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PubMed1986

Structural and functional integrity of rat liver perfused in backward and forward directions.

The purpose of this study was to assess if reversal of the direction of isolated rat liver perfusion would cause significant alterations in hepatic functions and structure. Five isolated rat livers were perfused forward and another five backward with oxygenated Ringer's solution for up to 90 min (hydrostatic pressure: less than or equal to 13 cm H2O; flow rate: forward 3.88 +/- 0.34 ml/min per gram and backward 3.76 +/- 0.34 ml/min per gram). At the end of the experiment, livers were perfusion-fixed for morphological examination. The following results were obtained: No significant differences were noted between the forward and backward perfusions with respect to oxygen uptake, mean bile flow (forward 0.57 +/- 0.12; backward 0.60 +/- 0.14 ml/min per gram), average bile acid excretion (forward 2.39 +/- 1.11; backward 2.83 +/- 0.94 nmol/min per gram), hydroxylation pattern of bile acids, urea synthesis, release of lactic dehydrogenase, glucose secretion, and redox ratios. Light and electron microscopy, including morphometry of parenchymal and sinusoidal areas, revealed that the backward perfusion caused a greater degree of sinusoidal distension, but no other noteworthy differences. Hepatic ultrastructure was well preserved. We conclude that reversing the direction of perfusion does not alter structure and major hepatic functions significantly.

Animals↗

PubMed2006

Testing of functional integrity of p53 protein in primary breast cancer by a rapid quantitative p53-p21 double assay may improve the clinical value of p53.

We hypothesized that inclusion of p21(WAF1), an indicator of biological function, into the p53 assay might improve the clinical value of p53 in breast cancer diagnosis. In primary breast carcinomas (n = 146) and healthy/benign controls (n = 40), the p53 protein was quantified by luminescence immunoassay. The p21 protein was simultaneously measured by quantitative ELISA in a representative subgroup of breast cancers (n = 52) and controls (n = 17). In controls, p53 but not p21 was detectable. In almost all cancer tissues, p53 and p21 expression could be quantified. There was no correlation between the concentrations of both proteins. However, if p53 exceeded a threshold of 1.0 ng/mg protein, p21 expression was significantly reduced compared with samples with p53 below threshold. p21 was normally distributed in the low-p53 subpopulation, but not in the high-p53 group. The histologic parameter 'grade III' was more often found (p = 0.002) in tumors with p53 >1.0 ng/mg protein than in those with p53 below the threshold. Histological criteria of high tumor malignancy were found more often in cases with high p53 but low p21. Consequently, in clinical routine, a quantitative double assay of p53 and p21(WAF1) might help to discriminate breast cancers with preserved or impaired/lost p53 function.

Biomarkers, Tumor↗

PubMed2003

Integrating functional genomics data.

Functional annotation of fully sequenced genomes is still a major issue. High-throughput data sets could be used to provide more and better functional annotations. However differences in data quality need to be taken into account. For this purpose these high-throughput data sets need to be integrated so that the data quality can be assessed, hypotheses can be prioritized and existing annotations can be improved and extended.

Computational Biology↗

PubMed1997

Integrative functions of lactational hormones in social behavior and stress management.

For mammalian reproduction to succeed, self-defense and asociality must be subjugated to positive social behaviors, at least during birth, lactation, and sexual behavior. Perhaps the important task of regulating the interaction between social and agonistic behaviors is managed, in part, by interactions between two related neurochemical systems that incorporate oxytocin and vasopressin in their functions. The neuropeptides oxytocin and vasopressin participate in important reproductive functions, such as parturition and lactation, and homeostatic responses, including modulation of the adrenal axis. Recent evidence also implicates these hormones in social aspects of reproductive behaviors. For example, oxytocin is important for a variety of positive social behaviors, including the regulation of maternal-infant interactions. In adult animals, oxytocin may facilitate both social contact and selective social interactions associated with social attachment and pair bonding, and it participates in the regulation of parasympathetic functions. Vasopressin, in contrast, is associated with behaviors that might be broadly classified as "defensive" including enhanced arousal, attention, or vigilance, increased aggressive behavior, and a general increase in sympathetic functions. On the basis of the literature on the functions of these hormones and our own recent findings, we propose that dynamic interactions between oxytocin and vasopressin are components of a larger system which integrates the neuroendocrine and autonomic changes associated with mammalian social behaviors and the concurrent regulation of the stress axis. In addition, studies of lactating females provide a valuable model for understanding the more general neuroendocrinology of the stress axis. Peptide hormones, including oxytocin and vasopressin, do not readily cross the blood-brain barrier and must be administered centrally (i.c.v.) to reach the brain. Nasal sprays have been used to promote milk let down and have been used in some behavioral studies, but the extent to which such compounds reach the brain is not known. Therefore, virtually nothing is known regarding the effects in humans of centrally administered oxytocin. The study of human lactation, in conjunction with animal research, provides an opportunity to begin to develop viable hypotheses regarding the behavioral effects of oxytocin.

