting to V genes can be attained by a paused replication fork that has collided with a transcription complex stalled by a defective Ig transcription activator; the paused replication fork results in recruitment of an error-prone translesion synthesis DNA polymerase (somatic hypermutation) or of DNA repair mechanisms with homologous recombination (gene conversion). In addition, the pathway recruited in different species may be directed by the degree of homology among V genes.
Animals↗
Indium-111-pentetreotide in Graves' disease.
UNLABELLED: Thyroidal and orbital lymphocytic infiltration in Graves' disease, as well as identification of somatostatin receptors on lymphocytes, has provided a rationale for receptor imaging with the radiolabeled somatostatin analog pentetreotide. Recently, we demonstrated that in contrast to controls, Graves' patients showed markedly increased orbital accumulation of pentetreotide. Longitudinal and follow-up data are presented here. METHODS: In 20 (16 hyperthyroid) Graves' patients with active eye disease, planar (thyroid) and SPECT (orbit) images were performed 4 and 24 hr after injection of 111In-pentetreotide (222 MBq) before and 3 mo after starting antithyroid and combined steroid and orbital radiotherapy. RESULTS: Thyroidal uptake decreased during methimazole treatment (4 hr postinjection, median: hyperthyroid 989 counts/pixel/MBq injected activity, euthyroid 253 counts, p = 0.001; 24 hr, 437 versus 95 counts/pixel/MBq, p = 0.005). Fourteen patients (70%) responded to steroid and radiotherapy. The pentetreotide orbit-to-brain ratio decreased markedly after completion of therapy (4 hr: 25 before versus 6.2 after therapy, p = 0.0003; 24 hr: 9.6 versus 2.7, p = 0.003). A high pretreatment ratio correlated with a response to therapy (p = 0.001: in 14 of 16 patients with a ratio > 10, 4 hr postinjection, ophthalmopathy improved; positive predictive value: 90%; median activity score before 6 versus 2 after therapy, p = 0.0001) in contrast to none of the four cases with a ratio less than 10 (score 5 versus 4, p = 0.08). CONCLUSION: Pentetreotide scans may be regarded as a semiobjective tool in the evaluation of Graves' disease, both at initial stages as well as during treatment.
Anti-Inflammatory Agents↗
The role of liver transplantation in the subacute trauma patients.
Two case reports are presented involving complex liver traumas requiring the need for liver transplantation. Both of these patients were designated unsalvageable until the transplant team was consulted. It is imperative that surgeons involved with complex hepatic trauma not give up hope and include these patients as potential liver recipients when irreversible liver failure occurs.
Adult↗
Modulation of neuroendocrine differentiation in prostate cancer by interleukin-1 and -2.
Neuroendocrine differentiation in prostate cancer has received much attention recently because it has been found to be associated with androgen independence and shortened patient survival in some studies. We have investigated the effect of the cytokines interleukin-1 (IL-1), IL-2, and IL-6 on the expression of the neuroendocrine marker chromogranin A in human prostate cancer cell lines. Chromogranin A was measured by fluorescence-immunoassay, as well as by immunoblotting. We find that IL-1beta and IL-6 increase the cellular content and chromogranin A secretion by LNCaP and DU-145 cells. By contrast, IL-2 decreases the cellular and secreted chromogranin A levels in the two cell lines. Our results suggest that these proinflammatory cytokines can influence neuroendocrine differentiation in prostate cancer and be involved in disease progression.
Cell Differentiation↗
Striped bass population subdivision within the santee-cooper system, south carolina
Population subdivision was indicated in striped bass (Morone saxatilis) from the Santee-Cooper system, South Carolina. Samples from the two major spawning grounds, the Congaree River (n = 273) and Wateree River (n = 111), and from the Santee River, the source of hatchery broodstock (n = 128), were collected during the 1992, 1993, and 1994 spawning seasons. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assays of three independently segregating loci were used to screen population samples from the system. An allele frequency difference among samples from the three rivers was detected at the SB83 locus. In addition, the SB14 locus showed a significant temporal change in allele frequencies in the Santee River sample. Furthermore, a heterozygote deficiency was observed in the Santee and Congaree River samples, suggesting either inbreeding due to hatchery augmentation or admixture of two distinct populations. These data suggest that there is population substructure in the Santee-Cooper system and that future hatchery augmentation efforts should recognize this population subdivision.
Journal Article↗
Physiological changes in the juvenile euryhaline teleost, the tilapia Oreochromis hornorum, injected with E. coli-derived homologous growth hormone.
