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J C Howard

Publications and source records attributed to J C Howard.

138 records · Page 8Linked to original sources

Investigation of the conformations of four tetrapeptides by nuclear magnetic resonance and circular dichroism spectroscopy, and conformational energy calculations.

Proton nuclear magnetic resonance and circular dichroism studies were carried out on aqueous solutions of the tetrapeptide Asp-Lys-Thr-Gly (which appears as a bend at residues 35-38 of alpha-chymotrypsin) and its sequence variants Gly-Thr-Asp-Lys, Asp-Lys-Gly-Thr, and Lys-Thr-Gly-Asp; the N and C termini of all four tetrapeptides were blocked with CH3CO and NHCH3 groups, respectively. The spectroscopic data suggest that bend conformations may exist, to some extent, among the distributions of conformations in the first, third, and fourth, but not in the second, tetrapeptide. This result is consistent with empirical probabilities for the prediction of bend conformations in proteins. Conformational energy calculations on these four tetrapeptides support the indications from the experimental data. It thus appears that, because of short-range interactions, the tendency toward bend formation exists in short peptides, provided that both the composition and amino acid sequence are energetically favorable for bend formation.

Circular Dichroism↗

MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters.

The T-cell immune response is directed against antigenic peptide fragments generated in intracellular compartments, the cytosol or the endocytic system. Peptides derived from cytosolic proteins, usually of biosynthetic origin, are presented efficiently to T-cell receptors by major histocompatibility complex (MHC) class I molecules, with which they assemble, probably in the endoplasmic reticulum (ER). In the absence of recognizable N-terminal signal sequences, such cytosolic peptides must be translocated across the ER membrane by a novel mechanism. Genes apparently involved in the normal assembly and transport of class I molecules may themselves be encoded in the MHC. Here we show that one of these, the rat cim gene, maps to a highly polymorphic part of the MHC class II region encoding two novel members of the family of transmembrane transporters related to multidrug resistance. Other members of this family of transporter proteins are known to be capable of transporting proteins and peptides across membranes independently of the classical secretory pathway. Such molecules are credible candidates for peptide pumps that move fragments of antigenic proteins from the cytosol into the ER.

Amino Acid Sequence↗

Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter.

In mammalian cells, short peptides derived from intracellular proteins are displayed on the cell membrane associated with class I molecules of the major histocompatibility complex (MHC). The surface presentation of class I-peptide complexes presumably alerts the immune system to intracellular viral protein synthesis. Peptides derived from the cytosol must reach the cisternae of the endoplasmic reticulum where they are required for the assembly of stable class I molecules, and it has been proposed that the products of the two MHC-encoded ATP-binding cassette (ABC) transporter genes function to deliver the peptides across the membrane of the endoplasmic reticulum. This idea is supported by experiments in which transfection of a human cell line defective in class I expression with a complementary DNA of one of these genes restored cell surface expression levels. Here we show that the complete phenotype of the mouse mutant cell line RMA-S, in which lack of surface expression of stable class I molecules correlates with an inability to present viral peptides originating in the cytosol, is repaired by the cDNA of the other transporter gene. These results are consistent with the possibility that the two transporter polypeptides form a heterodimer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Traumatic fetal death.

Trauma during pregnancy increases the mortality risk to both victims: mother and child. The critical care nurse assumes a major role in assessing needs from both the trauma and obstetric perspectives. Collaboration between the critical care and obstetric nurse is essential to meet the complex physical, emotional, social, and spiritual needs of the entire family. A bereavement protocol can be helpful in suggesting specific interventions for long-term follow-up of the family suffering fetal loss.

Adult↗

Validation of increased intracranial pressure and high risk for increased intracranial pressure.

The authors designed this validation study to determine the defining characteristics of increased intracranial pressure and the risk factors for high risk for increased intracranial pressure. Using Fehring's Diagnostic Content Validity Model, a purposive sample of 219 nurses validated 17 major and 16 minor defining characteristics of increased intracranial pressure and nine major and six minor risk factors for high risk for increased intracranial pressure. Ratings were similar among nurses with diverse educational preparation but varied among nurses in different specialty areas, suggesting that practice setting is important in nursing diagnosis validation studies.

Humans↗