Analysis of Financial Barriers Experienced by Prospective Genetic Counseling Students.

PURPOSE: High costs of applying to genetic counseling graduate programs (GCGPs) are likely a barrier to workforce diversification. We sought to determine application costs and assess differences between individuals of historically underrepresented racial and ethnic backgrounds in medicine (hURM) and non-hURM applicants. METHODS: Applicants to GCGPs between 2005-2020 were surveyed about application history, related expenses, volunteer hours, and financial resources; 383 responses were analyzed. RESULTS: Median total application costs (MTAC) were $2,634, $4,762, and $5,607 (one, two, and three or more application cycles, respectively). Interview-related items (which includes travel) had the highest median cost (one application cycle: $879). Among those who applied to multiple cycles, hURM respondents had higher MTAC than those of non-hURM ($6,713 versus $4,762, p=0.03) and lower median total volunteer hours (246 versus 381, p=0.03). Parental education level differed by hURM status (p=0.04). Median financial contribution from parents with and without advanced degrees varied significantly (60% vs 2%, p=0.0009). CONCLUSION: Significant costs are incurred during the GCGP application process, but notable differences in costs and resources were observed between hURM and non-hURM applicants. Stakeholders within the profession should implement strategies to reduce financial barriers and the resulting inequities in the application process.

Effect of triple antibiotic paste with or without ethylenediaminetetraacetic acid on surface loss and surface roughness of radicular dentine.

This study aimed to compare the effect of two concentrations of triple antibiotic paste (TAP) with or without ethylenediaminetetraacetic acid (EDTA) on surface loss and surface roughness of radicular dentine. Human radicular dentine specimens were randomized into six experimental groups (n = 16 per group). The first and second groups were treated with 1,000 mg/mL or 1 mg/mL of TAP for 4 weeks. The third and fourth groups were treated with 1,000 mg/mL or 1 mg/mL of TAP for 4 weeks followed by 17 % EDTA for 5 min. The fifth group was treated with 17 % EDTA for 5 min and the sixth group received no treatment (control). Dentine surface loss and surface roughness were quantified after various treatments using optical and contact profilometry, respectively. One-way ANOVA followed by Fisher's protected least significant differences was used for statistical analyses. All treatment groups showed significantly higher surface loss compared to the untreated dentine. Dentine treated with 1,000 mg/mL had significant increase in surface loss and surface roughness compared to dentine treated with 1 mg/mL of TAP. The use of EDTA after both concentrations of TAP did not have significant additive effect on surface loss and surface roughness of dentine. The clinically used concentration of TAP (1,000 mg/mL) caused significantly higher surface loss and surface roughness of radicular dentine compared to the use of 1 mg/mL of TAP. Furthermore, the substantial amount of dentine surface loss and surface roughness detected in the current study may be attributed to TAP rather than EDTA.

Xenotransplantation and other means of organ replacement.

Exciting new technologies, such as cellular transplantation, organogenesis and xenotransplantation, are thought to be promising approaches for the treatment of human disease. The feasibility of applying these technologies, however, might be limited by biological and immunological hurdles. Here, we consider whether, and how, xenotransplantation and various other technologies might be applied in future efforts to replace or supplement the function of human organs and tissues.

Cryptic B cell response to renal transplantation.

Transplantation reliably evokes allo-specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor-specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor-specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third-party fibroblasts as targets. We enumerated donor-specific antibody-secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor-specific antibodies before or after transplantation, all exhibited increases in the frequency of donor-specific antibody-secreting cells eight weeks after transplantation. The responses were directed against the donor HLA-class I antigens. The increase in frequency of donor-specific antibody-secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought.

Genotype-phenotype studies of VCP-associated inclusion body myopathy with Paget disease of bone and/or frontotemporal dementia.

