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PubMed2002

Pestivirus internal ribosome entry site (IRES) structure and function: elements in the 5' untranslated region important for IRES function.

The importance of certain structural features of the 5' untranslated region of classical swine fever virus (CSFV) RNA for the function of the internal ribosome entry site (IRES) was investigated by mutagenesis followed by in vitro transcription and translation. Deletions made from the 5' end of the CSFV genome sequence showed that the IRES boundary was close to nucleotide 65: thus, the IRES includes the whole of domain II but no sequences upstream of this domain. Deletions which invaded domain II even to a small extent reduced activity to about 20% that of the full-length structure, and this 20% residual activity persisted with more extensive deletions until the whole of domain II had been removed and the deletions invaded the pseudoknot, whereupon IRES activity fell to zero. The importance of both stems of the pseudoknot was verified by making mutations in both sides of each stem; this severely reduced IRES activity, but the compensating mutations which restored base pairing caused almost full IRES function to be regained. The importance of the length of the loop linking the two stems of the pseudoknot was demonstrated by the finding that a reduction in length from the wild-type AUAAAAUU to AUU almost completely abrogated IRES activity. Random A-->U substitutions in the wild-type sequence showed that IRES activity was fairly proportional to the number of A residues retained in this pseudoknot loop, with a preference for clustered neighboring A residues rather than dispersed As. Finally, it was found that the sequence of the highly conserved domain IIIa loop is, rather surprisingly, not important for the maintenance of full IRES activity, although amputation of the entire domain IIIa stem and loop was highly debilitating. These results are interpreted in the light of recent models, derived from cryo-electron microscopy, of the interaction of the closely related hepatitis C virus IRES with 40S ribosomal subunits.

5' Untranslated Regions↗

PubMed1979

A study of the Stiles-Crawford (S-C) function at 35 degrees in the temporal field and the stability of the foveal S-C function peak over time.

Directional sensitivity of the retina (the Stiles-Crawford function of the first kind) was measured at a point 35 degrees from fixation and at the point of fixation. Three normal observers were used. The peripheral test point intercepted the retina between the optic nerve head and the ora serrata. At both test points, photopic and scotopic (one subject) Stiles-Crawford function peaks were contained within the pupillary bound and approximated the center of the pupil. Directionality at the two points was rather similar. These findings add strength to the argument that retinal receptors align approximately with the center of the exit pupil of the eye. Evidence for stability in Stiles-Crawford peak location in time is also presented.

Adolescent↗

PubMed1977

Effect of finite exposure slits in determination of the line spread function and modulation transfer function.

The modulation transfer function of radiologic imaging systems is commonly obtained by determining the line spread function (LSF) of the system and computing its Fourier transform. Ideally, LSF should be obtained with infinitesimally narrow slits. The use of finite slits for obtaining the LSF is analyzed theoretically. An expression for the MTF of a finite rectangular slit is derived. Slit width correction of observed MTF is discussed as well as the correction for any generalized slit configuration.

Computers↗

PubMed1979

[The Cerebral Function Monitor. Description, functioning and interpretation principles].

The Monitor of Cerebral Function enables continuous monitoring of the cerebral electrical activity and this over long periods due to the slow recording speeds. The cerebral electrical signals picked up by the electrodes attached to the scalp are registered in the form of a curve which fluctuates to a greater or lesser extent depending on the recording speed. The examination of the height of the curve with respect to zero and its amplitude indicates the voltage of the cerebral activity and yields information regarding polymorphism. It is thus possible to monitor variations in cerebral activity over a prolonged period during anaesthesia as well as during the revival phase with the Monitor of Cerebral Function, the electroencephalogram being reserved as an aid to precise diagnosis and for localization and close scruting of the anomalies.

Brain↗

PubMed1975

Carrier and hapten functions in immune deviation. I. Contrary effects of hapten and carrier on cellular and helper functions of T cells.

Carrier and hapten functions have been studied in the immune deviation phenomenon. Delayed hypersensitivity to the carrier and anaphylaxis and Arthus hypersensitivities to the hapten and to the carrier were studied in guinea-pigs injected intravenously with large doses of carrier, homologous and heterologous hapten-carrier conjugates and subsequently immunized with the hapten-carrier conjugate in Freund's complete adjuvant. Pretreatment with DNP-BSA or with HGG were found to modify, in opposite directions, the hypersensitivity reactions induced by DNP-HGG in adjuvant. It is suggested that the hapten and carrier moieties of the antigen molecule might have antagonistic effects on the T cells responsible for cellular immunity as well as on T cells involved in helper functions for B cells.

