Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement.

PURPOSE: The serum metabolic changes occurring during the transition from hypothyroidism to euthyroidism are not known. This study aimed to determine the metabolomic profile in hypothyroid patients before (HypoT0) and after (HypoT1) euthyroidism achieved through levothyroxine (L-T4) treatment. METHODS: Eighteen patients with overt primary hypothyroidism were recruited for the study. All patients were treated with L-T4 to achieve euthyroidism. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and metabolomics profiles were measured before and after 3 months of treatment. The euthyroid control group consisted of 28 healthy volunteers. Metabolomics analysis was performed using Nuclear Magnetic Resonance (NMR) spectroscopy. RESULTS: 1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls. Interestingly, some metabolic changes were persistent three months after pharmacological treatments, despite normal serum TSH and thyroid hormone concentrations (HypoT1). When an Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model was built to evaluate possible differences in the metabolic profile between HypoT0 and HypoT1, the data obtained were not significantly different. CONCLUSION: These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology. So, the metabolomics approach may contribute to integrate classical hormone assays and to determine the euthyroid status achievement with greater efficacy.

Intensive care in patients with lung cancer: a multinational study.

BACKGROUND: Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS: Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS: Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS: ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.

Spinal cord MRI activity in multiple sclerosis: Predictive value for relapses and impact on treatment decisions.

INTRODUCTION: Emerging evidence suggests the prognostic value of spinal cord (SC) pathology in multiple sclerosis (MS). However, the 2021 MAGNIMS-CMSC-NAIMS guidelines don't recommend routine SC MRI for disease monitoring. This study investigates the frequency of new asymptomatic and isolated SC lesions, exploring their potential to predict clinical activity and guide treatment decisions. METHODS: We enrolled relapsing-remitting MS (RRMS) patients who underwent brain and SC MRI at baseline and after 12 months. New, enlarged, or gadolinium-enhanced (Gd+) lesions on MRI were considered disease activity markers. Clinical relapses and treatment changes observed 3 months after the 12-month MRI were analyzed using regression analysis, evaluating their association with worsening SC findings. RESULTS: A total of 201 RRMS patients (56 males, 27.9%, mean age 42.5 ± 12.1 years, mean EDSS 2.7 ± 1.9) were included. Isolated worsening of T2 lesion burden in the SC occurred in 16 patients (8%), and 12 (6%) had Gd + lesions. Among patients without brain MRI activity (n = 138), regression analysis revealed a significant association between new Gd + SC lesions and clinical relapses within 3 months of the 12-month MRI (p = 0.024). Worsening SC findings (p = 0.021) and SC lesion enhancement (p = 0.046) emerged as key factors influencing disease-modifying therapy changes within 3 months in these patients. Notably, even without clinical symptoms, worsening SC findings significantly predicted treatment changes (p = 0.003). CONCLUSION: Our findings highlight the independent value of SC MRI findings in MS monitoring. Importantly, isolated and asymptomatic SC worsening significantly impacted treatment decisions.

Clinical effect of corticosteroids in asthma-affected horses: A quantitative synthesis.

BACKGROUND: There are limited findings from low-powered studies based on few number of subjects with equine asthma. Furthermore, no studies have been performed to assess a meaningful clinically detectable impact of corticosteroids in equine asthma. OBJECTIVES: To assess and compare the clinical effect of inhaled and systemic corticosteroids in equine asthma and identify a quantitative clinical score suitable to assess the Minimal Important Difference (MID), expressed as the Minimally Clinically Detectable Difference (MCDD). STUDY DESIGN: Pair-wise and network meta-analysis. METHODS: Literature searches for studies on corticosteroid therapy in equine asthma were performed. The risk of publication bias was assessed by Funnel plots and Egger's test. The effect on changes in clinical scores vs. control was analysed via random-effects models and Bayesian networks. RESULTS: Corticosteroids significantly improved the clinical condition (Standardised Mean Difference: -1.52, 95% CrI -2.07 to -0.98; P<0.001 vs. control). No difference was detected between inhaled and systemic corticosteroids with regard to the changes in clinical scores (Relative Effect: 0.08, 95% CrI -1.45 to 1.32; P = 0.8). An Improved clinically Detectable Equine Asthma Scoring System (IDEASS) indicated that corticosteroids improved the clinical condition of asthmatic horses by 30% compared with controls (IDEASS value: -2.36, 95% CI -3.39 to -1.33; P<0.001). A one-point change in IDEASS represented the MCDD in equine asthma. MAIN LIMITATIONS: Moderate quality of evidence for systemic corticosteroids. CONCLUSIONS: Inhaled corticosteroids are effective in improving the clinical condition of horses with equine asthma and prevent exacerbations. Systemic corticosteroids should be used only in selected cases with symptomatic airway hyperresponsiveness during exacerbation. IDEASS requires further validation but may represent a suitable approach to rank the level of asthma severity and assess the clinical effect of pharmacotherapy in horses with equine asthma.

