Showing papers by "University of Utah published in 1990"
TL;DR: Evidence suggests that NF1 encodes a cytoplasmic GAP-like protein that may be involved in the control of cell growth by interacting with proteins such as the RAS gene product.
1,073 citations
TL;DR: The TBR gene is established as the NF1 gene and a description of a major segment of the gene is provided, indicating base pair changes in the gene.
1,048 citations
TL;DR: It is reported that administration of anti-TGF-βl at the time of induction of the glomerular disease suppresses the increased production of extracellular matrix and dramatically attenuates histological manifestations of the disease.
Abstract: GLOMERULONEPHRITIS is an inflammation of the kidney characterized by the accumulation of extracellular matrix within the damaged glomeruli1–4, impaired filtration and proteinuria. In its progressive form, the disease destroys kidney function leading to uraemia and death, unless dialysis therapy or kidney transplantation is available. The pathogenesis of glomerulonephritis is incompletely understood, but the eliciting factor is thought often to be an immunological injury to mesangial and/or other resident cells in the glomeruli5,6. We have used an animal model of acute mesangial proliferative glomerulonephritis7,8 to show that this disease is associated with increased production and activity of transforming growth factor β1 (TGF-βl)9, an inducer of extracellular matrix production10–17. Here we report that administration of anti-TGF-βl at the time of induction of the glomerular disease suppresses the increased production of extracellular matrix and dramatically attenuates histological manifestations of the disease. These results provide direct evidence for a causal role of TGF-βl in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis.
1,024 citations
TL;DR: These findings strongly suggest that the TBR gene is the NF1 gene, and a number of cDNA clones from the translocation breakpoint region (TBR), one of which hybridizes to an approximately 11 kb mRNA.
1,019 citations
TL;DR: It is demonstrated that GMP-140 can mediate leukocyte adhesion, thus establishing a functional similarity with the other selectins, and might promote rapid neutrophil targeting to sites of acute inflammation.
Abstract: GRANULE membrane protein-140 (GMP-140), a membrane glycoprotein of platelet1–5 and endothelial cell6–8 secretory granules, is rapidly redistributed to the plasma membrane during cellular activation and degranulation1,2,6,7. Also known as PADGEM protein4, GMP-140 (ref. 9) is structurally related to two molecules involved in leukocyte adhesion to vascular endothelium: ELAM-1, a cytokine-inducible endothelial cell receptor for neutrophils10, and the MEL-14 lymphocyte homing receptor11,12. These three proteins define a new gene family, termed selectins, each of which contains an N-terminal lectin domain, followed by an epidermal growth factor-like module, a variable number of repeating units related to those in complement-binding proteins, a transmembrane domain, and a short cytoplasmic tail. Here we demonstrate that GMP-140 can mediate leukocyte adhesion, thus establishing a functional similarity with the other selectins. Human neutrophils and promyelocytic HL-60 cells bind specifically to COS cells transfected with GMP-140 complementary DNA and to microtitre wells coated with purified GMP-140. Cell binding does not require active neutrophil metabolism but is dependent on extracellular Ca2+. Within minutes after stimulation with phorbol esters or histamine, human endothelial cells become adhesive for neutrophils; this interaction is inhibited by antibodies to GMP-140. Thus, GMP-140 expressed by activated endothelium might promote rapid neutrophil targeting to sites of acute inflammation.
1,019 citations
TL;DR: Kinetic measurements suggest that NF1 may be a significant regulator of ras p21 activity, particularly at low rAS p21 concentrations.
920 citations
01 Sep 1990
TL;DR: The diverse inheritance mechanisms provided by Smalltalk, Beta, and CLOS are interpreted as different uses of a single underlying construct, which is subsumed in a new inheritance model based on composition of mixins, or abstract subclasses.