Valosin containing protein (VCP) disease associated with inclusion body myopathy, Paget disease of the bone and frontotemporal dementia is a progressive autosomal dominant disorder caused by mutations in Valosin containing protein gene. To establish genotype-phenotype correlations we analyzed clinical and biochemical markers from a database of 190 members in 27 families harboring 10 missense mutations. Individuals were grouped into three categories: symptomatic, presymptomatic carriers and noncarriers. The symptomatic families were further divided into ten groups based on their VCP mutations. There was marked intra and inter-familial variation; and significant genotype-phenotype correlations were difficult to establish because of small numbers. Nevertheless when comparing the two most common mutations, R155C mutation was found to be more severe, with an earlier onset of myopathy and Paget (p = 0.03). Survival analysis of all subjects revealed an average life span after diagnosis of myopathy and Paget of 18 and 19 years respectively, and after dementia only 6 years. R155C had a reduced survival compared to the R155H mutation (p = 0.03).We identified amyotrophic lateral sclerosis (ALS) was diagnosed in 13 individuals (8.9%) and Parkinson's disease in five individuals (3%); however, there was no genotypic correlation. This study represents the largest dataset of patients with VCP disease and expands our understanding of the natural history and provides genotype-phenotype correlations in this unique disease.

The effect of nonsetting calcium hydroxide on root fracture and mechanical properties of radicular dentine: a systematic review.

The aim of this review was to identify and analyse all studies related to the effect of nonsetting calcium hydroxide [Ca(OH)(2)] on root fracture and various mechanical properties of radicular dentine. A PubMed search was conducted using the keywords 'calcium hydroxide' and 'dentistry' combined with MeSH terms 'tooth fractures' or 'mechanical phenomena' or 'compressive strength'. The search was expanded by including Embase and Web of Science databases, using the keywords 'calcium hydroxide' and 'root' and 'fracture'. The search was supplemented by checking the reference lists from each selected article. Each study had to meet the following criteria to be selected for review: (i) Inclusion of at least one experimental group with root or radicular dentine either filled with or exposed to nonsetting Ca(OH)(2); (ii) inclusion of at least one appropriate control group; and (iii) a minimum of five samples per experimental group. Only articles written in English were included. Of the 16 studies selected initially, 12 in vitro studies fulfilled the selection criteria for inclusion in the final review. No clinical studies that directly supported the correlation between Ca(OH)(2) intracanal dressing and root fracture were found in the literature. However, the majority of in vitro studies showed reduction in the mechanical properties of radicular dentine after exposure to Ca(OH)(2) for 5 weeks or longer. Conversely, the data were inconclusive regarding whether Ca(OH)(2) exposure for 1 month or less had a negative effect on the mechanical properties of radicular dentine.

The effect of medicaments used in endodontic regeneration on root fracture and microhardness of radicular dentine.

AIM: To investigate the effect of medicaments used in endodontic regeneration on root fracture resistance and microhardness of radicular dentine. METHODOLOGY: The root canals of mandibular premolars (n = 180) were instrumented and randomized into three treatment groups and an untreated control group. Each treatment group received either triple antibiotic paste (TAP), double antibiotic paste (DAP) or calcium hydroxide paste [Ca(OH)2] intracanal medicament. Teeth were kept in saline for 1 week, 1 month or 3 months. After each time-point, 15 teeth were randomly selected from each group and two root cylinders were obtained from each tooth. One cylinder was subjected to a fracture resistance test, and the other cylinder was used for a microhardness test. Two-way ANOVA and Tukey's pairwise comparisons were used for statistical analysis. RESULTS: For the microhardness test, the two-way interaction between group and time was significant (P < 0.001). The intracanal application of TAP and DAP caused significant and continuous decrease in root dentine microhardness after one (P < 0.05) and 3 months (P < 0.001), respectively. The three-month intracanal application of Ca(OH)2 significantly increased the microhardness of root dentine (P < 0.05). The time factor had a significant effect on fracture resistance (P < 0.001). The three intracanal medicaments caused significant decreases in fracture resistance ranging between 19% and 30% after 3-month application compared to 1-week application. CONCLUSION: In this laboratory study, the 3-month application of triple antibiotic paste, double antibiotic paste or calcium hydroxide paste medicaments significantly reduced the root fracture resistance of extracted teeth compared to a 1-week application.

Effect of surface treatments on microtensile bond strength of repaired aged silorane resin composite.

