Screening of peptide probe binding to particulate matter with a high metal content

Particulate matter (PM) is becoming an increasing health concern and there is a need to develop detection methods to keep its harmful effects in check. Generation of reactive oxygen species (ROS) by PM is often associated with metal compounds, hence our aim is to screen for a peptide probe towards improved collection and the detection of PM having a high metal content. Peptides are putative recognition molecules due to their versatility and ease of modification to enhance their binding selectivities. PM binding peptides were screened using the peptide array and different binding behaviors in terms of different spot colors (yellow, mixed and gray), indicating the different composition of bound PMs, were observed. The strongest binding peptides were identified as follows: NHVNTNYYPTLH (gray), NGYYPHSHSYHQ (mixed) and HHLHWPHHHSYT (yellow), with relative binding ratios of 125%, 144% and 136%, in comparison with WQDFGAVRSTRS, a peptide screened from a phage display in our previous study. Inductively coupled plasma mass spectrometry (ICPMS) analyses revealed that Co, Ni and Zn content in the PM bound to the HHLHWPHHHSYT peptide spot were respectively 12.5, 15.8 and 7.8 times that of the PM bound to no peptide spot, suggesting this peptide probe is applicable to collect PM with a high metal content.

Using peptide array, peptides binding to particulate matter with high metal content were screened and characterized by focusing on the different spot colors (yellow, mixed and gray).     

Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia

Three patients had leukocytosis of large granular lymphocytes and chronic neutropenia. Clonal chromosomal abnormalities (trisomy 8 and trisomy 14) and lymphocytic infiltration of splenic red pulp, hepatic sinusoids, and bone marrow indicated the neoplastic nature of the large granular lymphocytes. Demonstration of a T3+, T8+, HNK-1 + phenotype and low natural killer cell activity that was augmented by interferon treatment showed the leukemic cells to be immature natural killer cells. Multiple autoantibodies were present and included rheumatoid factor and antinuclear, antineutrophil, antiplatelet, and antierythrocyte antibodies, suggesting a defect of B-cell immunoregulation. In addition, in-vitro studies showed impaired suppression of immunoglobulin biosynthesis by abnormal cells from one patient. Antineutrophil antibodies and absence of direct cell-mediated inhibition of granulocyte-macrophage colony formation supported a humoral immune mechanism for the neutropenia. In these patients the syndrome of splenomegaly, multiple autoantibodies with neutropenia, and lymphocytosis of large granular lymphocytes is due to a neoplastic proliferation of immature natural killer cells.     

Dynamics of serum thyrotropin and thyroid hormone changes in fasting

This study was designed to address the question of whether decreased hypothalamic TRH secretion was responsible for the transient decline in serum TSH levels characteristic of the early phase of fasting in man. Changes in serum TSH, total T4 (TT4), free T4 (FT4), and total T3 (TT3)/TT4 and total rT3(TrT3)/TT4 ratio values together with plasma TRH levels were evaluated before, during, and after a constant 48-h infusion of either TRH (75 ng/min), or saline, initiated at 10 h into a 6-day fast, in groups of six ambulating, mildly obese female subjects. On the first day of the fast, no change in serum TSH levels was seen with saline infusion relative to control, whereas mean TSH levels rose 2 1/2-fold with TRH infusion. On the second day of the fast, serum TSH levels simultaneously declined in both the saline- (43%, P less than 0.005) and TRH- (52%, P less than 0.005)-infused groups relative to the previous day. On the third day of the fast, after stopping the infusions, mean serum TSH levels fell below control in both the saline- and TRH-treated groups, but subsequently returned to prefasting levels. A distinct circadian pattern of TSH release was present throughout the study. Plasma TRH values were unaffected by fasting in the saline-infused group, but rose 2 1/2-fold in the TRH-infused group. The sequence of changes in the serum thyroid hormone indices were similar for the two groups: a rapid rise in FT4 was followed by a gradual fall in TT3/TT4 ratios during the first 24 h of fast, which was followed by a rise in TrT3/TT4 ratios after 48 h of fast. This study in fasting, mildly obese females suggests that: 1) The transient suppression of serum TSH during early fasting is not TRH mediated. 2) Fasting does not alter plasma TRH levels. 3) A temporal sequence of changes in serum thyroid hormone indices occurs in fasting, this being an initial rise in FT4 (10 h) followed by a fall in both serum TT3/TT4 (12-14 h) and TSH (30-36 h) and finally by a rise in TrT3/TT4 levels (48 h). This sequence of events suggests that the initial inhibition of serum TSH levels in early fasting results from the acute elevation in FT4 levels, and that the reestablishment of normal serum TSH levels with continued fasting is associated with declining serum TT3 levels.     