Adrenal Glands↗

PubMed1991

Analysis of the integration function of the streptomycete bacteriophage phi C31.

A 2.1 kb (1 kb = 10(3) base-pairs) segment of DNA from the streptomycete bacteriophage phi C31 was found to be sufficient to direct site-specific integration of plasmid vectors in Streptomyces ambofaciens and Streptomyces fradiae in the absence of any streptomycete origin of replication. Sequencing and analysis of phage, chromosomal and junction attachment sites of S. ambofaciens and S. fradiae revealed that recombination is conservative and that crossover takes place within three bases of homology between phage and host. Deletion analysis, sequencing and site-specific mutagenesis of the phi C31 DNA revealed a large open reading frame (ORF 613) whose expression was necessary for integration. This ORF begins near the point of crossover and reads away from the attachment site. A comparison of the predicted amino acid sequence of ORF 613 with known recombinases did not reveal any significant similarities. A genetic analysis of the amino-terminal region of ORF 613 suggested that translation could initiate at any one of three possible start codons. Primer extension experiments showed that transcriptional initiation occurred at a T and a C only four and five bases, respectively, from the site of crossover. This analysis suggested that ORF 613 would be separated from its promoter upon integration.

Amino Acid Sequence↗

PubMed1984

Integrated function of a kinetic proofreading mechanism: dynamic analysis separating the effects of speed and substrate competition on accuracy.

All of the data relating to isoleucyl-tRNA synthetase and its proofreading of valyl-tRNAIle have been integrated into a single model whose dynamic behavior has been determined by numerical solution of the relevant kinetic equations. The results indicate that (1) the system normally operates in vivo with amino acid concentrations slightly above the apparent Km of the system, (2) increases in the displacement of reactants from thermodynamic equilibrium increase the net reaction velocity when the appropriate nominal parameter values are selected, (3) the cost of proofreading decreases with an increase in displacement of reactants from equilibrium, (4) accuracy and reaction velocity tend to be inversely related when substrate competition is unchanged but directly related or unrelated when substrate competition is altered, (5) changes in substrate competition are about twice as effective as changes in reaction velocity in altering the overall accuracy of aminoacylation, and (6) simultaneous changes in substrate competition and reaction velocity have a cumulative but not additive effect upon accuracy. With regard to the temporal development of errors and proofreading costs, we have seen two different patterns. In one, errors or costs gradually change with time following an abrupt alteration; in the other, errors or costs change dramatically in one direction and then more slowly reverse themselves. In all cases, the system responds to change quickly (less than 0.02-0.2 s) but shows no tendency to oscillate.

Amino Acyl-tRNA Synthetases↗

PubMed2006

Effects of cigarette smoking on serum fluoride concentrations and renal function integrity after 1 MAC-h sevoflurane anaesthesia.