Geographical characteristics influencing the risk of poisoning in pet dogs: Results of a large population-based epidemiological study in Italy.

Pets can act as sentinels for human health and thus surveillance of pet dogs has the potential to improve awareness of emerging risks for animal and public health. The aim of this study was to investigate factors associated with the risk of canine poisoning. In a large population-based epidemiological investigation in Italy performed from January 2015 to January 2016 and April 2016 to April 2017, descriptive statistics were acquired and analysed to determine variables associated with poisoning events in pet dogs. Results were validated in a test population and forecast analysis of risk was performed. The cumulative incidence of poisoning events was low (10.2/1000 dogs/year). Anticoagulant rodenticides, organophosphate pesticides, metaldehyde and strychnine were the most frequent causes of intoxications. Territory characteristics significantly modulated both the frequency and the nature of the involved substances. The seashore area was associated with poisoning by rodenticides (odds ratio, OR, 1.81, 95% confidence interval, CI, 1.54-2.13) and metaldehyde (OR 1.61, 95% CI 1.16-2.28). The hill country area was associated with poisoning by organophosphate pesticides (OR 1.73, 95% CI 1.38-2.15), metaldehyde (OR 2.26, 95% CI 1.53-3.25) and strychnine (OR 1.86, 95% CI, 1.34-2.57). The mountain area was associated with strychnine poisoning (OR 3.79, 95% CI 2.84-5.06). The prospective cumulative incidence of poisoning over 10 years was 9.74% (95% CI 9.57-9.91). These results may be useful for predicting the risk of poisoning and for estimating the risk index related to specific toxic compounds in specific territories. This study suggests that poisoning events in dogs may represent a problem of public health with the potential to affect wildlife and human beings.

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs).

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.

Peripheral blood CD8+ T-cell profiles in patients with psoriatic arthritis: a cross-sectional case-control study.

OBJECTIVE: While CD4+ T-cells are traditionally regarded as the main pathogenic T-cell subpopulation in psoriatic arthritis (PsA), the role of circulating CD8+ T-cells remains poorly characterized. We evaluated the differential representation of CD8+ T-cell subpopulations in peripheral blood (PB) of PsA patients. PATIENTS AND METHODS: CD8+IL-17+, CD8+IFNγ+ and CD8+IL-17-IL-22+ T-cells were evaluated by flow-cytometry in 25 consecutive PsA patients, 7 rheumatoid arthritis (RA) patients, 16 patients with psoriasis, and 26 healthy controls (HC). RESULTS: We observed a significant expansion of circulating IFN-γ producing CD8+ T-cells in PsA when compared to psoriasis [21.2 (6.9-55.8)% vs. 3.8 (0.7-11.8)%, p < 0.0001] and HC samples [21.2 (6.9-55.8)% vs. 4.05 (0.44-19.8)%, p < 0.0001]. A frequency of circulating IFN-γ producing CD8+T-cells ≥ 9% distinguished PsA from psoriasis patients with a specificity of 84% and a sensitivity of 87.5% [AUC = 0.9 (0.80-0.99), p < 0.0001]. In addition, we found a significant expansion of circulating IL-17 producing CD8+ T cells in RA patients when compared to PsA, psoriasis and HC samples. By contrast, there were no significant between-group differences in the prevalence of circulating IL-22 producing CD8+ T-cells. In PsA patients there was a significant correlation between number of swollen joints and frequency of circulating IFN-γ producing CD8+ T-cells, and between extent and severity of psoriasis and frequency of circulating IL-17 producing CD8+ T-cells. CONCLUSIONS: Circulating IFNγ-producing CD8+ T-cells are raised in PsA when compared to psoriasis, suggesting a potential pathogenetic involvement of CD8+ T-cells and IFNγ production in chronic joint inflammation and damage. The significant enrichment of circulating IL-17 producing CD8+ T-cells in RA when compared to PsA warrants functional characterization and confirmation in larger studies. We found no significant enrichment of circulating IL-22 producing CD8+ T-cells in PsA, RA and psoriasis.

Desulfovibrio desulfuricans iron hydrogenase: the structure shows unusual coordination to an active site Fe binuclear center.