Abstract: The diverse inheritance mechanisms provided by Smalltalk, Beta, and CLOS are interpreted as different uses of a single underlying construct. Smalltalk and Beta differ primarily in the direction of class hierarchy growth. These inheritance mechanisms are subsumed in a new inheritance model based on composition of mixins, or abstract subclasses. This form of inheritance can also encode a CLOS multiple-inheritance hierarchy, although changes to the encoded hierarchy that would violate encapsulation are difficult. Practical application of mixin-based inheritance is illustrated in a sketch of an extension to Modula-3.
880 citations
879 citations
TL;DR: Under typical operating conditions, a class of suboptimum detectors for data transmitted asynchronously by K users employing direct-sequence spread-spectrum multiple access on the additive white Gaussian noise channel will perform much better than the conventional receiver and often nearly as well as the optimum detector.
Abstract: Consideration is given to a class of suboptimum detectors for data transmitted asynchronously by K users employing direct-sequence spread-spectrum multiple access (DS/SSMA) on the additive white Gaussian noise (AWGN) channel. The general structure of these detectors consists of a bank of matched filters, a linear transformation that operates on the matched-filter outputs, and a set of threshold devices. The linear transformations are chosen to minimize either a mean-squared-error or a weighted-squared-error performance criterion. Each detector can be implemented using a tapped delay line. The number of computations performed per detected bit is linear in K in each case, and the resulting detectors are thus much simpler than the optimum detector. Under typical operating conditions, these detectors will perform much better than the conventional receiver and often nearly as well as the optimum detector. >
852 citations
TL;DR: Three structural aberrations were found in COL4A5, in intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah.
Abstract: X-linked Alport syndrome is a hereditary glomerulonephritis in which progressive loss of kidney function is often accompanied by progressive loss of hearing. Ultrastructural defects in glomerular basement membranes (GBM) of Alport syndrome patients implicate an altered structural protein as the cause of nephritis. The product of COL4A5, the alpha 5(IV) collagen chain, is a specific component of GBM within the kidney, and the gene maps to the same X chromosomal region as does Alport syndrome. Three structural aberrations were found in COL4A5, in intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah.
781 citations
TL;DR: It is demonstrated that this homology domain of the NF1 protein interacts with ras proteins, and has ras GAP activity similar to that found with IRA2 protein and mammalian GAP, and therefore may also regulate ras function in vivo.
TL;DR: In this article, a general framework is given for the phenomenological kinetics of phase transitions in which not only the order parameter but also the temperature may vary in time and space.
TL;DR: In this paper, a review examines whether children of depressed mothers have elevated rates of psychopathology and if so, why, and concludes that maternal depression is associated with undesirable parenting practices such as unresponsiveness, inattentiveness, intrusiveness, inept discipline and negative perceptions of children.
TL;DR: Combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea, andequate precautions are recommended when benzodiazepines are administered in combination with opioids.
Abstract: More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.
TL;DR: The authors showed that TGF-beta is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro.
Abstract: Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological extracellular matrix in glomerulonephritis.
TL;DR: It now seems that the Conus species will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms.
Abstract: Conus venoms contain a remarkable diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It now seems that the Conus species (approximately 500 in number) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lock-cut" synthetic pathway. These peptides are specific enough to discriminate effectively between closely related receptor subtypes and can be used for structure-function correlations.
TL;DR: In this article, the swelling of crosslinked poly(N,N-alkyl substituted acrylamides) in water was studied in relation to changes in external temperature, and significant swelling changes of the polymer in water in response to temperature can be attributed to the delicate hydrophilic/hydrophobic balance of polymer chain, and was affected by the size, configuration and mobility of the alkyl side chains on the substituted acylamides.
TL;DR: Analysis of 13 clinically heterogeneous SMA families finds that 'chronic' childhood-onset SMA (including intermediate SMA or SMA type II, and KugelbergWelander or S MA type III) is genetically homogeneous, mapping to chromosomal region 5ql 1.3.
