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At least 181 records · Page 10Linked to original sources

PubMed1988

Functional heterogeneity of L3T4+ T cells in MRL-lpr/lpr mice. L3T4+ T cells suppress major histocompatibility complex-self-restricted L3T4+ T helper cell function in association with autoimmunity.

The present study demonstrates in MRl-lpr/lpr autoimmune mice an age-dependent loss of MHC-self-restricted function by L3T4+ Th. This defect is not present in age-matched, congenic MRL-+/+ spleen cells and appears to be due to the presence of suppressor cells that are selective for L3T4+ Th and not for Lyt-2+ Th. Surprisingly, the suppressor cells are also L3T4+ T cells and can suppress the IL-2 production of congenic MRL/+ L3T4+ Th to MHC-self-restricted antigens. These data support the idea of functional specialization within the L3T4+ population of T cells. Because L3T4+ suppressor cells are detected late in the course of autoimmunity, we interpret their presence not as a primary initiating event in the development of autoimmunity, but rather as a compensatory mechanism. Additionally, similar suppression of L3T4+ Th function has also been reported in a murine graft-vs.-host model of autoimmunity, suggesting that the suppressor cells represent an immunoregulatory mechanism that is a common feature of autoimmunity. Since excessive class II-restricted Th activity for B cells has been reported for both models of autoimmunity, L3T4+ suppressor cells may represent an attempt to down regulate such excessive Th activity. These findings may be relevant to human autoimmune diseases, such as systemic lupus erythematosus, in which B cell hyperactivity is also associated with reduced IL-2 production by Th.

Aging↗

PubMed1992

Transfection of HLA-DR-expressing DAP.3 cells with a cDNA clone encoding the glycosyl phosphatidylinositol-linked form of lymphocyte function associated antigen-3: biochemical features and functional consequences.

Structural and functional aspects of the accessory molecule lymphocyte function associated antigen (LFA)-3 (CD58) have been examined following the transfection of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier observations that DAP.3 cells are deficient in GPI anchoring LFA-3 was expressed efficiently on DAP.3, as well as on P815 cells. Immunoprecipitation of LFA-3 from 35S-labelled cells revealed that the molecule expressed on the DAP.3 cells had a molecular weight intermediate between the transmembrane and GPI-linked forms expressed by human B cells. This suggests that the DAP.3 cells have a default pathway whereby the RNA transcript which encodes the GPI-linked form of the molecule can also encode an integral membrane protein. Functionally, expression of LFA-3 by DAP.3 which had previously been transfected with the genes encoding HLA-DR1 led to a marked augmentation of the proliferative response of five out of eight anti-DR1 human T cell clones. This effect was not reproduced when DR1 and LFA-3 were expressed by separate populations of DAP.3 cells, suggesting that the ligands for CD2 and for the T cell's receptor must be expressed on the same cell membrane. Expression of human LFA-3 also led to a substantial increase in the proliferative response of human peripheral blood T cells to a DR alloantigen. Separation of T cells into CD45RO+ and CD45RO- populations revealed that the augmentation was more marked for the memory than the virgin population. The mechanisms responsible for these differences are discussed.

Animals↗

PubMed1988

Conservation of short patches of amino acid sequence amongst proteins with a common function but evolutionarily distinct origins: implications for cloning genes and for structure-function analysis.

Small patches of identical amino acid sequences commonly occur in proteins that have the same function but are derived from evolutionarily distant organisms. Reverse translation of such patches into degenerate pools of oligonucleotides provide useful hybridization probes for cloning the gene for the corresponding protein from other organisms. Since the conserved patches of identical amino acid sequence are probably important for the protein's biological function, they are preferred targets for reverse genetic studies aimed at defining structure-function relationships.

Amino Acid Sequence↗

PubMed1991

Structure-function relationships of the C-terminal functional domain of hirudin and its variants.

