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Biomedical subjects

M E Shapiro

Publications and source records attributed to M E Shapiro.

9 recordsLinked to original sources

The strong correlation of cytotoxic T lymphocyte-specific serine protease gene transcripts with renal allograft rejection.

Several immune mechanisms are likely to be responsible for renal allograft rejection. The relative importance of delayed-type hypersensitivity versus cytotoxic T lymphocytes is controversial. We analyzed human renal allografts biopsies for intragraft expression of IL-1 beta, IL-6, and TNF alpha genes--putative mediators of DTH--as well as IL-2, IL-2 receptor (R) beta, and a CTL-specific serine protease gene. Total RNA was extracted from tissue samples and the mRNA fraction was converted to cDNA using oligo dT and reverse transcriptase. Then cDNA was amplified by the polymerase chain reaction (PCR) for 35 cycles using specific oligonucleotide primers. Each PCR analysis included beta-actin oligonucleotide primers to coamplify this constitutively expressed gene as an internal control. A total of 24 core allograft biopsies were studied and classified into a 3 histological categories: acute cellular rejection, equivocal components of rejection, and no evidence of rejection. There was no statistically significant difference in beta-actin expression among these histologic categories (P greater than 0.08). Interestingly, in this sample size, no significant difference was found between rejecting and nonrejecting samples for transcripts of any of the cytokines or IL-2R beta mRNAs. Apparently, DTH-like mechanisms are present in all allografts. However, detection of CTL-specific serine protease gene expression was almost exclusive to rejecting samples (P less than 0.003). These findings suggest that activation of CTLs play an active, but hardly exclusive, role as effectors of graft dysfunction in the rejection process. While this study does not define the relative importance of the genes examined, it does suggest that evidence of CTL-specific serine protease expression may provide a means of monitoring for rejection episodes or as a diagnostic aid when conventional diagnostic criteria are not conclusive.

Adolescent

Application of the Allen Cognitive Level Test in assessing cognitive level functioning of emotionally disturbed boys.

The purpose of this study was to ascertain the applicability of the Allen Cognitive Level Test (ACL) (Allen, 1982, 1985), developed for use with adult psychiatric patients, to emotionally disturbed children aged 8 to 15 years. The subjects' performance on the ACL was compared with their performance on two other instruments that measure features of cognition: the Developmental Test of Visual-Motor Integration (VMI) (Beery & Buktenica, 1982) and the Perceptual Memory Task (McCarron, 1984). Pearson product-moment correlations were computed to study the relationships of the ACL, the Perceptual Memory Task full-scale and subscale scores, and the VMI raw and age-equivalent scores. The Perceptual Memory Task scores showed little or no correlation with the ACL scores. Correlations of the ACL with the VMI scores revealed moderate but significant coefficients. A relationship between age and ACL score was found. Preliminary data would indicate that the ability of emotionally disturbed children to function in the school environment depends on their mastery of task demands and that occupational therapy intervention cannot be based solely on age or level of intelligence.

Adolescent

A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation.