Anaphylaxis↗

PubMed1978

[Cardia function following Billroth I and Billroth II gastrectomy (studies on the significance of duodenal passage for cardia function)].

To clarify whether the duodenum is important to the regulation of cardia function, patients with B-I and B-II resections were investigated manometrically. A test meal can stimulate the LES in patients with a B-I resection almost to the same extent as that in healthy test persons. Symptom-free patients with the distal stomach resection and gastrojejunostomy (B-II) do not show this pressure reaction. Therefore, the duodenal passage could be of importance to cardia function. In patients with a transformation operation of B-II in B-I, because of postgastrectomy symptoms a stimulation of the LES cannot be achieved either before or after the transformation operation. We cannot presently clarify the type of the cardia regulation since the IRG levels measured do not explain this phenomenon.

Adult↗

PubMed1976

The structure and function of immunoglobulin domains. IV. The distribution of some effector functions among the Cgamma2 and Cgamma3 homology regions of human immunoglobulin G1.

The fragments related to the Cgamma2 and Cgamma3 homology regions of human IgG, described in the preceding paper by Ellerson, et al. were assayed for their ability to interact with complement, engage in cytophilic activity toward macrophages, and to play a role in controlling the catabolism of the whole IgG. The Cgamma2-fragment retained about 3% of the activity of intact IgG in a whole complement-fixing assay in which the test proteins were absorbed as mono-layers onto polystyrene latex beads. However, in a fluid-phase C1-binding assay this fragment showed the same activity as IgG and Fc fragment, when compared on a molar basis. Since the Cgamma2-fragment represented only one intact domain, full expression of complement-fixing activity appeared to be independent of quaternary interactions. Thus IgG possesses two C1-binding sites. The Cgamma3-fragment was inactive in both of the complement assays. The ability of IgG to interact with the Fc-receptor on guinea-pig macrophages was shown to be entirely a function of the Cgamma3 region. This was demonstrated both in a direct assay in which tanned red cells coated with Cgamma3-fragment formed rosettes with macrophages and in an indirect assay in which this fragment was able to inhibit rosette formation between IgG-coated red cells and macrophages. The rate of clearance of radiolabeled Cgamma2-, Cgamma3-, Fab, Fc fragments, and IgG from the circulation was measured in rabbits. The Cgamma2 fragment was cleared with a half-time similar to that shown by intact IgG and Fc (about 70 hr) whereas Cgamma3- and Fab fragments were cleared more rapidly (half-time, about 15 hr). The rate of cleaance was not related to the presence of sialic acid or exposed galactosyl residues at the termini of the carbohydrate prosthetic groups. These data clearly show that at least three of the biologic functions of IgG are mediated fully and independently by one or other of the Fc domains.

Animals↗

PubMed2026

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with fragile brain function during the non-acute phase undergoing laparoscopic colorectal surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Older adults with non-acute fragile brain function (NFBF) may be particularly susceptible to perioperative disturbances in cerebral oxygenation and postoperative neurocognitive decline. Permissive hypercapnia (PHC) may enhance cerebral oxygenation, but its effects in this population remain unclear. We examined whether PHC-based ventilation improves intraoperative regional cerebral oxygen saturation (rSO2) and early postoperative cognitive outcomes in older patients with NFBF undergoing elective laparoscopic colorectal surgery. METHODS: In this single-center, single-blind randomized trial, 76 patients were assigned in a 1:1 ratio to PHC-based or conventional ventilation. The primary outcome was the absolute change in rSO2 from baseline (T0) to the end of surgery (T4). Analyses followed the intention-to-treat principle, with prespecified per-protocol sensitivity analysis. Secondary outcomes included intraoperative rSO2 trajectories, cerebral oxygen extraction-related indices, early postoperative cognitive screening, serum neuron-specific enolase and interleukin-6, and safety outcomes. RESULTS: PHC significantly increased rSO2 relative to conventional ventilation (left: adjusted mean difference [aMD] 10.64, 95% CI 8.96-12.33; right: aMD 10.16, 95% CI 8.22-12.11; both P < 0.001), with consistent sensitivity results. Repeated-measures analyses showed persistently higher intraoperative rSO2 in the PHC group. Cerebral oxygen extraction-related indices were generally lower with PHC. However, early postoperative cognitive outcomes and serum biomarkers did not differ between groups. Emergence time was modestly longer with PHC, whereas adverse events were comparable. CONCLUSIONS: PHC-based ventilation favorably modified intraoperative cerebral oxygenation and oxygen-extraction profiles but did not translate into detectable early postoperative cognitive or biomarker benefits in older adults with NFBF.