The C-terminal functional domain of hirudin, hirudin variant 1 (residues 55-65), binds to a non-catalytic site on thrombin. In doing so, it is capable of inhibiting the procoagulant actions of thrombin. In terms of free energy of binding, this domain, which comprises 17% of the total sequence of the protein, contributes approximately half of the binding energy of the whole protein to thrombin. This situation also appears to hold true for the known variants of hirudin, some of which differ in the functional nature of their C-terminal regions. Extensive structure-function studies on this domain yield insights into the differences and similarities in the modes of thrombin interaction of hirudin and its variants. In particular, hirudin and hirudin PA have a similar and somewhat interchangeable structure-activity relationships (SAR) profile that indicates that they interact with thrombin in a similar manner. Hirullin P18, a 62 amino acid member of the hirudin family and isolated from Hirudinaria manillensis, is substantially different in sequence and its SAR, which shows that, although it seems to utilize the same non-catalytic binding domain as hirudin, it must utilize a different mode of interaction with thrombin.

Amino Acid Sequence↗

PubMed1988

The engymetric determination of acute functional impairment in kidney graft function caused by cyclosporine A.

Engymetry offers a new means of continuously measuring nuclear radiation fields without any need of restricting the patient's mobility. In this study, kidney function was measured simultaneously and continuously for 6.6 h with engymetry, after application of a 12 h therapy dose of Cyclosporine A (CsA) of 4.0 +/- 1.8 mg per kg bodyweight (bw). 15 kidney transplanted patients participated in this study. 370 MBq 99Tcm-DTPA and 10 MBq 131I-OIH were injected during routine transplant scintigraphy. Renal function was monitored from the external disappearance curves of the tracers recorded by portable double radionuclide detectors. Renal impairment could be seen in the rising phase of CsA or coincided with the CsA maximum in 13 of the 15 patients. Under the impairment the half-life of 99Tcm-DTPA increased from 4.1 +/- 1.2 to 15.9 +/- 12.3 h (p less than 0.005) for 61 +/- 45 min and the half-life of 131I-OIH increased from 3.2 +/- 0.7 to 12.7 +/- 8.4 h (p less than 0.001) for 71 +/- 37 min. With noninvasive engymetry it is possible to detect renal functional impairment during long observation periods. Acute restriction in glomerular filtration and renal blood flow was discovered in human kidney graft recipients after the application of a low therapeutic CsA dose.

Acute Kidney Injury↗

PubMed1986

Activated T cells with immunoregulatory functions at different sites of involvement in sarcoidosis. Phenotypic and functional evaluations.

Cells from recovered BAL fluid and from infiltrates in different involved tissues (lungs, lymph nodes, conjunctiva, liver, spleen, and skin) were studied in 22 patients with active sarcoidosis in order to define the surface phenotype, functional in vitro properties, and topographic distribution of the cells in granulomatous lesions. Our data demonstrated a compartmentalization of activated T cells with immunoregulatory functions from the blood to all sites of disease activity. In fact, these cells were found to express the T4+ Leu 8- 5/9+ T17- phenotype, which belongs to cells with helper activity, and that provide heightened responses in functional assays of helper activity, IL-2 release, and the ability to respond in AMLR's. Both a cellular redistribution and a local in vitro replication account for this tissue compartmentalization in sarcoidosis. The microanatomic location of activated T cells, as defined by immunohistological evaluation, showed that the state of activation in these T cells may be a consequence of an intimate contact between helper cells and macrophages within the sarcoidosis granulomas.

Adult↗

PubMed1988

Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis.

The single-dose pharmacokinetics of intravenously administered cefoperazone (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of renal failure. In an open, parallel experimental design, six normal subjects (creatinine clearance, greater than 90 ml/min), two patients with mild renal failure (creatinine clearance, 31 to 60 ml/min), eight patients with moderate renal failure (creatinine clearance, 7 to 30 ml/min), and four functionally anephric patients (creatinine clearance, less than 7 ml/min) were studied. The functionally anephric patients were given two test doses to allow study of drug disposition both on and off hemodialysis. Serial blood and urine samples were collected from time zero to 12 h after dosing in normal subjects and from 0 to 72 h in renal patients. Serum concentrations of both drugs declined biexponentially. For cefoperazone, the terminal elimination half-lives averaged from 1.6 to 3.0 h and were similar in subjects and patients. No cefoperazone pharmacokinetic parameters were appreciably altered by renal failure or hemodialysis, and there was no correlation between the total body clearance of cefoperazone and estimated creatinine clearance. In contrast, the sulbactam total body clearance was highly correlated with estimated creatinine clearance (r = 0.92, P less than 0.01) and was significantly higher in normal volunteers than in the renally impaired groups (P less than 0.01). The sulbactam terminal elimination half-life in functionally anephric patients (9.7 +/- 5.3 h) differed significantly from that of normal volunteers (1.0 +/- 0.2 h) and patients with mild renal failure (1.7 +/- 0.7 h, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Killed Escherichia coli stimulates macrophage-mediated alterations in hepatocellular function during in vitro coculture: a mechanism of altered liver function in sepsis.