Abstract: SPINAL muscular atrophy (SMA) describes a group of heritable degenerative diseases that selectively affect the α-motor neuron. Childhood-onset SMAs rank second in frequency to cystic fibrosis among autosomal recessive disorders, and are the leading cause of heritable infant mortality. Predictions that genetic heterogeneity underlies the differences between types of SMA, together with the aggressive nature of the most-severe infantile form, make linkage analysis of SMA potentially complex. We have now analysed 13 clinically heterogeneous SMA families. We find that 'chronic' childhood-onset SMA (including intermediate SMA or SMA type II, and Kugelberg–Welander or SMA type III) is genetically homogeneous, mapping to chromosomal region 5ql 1.27#150;13.3.
TL;DR: In this paper, the swelling of crosslinked poiy(N,N′-alkyl substituted acrylamides) in water was studied in relation to temperature changes and a sharp swelling transition may occur at an optimum hydrophilic/hydrophobic balance but was found only in the N-isopropylacrylamide network.
Abstract: The swelling of crosslinked poiy(N,N′-alkyl substituted acrylamides) in water was studied in relation to temperature changes. Conventional swelling theory and separation of the polymer solvent interaction parameter into enthalpic and entropic contributions were used to characterize the temperature dependence of swelling in water. The thermosensitivity of swelling can be attributed to the delicate hydrophilic/hydrophobic balance of polymer chains and is affected by the size, configuration, and mobility of alkyl side groups. A sharp swelling transition may occur at an optimum hydrophilic/hydrophobic balance but was found only in the N-isopropylacrylamide network among the networks tested. This swelling transition pattern was also reflected by the endothermic peak of the DSC thermogram of the swollen sample.
TL;DR: Reinforced or degradable polymeric fiber reinforced materials have been used successfully clinically, but the key has been careful selection of applications, plus use of designs and fixation methods distinctly different from those appropriate for stainless steel devices.
Abstract: The mechanical properties of biodegradable polymers and composites proposed for use in internal fixation (in place of stainless steel) are crucial to the performance of devices made from them for support of healing bone. To assess the reported range of properties and degradation rates. we searched and reviewed papers and abstracts published in English from 1980 through 1988. Mechanical property data were found for poly(lactic acid), poly (glycolic acid), poly(ϵ-caprolactone), polydioxanone, poly(ortho ester), poly(ethylene oxide), and/or their copolymers. Reports of composites based on several of these materials, reinforced with nondegradable and degradable fibers, were also found. The largest group of studies involved poly(lactic acid). Mechanical test methods varied widely, and studies of the degradation of mechanical properties were performed under a variety of conditions, mostly in vitro rather than in vivo.
Compared to annealed stainless steel, unreinforced biodegradable polymers were initially up to 36% as strong in tension and 54% in bending, but only about 3% as stiff in either test mode. With fiber reinforcement, reported highest initial strengths exceeded that of stainless steel. Stiffness reached 62% of stainless steel wiht nondegradable carbon fibers, 15% with degradable inorganic fibers, but only 5% with degradable polymeric fibers.
The slowest-degrading unreinforced biodegradable polymers were poly(L-lactic acid) and poly(ortho ester). Biodegradable composites with carbon or inorganic fibers generally lost strength rapidly, with a slower loss of stiffness, suggesting the difficulty of fiber-matrix coupling in these system. The strength of composites reinforced wiht (lower modulus) degradable polymeric fibers decreased more slowly.
Low implant stiffness might be expected to allow too much bone motion for satisfactory healing. However, unreinforced or degradable polymeric fiber reinforced materials have been used successfully clinically. The key has been careful selection of applications, plus use of designs and fixation methods distinctly different from those appropriate for stainless steel devices.
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TL;DR: In this article, the authors describe the traits within the resiliency model as a process applicable to health education and suggest that the process of psychological reintegration is the ability to learn new skills from the disruptive experience and put life's perspective back in a way that will increase abilities to negotiate life events.