Humans↗

PubMed1977

Blood and urinary concentrations of fosfomycin as a function of the renal function value.

The following parameters were considered in studying 43 subjects under treatment for urinary infections with different degrees of renal insufficiency: the maximum blood concentrations, the plasmatic half-life, and the urinary concentrations of fosfomycin as a function of the plasma creatinine of the subject treated. The curve of the average maximum blood concentrations show a parabola-like increase, the plasmatic half-life followed the same tendency, while the curve of the average urinary concentrations presented an exponential decrease. The urinary concentrations were, nevertheless, always higher than 100 mug/ml regardless of the degree of renal insufficiency and even in the subjects who had a very high plasma creatinine. Given its absence of renal and systemic toxicity, the daily dosage of fosfomycin could remain unchanged regardless of the degree of insufficiency.

Anti-Bacterial Agents↗

PubMed1979

[Morphological and functional evaluation criteria of hepatobiliary functional scintigraphy with 99mTc-diethyl-IDA in hepatocellular jaundice].

In 31 patients with histologically proven hepatocellular jaundice hepatobiliary scintigraphy with Tc-99m labelled IDA derivatives was performed. Results were classified under morphological (demonstration of liver parenchyma, ductus choledochus, bile ducts, gallbladder, kidney) and functional (Tmax, half time of bile excretion, appearance of activity in ductus choledochus, gallbladder, and intestines) criteria. The liver parenchyma could be demonstrated in 90.3% of cases, ductus choledochus in 71%, and the gallbladder in 72.4%. The type of tracer excretion into the intestines showed 9.5% activity accumulation in the gallbladder with late bile excretion into the intestines and 90.5% early activity excretion into the duodenum with late filling of the gallbladder. The intrahepatic bile ducts were demonstrated in 22.6% (left hepatic duct) and 6.5% (right hepatic duct). In 35.5% of cases the kidneys were still visible after 15 min p.i. All cases showed - sometimes delayed - bile excretion into the GI tract. The time of appearance of activity in ductus choledochus (18.4 min) and gallbladder (39.5 min) was delayed. The liver histogram showed likewise delayed values concerning Tmax (14.3 min) and half life of tracer excretion (greater than 30 min) when compared to controls. The differentiation of hepatocellular jaundice from obstructive jaundice is possible by the demonstration of bile excretion into the intestines, normal width of the bile ducts, and filling of the gallbladder.

Adult↗

PubMed1978

Estimation of cardiac function by means of radiocardiographic function analysis.

The radiocardiographic function analysis represents a relatively simple procedure for the clinician to collect information concerning the changes of cardiac dynamics. The advantage of this method is to register non-invasively changes in cardiac dynamics at rest and during exercise such as those of enddiastolic volume, stroke volume, endsystolic volume, ejection time and filling time, and to permit the calculation of mean ejection velocity, etc. After insertion of a cardiac catheter, it is possible to record the corresponding pressure pulse in the right ventricle or in the pulmonary vessels simultaneously.

Cardiac Catheterization↗

PubMed1977

Diagnostic effectiveness of biochemical liver-function tests, as evaluated by discriminant function analysis.

I evaluated the diagnostic value of routinely ordered liver-function tests in 175 biopsy-proven cases of hepatic disease by use of stepwise discriminant analysis. The tests studied-total and "direct" bilirubin, alkaline phosphatase, lactate dehydrogenase, and aspartate aminotransferase-correctly classified 45-73% of cases, depending on the homogeneity of the diagnostic groups. Aspartate aminotransferase and alkaline phosphatase were the best discriminators. When all tests were used in the most homogeneous groups (tumors, cirrhosis, and hepatitis), there was a stepwise improvement in diagnostic accuracy from 51 to 73%.

Alkaline Phosphatase↗

PubMed1978

Ontogeny of B lymphocyte function. VI. Ontogeny of thymus cell capacity to facilitate the functional maturation of B lymphocytes.

The differentiation of the B cell population from fetal mice to produce a normal, adult-like, heterogeneous reponse, with respect to antibody affinity, has been shown to require (or to be facilitated by) thymus cells. The maturation of the thymus cell population to be capable of facilitating this differentiation of the B cell population was studied. It was found that the thymus cell population acquires the capacity fo facilitate (or induce) this maturation of the B cell population between seven and ten days after birth. Thus, the normal maturation of the B cell population to give a response which is heterogeneous with respect to affinity, appears to be controlled by the maturation of thymus function.