BACKGROUND: Tobacco smoke contains various chemicals which may affect drug metabolism. Sevoflurane is metabolized to inorganic fluoride, and elevated serum fluoride concentrations (S-F(-)) may cause deterioration of renal function. Whether smokers develop high S-F(-) and associated disturbances in renal function is not known. METHODS: We investigated sevoflurane metabolism in 25 non-smoking and 25 smoking (> 10 cigarettes/day) generally healthy women, aged 19-68 years, undergoing gynaecological elective surgery under one minimum alveolar concentration-hour (1 MAC-h) standardized sevoflurane anaesthesia. S-F(-) was measured for 24 h. Glomerular and tubular function was assessed by measuring serum and urine tumour-associated trypsin inhibitor (TATI), beta(2)-microglobulin and serum creatinine for 48 h after sevoflurane inhalation. RESULTS: There were no differences between the two study groups with regard to S-F(-). It increased significantly in both groups: in non-smokers, from a baseline between 1.0 and 11 micromol/l (median, 1.6 micromol/l) to a maximum between 8.2 and 40 micromol/l (26 micromol/l) (P < 0.001) and, in smokers, from a baseline between 0.5 and 5.2 micromol/l (1.7 micromol/l) to a maximum between 19 and 71 micromol/l (25 micromol/l) (P < 0.001). In both groups, S-F(-) remained elevated for the entire sampling period (P < 0.001). In all five women (one non-smoker and four smokers) with a maximum S-F(-) of 40 micromol/l or higher and an area under the serum fluoride concentration-time curve (AUC(F0-24)) of 500 micromol/h/l or higher, serum TATI increased above the pathological concentration of 3.0 nmol/l, whereas only six of the 45 patients with S-F(-) below 40 micromol/l had serum TATI above 3.0 nmol/l (P < 0.001). Beta(2)-Microglobulin increased significantly (> 1 mg/l) in two patients with high S-F(-) relative to two of the 45 patients with S-F(-) below 40 micromol/l (P= 0.005). None of the patients developed clinically detectable renal dysfunction. CONCLUSION: Smoking did not affect S-F(-) after sevoflurane anaesthesia. Glomerular dysfunction, seen as increased serum TATI, was noted in five women with S-F(-) above 40 micromol/l. Our results suggest that the renal toxic threshold of S-F(-) seems to be lower than the earlier reported value of 50 micromol/l.

Adult↗

PubMedDate not supplied

Endothelial cells reestablish functional integrity after reversible permeabilization.

Permeabilization is an important tool in cell biology that allows manipulation of intracellular mechanisms by introduction of probes and regulatory molecules into the cell cytoplasm. We found that incubation of endothelial cells (ECs) with glass beads resulted in nonspecific permeabilization of human and bovine ECs without removal of the cells from monolayer culture. This poration of the plasma membrane allowed the introduction of macromolecules (dextrans less than or equal to 152 kd and immunoglobulins) as well as small, charged molecules (Lucifer Yellow). We found that nonspecific permeabilization of the EC was transient and defined the conditions under which integrity of the plasma membrane was reestablished. This process was dependent on time, temperature, and the presence of extracellular calcium. We also demonstrated that permeabilized ECs regain functional characteristics. This was defined by a number of criteria, including the ability to rapidly reestablish confluent monolayer morphology, to extrude Lucifer Yellow, to adhere and spread after passage, and to synthesize biologically active molecules after stimulation with a receptor-mediated agonist. Thus, transiently porated ECs loaded with appropriate probes can be used in studies of regulatory mechanisms while remaining in monolayer culture, a condition in which many phenotypic features are similar to in situ endothelium. Furthermore, the porated EC may be a useful model for defining the mechanisms that influence the repair of endothelial plasma membrane injury.

Acid-Base Equilibrium↗

PubMed1990

Preservation of integrative function in a perfused guinea pig brain.

The mammalian brain has been one of the most difficult organs to maintain using artificial perfusion. Normal biochemistry, histology, and electrophysiology of the brain have been demonstrated for limited periods in vitro, but it has been more difficult to maintain complex, integrative neuronal activity such as the electroencephalogram (EEG) or programmed motor output. Normal motor output, other than reflex activity, has not previously been demonstrated in a perfused brain preparation. This paper reports the first preservation of normal function in a complete motor network, including intact afferent and efferent pathways, during perfusion of the mammalian brain. The brain, rostral spinal cord and peripheral nervous system of the guinea pig were perfused in situ using an artificial blood containing the oxygen carrier, perfluorotributylamine (FC-43). This preparation was maintained normothermic, whereas many other perfused brain preparations have been maintained hypothermic to prolong viability. Survival was enhanced by the addition of HEPES buffer to the perfusion medium, probably by increasing carbon dioxide transport. The duration of normal EEG was extended to 8 h. Spontaneous respiratory motor output with normal waveform and temporal pattern was recorded from the phrenic nerve for an average of 6 h. The respiratory motor output responded appropriately to blood pCO2, temperature, blood flow, drug concentrations, and electrical stimulation of vagal afferent fibers. This preparation represents a significant advance in the ability to preserve neural function during perfusion, and should offer advantages for studying cellular electrophysiology of intact, functioning neural networks, as well as neurochemistry and neuropharmacology.

Animals↗

PubMed2005

The functional integrity of platelets in volume-reduced platelet concentrates.