BACKGROUND: Many microorganisms have the ability to either oxidize molecular hydrogen to generate reducing power or to produce hydrogen in order to remove low-potential electrons. These reactions are catalyzed by two unrelated enzymes: the Ni-Fe hydrogenases and the Fe-only hydrogenases. RESULTS: We report here the structure of the heterodimeric Fe-only hydrogenase from Desulfovibrio desulfuricans - the first for this class of enzymes. With the exception of a ferredoxin-like domain, the structure represents a novel protein fold. The so-called H cluster of the enzyme is composed of a typical [4Fe-4S] cubane bridged to a binuclear active site Fe center containing putative CO and CN ligands and one bridging 1, 3-propanedithiol molecule. The conformation of the subunits can be explained by the evolutionary changes that have transformed monomeric cytoplasmic enzymes into dimeric periplasmic enzymes. Plausible electron- and proton-transfer pathways and a putative channel for the access of hydrogen to the active site have been identified. CONCLUSIONS: The unrelated active sites of Ni-Fe and Fe-only hydrogenases have several common features: coordination of diatomic ligands to an Fe ion; a vacant coordination site on one of the metal ions representing a possible substrate-binding site; a thiolate-bridged binuclear center; and plausible proton- and electron-transfer pathways and substrate channels. The diatomic coordination to Fe ions makes them low spin and favors low redox states, which may be required for catalysis. Complex electron paramagnetic resonance signals typical of Fe-only hydrogenases arise from magnetic interactions between the [4Fe-4S] cluster and the active site binuclear center. The paucity of protein ligands to this center suggests that it was imported from the inorganic world as an already functional unit.

Structural features of the interaction between an anti-clonotypic antibody and its cognate T-cell antigen receptor.

The crystal structure of the complex between a single chain Fv fragment of the KB5-C20 T-cell antigen receptor (TCR) and the specific anti-clonotypic antibody (Ab) Désiré-1 provides the first description of the interface between a clonotype and an anti-clonotype. In the four idiotype/anti-idiotype complexes of known three-dimensional structures, the interacting Fv fragments associate largely through their complementarity-determining regions (CDRs). In marked contrast, Désiré-1 binds to a face of the KB5-C20 TCR that is almost perpendicular to the TCR antigen binding site, and recognizes discontinuous stretches of TCR Valpha and Vbeta residues that belong to both the CDRs and the framework. Despite this peculiar mode of interaction, Désiré-1 constitutes a genuine anti-clonotypic Ab. Moreover, in spite of the fact that the Désiré-1 contact residues do not constitute a molecular mimic of the physiological ligand normally recognized by the KB5-C20 TCR, the bivalent Désiré-1 Ab is capable of efficiently activating T-cells expressing the KB5-C20 TCR.

Crystallization and preliminary X-ray diffraction study of the nickel-binding protein NikA of Escherichia coli.

NikA, a periplasmic nickel-binding protein involved in nickel-repellent chemotaxis has been crystallized. The crystals are hexagonal with space group P6(2) (or its enantiomorph) with a = 160.3 A and c = 138.4 A and they diffract to at least 3.0 A resolution in the laboratory. NikA presents sequence homology with several periplasmic solute-binding proteins from Gram-negative bacteria.

Hydrogenase: a hydrogen-metabolizing enzyme. What do the crystal structures tell us about its mode of action?

Hydrogenases are proteins which metabolize the most simple of chemical compounds, molecular hydrogen, according to the reaction H2<-->2H+ + 2e-. These enzymes are found in many microorganisms of great biotechnological interest such as methanogenic, acetogenic, nitrogen fixing, photosynthetic or sulfate-reducing bacteria. The X-ray structure of a dimeric [NiFe] hydrogenase together with a wealth of biophysical, biochemical and genetic studies have revealed that the large subunit contains the bimetallic [Ni-Fe] active site, with biologically uncommon CO and CN ligands to the iron, whereas the small subunit contains three iron-sulfur cluster. During catalysis, the nickel atom is most likely responsible for a base-assisted heterolytic cleavage of the hydrogen molecule whereas the iron atom could be redox active. Specific channels are probably required for the transfer of the chemical reaction partners (H2, H+ and e-) between the active site, deeply buried inside the protein, and the molecular surface. The generation of a functional enzyme, including the assembly of the complex catalytic center, requires maturation and involves a large number of auxiliary proteins which have been partly characterized by molecular biology.

The relationship between the papillary muscles and the anatomicosurgical segments of the left ventricle of the human heart.

