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PubMed1977

[Characteristics of disorders of renal function in circulatory insufficiency (according to I131-hippuran clearance and diurnal rhythm of the indicators of renal function].

The paper is based on a study of 270 cases of different stages of chronic circulatory insufficiency. A whole set of functional-diagnostic (radio-isotope including) methods of examination was employed to solve the task in question. It was found that one of the early signs of functional disorders in the kidneys in cases of circulatory insufficiency is, along with renal ischaemia, the pathology that is discovered during the examination of the functional phases of renograms. The characteristics of the circadian fluctuations of some renal function parameters are given. Two stages of the formation of the so-call renal syndrome in cases of chronic circulatory insufficiency were distinguished and discussed.

Adult↗

PubMed1975

Exocrine pancreatic function in protein-deficient patas monkeys studied by means of a test meal and an indirect pancreatic function test.

Exocrine pancreatic secretion was studied in 9 patas monkeys before and during protein depletion, and in 4 of them also during recovery from protein depletion. Pancreatic function was estimated by measuring enzymatic activities in the duodenal contents after a test meal and by determination of urinary excretion of p-aminobenzoic acid (pancreatic function test) after oral ingestion of the chymotrypsin-labile peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid. The average serum albumin dropped by 34.8% to 2.6 g per 100 ml. Significant decrease of trypsin, lipase, amylase, and chymotrypsin was observed in the duodenal samples during protein deficiency. Urinary excretion of p-aminobenzoic acid was also reduced significantly. The two tests correlated well. In 3 of 4 animals, recovery of pancreatic function was noted after refeeding a full protein diet. Pancreatic atrophy was noted in 2 animals which died. The study shows that exocrine pancreatic secretion can be seriously impaired even at a moderate protein deficiency and may not be reversibly in all instances. Therefore, function tests have to be evaluated with caution when hypoproteinemia, i.e., hypoalbuminemia, is present.

Aminobenzoates↗

PubMed1992

Combined invasive and noninvasive study of left ventricular systolic and diastolic function following acute administration of cicloprolol to subjects with normal cardiac function.

Cicloprolol is a new beta-blocking agent with high selectivity for beta 1 receptors and high intrinsic sympathomimetic activity. We studied the acute hemodynamic effects of cicloprolol in nine subjects with no evidence of left ventricular dysfunction who underwent cardiac catheterization for the evaluation of chest pain. All patients had normal coronary angiography and left ventriculography. Left ventricular pressure was determined throughout the cardiac cycle using a Millar 8Fr Minotip catheter; an echocardiogram, phonocardiogram, and ECG were simultaneously recorded to obtain left ventricular pressure-diameter loops. All the measurements were repeated before and after the intravenous administration of cicloprolol. Cicloprolol was administered at increasing doses of 0.05, 0.10, and 0.25 mg/kg until a cardiac output increase of at least 15% over basal values was achieved. A decrease of mean arterial pressure or cardiac output after cicloprolol was not observed in any patient. Cicloprolol administration significantly increased cardiac output (24%), stroke volume (22%), and peak positive dP/dt (25%); no significant changes in heart rate, systemic blood pressure, right atrial pressure, or pulmonary artery pressures were observed. No significant change in the echocardiographic parameters occurred. Among the indices of left ventricular diastolic function, the time constant of isovolumetric relaxation was significantly decreased (-43%) after cicloprolol; moreover, the left ventricular pressure-diameter loop in the protodiastolic phase was shifted to the left following cicloprolol infusion. This study confirms that in subjects with normal left ventricular function cicloprolol can improve resting left ventricular systolic function, and it shows that this action can also be attended by a more rapid isovolumetric relaxation, similar to what has been observed with other sympathomimetic amines.

Adrenergic beta-Agonists↗

PubMed1975

Left atrial transport function in myocardial infarction. Importance of its booster pump function.