Premature and low-birth-weight infants usually require small-volume platelet transfusions to treat thrombocytopenia. Also, infants undergoing open-heart surgery with extracorporeal circulation and with compromised cardiac function are at risk for excessive intravascular volume. The small-volume platelet substitution can be achieved by dispensing an aliquot from the unit of a standard single-donor platelet concentrate (PC). Alternatively, there is an indication for volume reduction of PCs to maximize the number of platelets transfused in the smallest possible volume. We determined the spontaneous and induced activation of platelets before and after volume reduction in 20 consecutive single-donor-apheresis PCs. After a mean storage time of 2 days, the PCs were plasma-depleted by centrifugation. Spontaneous, adenosine diphosphate (ADP)-induced, and collagen-induced activation were determined by flow cytometry. Furthermore, ADP- and collagen-induced aggregation were measured. A total of 33.8% of platelets in standard PCs were activated spontaneously. Volume reduction of PCs led to a mild but significant increase of spontaneous activation of platelets (43.2%). Additionally, volume reduction resulted in an impaired ADP-induced aggregability of platelets, whereas collagen induction was unaffected. Transfusion of volume-reduced PCs is an effective alternative to use of standard PCs in patients at frequent risk for excessive intravascular volume, because equal volumes increase the platelet count twice as effectively.

Adenosine Diphosphate↗

PubMed1995

Lack of selective V beta deletion in CD4+ or CD8+ T lymphocytes and functional integrity of T-cell repertoire during acute HIV syndrome.

OBJECTIVE: To study the V beta T-cell repertoire in peripheral blood lymphocytes (PBL) during acute HIV syndrome by using several anti-V beta monoclonal antibodies (MAb) and to analyse its functionality by stimulating PBL with superantigens (SAg) such as Staphylococcus aureus enterotoxins. METHODS: Cytofluorimetric analysis of V beta T-cell-receptor expression was performed on PBL from eight patients with symptomatic, acute HIV-1 primary infection, showing a dramatic decrease of CD4+ PBL accompanied by a marked increase in activated/memory CD8+ T cells, and on 12 age- and sex-matched healthy controls. PBL were then isolated, stimulated with different SAg, anti-CD3 MAb or phytohaemagglutinin and cultured for 3 days. PBL capability to progress through cell cycle was studied by the classic cytofluorimetric method of bromodeoxyuridine incorporation and DNA staining with propidium iodide. RESULTS: Despite the presence of a few expansions of some V beta families among CD8+ T lymphocytes, no gross alterations in T-cell repertoire were present in patients with acute HIV syndrome. Its functionality was maintained overall, as PBL responsiveness to SAg was well preserved. Interestingly, all CD8+ T cells, although bearing different V beta T-cell receptors, expressed marked signs of activation, i.e., CD45R0, CD38 and major histocompatibility complex class II molecules, and also high amounts of CD11a and CD18. CONCLUSIONS: Our data suggest, at least in the early phases and in the acute form of the infection, that HIV is not likely to act as a SAg. However, further studies are needed to analyse other sites, such as lymph nodes, where HIV could exert other, significant effects, and to study the expression of other V beta families than those investigated here.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

From perception to action: temporal integrative functions of prefrontal and parietal neurons.

The dorsolateral prefrontal cortex (DPFC) and the posterior parietal cortex (PPC) are anatomically and functionally interconnected, and have been implicated in working memory and the preparation for behavioral action. To substantiate those functions at the neuronal level, we designed a visuomotor task that dissociated the perceptual and executive aspects of the perception-action cycle in both space and time. In that task, the trial-initiating cue (a color) indicated with different degrees of certainty the direction of the correct manual response 12 s later. We recorded extracellular activity from 258 prefrontal and 223 parietal units in two monkeys performing the task. In the DPFC, some units (memory cells) were attuned to the color of the cue, independent of the response-direction it connoted. Their discharge tended to diminish in the course of the delay between cue and response. In contrast, few color-related units were found in PPC, and these did not show decreasing patterns of delay activity. Other units in both cortices (set cells) were attuned to response-direction and tended to accelerate their firing in anticipation of the response and in proportion to the predictability of its direction. A third group of units was related to the determinacy of the act; their firing was attuned to the certainty with which the animal could predict the correct response, whatever its direction. Cells of the three types were found closely intermingled histologically. These findings further support and define the role of DPFC in executive functions and in the temporal closure of the perception-action cycle. The findings also agree with the involvement of PPC in spatial aspects of visuomotor behavior, and add a temporal integrative dimension to that involvement. Together, the results provide physiological evidence for the role of a prefrontal-parietal network in the integration of perception with action across time.