The relationship between the blood supply of the papillary muscles of the left ventricle of 90 adult human Caucasian hearts and the arteries of the cardiac anatomicosurgical segments was studied after arterial injection of Vinyl acetate and partial or total corrosion. The anterior papillary muscle belongs in most cases to the I SV segment whereas the posterior muscle belongs to the III DV segment, the former pertaining to the left coronary a. and the latter to the right a.

Lipid components and water soluble metabolites in salted and dried tuna (Thunnus thynnus L.) roes.

The salted and dried product of tuna roe (bottarga) is a seafood characteristic of the Mediterranean area and exported all over the world. Samples of bottarga from bluefin tunas (Thunnus thynnus, L.) caught in the southwest Mediterranean sea were analysed. The samples were characterised by high content of marine wax esters (55-67 mol% of lipid classes), of docosahexaenoic (22:6 n-3, 25 w%) and oleic (18:1 n-9, 19 w%) fatty acids. Cholesterol was detected as 7-9 w% of lipids. Free fatty acids, index of lipid hydrolysis, represented 32-39 mol% over total fatty acids. Among metabolites, nutrients as taurine, nicotinamide and ß-alanine, were found. The microflora comprised staphylococci, enterococci (2.2 log(10)CFU/g) and lactic acid bacteria (3 log(10) CFU/g). The food-borne pathogens Staphylococcus aureus, Listeria monocytogenes and Salmonella spp. were not detected. These findings indicate tuna bottarga as valuable source of nutrients.

Main causes of nonfulfillment of corneal donation in five hospitals of a Brazilian state.

The waiting list for corneal transplantation in Brazil had 6684 patients in June 2012, with great variations in the number of patients among different states. The mean waiting time for a corneal transplant also differs substantially across the states: it is 2 years in State of Espirito Santo (ES) at the time of this study. The aim of the study was to determine the main reasons for nonfulfillment of corneal donation in five ES hospitals. The data collection was performed from March to August 2010. The data were collected using forms completed daily by the Intrahospital Commissions of Organ and Tissues Donation for Transplantation. The total number of deaths was 1347. The main causes of nonfulfillment of donations were medical contraindications (67.86%), logistical/structural problems (27.84%), and family refusal (2.15%). The main medical contraindications were age outside the required range (24.49%), the presence of infectious disease (11.36%), or age outside the range plus infection (15.66%). In 2010, there were 459 people on the waiting list for corneas in ES. Considering the average of failures in these five hospitals multiplied by the number of hospitals in the ES, it seems clear that the solutions to these problems might eliminate the waiting list of the State. In fact, the number of individuals on the waiting list in ES did reach zero in August 2011, after the inauguration of a new Eye Bank that trains employees to interview and perform procurements, in addition to keeping them available in the most important hospitals. Additionally, the maximal age for donation in ES was increased.

Reasons for noneffectiveness of organ donation programs in five hospitals in the state of Espírito Santo, Brazil.

Although, in absolute numbers, more organ transplantations are performed in Brazil than in many other countries, the donation rate (the number of donors per million individuals) remains quite low. The aim of this study was to determine the reasons for nonfulfillment of organ donations in five hospitals in the State of Espirito Santo, Brazil. This knowledge could help to identify strategies and implement changes to improve the organ donation process and to increase the rate in Brazil and other countries that face similar challenges. This prospective study collected data including the numbers of patients with suspected brain death (both confirmed and nonconfirmed), effective, and of nonfulfilled donations. Data were collected using forms completed daily by the Intra-Hospital Commission for Organ and Tissue Donation of the hospitals during the period from March to August 2010. There were 1386 deaths. The protocol for brain death diagnosis was initiated in 2.8% of them, but only 28.21% of confirmed brain death patients became effective donors. The causes of nondonation differed among the hospitals surveyed, suggesting that different strategies should be implemented to combat the specific weaknesses of each service, which must be continuously evaluated to increase the efficiency of the organ donation process.

A discovery-phase urine proteomics investigation in type 1 diabetes.