OBJECTIVE: This laboratory study compared the repaired microtensile bond strengths of aged silorane resin composite using different surface treatments and either silorane or methacrylate resin composite. METHODS: One hundred eight silorane resin composite blocks (Filtek LS) were fabricated and aged by thermocycling between 8°C and 48°C (5000 cycles). A control (solid resin composite) and four surface treatment groups (no treatment, acid treatment, aluminum oxide sandblasting, and diamond bur abrasion) were tested (N=12 blocks, 108 beams/group). Each treatment group was randomly divided in half and repaired with either silorane resin composite (LS adhesive) or methacrylate resin composite (Filtek Z250/Single Bond Plus). After 24 hours in 37°C distilled water, microtensile bond strength testing was performed using a non-trimming technique. Surface topography after surface treatment was analyzed using scanning electron microscopy (SEM). Failure mode was examined using optical microscopy (50×). RESULTS: Weibull-distribution survival analysis revealed that aluminum oxide sandblasting followed by silorane or methacrylate resin composite and acid treatment with methacrylate resin composite provided insignificant differences from the control (p>0.05). All other groups were significantly lower than the control. Failure was primarily adhesive in all groups. CONCLUSION: Aluminum oxide sandblasting produced microtensile bond strength not different from the cohesive strength of silorane resin composite. After aluminum oxide sandblasting, aged silorane resin composite can be repaired with either silorane resin composite with LS system adhesive or methacrylate resin composite with methacrylate dental adhesive.

Physical Properties and Clinical Performance of Short Fiber Reinforced Resin-based Composite in Posterior Dentition: Systematic Review and Meta-analysis.

OBJECTIVE: This study compares the physical properties and clinical performance of short fiber reinforced composites (SFRC) to those of particulate-filled resin-based composites (PFRC) for class I and II direct restorations in permanent dentition. METHODS: Systematic review and meta-analysis was conducted using PubMed, Embase (Elsevier), and Dentistry and Oral Sciences Source (EBSCO) databases. The outcomes evaluated were physical properties including flexural strength, flexural modulus, elastic modulus, microhardness, shrinkage, fracture toughness, degree of conversion, and depth of cure. Clinical performance was evaluated with a systematic review. RESULTS: The meta-analyses favored SFRC for flexural strength and fracture toughness compared to every PFRC subgroup, with a high quality of evidence. For all other properties, the meta-analyses favored SFRC to overall PFRC, with some non-significant differences with certain PFRC subgroups. The most recent clinical trial showed SFRC performed similarly to PFRC, however older studies suggest inferior surface texture and discoloration of SFRC compared to PFRC. CONCLUSION: This study can aid dental professionals in clinical decision making, supporting that SFRC offers improved physical properties, especially fracture resistance and flexural strength, compared to PFRC.

Decision-Making Time Cells in Hippocampal Dorsal CA1.

Sequential neural dynamics encoded by "time cells" play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. In this manuscript, we used two-photon Ca2+ imaging of dorsal CA1 pyramidal neurons in head-fixed mice performing a go-no-go associative learning task. We found that pyramidal cells responded differentially to the rewarded or unrewarded stimuli. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual pyramidal cells that responded differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior indicating that sequential activity of pyramidal cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning.

FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty.

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults.

Influence of glazed zirconia on dual-cure luting agent bond strength.

The current study evaluated the influence of a novel surface treatment that uses a low-fusing porcelain glaze for promoting a bond between zirconia-based ceramic and a dual-cure resin luting agent. Bond strengths were compared with those from airborne particle abrasion, hydrofluoric acid etching, and silanization-treated surfaces. Twenty-four yttrium-stabilized tetragonal zirconia (Cercon Smart Ceramics, Degudent, Hanau, Germany) discs were fabricated and received eight surface treatments: group 1: 110 µm aluminum oxide air-borne particle abrasion; group 2: 110 µm aluminum oxide airborne particle abrasion and silane; group 3: 50 µm aluminum oxide airborne particle abrasion; group 4: 50 pm aluminum oxide airborne particle abrasion and silane; group 5: glaze and hydrofluoric acid;group 6: glaze, hydrofluoric acid, and silane;group 7: glaze and 50 pm aluminum oxide airborne particle abrasion; and group 8: glaze,50 pm aluminum oxide airborne particle abrasion and silane. After treatment, Enforce resin cement (Dentsply, Caulk, Milford, DE, USA) was used to fill an iris cut from microbore Tygontubing that was put on the ceramic surface to create 30 cylinders of resin cement in each treatment group (n=30). Micro shear bond test-ing was performed at a cross head speed of 0.5mm/min. One-way analysis of variance, and multiple comparisons were made using Tukey's test (p<0.5). The bond strength was affected only by surface treatments other than silanization. The groups that utilized the low-fusing porcelain glaze with airborne particle abrasion or hydrofluoric acid showed bond strength values statistically superior to groups that utilized conventional airborne particle abrasion treatments with 50 or 110 pm aluminum oxide (p<0.001). The treatment that utilized low-fusing porcelain glaze and hydrofluoric acid showed bond strength values statistically superior to remaining groups (p<0.001). Treatment of zirconia ceramic surfaces with a glaze of low-fusing porcelain significantly increased the bond strength of a dual-cure resin luting agent to the ceramic surface.