After myocardial infarction (MI), left ventricular (LV) end-diastolic pressure (EDP) is higher than mean pulmonary artery wedge pressure because of powerful atrial contraction. To evaluate the significane of atrial contraction to left ventricular function we studied 10 control (C) patients without cardiac disease and 17 patients from three to six weeks after acute myocardial infarction. Cardiac catheterization with simultaneous left ventricular diastolic pressure (DP) and left ventricular cineangiograms were obtained. Left ventricular volumes and pressure were (mean +/- SD): (SEE ARTICLE). Although left ventricular stroke volume was lower in the patients with myocardial infarction than in the control subjects (46 versus 56 ml/m2), atrial contraction contributed more to left ventricular filling during diastole (which is the same as left ventricular stroke volume) in the patients with myocardial infarction than in the controls (16 versus 10 ml/m2). The average atrial contribution to left ventricular end-diastolic volume was 11.9 per cent (C), 15.4 per cent (MI); to left ventricular end-diastolic pressure 20 per cent (C), 38.7 per cent (MI); and to left ventricular stroke volume 21.7 per cent (C), 35.1 per cent (MI). Atrial contribution to left ventricular stroke volume was 56 per cent in patients with a cardiac index less than or equal to 2.0 liters/min/m2 and 31 per cent in those with a cardiac index greater than 2 liters/min/m2 (p less than 0.01). Atrial contraction contributed 35 per cent to left ventricular stroke volume in patients with normal end-diastolic volume and in those with increased end-diastolic volume and 10 per cent to end-diastolic volume in patients with increased end-diastolic volume (p less than 0.001). In patients with myocardial infarction, atrial contraction made a large contribution to left ventricular filling and stroke volume irrespective of the type of left ventricular functional derangement that was present. The "booster pump" function of the atrium cannot be ignored in assessing left ventricular performance.

Adolescent↗

PubMed1977

Maximal expiratory flows at functional residual capacity: a test of lung function for young children.

Maximal expiratory flows at functional residual capacity were measured noninvasively from partial expiratory flow-volume curves in 65 awake, healthy children, 4 to 6 years of age. The variabilities within and between subjects were nearly identical to those reported for flows low in the vital capacity obtained from older subjects. This test of maximal expiratory flow at functional residual capacity has the advantage that the subject does not have to inspire to total lung capacity, exhale to residual volume, or make a maximal effort, and it is therefore applicable to the testing of young children who cannot perform a vital capacity maneuver. Measurement of this flow rate in 20 patients of the same age with lung disorders of varying severity revealed abnormal flow rates in more than 50 per cent of patients. Functional residual capacity was measured by the closed-circuit helium-equilibration method. When flow rates in liters per sec were compensated for lung size, girls had significantly larger flow rates than did boys. This suggests that the lungs of young children may grow differently according to genetic determinants related to sex.

Adolescent↗

PubMed1975

[Functional conditions of the respiratory system and work site pollution. II. Prevalence of respiratory function changes in workers employed in bichromate and chromic acid production (author's transl)].

The authors report the prevalence of respiratory function changes in two groups of workers employed in bichromate and chromic acid production. In the first group (82 subjects) examined at the Institute of Occupational Medicine, the following tests were performed: filling out of a questionnaire for cronic bronchitis; chest x-ray; spirometry; pulmonary diffusing capacity (DLco) measurement; blood gas analysis on arteriolized capillary; He and CO2 rapid expiratory curves determination. No environmental pollution data were available. In the second group (180 subjects) examined at the working site, the following tests were performed: filling out of a questionnaire -or chronic bronchitis; spirometric determination. Environmental pollution data were available. A causal connection is hypothesized by the authors between either roentgenologic or respiratory functional changes and chromium exposure, and an increased proportion between lung function changes and exposure length is stressed.

Adult↗

PubMed1979

In vitro functional studies of mononuclear cells in patients with CLL: evidence for functionally normal T lymphocytes and monocytes and abnormal B lymphocytes.

In vitro functional studies of mononuclear cells from 34 patients with B-cell type CLL were investigated and the results of these studies were as follows: 1) The T lymphocytes from patients with CLL were capable of responding normally to PHA or PWM, of inducing allogeneic normal B lymphocytes to respond to these mitogens and of stimulating normally to allogeneic lymphocytes in "one-way" mixed lymphocyte reaction; 2) The monocytes from these patients were capable of enhancing the T lymphocyte response to mitogens and of stimulating normally to allogeneic lymphocytes; and 3) The leukemic B lymphocytes were incapable of responding to mitogens even in the presence of normal T lymphocytes and their enhancer cell activity on T lymphocyte response or their stimulating capacity on allogeneic lymphocytes was depressed. These observations suggest that the T lymphocytes and monocytes from patients with CLL are functionally normal while the leukemic B lymphocytes from these patients are functionally abnormal.

Adult↗

PubMed2026

Clinical and Functional Characterization of Gain-of-Function ABL1 Variants Expands the Phenotypic Spectrum of CHDSKM.