MIDA boronate allylation – synthesis of ibuprofen

MIDA boronates are among the most useful reagents for the Suzuki–Miyaura reaction. This chemistry typically generates new bonds between two aromatic rings, thereby restricting access to important areas of chemical space. Here we demonstrate the coupling of MIDA boronates to allylic electrophiles, including a new synthesis of the well-known COX inhibitor ibuprofen.

Here we demonstrate the coupling of MIDA boronates to allylic electrophiles, including a new synthesis of the well-known COX inhibitor ibuprofen.     

In Vitro Assembly of Neurospora Assimilatory Nitrate Reductase from Protein Subunits of a Neurospora Mutant and the Xanthine Oxidizing or Aldehyde Oxidase Systems of Higher Animals

In vitro assembly or complementation of a hybrid assimilatory nitrate reductase was attained by mixing a preparation of nitrate-induced N. crassa mutant nit-1 specifically with acid-treated (pH 2.5) bovine milk or intestinal xanthine oxidase, rabbit liver aldehyde oxidase, or chicken liver xanthine dehydrogenase. The complementation reaction specifically required induced nit-1, the only nitrate reductase mutant of Neurospora that lacked xanthine dehydrogenase and was unable to use hypoxathine or nitrate as a sole nitrogen source. The complementing activities of the above acid-treated enzymes correspond to their xanthine or aldehyde oxidizing activity profiles on sucrose density gradients. The resulting soluble, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductases are the same as the Neurospora wild type enzyme in sucrose density gradient profile, molecular weight, substrate affinities, and sensitivity to inhibitors and temperature. By analogy to a similar in vitro complementation of nitrate reductase in mixtures of induced nit-1 and individual nonalleic Neurospora mutants, or uninduced wild type, the complemented nitrate apparently consists of an inducible protein subunit (possessing inducible NADPH-cytochrome c reductase) furnished by nit-1 and a subunit from the acid-treated xanthine or aldehyde oxidizing system which can substitute for the constitutive component furnished by the other mutants or uninduced wild type. The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.     

The quality of care under a managed-care program for dual eligibles

PURPOSE: Our objective in this study was to compare the quality of care provided under the Minnesota Senior Health Options (MSHO), a special program designed to serve dually eligible older persons, to care provided to controls who received fee-for-service Medicare and Medicaid managed care. DESIGN AND METHODS: Two control groups were used; one was drawn from nonenrollees living in the same area (Control-In) and another from comparable individuals living in another urban area where the program was not available (Control-Out). Cohorts living in the community and in nursing homes were included. Quality measures for both groups included mortality rates, preventable hospital admissions, and preventable emergency room (ER) visits. For the community group, nursing home admission rates were also tracked. For nursing home residents, quality measures included quality indicators derived from the Minimum Data Set. RESULTS: There were no differences in mortality rates for either cohort. MSHO had fewer short-stay nursing home admissions but no difference for stays 90 days or longer. MSHO community and nursing home residents had fewer preventable hospital and ER visits compared to Control-In. There were no major differences in nursing home quality indicator rates. IMPLICATIONS: The cost of changing the model of care for dual eligibles from a mixture of fee-for-service and managed care to a merged managed-care approach cannot be readily justified by the improvements in quality observed.