Search PubMed⌕ Search

Biomedical subjects

R Shapiro

Publications and source records attributed to R Shapiro.

At least 181 records · Page 10Linked to original sources
PubMed1996

Patellofemoral alignment: reliability.

Clinical assessment of the patellofemoral alignment is frequently performed, yet the repeatability of these measurements has not been previously investigated. This study examined the reliability of measuring patellofemoral alignment. The Q angle, A angle, and patellar orientation (mediolateral tilt, mediolateral position, superoinferior tilt, and rotation) of 27 healthy subjects were measured over three trials using standardized positioning and operationally defined goniometric, pluri-cal caliper, and visual estimation measurement techniques. Intratester and intertester intraclass correlation coefficients of measurements obtained with the pluri-cal caliper and goniometer ranged from .52 to .86 and .003 to .61, respectively. Intratester and intertester standard errors of the instrumented measurements ranged from 1.6 to 3.5 degrees and 3.2 to 6.8 degrees (.28 and .55 cm for mediolateral position), respectively. Intratester kappa's of visually estimating patellar orientation ranged from .40 to .57. Intertester kappa's were between .03 and .30. The results suggest that both clinical estimation and instrumented measurement of patellofemoral alignment may be unreliable.

Adolescent↗
PubMed1995

Combined simultaneous kidney/bone marrow transplantation.

On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.

Adolescent↗
PubMed1995

Analysis of clinical variation seen in patients with 18q terminal deletions.

Twenty-six patients with deletions of 18q were analyzed at the clinical and molecular levels in an attempt to delineate regions of chromosome 18 important to the 18q- syndrome phenotype. Molecular cytogenetic analysis was carried out using fluorescence in situ hybridization (FISH), and deletions ranging from 18q21.1-qter to 18q22.3-qter were detected. The parental origin of the deletions was determined by the analysis of inheritance of microsatellite markers. No correlation between size, parental origin, or severity of the resulting phenotype was found. The results suggest that a critical region for 18q- syndrome lies in the most distal portion of 18q and that it confers susceptibility for the various clinical manifestations of the 18q- syndrome when present in one copy.

Abnormalities, Multiple↗
PubMed1995

The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes.

Angiogenin, a homologue of pancreatic ribonuclease, is a potent inducer of blood vessel formation. As an initial step toward investigating the in vivo functional role of this protein via gene disruption, we undertook the isolation of the angiogenin gene (Ang) from the 129 strain mouse, which will be used for generating targeting constructs. Unexpectedly, screening of a genomic library with an Ang gene probe obtained previously from the BALB/c strain yielded two new genes closely similar to Ang rather than Ang itself. One of these encodes a protein with 78% sequence identity to angiogenin and is designated "Angrp" for "angiogenin-related protein." The ribonucleolytic active site of angiogenin, which is critical for angiogenic activity, is completely conserved in Angrp, whereas a second essential site, thought to bind cellular receptors, is considerably different. Thus, the Angrp product may have a function distinct from that of angiogenin. The second gene obtained by library screening is a pseudogene, designated "Ang-ps1," that contains a frameshift mutation in the early part of the coding region. Although the Ang gene was not isolated from this library, it was possible to amplify this gene from 129 mouse genomic DNA by the polymerase chain reaction (PCR). Sequence analysis showed that the 129 strain Ang gene is identical to the BALB/c gene throughout the coding region. PCR cloning also yielded a second Ang-like pseudogene, designated "Ang-ps2." Southern blotting of genomic DNA confirmed the presence of Ang, Angrp, and at least one of the pseudogenes in an individual mouse and suggested that the mouse Ang gene family may contain more than the four members identified here.

Amino Acid Sequence↗
PubMed1995

Crystal structure of the superantigen enterotoxin C2 from Staphylococcus aureus reveals a zinc-binding site.