Germline gain-of-function (GOF) variants in ABL1 cause congenital heart defects and skeletal malformations syndrome (CHDSKM), a multisystem developmental disorder characterized by congenital heart disease, skeletal abnormalities, dysmorphic features, and variable developmental delay. More recently, biallelic loss-of-function variants and ABL haploinsufficiency have been associated with distinct phenotypes, expanding the allelic spectrum of ABL1-related disorders. We report three individuals with ABL1 variants. A female infant with tetralogy of Fallot, critical pulmonary stenosis, covered omphalocele, and a lethal outcome was found by rapid trio genome sequencing to harbor a de novo likely pathogenic ABL1 variant, NM_007313.2:c.354G>T p.(Trp118Cys). We also provide updated clinical follow-up of a previously reported individual and describe a third individual, both carrying the recurrent p.(Tyr245Cys) variant. Functional studies were performed and support a GOF mechanism. Similar activation was observed for Tyr245Cys despite the differences in clinical severity. Our findings expand the phenotypic spectrum of ABL1-related CHDSKM to include severe conotruncal heart disease and covered omphalocele. The comparison of two biochemically activating ABL1 variants demonstrates substantial clinical variability despite a shared molecular mechanism. Furthermore, the overlap between ventral body wall abnormalities in GOF disease and omphalocele associated with ABL1 haploinsufficiency suggests that precise regulation of ABL1 signaling is critical for normal ventral body wall formation.

ABL1↗

PubMed1976

Structural and functional changes in an identified cricket neuron after separation from the soma. II. Functional changes.

Physiological and behavioural effects of separation from the soma were examined in isolated arborization and isolated axon segments of an identified motor neuron in the Polynesian field cricket, Teleogryllus oceanicus. The identified neuron, the contralateral dorsal longitudinal motor neuron of the metathoracic ganglion (CDLM), has an arborization most of which lies contralateral to its soma within the ganglion. Midline lesions in the ganglion separated CDLM into a distal segment composed of the axon and most of the arborization, and a proximal segment made up of the remaining arborization, neurite and soma. Isolated axonal segments were produced by cutting the nerve containing the CDLM axon. The function of the neuron-muscle system composed of CDLM, its pre-synaptic inputs, and its innervated muscle bundle was examined in contrl and experimentally operated animals. Extracellular recording assessed function in the axon. Electrical or tactil stimulation was used to excite pre-synaptic inputs to the CDLM arborization. Intracellular recording determined changes in post-synaptic potentials and miniature end-plate potentials in the muscle bundle innervated by CDLM. Normal axonal conduction, competence to respond to pre-synaptic input, neuron-muscle transmission, and miniature end-plate potential appearance can remain in the isolated arborization preparation. Physiological viability is longer in the cricket isolated arborization than in other insect distal segments described. Survival times of axonal conduction and the competence of the isolated arborization to respond to pre-synaptic input are roughly correlated with disappearance of the whole distal segment at 100 or more postoperative days. A naturally-occurring breakdown of the metathoracic dorsal longitudinal muscles in Teleogryllus eventually prevents measurements of post-synaptic potentials and miniature end-plate potentials. Normal post-synaptic function mediated by the distal arborization is maintained up to this breakdown, to a maximum of 44 days postoperative. The distal axonal segment of CDLM degenerates physiologically within four days postoperative, a time course approximating that of degeneration in vertebrate peripheral nerve distal axons.

Animals↗

PubMed1992

Preferential expression and activity of multidrug resistance gene 1 product (P-glycoprotein), a functionally active efflux pump, in human CD8+ T cells: a role in cytotoxic effector function.

The multidrug resistance gene 1 (mdr 1) product, the P-glycoprotein (Pgp), is a 170-kD transmembrane transport protein, whose overexpression is associated with multidrug resistance in cancer cells and in chloroquine-resistant Plasmodium falciparum infection. In this study we show that normal freshly isolated human lymphocytes express low levels of mdr 1 mRNA and membrane Pgp. Although Pgp is expressed in both CD4+ and CD8+ T cells, it is preferentially expressed in CD8+ T cells. Activation of T lymphocytes with phytohemagglutinin leads to an amplification of both mdr 1 mRNA and membrane Pgp in T cells. P-glycoprotein in T cells is a functionally active efflux pump as demonstrated by decreased retention of rhodamine-123 and its increased accumulation by cyclosporin A, an inhibitor of Pgp function. In addition, MRK-16 antibody increased accumulation of Rh123 in CD8+ T cells. Furthermore, MRK16 anti-P-glycoprotein monoclonal antibody, in a concentration-dependent manner, inhibited T lymphocyte-mediated cytotoxicity. These data suggest a physiologic role of P-glycoprotein in cytotoxic T-lymphocyte effector function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1977

[Carbenicillin induced disturbance of platelet function: a study in patients with normal renal function (author's transl)].