Relationship between preoperative comorbidity, systemic inflammatory response, and survival in patients undergoing curative resection for colorectal cancer.

BACKGROUND: Besides tumor characteristics, colorectal cancer (CRC) outcomes are also determined by host factors, in particular the systemic inflammatory response. The basis of this relationship with survival is not known; however, systemic inflammation may reflect comorbidity. The present study examines relationships between host factors (including age, comorbidity, deprivation, and systemic inflammation) and survival in CRC. METHODS: A total of 302 patients underwent curative elective CRC resection between 1997 and 2005. Data was collected on patient comorbidity (Charlson Comorbidity Index [CCI], Lee Cardiac Risk Index [LCRI], National Institute on Aging and National Cancer Institute Comorbidity Index [NIA/NCI], and Adult Comorbidity Evaluation-27 [ACE-27]), systemic inflammatory response (Glasgow Prognostic Score [mGPS]), deprivation [Carstairs Deprivation Index], body mass index, and smoking status. RESULTS: For cancer-specific survival, age (P = 0.047), tumor, node, metastasis system stage (P < 0.001), high-risk Petersen Index (P < 0.001), LCRI (P = 0.021), and mGPS (P < 0.001) were independent factors by multivariate analysis. For overall survival, age (P < 0.001), tumor, node, metastasis system stage (P = 0.001), high-risk Petersen Index (P = 0.002), postoperative infective complications (P = 0.002), ACE-27 (P = 0.008), and mGPS (P < 0.001) were independent factors. Older age related to increasing comorbidity (ACE-27, CCI, LCRI [P < 0.005]) and increased mGPS (P < 0.005). Smoking and deprivation related to increasing comorbidity (P < 0.05). The mGPS was associated with high comorbidity burden assessed with ACE-27 (P = 0.065), CCI (P = 0.016), LCRI (P = 0.095), and NIA/NCI (P = 0.084). CONCLUSIONS: Comorbidity does not fully explain the relationship between the mGPS and cancer-specific survival in CRC patients. Furthermore, comorbidity, in particular that measured by the LCRI, is an important independent indicator of cancer survival.

Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury.

The susceptibility of xenografts to hyperacute rejection is postulated to reflect in part failure of complement regulatory proteins (CRPs) to control activation of heterologous complement on graft endothelium. To test this concept, transgenic swine expressing the human CRP decay accelerating factor and CD59 were developed using a novel expression system involving transfer of the proteins from erythrocytes to endothelial cells. Hearts from transgenic swine transplanted into baboons had markedly less vascular injury and functioned for prolonged periods compared to hearts from nontransgenic swine. These results indicate that expression of human CRPs in xenogeneic organs may contribute to successful xenografting and suggest that intercellular protein transfer might be a useful approach for expression of heterologous proteins in endothelial cells.

Curing efficiency of three different curing modes at different distances for four composites.