Hepatic dysfunction is a poorly understood and highly lethal component of multiple-system organ failure. Both in vivo and in vitro studies of "liver" function have generally neglected hepatocyte-Kupffer cell interactions. In the following experiments, isolated hepatocytes were cocultivated with unstimulated peritoneal cells, predominately macrophages, which served as a readily available Kupffer cell analog. Coculture of hepatocytes with peritoneal cells resulted in little or no change in [3H]leucine incorporation into hepatocyte protein. When gentamicin-killed Escherichia coli cells (GKEC) were added to coculture, there was a marked decrease in hepatocyte [3H]leucine incorporation. In contrast, GKEC added to hepatocytes alone had no effect. Kinetic data revealed an 8-h delay before any significant decrease in leucine incorporation into hepatocyte protein after the addition of GKEC to the coculture. The maximal decrease in hepatocyte [3H]leucine incorporation occurred 24 h after GKEC were added. The decrease observed 24 h after GKEC were added disappeared almost completely after 48 h of coculture. Similar alterations in cocultured hepatocyte protein synthesis were observed after the addition of phorbol myristate acetate, lipopolysaccharide, or muramyl dipeptide, a component of bacterial peptidoglycan. Hepatocyte viability by trypan blue exclusion was unchanged, and gross morphology by light or electron microscopy was unaffected. We propose that during sepsis, macrophages (Kupffer cells) respond to circulating microbial products and mediate alterations in hepatocyte function. These experiments underscore the important role of Kupffer cell function in attempts to understand hepatic malfunction in multiple-system organ failure.

Animals↗

PubMed1990

Analysis of E1A-mediated growth regulation functions: binding of the 300-kilodalton cellular product correlates with E1A enhancer repression function and DNA synthesis-inducing activity.

Adenovirus E1A transforming function requires two distinct regions of the protein. Transforming activity is closely linked with the presence of a region designated conserved domain 2 and the ability of this region to bind the product of the cellular retinoblastoma tumor suppressor gene. We have investigated the biological properties of the second transforming region of E1A, which is located near the N terminus. Transformation-defective mutants containing deletions in the N terminus (deletion of residues between amino acids 2 and 36) were deficient in the ability to induce DNA synthesis and repress insulin enhancer-stimulated activity. The function of the N-terminal region correlated closely with binding of the 300-kilodalton E1A-associated protein and not with binding of the retinoblastoma protein. These results indicate that transformation by E1A is mediated by two functionally independent regions of the protein which interact with different specific cellular proteins and suggest that the 300-kilodalton E1A-associated protein plays a major role in E1A-mediated cell growth control mechanisms.

Adenovirus Early Proteins↗

PubMed1985

Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMedDate not supplied

Topographical distribution of barrier function in cervico-cephalic arteries of dog. Major cerebral arteries possess definite barrier function?

Topographic distribution of barrier function in normal canine cervico-cephalic arteries was studied using horseradish peroxidase (HRP) and Evans blue as tracers. The carotid sinus of the internal carotid artery (ICA) was conspicuously permeable to HRP when compared to other areas of major cervical arteries. The cavernous portion of the ICA also showed prominent permeation of HRP, especially through the outer surface, which is covered with venous endothelial cells. On the luminal side of the cavernous portion of the ICA, barrier deficiency was noted at angulated segments such as the carotid siphon. Intracranial segments of both ICA and vertebral arteries demonstrated incomplete barrier function of the first 1 to 4 mm from the origin of the intradural segments. These areas were considered to be transitional sites in barrier function between extra- and intracranial arteries. Focal, but definite, barrier disruption was also noted at the distal ends of the ICA and other arterial branching sites of major intracranial arteries. While opening of the interendothelial junctions was considered to be one of the mechanisms causing increased permeability in the cavernous ICA, the mechanisms for the permeation of HRP into the major cerebral arteries could not be confirmed ultrastructurally.