After therapeutic doses of carbenicillin (3X10 g/24 h) prolongation of bleeding time, measured according to Ivy, was observed (median time prior to therapy 4 min 08 s-4 min 18 s; 24 h after therapy 15-20 min; 72 h after therapy greater than 30 min) in 5 patients with normal renal function and 2 patients with slight impairment of renal function (Ccr60-70 mlX1.73 m(2)). Prolongation of bleeding time was observed at serum concentrations between 13 and 180 microgram/carbenicillin/ml. After carbenicillin was withdrawn, prolongation of bleeding time was demonstrable for 4 days, i.v. even after the drug had been eliminated completely by urinary excretion. Higher doses of carbenicillin caused more severe disturbances of platelet function. The finding of prolonged bleeding time after carbenicillin may have clinical relevance (e.g. interaction with other anticoagulants, p.o. wound bleeding, gastro-intestinal hemorrhage, thrombopenia).

Adult↗

PubMed1979

Ovarian cancer: a solid tumor with evidence of normal cellular immune function but abnormal B cell function.

Immunologic assays of B and T lymphocyte function were performed on 21 patients with epithelial ovarian cancer prior to either chemotherapy or radiotherapy. The results were compared to similar studies on 12 age-matched normal women. The total peripheral blood lymphocyte counts, proportion of E rosette positive cells, stimulation of T cells by phytohemagglutinin and concanavalin A, recall skin tests, and the ability to have a primary delayed hypersensitivity response to keyhold limpet hemocyanin did not differ between patients and controls. However, patients with ovarian cancer had statistically significant reduction in surface immunoglobulin positive cells, proliferative response to pokeweed mitogen and primary antibody response to keyhole limpet hemocyanin. In contrast to results in patients with other solid tumors, these data indicate that untreated patients with ovarian cancer have evidence of normal cellular immune function but abnormal B cell function.

Adult↗

PubMed1979

Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function.

The function of complement receptors of mouse peritoneal macrophages was converted in vitro from mediating only attachment of macrophage complement receptor function was achieved by treating freshly explanted macrophages with supernates from cultures containing T lymphocytes and appropriately triggered macrophages. Fc receptor-mediated phagocyctosis by macrophages was required for the production of active supernates, for neither ingestion via the cells' complement receptors nor ingestion via nonimmunologic means was a sufficient stimulus for the macrophages' participation in the generation of supernatant activity. Fc receptor-triggered macrophages interacted by a contact dependent, but histocompatibility independent, mechanism with T lymphocytes, thereby signalling the lymphocytes to elaborate the active product. The possible significance of enhanced macrophage complement receptor function in inflammation, host defense against microbial pathogens, immune complex disease, and neoplasia is discussed.

Animals↗

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↗

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↗

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↗

PubMed1975

[Breath rate as a function of parameters of pulmonary function in body plethysmography (author's transl)].

Parameters of pulmonary function were measured at resting breathing rates (mean 15-17/min) and at breathing rates of 20-40/min in 238 subjects (79 normals, 44 patients with normal pulmonary function in spite of lung disease, and 115 patients, most of whom had obstructive-emphysematous lesions) in a constantvolume body plethysmograph with a respiratory bag. In the subjects with normal pulmonary function the resistance increased significantly by 25 and 45 percent, resp., with more rapid respiration (p smaller than 0,01). Nevertheless it is assumed that this rarely accounts for false interpretations in everyday routine practice. No relationship of breathing rate to respiratory passage resistance was observed in patients with increased total resistance. By way of contrast, ventilation work of breathing (pV diagram) and the index of ventilation work of breathing (defined Vp ratio) showed a close correlation to breathing rate in all 3 groups. This leads us to conclude that these parameters provide more exact information on the breathing mechanism than does total resistance. Studies on ventilation work of breathing must be conducted under clearly defined breathing rates and consideration of the respiratory volume. intrathoracic gas volume was not correlated to the breath rate.

Adult↗