BACKGROUND: Staphylococcus aureus enterotoxin C2 (SEC2) belongs to a family of proteins, termed 'superantigens', that form complexes with class II MHC molecules enabling them to activate a substantial number of T cells. Although superantigens seem to act by a common mechanism, they vary in many of their specific interactions and biological properties. Comparison of the structure of SEC2 with those of two other superantigens--staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1)--may provide insight into their mode of action. RESULTS: The crystal structure of SEC2 has been determined at 2.0 A resolution. The overall topology of the molecule resembles that of SEB and TSST-1, and the regions corresponding to the MHC class II and T-cell receptor binding sites on SEB are quite similar in SEC2. A unique feature of SEC2 is the presence of a zinc ion located in a solvent-exposed region at the interface between the two domains of the molecule. The zinc ion is coordinated to Asp83, His118, His122 and Asp9* (from the neighbouring molecule in the crystal lattice). Atomic absorption spectrometry demonstrates that zinc is also bound to SEC2 in solution. CONCLUSIONS: SEC2 appears to be capable of binding to MHC class II molecules in much the same manner as SEB. However, structure-function studies have suggested an alternative binding mode that involves a different site on the toxin. The zinc ion of SEC2 lies within this region and thus may be important for complex formation, for example by acting as a bridge between the two molecules. Other possible roles for the metal cation, including a catalytic one, are also considered.

Amino Acid Sequence↗
PubMed1995

Crystal structure of bovine angiogenin at 1.5-A resolution.

The capacity of angiogenin (Ang) to induce blood vessel growth is critically dependent on its ribonucleolytic activity. Crystallography and mutagenesis of human Ang have previously shown that its pyrimidine binding site is obstructed by Gln-117, implying that a conformational change is a key part of the mechanism of Ang action. The 1.5-A-resolution crystal structure of bovine Ang, in which glutamic acid is substituted for Gln-117, now confirms that a blocked active site is characteristic of these proteins. Indeed, the inactive conformation of bovine Ang is stabilized by a more extensive set of interactions than is that of human Ang. The three-dimensional structure of the putative receptor binding site is also well conserved in the two proteins. The Arg-Gly-Asp segment of this site in bovine Ang, which is replaced by Arg-Glu-Asn in human Ang, does not have a conformation typical of an integrin recognition site.

Amino Acid Sequence↗
PubMed1995

Immune status of recipients following bone marrow-augmented solid organ transplantation.

It has been postulated that the resident "passenger" leukocytes of hematolymphoid origin that migrate from whole organ grafts and subsequently establish systemic chimerism are essential for graft acceptance and the induction of donor-specific nonreactivity. This phenomenon was augmented by infusing 3 x 10(8) unmodified donor bone-marrow cells into 40 patients at the time of organ transplantation. Fifteen of the first 18 analyzable patients had sequential immunological evaluation over postoperative intervals of 5 to 17 months, (which included 7 kidney (two with islets), 7 liver (one with islets), and one heart recipient). The evolution of changes was compared with that in 16 kidney and liver nonmarrow controls followed for 4 to 5 months. The generic immune reactivity of peripheral blood mononuclear cells (PBMC) was determined by their proliferative responses to mitogens (PHA, ConA). Alloreactivity was measured by the recipient mixed lymphocyte reaction (MLR) to donor and HLA-mismatched third-party panel cells. Based on all 3 tests, the recipients were classified as donor-specific hyporeactive, intermediate, and responsive; patients who were globally suppressed made up a fourth category. Eight (53%) of the 15 marrow-treated recipients exhibited progressive modulation of donor-specific reactivity (3 hyporeactive and 5 intermediate) while 7 remained antidonor-responsive. In the nonmarrow controls, 2 (12.5%) of the 16 patients showed donor-specific hyporeactivity, 10 (62.5%) were reactive, and 4 (25%) studied during a CMV infection had global suppression of responsiveness to all stimuli.

Adult↗
PubMed1995

A prospective randomized trial of FK506-based immunosuppression after renal transplantation.

