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C McSherry

Publications and source records attributed to C McSherry.

11 recordsLinked to original sources

Correlation of donor antigen-specific hyporeactivity with allogeneic microchimerism in kidney and lung recipients.

Our previous studies indicate donor antigen-specific hyporeactivity is a useful marker for identifying solid organ transplant recipients at low risk for immunological complications; the hyporeactive subgroup experiences a lower incidence of chronic rejection. One purpose of the current study was to determine whether hyporeactivity could be identified in pediatric kidney recipients and whether it correlated with improved graft outcome. Of 18 pediatric kidney recipients tested, 6 (33%) had developed donor antigen-specific hyporeactivity. All 18 experienced good graft outcome. Second, we determined whether donor antigen-specific hyporeactivity correlates with peripheral blood microchimerism and outcome in adult kidney recipients. Our previous studies of lung recipients demonstrated development of obliterative bronchiolitis in recipients with microchimerism who remain responsive, but not in recipients who had become hyporesponsive to donor antigen. Preliminary results in our current study of 23 adult kidney recipients indicate microchimerism for 6 (26%): 4 hyporesponsive and 2 responsive to donor antigen. Microchimerism was not detected for 17 recipients: 6 hyporesponsive and 11 responsive to donor antigen. One hyporesponsive/chimeric patient and 4 recipients negative for both parameters have been diagnosed with biopsy-proven chronic rejection. In summary, both hyporeactivity and chimerism are found at a higher frequency in lung than kidney recipients. Unlike lung recipients, not all hyporesponsive kidney recipients had peripheral blood chimerism. Additional numbers are needed to determine if microchimerism correlates with donor antigen-specific hyporeactivity or graft outcome.

Adult

Initial experience with laparoscopic cholecystectomy at the Beth Israel Medical Center.

Laparoscopic cholecystectomy has changed the treatment of symptomatic gallstones. We present an initial experience with this technique. From March 1990 to March 1991, there were 250 patients who were studied. There were 182 females and 68 males, with most classified as American Society of Anesthesiology Index Class I or II. All procedures were done using electrocautery. There was a definite learning curve for the procedure as evidenced by the duration of the operation. The mean time to perform the procedure was 112 minutes for the first 50 patients and 79 minutes for the last 50 patients. We converted 12 percent of the procedures to an open cholecystectomy for a variety of reasons, the most common being inflammation and adhesions in the triangle of Calot. However, we only had a 4 percent conversion rate in the last 50 patients. There were nine serious complications, with no deaths. The most frequent was a bile leak from the cystic duct stump. Other complications included a pneumothorax, requiring chest tube drainage and an unobserved carcinoma of the stomach. There were no injuries to the common bile duct. The results of our current experience confirm the safety and efficacy of laparoscopic cholecystectomy for the treatment of symptomatic gallstones. The use of electrocautery is safe during laparoscopy and the need for a laser is optional. Laparoscopic cholecystectomy will continue to evolve as more experience is gained and new instruments are introduced.

Adult

DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells.

We have previously described the isolation of a cDNA clone, designated NKG2, that was expressed in all natural killer (NK) cells tested but not in T or B cells. In the present communication, the original isolate, when used to probe a cDNA library prepared from a CD3- NK cell clone, was found to crosshybridize with a family of transcripts that fell into four distinct groups designated NKG2-A, -B, -C, and -D. Full-length cDNA sequences were determined for each group, and the DNA and inferred peptide sequences were analyzed. All four transcripts encode type II membrane proteins of 215-233 amino acids. NKG2-A and -B peptides appear to be alternative splicing products of a single gene. NKG2-C is highly homologous with group A, having 94% homology in the external (COOH-terminal) domain and 56% homology throughout the internal and transmembrane regions. NKG2-D is distantly but significantly related (21% amino acid homology) to the first three groups. Therefore, NKG2-A, -C, and -D appear to be encoded by distinct genes within a family of NK cell-specific genes. Peptide sequence homology searches demonstrate that the NKG2 peptides are members of a supergene family that includes several other type II membrane proteins. This family is characterized by the presence of a C-type animal lectin domain, and several of its members have demonstrated transmembrane signaling capability.

Amino Acid Sequence

A cDNA clone expressed in natural killer and T cells that likely encodes a secreted protein.

We have isolated a series of cross-hybridizing cDNA clones, as a group designated as NKG5, from a human natural killer (NK) cell clone cDNA library. These clones show a high degree of homology with a previously described gene, 519, which was thought to be T cell specific. A comparison of the full-length cDNA sequence of NKG5 and the published sequence of 519 shows that NKG5 lacks a 242-base segment that is found in 519 and that this deletion leads to the use of a different putative translational start codon. Unlike 519, the predicted NKG5 polypeptide has an NH2-terminal sequence that is strongly hydrophobic, characteristic of a signal peptide, and lacks any additional hydrophobic regions in the remainder of the peptide, suggesting that NKG5 encodes a secreted protein. Both NKG5 and 519 are expressed in NK and T cells but not in a variety of other hematopoietic cell lines. NKG5 is an abundant transcript and its level of expression is about 40 times that of 519 in NK and T cells. Southern blot and DNA sequence analyses suggest that NKG5 and 519 mRNAs are transcripts from a single gene that has allelic polymorphism.

Amino Acid Sequence

Isolation and characterization of NK cell or NK/T cell-specific cDNA clones.

Natural killer (NK) cells are cytotoxic lymphocytes that share numerous cell surface antigens and functional components with T cells. However, in comparison with our knowledge of T cells, little is known about the molecular mechanisms of NK cell activation and function. The following study was initiated as an effort to obtain further information about similarities and differences between NK and T cells at the level of gene expression and also to identify NK-specific cDNA clones for future functional studies of the corresponding gene products. The study used cDNA libraries prepared from an NK clone and from an Epstein-Barr virus transformed B cell lymphoblastoid cell line (LCL). We employed a combination of differential and subtractive hybridization methodologies, which can successfully identify cell-specific cDNA clones representing medium to high abundance transcripts, to identify genes that are expressed in NK cells but not in the LCL. We were particularly interested to ascertain to what extent genes isolated in this manner would be expressed only in NK cells as opposed to being expressed in NK and T cells. Twelve different cross-hybridizing groups were identified that were not expressed in the LCL, and these groups were further characterized: (1) they were used to probe Northern blots prepared from a panel of cells including NK cells, T cells, and B cells: (2) changes in the steady-state level of message following T cell growth factor (TCGF)-induced activation of an NK cell clone were examined for selected isolates; and (3) a partial DNA sequence was determined for each cross-hybridizing group. The DNA sequences of seven groups were identical to previously reported sequences. One group was highly homologous with but not identical to what has been reported as a T cell specific gene, named 519. The DNA sequences of four groups showed no significant homology with the sequences in the GenBank and EMBL databases. The mRNA expression of the newly-identified groups demonstrated several different regulation patterns with respect to cell distribution and level of expression in response to TCGF-activation. Expression of the twelve different genes was examined in three populations of NK cells all of which were CD3- and possessed NK activity. Although these cells differentially expressed the prototype NK markers CD16 and CD56 (the cells were CD16+, CD56-, CD16-, CD56+ and CD16+, CD56+), the expression of all groups of cDNA clones was comparable in the three different types of NK cells despite the phenotypic differences.(ABSTRACT TRUNCATED AT 400 WORDS)

Blotting, Northern