Animals↗

PubMed1996

Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device.

Microfabricated silicon PCR reactors and glass capillary electrophoresis (CE) chips have been successfully coupled to form an integrated DNA analysis system. This construct combines the rapid thermal cycling capabilities of microfabricated PCR devices (10 degrees C/s heating, 2.5 degrees C/s cooling) with the high-speed (< 120 s) DNA separations provided by microfabricated CE chips. The PCR chamber and the CE chip were directly linked through a photolithographically fabricated channel filled with hydroxyethylcellulose sieving matrix. Electrophoretic injection directly from the PCR chamber through the cross injection channel was used as an "electrophoretic valve" to couple the PCR and CE devices on-chip. To demonstrate the functionality of this system, a 15 min PCR amplification of a beta-globin target cloned in M13 was immediately followed by high-speed CE chip separation in under 120 s, providing a rapid PCR-CE analysis in under 20 min. A rapid assay for genomic Salmonella DNA was performed in under 45 min, demonstrating that challenging amplifications of diagnostically interesting targets can also be performed. Real-time monitoring of PCR target amplification in these integrated PCR-CE devices is also feasible. Amplification of the beta-globin target as a function of cycle number was directly monitored for two different reactions starting with 4 x 10(7) and 4 x 10(5) copies of DNA template. This work establishes the feasibility of performing high-speed DNA analyses in microfabricated integrated fluidic systems.

DNA↗

PubMed2025

Functional integration of the bacteriophage T4 DNA replication complex: The multiple roles of the ssDNA binding protein (gp32).

Single-stranded DNA binding protein (gp32) serves as the central regulatory component of the multi-subunit T4 bacteriophage DNA replication system by coordinating the system's three functional sub-assemblies, resulting in phage DNA synthesis in T4-infected E. coli cells at the high speeds (~1,000 nts s-1) and the high fidelity (< 1 error per 107 nts) required for genomic function within this cellular eco-system. Gp32 proteins continuously bind to, slide as cooperatively-linked clusters on, and un-bind from transiently exposed single-stranded (ss) DNA templates to carry out their coordinating functions, as well as to protect genomic sequences from nuclease activity and block the formation of interfering secondary structures. The N-terminal domains (NTDs) of gp32 mediate cooperative interactions within ssb clusters, but the roles of the disordered C-terminal domains (CTD) in the nucleation of gp32-ssDNA filaments at ss-dsDNA junctions are less well understood. We here present microsecond-resolved single-molecule Förster resonance energy transfer studies of the initial steps of gp32 assembly on short oligo-deoxythymidine lattices of varying lattice length and polarity near model ss-dsDNA junctions. These data are analyzed to define the molecular steps and related free energy surfaces involved in initiating gp32 cluster formation, which show that the nucleation mechanisms and regulatory interactions driven by gp32 proteins at ss-dsDNA junctions are significantly directed by lattice polarity. We propose a model for the role of the CTDs in orienting gp32 monomers at lattice positions close to ss-dsDNA junctions that suggests how intrinsically disordered CTD domains might facilitate and control non-base-sequence-specific binding in both the nucleation and the dissociation of the gp32-ssDNA filaments involved in phage DNA replication and related processes.

Journal Article↗

PubMed2003

The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant.

C1-inhibitor (C1-Inh) is a serine protease inhibitor (serpin) with a unique, non-conserved N-terminal domain of unknown function. Genetic deficiency of C1-Inh causes hereditary angioedema. A novel type of mutation (Delta 3) in exon 3 of the C1-Inh gene, resulting in deletion of Asp62-Thr116 in this unique domain, was encountered in a hereditary angioedema pedigree. Because the domain is supposedly not essential for inhibitory activity, the unexpected loss-of-function of this deletion mutant was further investigated. The Delta 3 mutant and three additional mutants starting at Pro76, Gly98, and Ser115, lacking increasing parts of the N-terminal domain, were produced recombinantly. C1-Inh76 and C1-Inh98 retained normal conformation and interaction kinetics with target proteases. In contrast, C1-Inh115 and Delta 3, which both lack the connection between the serpin and the non-serpin domain via two disulfide bridges, were completely non-functional because of a complex-like and multimeric conformation, as demonstrated by several criteria. The Delta 3 mutant also circulated in multimeric form in plasma from affected family members. The C1-Inh mutant reported here is unique in that deletion of an entire amino acid stretch from a domain not shared by other serpins leads to a loss-of-function. The deletion in the unique N-terminal domain results in a "multimerization phenotype" of C1-Inh, because of diminished stability of the central beta-sheet. This phenotype, as well as the location of the disulfide bridges between the serpin and the non-serpin domain of C1-Inh, suggests that the function of the N-terminal region may be similar to one of the effects of heparin in antithrombin III, maintenance of the metastable serpin conformation.