Growth is a complex process in fish. This study was designed to test the effect of different levels of recombinant tilapia growth hormone (tiGH) injected intraperitoneally in juvenile hybrid tilapia Oreochromis hornorum. Tilapia GH cDNA was cloned from hybrid O. hornorum tilapia. The mature protein was expressed in E. coli under regulation of the phage T7 promoter. The E. coli-derived tiGH was partially purified to 67% purity and, following renaturation, was shown to be biologically active in in vivo and in vitro assays. Recombinant tiGH stimulated extracellular matrix synthesis as shown by 35S-sulfate uptake in ceratobranchial cartilage explants. Zero, 0.1, 0.5 and 2.5 µg tiGH/g body weight (gbw) were injected in tilapia, and the effects on the growth-promoting action, hepatosomatic index (HSI), and mRNA insulin-like growth factor (IGF) induction were measured. A significant increase in the body weight (P < 0.05) and length (P < 0.01) was observed in tilapia receiving 0.5 µg tiGH/gbw. However, tilapia receiving 0.1 and 2.5 µg tiGH/gbw did not show an increase in body weight and length with respect to the control group receiving BSA injections. Binding sites for the recombinant tiGH were identified in the liver. Consistent with its somatotropic actions, the IGF mRNA induction was observed in the groups injected with 0.1 and 0.5 µg tiGH/gbw (P < 0.05). No significant increase in the HSI was detected in the injected groups when compared to the control group. These results demonstrated that the injection of biologically active E. coli-derived tiGH produces physiological changes in juvenile tilapia that ultimately resulted in a growth-promoting action only at a dose of 0.5 µg tiGH/gbw.
Journal Article↗
Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras.
To study the role of Th0 and Th1 cells in autoimmune thyroid disease, thyroid tissues from patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and colloid nodular disease were xenografted into SCID mice, followed by ip injection of peripheral blood mononuclear cells (PBMC), T cell lines, and T cell clones (TCC). The antigen-specific TCC reactive to TSH receptor (TSH-R), thyroid peroxidase (TPO), or thyroglobulin (Tg), and their respective peptides, were classified into Th0 (secreting IL-4 and/or IL-5 and IFN-gamma) and Th1 (secreting IFN-gamma) according to their cytokine profile. Engraftment of autologous or HLA-matched allogeneic CD4+ thyroid-specific clones with Th0 or Th1 phenotypes induced the production of total IgG and thyroid-specific autoantibodies by B cells present in xenografted thyroid tissues. TSH-R-specific clones mainly enhanced thyroid-stimulating antibodies (TSAb) production, while clones reactive to TPO and Tg increased the synthesis of TPO and Tg autoantibodies. Total IgG production, but not TSAb, was also stimulated by PBMC and TSH-R lines. TSAb correlated with the viability and hyperplasia of thyroid follicles, but not with the serum T3 levels, which were normal. Thyroid tissue viability was maintained or increased by antigen-specific Th0 clones, and decreased by Th1 clones reactive to TSH-R or TPO. Thyroid lymphocytic infiltration was variable; however, Th0 and Th1 clones from HT patients caused high degree of lymphocytic infiltration compared to the control groups. These results demonstrate for the first time that T cells clones reactive to specific epitopes of TSH-R, TPO, or Tg can generate antibody-mediated and/or cell-mediated responses in the xenografted thyroid tissue microenvironment. Such effects depend on clonal specificity, HLA class II restriction, and cytokine profile of the clone. Th0 clones reactive to TSH-R stimulate both total IgG production and TSAb in SCID mice engrafted with thyroid tissue from GD patients. Th0 and Th1 clones specific for TPO and Tg also function as helper T cells, stimulating total IgG synthesis and autoantibodies against TPO and Tg. Th1 clones may also cause tissue destruction in GD and HT.
Adolescent↗
Light and electron microscope study of nerve cells in traumatic oedematous human cerebral cortex.
The cerebral cortex of eight patients with complicated head and brain traumatic injuries has been examined with light and transmission electron microscopes. The neuronal and neuroglial cell bodies and their processes have been examined to study the changes induced by the brain injury and the associated vasogenic and cytotoxic, moderate or severe, brain oedema. Light microscopy study showed oedematous and ischaemic neurons and neuroglial cells in both moderate and severe oedema, and breakdown of the blood-brain barrier with perivascular and parenchymatous haemorrhagic foci. Astrocytes and oligodendrocytes exhibited oedematous and reactive changes. At the electron microscope level oedematous changes were found in intraneuronal and glial somatic compartment. Myelinated axons showed clear and dark degenerative features. Beaded dendrites and clear and dense synaptic degeneration were also found. The extracellular space appeared distended, with the presence of clear and electron-dense haematogenous oedema fluid and fibrinous organization. Phagocytosis of degenerated myelinated axons and synaptic endings by neuroglial cells and non-nervous invading cells were observed. The clinical evolution time of traumatic brain injuries was considered in relation to nerve cell degenerative features.
Adolescent↗