This study investigated the influence of the different curing distances with three polymerization modes in terms of the surface microhardness of four resin composites as a function of energy density. A hybrid resin composite and flowable composite from each of two manufacturers were evaluated. The specimens were polymerized with one of two light-curing units: 1) Mini LED AutoFocus (1500 mW/cm2) with a fast curing mode, for which two polymerization regimens were used: a) one AutoFocus function cycle and b) two AutoFocus function cycles, and 2) LEDemetron I (950 mW/cm2) with a 20-second curing time. Polymerization was performed with the curing tip at a distance of 0 mm, 3.0 mm, 6.0 mm, and 9.0 mm from the top surface of the specimen, and the power density of each light source was measured with a spectrophotometer. All specimens were stored in distilled water in a light-proof container at 37°C for 24 hours, and their top and bottom surface Knoop hardness numbers were determined. Microhardness data were submitted to two-way analysis of variance and multiple comparisons with a Tukey test. All statistical analyses were performed at a significance level of 0.05. Though the curing lights tested exhibited a decrease in power density with distance, the rate and extent of power density loss were not the same. The polymerization mode and curing tip distance had a significant effect on the composite microhardness. There was also a significant interaction among polymerization mode, curing tip distance, and microhardness. The curing ability of the three polymerization modes was ranked in terms of the hardness percent values: the LEDemetron I > two cycles of the Mini LED AutoFocus > one cycle of the Mini LED AutoFocus.

Effect of C-factor on microtensile bond strengths of low-shrinkage composites.

UNLABELLED: This study evaluated the microtensile bond strength (µ-TBS) of low-shrinkage composites with their corresponding adhesive systems, Filtek Silorane/Silorane adhesive (SIL, 3M ESPE AG, Seefeld, Germany) and Aelite LS/One-Step Plus (AL, BISCO Inc, Schaumburg, IL, USA) in cavities with different C-factors. Filtek Z250/Adper Single Bond Plus (Z, 3M ESPE, St Paul, MN, USA) was used as a control. METHOD: Standardized Class I cavities were prepared in extracted human molars after removing occlusal enamel. Cavities were assigned into six different C-factors by applying nail polish to four walls, three walls, two walls adjacent to each other, two walls opposite to each other, one wall, or no walls. Resin composites with their corresponding adhesive systems were applied according to manufacturer instructions. Specimens were sectioned to obtain four rectangular beams from the center of the restorations and µ-TBS was measured. Data were analyzed by Weibull survival analysis. Shrinkage stresses of the resin composites were determined after 30 minutes from the start of light-curing using a tensometer testing machine. Flexure elastic modulus was determined using standard procedures, in accordance with ISO 4049. Data for shrinkage stress and elastic modulus were analyzed by one-way analysis of variance followed by a Tukey multiple-comparisons test (p<0.05). RESULTS: µ-TBS of both SIL and AL were not affected by different C-factors; however, the bond strength of Z decreased significantly when the C-factor increased. Shrinkage stress results were 0.94 ± 0.1, 1.79 ± 0.18, and 2.14 ± 0.23 MPa for SIL, AL, and Z, respectively. The flexural modulus of both the SIL and the AL was significantly lower than that of Z. CONCLUSIONS: Increasing C-factor did not negatively affect the bond strength of low-shrinkage composites.

Transient perturbation of endothelial integrity induced by natural antibodies and complement.

The barrier function of blood vessels is though to be regulated at least in part by endothelium. This concept is supported by the dramatic loss of barrier function occurring in the hyperacute rejection of vascularized grafts mediated by anti-endothelial cell (EC) antibodies and complement. In this process, the endothelium is not destroyed but instead loses the ability to retain blood cells and plasma proteins within capillaries. The noncytotoxic mechanism that allows this change in EC function has been unknown. Here we report that within 10 to 20 min of exposure to human xenoreactive natural antibodies and complement, porcine EC undergo alterations in cell shape and in the cytoskeleton that disrupt monolayer integrity and lead to formation of intercellular gaps. Gap formation is not associated with cell death but requires the complement complex C5b67. The gaps induced by anti-EC antibodies and complement are transient; gap closure requires formation of C5b-9 complexes on the cells and the rate of recovery depends on the release of cellular products into the medium. Preincubation of EC with dibutyryl cAMP (0.5 mM) prevents gap formation and disruption of the cytoskeleton caused by antibodies and complement. These results provide evidence that the integrity of endothelium is regulated by components of the complement system and suggest a mechanism that may explain the prominent loss of endothelial integrity seen in humoral immune responses.

Stages of renal ontogenesis identified by monoclonal antibodies reactive with lymphohemopoietic differentiation antigens.