Animals↗

PubMed1987

Longitudinal study of pulmonary function development in childhood, adolescence, and early adulthood. Development of pulmonary function.

The growth of pulmonary function between 5.5 and 25 yr of age was determined using 1,511 observations over time on 353 subjects from a representative population sample of white non-Mexican-Americans in Tucson. There was an average of 8.8 yr of follow-up, with a maximum of 12. The method used was shown to be robust for span of follow-up from 3 to 12 yr (3 to 7 observations), and the results were verified by standard statistical methods. The standard error of the estimate decreased linearly with follow-up, indicating the need for longitudinal evaluation. Respiratory symptoms and diagnoses had the biggest negative impact on growth of lung function, using FVC, FEV1, Vmax50, and size-compensated flows (Vmax50/FVC). Smoking had the next biggest negative impact. Smoking cessation was shown to have a positive impact on growth of pulmonary function. Using a second linear model to adjust for individual variability and the random variability over surveys, individual growth showed similar trends. Further negative impacts were due to parental smoking, especially as it interacts with active smoking and respiratory disease. Flows at end of follow-up (Vmax50, Vmax50/FVC) were more sensitive than FEV1 to the effects of concurrent disease and smoking, and more persistent effects of these factors in early adulthood.

Adolescent↗

PubMed1974

Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function.

The functional and morphologic pattern of superficial nephron development was studied in guinea pigs ranging in age between 2 h and 38 days. Concomitent measurements of total kidney function and glomerular counts were also performed. Superficial nephron glomerular filtration rate was found to increase from 0.92 to 19.32 nl/min. The filtration rate of the entire kidney rose from 0.19 to 1.31 ml/min. During the first 15 days of life the average rate of increase in glomerular filtration rate per nephron (0.48 nl/min.day), obtained by dividing the increase in total kidney glomerular filtration rate by glomerular number, was more than twice the observed rate of increase in the superficial nephrons (0.21 nl/min.day). During the remainder of the first month, the increase in superficial nephron glomerular filtration rate (0.97 nl/min.day) was greater than the average increase for all nephrons (0.71 nl/min.day). Thus, the initial increase in total kidney glomerular filtration rate was primarily a consequence of the activity of the deep nephrons, whereas during the ensuing period the superficial nephrons appeared to be the sole contributors to the change in total kidney glomerular filtration rate.The increase in superficial nephron glomerular filtration rate was found to correlate closely with the increase in proximal tubular length. Functional glomerulotubular balance was maintained throughout the entire period of renal maturation.

Aging↗

PubMed1989

Assessment of testicular function after acute and chronic irradiation: further evidence for an influence of late spermatids on Sertoli cell function in the adult rat.

To study cell to cell communications within the testis of adult Sprague-Dawley rats, we used acute whole body neutron plus gamma-irradiation (0.99 Gray of neutron and 0.24 Gray of gamma-rays, 3 min; Exp A) over 7-121 days postirradiation and chronic whole body gamma-irradiation (7 cGy/day 60Co gamma-rays; Exp B) over 14-84 days of irradiation and 7-86 days postirradiation. Neither irradiation protocol had an effect on the body weight of the animals. Neutron plus gamma-rays induced dramatic damages to spermatogonia, preleptotene spermatocytes, spermatozoa, and, to a lesser extent, pachytene spermatocytes. In contrast, gamma-rays induced a selective destruction of spermatogonia. Subsequently, in both experiments a maturation-depletion process led to a marked decrease in all germ cell types. A complete or near complete recovery of the different germ cell types and spermatozoa took place during the two postirradiation periods. Under both irradiation protocols Sertoli cells number was unchanged. Androgen-binding protein and FSH levels were normal in spite of the disappearance of most germ cells from spermatogonia to early spermatids. However, the decline of androgen-binding protein as well as the rise of FSH and their subsequent recovery were highly correlated to the number of late spermatids and spermatozoa. Moreover, it appeared that spermatocytes may also interfere with the production of inhibin (Exp B). With neither irradiation was Leydig cell function altered, except in Exp B in which elevated LH levels were temporarily observed. Correlation analysis suggested a relationship between preleptotene spermatocytes and Leydig cell function. In conclusion, this study establishes that chronic gamma-irradiation is particularly useful in the study of intratesticular paracrine regulation in vivo and provides further support to the concept that late spermatids play a major role in controlling some aspects of Sertoli cell function in the adult rat.