Patient entry is now complete in a prospective trial of anti-Tac, a murine IgG2a monoclonal antibody directed against the p55 chain of the human IL-2 receptor, for the prevention of renal allograft rejection. Recipients of primary cadaver allografts were randomized to receive either anti-Tac (20 mg q.d. x 10 days beginning POD 1) plus low-dose CsA (4 mg/kg/day), azathioprine (2 mg/kg/day), and prednisone (30 mg q.d.), or conventional triple therapy with CsA (8 mg/kg/day), azathioprine, and prednisone. Forty patients were entered in each group, with current followup from 6 to 26 months. The results show a significant reduction in early rejection episodes in the anti-Tac-treated patients. During the 10-day treatment, 5 of 40 anti-Tac patients had rejection episodes, compared with 21 of 40 control patients (P less than 0.001). Anti-Tac significantly delayed the time to the first rejection (12.5 +/- 6.3 vs. 7.6 +/- 6.7 days) (P less than 0.05). Despite these effects, there were no differences in either actual or actuarial graft or patient survival between the two groups. Pneumonia, primarily CMV, developed in 5 treated and 4 control patients. In patients with functioning grafts mean serum creatinine at 3 months was 1.8 +/- 0.7 in the anti-Tac group and 2.0 +/- 0.8 in the control group (P = NS); at 12 months the values were 2.3 +/- 1.5 and 1.8 +/- 0.5, respectively (P = NS). The peak expression of IL-2 receptors on circulating T-cells was significantly lower in anti-Tac patients (15.1 +/- 3.6%) than in controls (21.9 +/- 4.5%) (P less than 0.05). Seven of 10 patients tested to date developed antimouse immunoglobulin antibodies, with antiidiotype shown in 6. These antibodies do not preclude subsequent treatment with OKT3. Five patients in this and previous anti-Tac protocols have received OKT3 for acute rejection despite known pretreatment antimouse antibodies, with resolution of rejection in all cases.

Adolescent

The effect of barium on blood in the gastrointestinal tract.

The effect of various commercial barium sulfate preparations on blood coagulation, flocculation, and hemolysis was studied. There was considerable variation not only among different barium products but also among different concentrations of the same product. There is no good experimental evidence that barium enemas do stop bleeding. It is probably best to avoid the use of any enema in attempting to control major colonic bleeding; but if an enema is given for this purpose, a tap-water enema is better, as it contains no anticoagulants and is more effective in producing clot formation than most barium suspensions.

Barium Sulfate

Use of a reperfusion catheter after angioplasty dissection for salvage of ischemic renal allograft: case report.

Percutaneous transluminal angioplasty was performed on a right common iliac artery stenosis presumed to be causing renovascular hypertension in a patient with a renal allograft anastomosis to the right external iliac artery. This was complicated by an obstructive dissection resulting in acute threatening renal allograft ischemia. Renal blood flow was restored by means of a transluminal reperfusion catheter until corrective surgery could be performed. This case is reported because such catheters can be acutely helpful to the interventionalist, and they have not been described in the radiology literature.

Angioplasty, Balloon

Iothalamate ethyl ester as hepatolienographic agent.

In search of a hepatolienographic agent, the iothalamate ethyl ester particulate suspension was prepared with the average particle size of 1.5 mu in diameter. When mixed with plasma of different animal species, the physical properties of the particular suspension changed significantly. The nature of this difference is not understood but is probably related to protein-particle interaction in the different species. Doses of 550 mg iodine per kg body weight as a single intravenous infusion of the particulate suspension resulted in satisfactory opacification of liver and spleen in rats, followed by complete loss of radiopacity within three days. Larger doses resulted in the death of the rats within 12-14 hours. In general, the mice tolerated larger doses than rats, but there was very poor opacification of the liver, despite good opacification of spleen. Further work is being carried out to improve the suspension and to better understand the difference in behavior of the particulate suspension in different animal species.

Animals

Protein binding to iothalamate ethyl ester.

A major problem in the development of a particulate hepatolienographic agent is the prevention of particle aggregation upon contact with blood. When iothalamate ethyl ester, a particulate suspension for potential use as an hepatolienographic agent, was mixed with human or animal plasmas, it resulted in moderate to severe flocculation. In a study conducted to define the binding of plasma proteins to the iothalamate ethyl ester particles, plasma was reversibly adsorbed to various particle preparations. Fractions obtained by incubation of the particle-plasma complexes in buffers of increased ionic strength and decreased pH were subjected to polyacrylamide disc gel electrophoresis. The fraction containing the specifically bound proteins produced three distinct bands corresponding to prealbumin, albumin, and fibrinogen. Since the particles flocculated only when mixed with plasma, it is postulated that the fibrinogen-particle interaction is a major factor leading to particle agglutination.

Blood Proteins