Differentiation antigens of T and B lymphocytes were sought in human fetal and adult kidney tissues with monoclonal antibodies by indirect immunofluorescence. Antibodies that identify B cells (BA-1 and anti-B1) and leukemia-associated antigens (BA-2, BA-3, and J5) reacted with renal glomerular and tubular epithelium at characteristic stages of nephron development. BA-1 and BA-2 identified primitive epithelium of the glomerulus, and ureteral bud and nephron development was characterized by loss of BA-1 and BA-2 binding by visceral glomerular and proximal tubular epithelium. In contrast, J5 and BA-3 did not react with primitive epithelium but identified visceral and proximal tubular epithelium after appearance of the glomerular basement membrane and throughout subsequent nephron differentiation. Anti-B1 reacted with ureteral bud and distal nephron epithelium in more mature fetal tissues. Monoclonal antibodies that identify populations of T cells and thymocytes did not react with parenchymal cells of fetal or adult kidneys. They did identify interstitial mononuclear cells whose size and relative numbers appeared gestationally related. Monoclonal antibodies that recognize a human monomorphic HLA-DR determinant reacted with glomerular and peritubular capillaries as early as 11 wk of gestation. The distribution and density of HLA-DR expression appeared more related to gestation than nephron development. The relationship between renal parenchymal expression of lymphohemopoietic antigens and glomerular acquisition of C3b receptor activity was determined using C3b-coated fluoresceinated Escherichia coli. In fetal tissues, C3b receptor activity appeared developmentally related to the loss of determinants recognized by BA-1 and BA-2 and to the appearance of J5 and BA-3 reactivity with visceral glomerular epithelium. Tissue binding and comparative avidity of J5 and BA-3 antibodies was studied in a series of experiments, the results of which suggest that these antibodies are directed against the same epitope or closely related epitopes of the common acute lymphoblastic leukemia antigen. The common expression of differentiation antigens and C3b receptors by cells of lymphohemopoietic lineage and renal epithelia suggests the possibility of heretofore unrecognized commonality of function or developmental experience.

Interstitial mononuclear cell populations in renal graft rejection. Identification by monoclonal antibodies in tissue sections.

The interstitial mononuclear cell populations of 22 renal grafts with interstitial rejection (IR), 6 grafts with interstitial nephritis without rejection (IN), and 5 kidneys without infiltration (3 donor kidneys, 2 grafts) were identified and quantitated by monoclonal antibodies recognizing T cells (TA-1, OKT3), helper inducer cells (OKT4), cytotoxic/suppressor cells (OKT8), B cells (BA-1), and monocytes and null cells (OKM1). Double-layer fluorochrome enhancement using F(ab')(2) reagents and nuclear counter staining with ethidium bromide enabled quantitation of the number of positive mononuclear cells, interstitial cells, and total cells on each of 30-55 microscopic fields per tissue section. T cells were the most abundant infiltrating cell in tissues with IR (35 +/- 9.8 percent), significantly higher than that seen in IN (21 +/- 16 percent) or in kidneys without infiltration (5.0 +/- 3.9 percent). The percentage of T cells identified by TA-1 or OKT3 was approximately equivalent to the summation of OKT4 plus OKT8. Although no differences were observed in the percentage of OKT4 cells, the percentage of OKT8 was significantly higher in IR (26 +/- 7.7 percent, P {less than} 10(-4)) than in IN (9.3 +/- 6.2 percent) or in kidneys with normal interstitium (3.0 +/- 2.4 percent). The ratio of OKT8/OKT4-positive T cells in 22 graft tissues with IR (3.2 +/- 1.4) was greater (P {less than} 0.0007) than 6 graft tissues with IN without rejection (0.82 +/- 0.39) and the 5 kidney tissues without interstitial infiltration (0.75 +/- 0.25). There was no significant difference between the groups in the relatively low percentage of interstitial cells identified as B cells reacting with BA-1 or containing S(IgD,M). The percentage of interstitial cells recognized by OKM1 was similar in rejection and interstitial nephritis, with both being greater than controls (P {less than} 0.02). The relative numbers of blood mononuclear cells identified by the monoclonal antibodies was generally not predictive of the proportions present in kidney tissue, although OKT4-positive blood cells were less numerous and OKMI+ blood cells were more numerous than in controls (P {less than} 0.002). Quantitative analysis of identifiable interstitial cells in graft rejection reveals that most infiltrating cells are T cells, the greater proportion of which are recognized by OKT8. OKT8-positive cells may play an important role in mediating renal graft rejection.