Diabetes is a chronic metabolic disease which can lead to serious health problems particularly in and to the development of cardiovascular and renal complications. The aim of this study is to possibly identify distinctive molecular features in urine samples which might correlate to the progression and complications of type 1 diabetes. Diabetic patients with normo- and micro-albuminuria have been analyzed and compared to a group of control subjects. Urine proteins of control and type 1 diabetes subjects were investigated in their proteome profiles, using high-resolution two-dimensional gel electrophoresis separation and protein identifications by MALDI-TOF-MS and LC-MS/MS analysis. Proteomics analysis highlighted differential expression of several proteins between control and type 1 diabetes subjects. In particular, five proteins were found to be down-regulated and four proteins up-regulated. Lower protein representations in diabetic subjects were associated with Tamm-Horsfall urinary glycoprotein, apolipoprotein A-I, apolipoprotein E, α2-thiol proteinase inhibitor, and human complement regulatory protein CD59, while higher protein representations were found for α-1-microglobulin, zinc-α2 glycoprotein, α-1B glycoprotein, and retinol-binding protein 4. These differences were maintained comparing control subjects with type 1 diabetes normo-albuminuric and micro-albuminuric subjects. Furthermore, these proteins are correlated to glycosylated hemoglobin and microalbuminuria, confirming their role in diabetic pathology. This study gives new insights on potential molecular mechanisms associated with the complications of type 1 diabetic disease providing evidences of urine proteins potentially exploitable as putative prognostic biomarkers.

Scalp-recorded oscillatory potentials evoked by transient pattern-reversal visual stimulation in man.

Replicable oscillatory potentials, time-locked to pattern stimuli (9.0 degrees central; counterphase reversal at 2.13 Hz) were dissociated from conventional, broad-band VEPs recorded in healthy volunteers at occipital scalp locations by high-pass digital filtering at 17.0-20.0 Hz. Nine consecutive wavelets were identified with a 56.4 +/- 8.4 msec mean latency of the first replicable wavelet and mean peak-to-peak amplitude varying between 0.9 and 2.0 muV. The first 2 wavelets had significantly shorter latencies than wave N70 of unfiltered VEP, whereas the last 2 wavelets had longer latencies than N145. Latency and amplitude values varied as a function of contrast and spatial frequency of the stimulus, with shorter latencies and larger amplitudes at 60-90% contrast level and tuning of amplitude at 5.0 c/deg. All wavelets were correlated with wave P100 of unfiltered VEP, while a correlation with N70 of VEP was observed only for those wavelets with latencies in the range of wave P100. Two patients with documented brain lesions involving the visual system are described as examples of oscillatory responses occurring irrespective of filter bandpass and instead of the expected conventional VEP when the generation of these is interfered with by brain pathology. A substantial cortical contribution to the origin of the oscillatory response is conceivable. It is suggested that the oscillatory response to pattern-reversal stimulation reflects events in the visual system that are parallel to, and partly independent of, the conventional VEP, with potential application in research or for clinical purposes.

Decrease of thyroid hormones in patients with familial hypercholesterolemia during dextran sulphate low-density lipoprotein apheresis.

Removal of low-density lipoproteins from plasma by dextran sulfate adsorption (DSA) in FH patients entails a decrease in plasma levels of thyroid hormones (-28.5% and -18.7%, respectively, for T3 and T4). This suggests that FH patients have a greater than normal fraction of thyroid hormones bound to lipoproteins, due to their expanded lipoprotein pool.

The three-dimensional structure of a T-cell antigen receptor V alpha V beta heterodimer reveals a novel arrangement of the V beta domain.

The crystal structure of a mouse T-cell antigen receptor (TCR) Fv fragment complexed to the Fab fragment of a specific anti-clonotypic antibody has been determined to 2.6 A resolution. The polypeptide backbone of the TCR V alpha domain is very similar to those of other crystallographically determined V alphas, whereas the V beta structure is so far unique among TCR V beta domains in that it displays a switch of the c" strand from the inner to the outer beta-sheet. The beta chain variable region of this TCR antigen-binding site is characterized by a rather elongated third complementarity-determining region (CDR3beta) that packs tightly against the CDR3 loop of the alpha chain, without leaving any intervening hydrophobic pocket. Thus, the conformation of the CDR loops with the highest potential diversity distinguishes the structure of this TCR antigen-binding site from those for which crystallographic data are available. On the basis of all these results, we infer that a significant conformational change of the CDR3beta loop found in our TCR is required for binding to its cognate peptide-MHC ligand.

Hordeum vulgare Seedlings Amine Oxidase: Purification and Properties.

Although no amine oxidase could be detected in crude extracts, the enzyme has been purified to apparent homogeneity from Hordeum vulgare seedlings using ammonium sulfate precipitation and chromatography on DEAE cellulose, Hydroxylapatite, and Sephadex G200 columns. Gel filtration experiments indicate a molecular weight of about 150,000. The pH optimum of the enzyme was found to be 7.5 in potassium phosphate buffer. The spectrum of ultraviolet and visible regions were similar to Cuamine oxidase from Leguminosae.