Animals↗

PubMed1979

Muscle function during treatment with the functional regulator.

Thirty subjects of approximately the same age, sex, and dental and skeletal relations were divided into three groups: a control group and two treatment groups, which were studied electromyographically over periods of six months and twelve months. The dental, skeletal and electromyographic data were analyzed and charted on multibargraphs. The investigation revealed the following: 1. The Class I control subjects could be differentiated from the Class II and III subjects on the basis of differences in muscle behavior. 2. The Class II treated subjects exhibited changes significantly different from those seen in the control group in the upper lip and suprahyoid group. 3. The overall changes in the four muscle groups studied in the Class II treated subjects were characterized by a decrease in muscle activity. 4. The Class III treated subjects had changes in lower lip activity and suprahyoid group significantly different from those seen in the control subjects. 5. The Class III treated subjects, with one exception, showed an increase in muscle activity in the four muscle groups. 6. The Class II treated subjects who exhibited the greatest changes in muscle behavior also had the greatest changes in skeletal and dental relations. The opposite was true for the Class III treated subjects. It cannot be stated whether muscle pattern alterations seen in this study are coincidental with the dental and skeletal changes or vice versa. However, it is quite clear that both orofacial muscle activity and dental and skeletal dimensions are altered with the wearing of the Functional Regulator.

Activator Appliances↗

PubMed1977

[C-peptide: secretion and metabolism in different functional states and with abnormal B-cell function (author's transl)].

Fasting C-peptide levels and those after tolbutamide or glucose stimulation were measured in normal subjects. In patients with various hypo- or hyper-functions of the endocrine pancreas, C-peptide levels were compared with the corresponding insulin levels. In insulin-dependent maturity-onset diabetics there were both normal and elevated serum C-peptide levels. In juvenile diabetics and patients with total duodenopancreatectomy there was no measureable C-peptide. It is concluded that the half-life of C-peptide is three times that of insulin.

C-Peptide↗

PubMed1978

Ontogeny of B-lymphocyte function. V. Thymus cell involvement in the functional maturation of B-lymphocytes from fetal mice transferred into adult irradiated hosts.

Lethally irradiated mice reconstituted with adult thymus cells and neonatal or fetal liver cells produce an anti-2,4-dinitrophenyl or anti-bovine gamma globulin response of restricted heterogeneity of affinity in comparison with the response of mice reconstituted with B cells from adult donors. In addition, mice reconstituted with day 15 fetal B cells and adult thymus cells produce relatively few indirect plaque-forming cells (PFC). It was found that B cells acquire the capacity to produce a heterogeneous response, of predominantly indirect PFC within 7 days of transfer only when thymus cells are transferred along with the B cells. B cells from fetal or neonatal donors transferred without young adult thymus cells develop the capacity to generate indirect PFC within 13 days after transfer to adult recipients, but continue to produce a response of restricted heterogeneity of affinity for up to 28 days after transfer. Thus, it has been shown that cells present in the thymus facilitate, or are necessary for the functional maturation of B lymphocytes. Furthermore, the data suggest that maturation of the B-cell population to produce a heterogeneous response is controlled independently of its maturation to be capable of producing indirect PFC.

Aging↗

PubMed1977

Separation of functional and non-functional beta subunits of thyrotropin preparations by polyacrylamide gel electrophoresis.

Electrophoretic patterns of intact human and bovine TSH and bovine LH can be clearly distinguished from those of their subunits in 12% polyacrylamide gels, thus providing an easy method of examining subunit recombination. Two distinct components of both bovine and human TSH-beta subunits are observed, of which only one recombines with alpha subunits. Both beta-components cross-react with antisera to TSH and TSH-beta and have, within experimental error, identical amino acid compositions. Thus, the non-recombining component is a non-functional form of TSH-beta which has retained its immunological specificity, and the data explain why the recovery of biological activity during the recombination of TSH subunits is substantially less than with several other glycoprotein hormone preparations.

Amino Acids↗

PubMed1977

Decreased parathyroid function in hyperthyroidism: interrelationships between serum parathyroid hormone, calcium-phosphorus metabolism and thyroid function.

Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid fe of hyperthyroidism. The prevalence of hypercalcaemia was 51.1% using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9% of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa%) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serarathyroid function.

Adolescent↗