A group of 204 adult patients was entered into a prospective, randomized trial comparing FK506/prednisone with FK506/azathioprine/prednisone after renal transplantation between August 1, 1991 and October 11, 1992. The purpose of the study was to see if the addition of azathioprine would reduce the incidence of rejection and improve graft survival. The recipient population was unselected, with 61 (30%) patients undergoing retransplantation, 37 (18%) having a panel-reactive antibody greater than 40%, and 33 (16%) over 60 years of age. The mean recipient age was 43.8 +/- 13.7 years (range 17.6-78). The mean donor age was 34.0 +/- 20.1 years (range 0.3-75); 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hr. Living donors were the source of 13% of the kidneys. The mean follow-up was 22 +/- 4 months (range 12-29). Overall one-year actual patient survival was 94%. Overall one-year actual graft survival was 87%. Patients starting on double therapy had a one-year actual patient survival of 96% and a one-year actual graft survival of 92%. Patients starting on triple therapy had a one-year actual patient survival of 91% (P = ns compared with double therapy), and a one-year actual graft survival of 82% (P < 0.02, compared with double therapy). Overall results with first cadaver transplants included a one-year actual patient survival of 94% and one-year actual graft survival of 88%, with no differences between double and triple therapy. The overall incidence of rejection was 48%, with 54% in the double therapy group and 41% in the triple therapy group (P < .07). The incidence of steroid-resistant rejection requiring antilymphocyte therapy (OKT3 or ATGAM) was 13%, and was not different between the double and triple therapy groups. The mean serum creatinine was 1.8 +/- 0.8 mg/dl. The mean BUN was 33 +/- 21 mg/dl, with no significant difference between the therapy groups. The mean serum cholesterol was 192 +/- 49 mg/dl. A total of 56% of the patients are off prednisone, and 35% of the patients are not taking any antihypertensive medications. Other complications included cytomegalovirus--14%; new-onset diabetes--16% (half of which was reversible); and posttransplant lymphoproliferative disorder--1%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Experience with liver and kidney allografts from non-heart-beating donors.

Given the shortage of cadaveric organs, we began a study utilizing NHBD for OLTx and KTx. There were 24 NHBD between January 1989 and September 1993. These donors were divided into 2 groups: uncontrolled NHBD (G1) (n = 14) were patients whose organs were recovered following a period of CPR; and controlled NHBD (G2) (n = 10) were patients whose organs were procured after sustaining cardiopulmonary arrest (CA) following extubation in an operating room setting. Eight kidneys and 5 livers were discarded because of macroscopic or biopsy findings. In G1, 22/27 (81.5%) kidneys were transplanted; 14/22 (64%) developed ATN; 20/22 (95%) recipients were off dialysis at the time of discharge. With a mean follow-up of 32.7 +/- 21.1 months, sixteen (73%) kidneys are still functioning, with a mean serum creatinine of 1.7 +/- 0.6 mg/dl. The one-year actuarial patient and graft survivals are 95% and 86%. In G2, 17/20 (85%) kidneys were transplanted; 13/17 (76%) kidneys experienced ATN. All patients were off dialysis by the time of discharge. With a mean follow-up of 17.6 +/- 15.4 months, twelve (70%) kidneys are still functioning, with a mean serum creatinine of 2.5 +/- 2.1 mg/dl. The one-year actuarial patient and graft survivals are 94% and 82%, respectively. In G1, 6/10 (60%) livers were transplanted; 3/6 (50%) livers functioned, the other 3 patients required ReOLTx in the first week postoperatively because of PNF (n = 2) and inadequate portal flow (n = 1). Two functioning livers were lost due to HAT (n = 1) and CMV hepatitis (n = 1). In G2, 6/7 (85.7%) livers were transplanted. All the livers (100%) functioned. 2 patients required ReOLTx for HAT at 0.9 and 1.0 months. Both patients eventually died. One patient with a functioning liver died 2 months post OLTx. The remaining 3 patients are alive and well at 27 months of follow-up. This study shows that the procurement of kidneys from both uncontrolled and controlled NHBD leads to acceptable graft function despite a high incidence of ATN. The function of liver allografts is adequate in the controlled NHBD but suboptimal in the uncontrolled NHBD, with a high rate of PNF.

Adolescent↗
PubMed1995

FK506 in pediatric kidney transplantation--primary and rescue experience.

Between 14 December 1989 and 17 December 1993, 43 patients undergoing kidney transplantation alone at the Children's Hospital of Pittsburgh received FK506 as the primary immunosuppressive agent. The mean recipient age was 10.2 +/- 4.8 years (range 0.7-17.4 years), with 7 (16%) children under 5 years of age and 2 (5%) under 2 years of age. Fifteen (35%) children underwent retransplantation, and 5 (12%) had a panel-reactive antibody level greater than 40%. Twenty-two (51%) transplants were with cadaveric donors and 21 (49%) were with living donors. The mean follow-up was 25 +/- 14 months; there were no deaths; 1- and 3-year actuarial graft survival was 98% and 85%. The mean serum creatinine and blood urea nitrogen were 1.2 +/- 0.6 mg/dl and 26 +/- 11 mg/dl; the calculated creatinine clearance was 75 +/- 23 ml/min per 1.73 m2. Twenty-four (62%) patients have been successfully withdrawn from steroids and 24 (62%) require no anti-hypertensive medication. Improved growth was seen, particularly in pre-adolescent children off steroids. Between 28 July 1990 and 2 December 1993, 24 children were referred for rescue therapy with FK506, 14.6 +/- 16.4 months (range 1.1-53.2 months) after transplantation. Nineteen (79%) were referred because of resistant rejection; 4 (17%) were referred because of proteinuria; 1 (4%) was switched because of steroid-related obesity. There were no deaths; 1- and 2-year graft survival was 75% and 68%; 17 (71%) patients were successfully rescued, including 1 of 2 patients who arrived on dialysis; 4 (24%) of the successfully rescued patients were weaned off steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