Abstract: The health education and prevention professions are in the midst of a philosophical revolution attempting to build upon negative directioned risk reduction programs, which are driven by the medical model, to competency models. Noted psychologists and psychiatrists have suggested that competency and resiliency characteristics are strengths that are more protective than risk reduction efforts. Many suggested traits have been proposed for the resilient individual. This article reviews those characteristics but more importantly, describes the traits within the resiliency model as a process applicable to health education. This expanded view of prevention includes perspectives on the value of personal disruption and adversity as avenues to promote growth and increased protective factors. The process of psychological reintegration is the ability to learn new skills from the disruptive experience and put life's perspective back in a way that will increase abilities to negotiate life events. The model als...
TL;DR: Findings imply that activation of the protein tyrosine kinase activity at the cell membrane is sufficient for the growth-enhancing effects of EGF, suggesting that downregulation can serve as an attenuation mechanism, without which transformation ensues.
Abstract: Identification of a mutant epidermal growth factor (EGF) receptor that does not undergo downregulation has provided a genetic probe to investigate the role of internalization in ligand-induced mitogenesis. Contact-inhibited cells expressing this internalization-defective receptor exhibited a normal mitogenic response at significantly lower ligand concentrations than did cells expressing wild-type receptors. A transformed phenotype and anchorage-independent growth were observed at ligand concentrations that failed to elicit these responses in cells expressing wild-type receptors. These findings imply that activation of the protein tyrosine kinase activity at the cell membrane is sufficient for the growth-enhancing effects of EGF. Thus, downregulation can serve as an attenuation mechanism, without which transformation ensues.
TL;DR: Investigation of the mechanism(s) by which homocysteine reduced protein C activation indicated that the metabolite did not induce an inhibitor to activated protein C, but in low concentrations acted as a competitive inhibitor to thrombin.
TL;DR: Determination of genotypes at this VNTR locus can now be routinely achieved within 24 h, without the need for Southern blots or radioactive materials.
Abstract: A genetic locus (D1S58, defined by DNA probe pMCT118) that contains a variable number of tandem repeats (VNTR) has been successfully amplified from a very small amount of genomic deoxyribonucleic acid (DNA) by the polymerase chain reaction (PCR). The DNA sequence of the locus was determined and was found to consist of a 16-base consensus sequence and flanking sequences. Oligonucleotide primers complementary to the flanking sequences were synthesized to serve as primers for amplification of MCT118 by the PCR method. Human genomic DNA isolated from blood (2 ng from each sample) was successfully amplified at the MCT118 locus, and polymorphic bands were detectable by ethidium bromide staining after electrophoresis on polyacrylamide gels. Determination of genotypes at this VNTR locus can now be routinely achieved within 24 h, without the need for Southern blots or radioactive materials. Furthermore, the small size (387 to 723 base pairs) of the DNA fragments produced in the PCR amplification permits good resolution of individual alleles that differ by only one repeat unit. The precise specification of the number of tandem repeats present in each allelic fragment is reproducible from one analysis to another.
TL;DR: These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures.
Abstract: Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded.
TL;DR: Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration and there was close correlation between activation- recovery intervals taken during cardiac sympathetic nerve stimulation and local epicardial warming.