Animals↗

PubMed1978

Clinical application of the functional matrix: mandibular reconstruction and monobloc functional therapy.

A 13-year-old black girl with an extensive ameloblastoma of the mandible required subtotal mandibular resection and immediate reconstruction with use of an autogenous, ipsilateral, corticocancellous graft from the iliac crest and monobic functional therapy. Twenty-seven months later, clinical evaluation showed normal mandibular function and no facial asymmetry. Bony architectural changes after 27 months included reformation of the coronoid process, angular process, and external oblique ridge; preservation of mandibular length and thickness; and maintenance of the alveolar ridge height. The reformation of the coronoid process suggests the importance of the functional matrix (temporalis muscle) in skeletal tissue growth. The monobloc appliance in conjunction with bone grafting is an effective means for transmission of biophysical stimuli and for maintenance of appropriate stress for remodeling of bone in the mandible.

Activator Appliances↗

PubMed1985

Deterioration of renal function during angiotensin converting enzyme inhibition in hypertensive patients with a poorly functioning solitary kidney.

During treatment with the angiotensin converting enzyme inhibitor, Captopril, glomerular filtration rate (GFR) decreased in three unilaterally nephrectomized hypertensive patients with a poorly functioning remaining kidney. The fall in GFR was not related to changes in the blood pressure, and was reversed when Captopril was stopped. In a fourth nephrectomized patient the initially normal GFR was not affected by captopril. These observations point to a functional reduction in GFR due to a withdrawal of an intrarenal action of angiotensin II. Maintenance of GFR may become critically dependent on a functioning renin-angiotensin system when renal perfusion pressure is reduced to a certain degree. Inhibition of angiotensin II formation may lead to a decrease in GFR in patients with renal hypertension and pre-existing renal insufficiency.

Aged↗

PubMed1976

Renal pelvic function following total alloplastic replacement of ureter in pigs. Electrophysiology, renal function and morphology.

Total replacement of one ureter was under-taken in pigs. After an observation period of 2-3 months further studies were made. Pelvic peristaltic activity as reflected by pelvic pressure waves and electrical activity was indistinguishable from that in normal pigs. In particular, retrograde activity was not observed. It appears that ureteric peristalsis is not a prerequisite of normal pelvic function. Providing only that the calibre is sufficient, function of a ureteric prosthesis is satisfactory, and no changes in kidney or pelvis function and morphology are apparent.

Action Potentials↗

PubMed1975

Long-term functional results of surgery for coronary artery disease in patients with poor ventricular function.

Thirty-two patients with coronary artery disease and an ejection fraction (EF) below 0.40 had coronary bypass and/or left ventricular aneurysm (LVA) resection. Twenty-four patients had a previous infarction, 12 had congestive heart failure (CHF), and left ventricular end-diastolic pressure averaged 15 mm. Hg. Nineteen patients had three-vessel involvement and there was an average of 2.4 vessels involved per patient. Bypass was accomplished on 87 per cent of vessels; 11 patients had resection of LVA; 11 had coronary endarterectomy. There were no hospital deaths, 63 per cent of the patients were improved, and 56 per cent were able to return to work or full activity. There were five late deaths (16 per cent). There was good functional improvement in 83 per cent of the survivors, followed 1 to 4 years. We believe that patients with poor ventricular function due to severe coronary artery disease should not categorically be denied surgery, and that operation can be done with a low hospital mortality rate and good functional results.

Adult↗