The prebiotic role of adenine: a critical analysis.

Adenine plays an essential role in replication in all known living systems today, and is prominent in many other aspects of biochemistry. It occurs among the products of oligomerization of HCN. These circumstances have stimulated the idea that adenine was a component in a replication system that was present at the start of life. Such replicators have included not only RNA, but also a number of simpler RNA-like alternatives which utilize a simpler backbone. Despite these encouraging indicators, a consideration of the chemical properties of adenine reveals reasons that disfavor its participation in such a role. These properties include the following: (1) Adenine synthesis requires HCN concentrations of at least 0.01 M. Such concentrations would be expected only in unique circumstances on the early Earth. Adenine yields are low in prebiotic simulations, and if a subsequent high-temperature hydrolysis step is omitted, the reported yield does not represent adenine itself, but 8-substituted adenines and other derivatives. (2) Adenine is susceptible to hydrolysis (the half life for deamination at 37 degrees C, pH 7, is about 80 years), and to reaction with a variety of simple electrophiles, forming a multiplicity of products. Its accumulation would not be expected over a geological time scale, and its regioselective incorporation into a replicator appears implausible. (3) The adenine-uracil interaction, which involves two hydrogen bonds (rather than three, as in guanine-cytosine pairing) is weak and nonspecific. Pairing of adenine with many other partners has been observed with monomers, synthetic oligonucleotides and in RNA. The hydrogen-bonding properties of adenine appear inadequate for it to function in any specific recognition scheme under the chaotic conditions of a prebiotic soup. New and fundamental discoveries in the chemistry of adenine would be needed to reverse this perception. An alternative and attractive possibility is that some other replicator preceeded RNA (or RNA-like substances) in the origin of life.

Adenine↗
PubMed1995

Plain-film assessment of the neonate with D-transposition of the great vessels.

The presenting chest radiographs of 27 new-born patients with D-transposition of the great vessels (D-TGV) were evaluated for the degree of pulmonary flow as well as other findings classically described in D-TGV (narrow superior mediastinum, radiographically absent thymus, inapparent main pulmonary artery, non-visualization of the malpositioned aortic arch, asymmetric pulmonary blood flow, and cardiomegaly). Of the 27 patients, 22 (82%) demonstrated normal or decreased flow. The majority of the D-TGV patients also failed to demonstrate any of the other classically described radiographic findings. A normal chest radiograph is the most common presenting scenario in the neonate with D-TGV.

Cardiac Catheterization↗
PubMed1995

Evaluation and management of bilateral renal artery stenosis in children: a case series and review.

This report describes the clinical course, diagnostic evaluation and management of six children with bilateral renal artery stenosis (RAS) and concurrent narrowing of the abdominal aorta. Except for one child with active arteritis, the others were asymptomatic. There were no clinical or laboratory features suggesting the etiology of hypertension in four of six patients, and diagnostic procedures, including Doppler duplex ultrasound and captopril scintigraphy, were unreliable in screening for such hypertension. Abdominal aortography and selective renal angiography confirmed the diagnosis of bilateral RAS and associated anatomical alterations of the aorta and its branches. The hypertension was severe and minimally responsive to antihypertensive agents. It was cured or improved after percutaneous transluminal angioplasty (PTA) of three vessels in two children with mid-vessel stenoses, while hypertension persisted after PTA of two mid-vessel stenoses in a third child and one vessel with ostium stenosis in a fourth child. Autotransplantation of seven kidneys in four children resulted in cure of significant improvement of the hypertension. Renal function was preserved in all children during a mean follow-up time of 41 months. Based on illustrative data from these six children, as well as information from a review of the literature, this report discusses the key diagnostic issues and stresses the potential advantages of renal autotransplantation in selected children with this disorder.

Adolescent↗