Abstract: Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration. Theoretic analysis demonstrated that the temporal derivative of the extracellular potential is proportional to a spatial weighting of the third temporal derivative of the transmembrane action potentials along a cable with uniform propagation in a homogeneous medium. Thus, the activation-recovery interval, measured as the interval between times of minimum derivative (Vmin) of the QRS and maximum derivative (Vmax) of the T wave, should be related to action potential duration, measured as the interval between times of Vmax of the upstroke and Vmin of the downstroke of the transmembrane action potential. This relation was examined experimentally in 12 anesthetized dogs. Unipolar electrograms and transmembrane action potentials were recorded simultaneously from sites within 2 mm of each other during control states, cardiac sympathetic nerve stimulation, localized epicardial warming, and graded reductions in myocardial perfusion. The heart was paced from several sites. There was close correlation between activation-recovery interval and action potential duration measurements taken during cardiac sympathetic nerve stimulation and local epicardial warming (r = 0.96 and 0.99 for cardiac sympathetic nerve stimulation and warming, respectively). In five animals in which coronary perfusion pressure was gradually lowered, the variables correlated closely over a range of values from 62 to 212 msec (r = 0.98). However, although the overall correlation was good and mean differences between activation-recovery interval and action potential duration were small, in individual cases there were differences up to 24 msec.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: A novel mechanism by which a cell-associated phospholipid, PAF, can serve as a signal for an intercellular adhesive event is demonstrated, indicating that PAF that is endogenously synthesized by ECs can mediate neutrophil adhesion.
Abstract: The binding of neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial cells (ECs) presents special requirements in the regulation of intercellular adhesion. ECs that are stimulated by certain agonists, including thrombin and cytokines (tumor necrosis factor alpha, interleukin-1), generate molecular signals that induce the adhesion of PMNs (endothelial cell-dependent neutrophil adhesion). Our experiments demonstrate that the mechanism of binding induced by thrombin is distinct from that induced by the cytokines based on the time courses, the requirement for protein synthesis, and differential binding of HL60 promyelocytic leukemia cells to ECs activated by the two classes of agonists. The rapid EC-dependent PMN adhesion (initiated in minutes) that occurs when the ECs are stimulated by thrombin is temporally coupled with the accumulation of platelet-activating factor, a biologically active phosphoglyceride that remains associated with ECs and that activates PMNs by binding to a cell surface receptor. A portion of the newly synthesized platelet-activating factor (PAF) is on the EC surface, as demonstrated by experiments in which the rate of hydrolysis of PAF synthesized by activated ECs was accelerated by extracellular PAF acetylhydrolase. When ECs were treated with exogenous PAF they became adhesive for PMNs; the PMN binding was prevented by incubating the ECs with PAF acetylhydrolase or by treating the PMNs with competitive PAF receptor antagonists. Thus PAF associated with the EC plasma membrane induces PMN binding, an observation supported by experiments in which PAF in model membranes (liposomes) stimulated rapid PMN adhesion to ECs and to cell-free surfaces. In addition, competitive antagonists of the PAF receptor inhibited the binding of PMNs to ECs activated by thrombin and other rapidly acting agonists, but not to ECs activated by tumor necrosis factor alpha, indicating that PAF that is endogenously synthesized by ECs can mediate neutrophil adhesion. These experiments demonstrate a novel mechanism by which a cell-associated phospholipid, PAF, can serve as a signal for an intercellular adhesive event.
TL;DR: The results demonstrate that the DnaK protein contributes to E. coli's growth not only by protecting some enzymes from denaturation but also by reactivating some once they are misfolded or aggregated.
TL;DR: It is shown that such a time-varying {Lambda} leads to creation of matter with a rate at present which is comparable to that in the steady-state cosmology, and alleviates some problems in reconciling observations with the inflationary scenario.
Abstract: We advocate the possibility that the (effective) cosmological constant \ensuremath{\Lambda} varies in time as ${R}^{\mathrm{\ensuremath{-}}2}$, R being the scale factor of our expanding Universe. This behavior can be obtained under some simple and general assumptions in conformity with quantum cosmology. After pointing out several advantages worth noticing, we show that such a time-varying \ensuremath{\Lambda} leads to no conflict with existing observations. However, it does change the predictions of the standard cosmology in the matter-dominated epoch and alleviates some problems in reconciling observations with the inflationary scenario. In particular, this ``medium'' time variation of \ensuremath{\Lambda} leads to creation of matter with a rate at present which is comparable to that in the steady-state cosmology.