Amino Acid Sequence↗

PubMed1975

Sensory integrative function in a child guidance clinic population.

Recent researchers in the area of mental health have recognized the influence of biological defects on psychosocial development and on the child's ability to acquire social and academic skills. This study was designed to determine whether or not senxory integrative disorders occurred in a child guidance population, to explore the nature of sensory integrative disorders found in such a group, and to ascertain any relationships between certain types of sensory integrative disorders and specific behavioral traits. The subjects were 87 children between 5 and 9 years of age, the total number referred to a child guidance clinic in southern California because of problems in behavior. All subjects (Ss) were administered the Southern California Sensory Integration Tests and were observed for neuromuscular deviations. The date were subjected to factor analyses. Results showed a high incidence of sensory integrative dysfunction in this population. There was considerable evidence of a syndrome known as postural and bilateral integration dysfunction as well as a strong tendency in this group to show various kinds of behavior problems.

Child↗

PubMed2001

Rumpshaker-like proteolipid protein (PLP) ratio in a mouse model with unperturbed structural and functional integrity of the myelin sheath and axons in the central nervous system.

The gene plp on the X chromosome encodes the isoforms proteolipid protein (PLP) and DM(20), two dominant integral membrane proteins of central nervous system (CNS) myelin. DM(20) results from the activation of the cryptic splice site in exon III of the PLP gene. We inserted a sense-orientated loxP flanked neomycin-gene into intron III of the plp sequence, using homologous recombination in embryonic stem cells and generated the homozygous neoS mouse line. Unlike the previously described complete PLP/DM(20) ablation (plp(-/-)), which has been obtained by introducing a neo-gene in antisense-orientation in the same position of intron III, the plp expression surprisingly revealed reduced mRNA levels. The PLP isoform was reduced to 50%, but DM(20) expression was unaffected. This protein pattern resembles the expression profile of the PLP isoforms in the natural occurring rumpshaker mutant. Electron microscopic examination revealed a normal compaction of CNS-myelin and maintenance of axon integrity. PLP expression levels of the wt control were recovered by Cre excision of the neo-selection gene after intercrossing neoS mice and oligodendrocyte-specific Cre-mice. These data strongly hint at different functions of intron III in PLP/DM(20)-specific splicing and mRNA stability. Furthermore evidence is provided for functionally affected translation products of the PLP gene in the rumpshaker mutant, whereas no PLP-isoform occur in plp(-/-) mice generated by introducing a selectable marker into intron III in antisense orientation.

Alternative Splicing↗

PubMedDate not supplied

Functional integrity of vascular allografts after endothelial removal.

Several studies have indicated that antigen-presenting endothelial cells represent the primary initiator of acute arterial graft rejection, leading to decreased arterial patency rates. Patency rates dramatically increase upon endothelial removal (denudation) prior to orthotopic transplantation into antigenically disparate hosts. Although patent, the biomechanical and functional changes seen in these allograft vessels (ACI rats to Lewis rats) have not been described. The present investigation examined functional differences between these allograft arteries and normal rat femoral arteries. Moreover, endothelial removal may also alter function; thus, an autograft injury model (Lewis to Lewis) was employed to discern the differences between injury and rejection. The results indicate that denudation injury alone caused no change in the passive stress-strain curve, the muscle length at which stress was maximum (Lo), or in phenylephrine- or nitroglycerin-induced concentration-response curves. Similarly, concentration-response curves were not affected by allograft transplantation; however, both the passive stress-strain curve and Lo values were shifted to significantly longer lengths (0.25 and 0.20 mm, respectively), suggesting an increase in arterial plasticity but not compliance. Furthermore, allografts produced significantly weaker KCl-induced contractions than did autografts (22 vs. 66% of control values, p < 0.05). Acetylcholine maximally relaxed phenylephrine-contracted arteries in the following descending order. ACI > Lewis > autograft > allograft. In conclusion, these data suggest that vascular rejection involves subendothelial tissues, is distinct from vascular injury, and that the denudation allograft transplantation model can be employed to examine this process.

Acetylcholine↗