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At least 1,765 records · Page 98Linked to original sources
PubMed1989

Structure-function relationships in rat brainstem subnucleus interpolaris: V. Functional consequences of neonatal infraorbital nerve section.

In a prior study (Jacquin et al., '86c), the response properties and projections of neonatally axotomized trigeminal (V) primary afferents were studied in the adult rat. Here, single-unit recording, electrical stimulation, and receptive field (RF) mapping techniques were also used to assess the functional consequences of neonatal infraorbital nerve section upon postsynaptic cells in V brainstem subnucleus interpolaris (SpVi). Of 904 cells studied, 385 were from normal adults and 519 were from neonatally deafferented adults. Infraorbital nerve section at birth resulted in: (1) a substantial reduction in those areas of SpVi containing cells with infraorbital RFs, and only a slight increase in areas solely responsive to noninfraorbital surfaces, (2) an absence of orderly topography within cells expressing regenerate primary afferent inputs, (3) a slight increase in mean discharge latency to V ganglion or thalamic shocks, (4) an increased relative percentage of cells orthodromically activated by diencephalic or cerebellar shocks, (5) a decreased relative percentage of mystacial vibrissa-sensitive local circuit neurons, with a corresponding increase in local circuit nociceptors and unresponsive cells, (6) an increased relative percentage of mystacial nociceptors, virbrissae, guard hair, and/or skin sensitive cells projecting to thalamus and/or cerebellum, (7) an increased percentage of local circuit neurons with RFs including more than one vibrissa, whereas projection neurons did not differ from normal in the number of vibrissae composing their RFs, and (8) an increased relative percentage of cells expressing interdivisional and intermodality convergence, split RFs, spontaneous activity, directional high velocity, and neuroma sensitivity. Thus neonatal nerve section produces changes in topography, inputs, projection status, and responses of surviving postsynaptic neurons. Although many of these centrally observed alterations can be attributed to altered peripheral projections in axotomized V primary afferents, others must reflect central reorganization. The central mechanisms responsible for the synthesis of deafferentation-induced RFs remain to be elucidated.

Action Potentials↗
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↗
PubMed1983

Alteration of immunologic function through early ontogenetic experiences. Selective inactivation of T15-positive B cells in neonatal mice is related to receptor avidity and is independent of thymus function.

The immunologic effects initiated by injecting neonatal mice with phosphorylcholine (PC)-protein conjugates were analyzed. Pretreated nude or thymus-bearing mice produced greater proportions of low-avidity, TEPC 15-negative antibody than control animals when challenged as adults with thymus-dependent (TD) or -independent (TI) PC-conjugated antigen. Furthermore, pretreatment had a greater inhibitory effect on responses elicited by TD compared with TI antigen. These results demonstrate that exposure of neonatal mice to PC-protein conjugates results in the selective inactivation of higher avidity, T15-positive, PC-reactive B cells; this process is independent of thymic function and the duration of hyporesponsiveness is linked to the relative T dependency of the challenge antigen.

Age Factors↗
PubMed1995

Repression of the immunoglobulin heavy chain 3' enhancer by helix-loop-helix protein Id3 via a functionally important E47/E12 binding site: implications for developmental control of enhancer function.

The activity of the immunoglobulin 3' enhancer is restricted to the late stages of B lymphoid development. Here we further examine the molecular basis for the temporally restricted activity of the B-lymphoid IgH 3' enhancer. We demonstrate that a binding site (E5 site) for the E47 and/or E12 proteins is functionally important for enhancer activity. The multimerized E5 site acts as a B cell-specific enhancer and, when assayed in COS cells, can be transactivated by E47/E12 proteins. This transactivation in COS cells, as well as the activity of the full length 3' enhancer in plasma cells, can be repressed by overexpression of the dominant negative nuclear regulator Id3. When examining the tissue distribution of Id3 in murine cell lines, we find that Id3 is expressed throughout the pre-B and B cell stages, but is down-regulated at the plasma cell stage. Thus, Id3 may contribute to the temporal regulation of the IgH 3' enhancer.

Animals↗
PubMed1995

Application of sciatic functional index in nerve functional assessment.

In order to confirm the reliability of the sciatic functional index (SFI) in the rat, SFI, muscle strength, electrophysiological, and morphometric assessments were carried out from the 10th day to the sixth month after nerve injury or repair. The results showed that the SFI has a positive correlation with all tested indices of muscle strength, electrophysiology, and morphology (r = 0.925-0.996, P < 0.01 or P < 0.001). These results indicate that the SFI is a reliable index for evaluating rat sciatic nerve regeneration and can be widely used.

Animals↗
PubMed1987

D1 dopamine receptor--the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications.

The present review focuses on the hypothesized D1/D2 dopamine (DA) receptor classification, originally based on the form of receptor coupling to adenylate cyclase activity. The pharmacological effects of compounds exhibiting putative selective agonist or antagonist profiles at those DA receptors positively coupled to adenylate cyclase activity (D1 DA receptors) are extensively reviewed. Comparisons are made with the effects of putative selective D2 DA receptor agonists and antagonists, and on the basis of this work, the DA receptor classification is critically evaluated. A variety of biochemical, behavioral, and electrophysiological evidence is presented which supports the view that D1 and D2 DA receptors can interact in both an opposing and synergistic fashion. Particular attention is focused on the possibility that D1 receptor stimulation is required to enable the expression of certain D2 receptor-mediated effects, and the functional consequences of this form of interaction are considered. A hypothetical model is presented which considers how both the opposing and enabling forms of interaction between D1 and D2 DA receptors can control behavioral expression. Finally, the clinical relevance of this work is discussed and the potential use of selective D1 receptor agonists and antagonists in the treatment of psychotic states and Parkinson's disease is considered.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Functional analysis of hepatitis B virus transactivator X: implication of the leucine zipper-like region and C-terminal seven conserved amino acids in functional regions.

X protein of hepatitis B virus (HBV-X) is a transactivator to a wide variety of viral and cellular transcriptional regulatory elements. Since HBV-X does not act on a common cis-regulatory element of a wide variety of regulatory elements nor does it bind to DNA directly, it has been proposed that HBV-X acts indirectly through protein-protein interactions with other transcription factors or signal transducing pathway. In order to determine the functional domain of HBV-X, we have constructed and analyzed a number of deletion and site specific mutants. Our results showed that leucine zipper-like sequences were found in the C-terminal region of HBV-X and were very important for its transactivating activity. In the analysis of deletion mutants, seven conserved and strong basic amino acids (amino acids 135-141) were essential for the transactivating activity of HBV-X.

Amino Acid Sequence↗
PubMed1994

Patterns of recovery and change in verbal and nonverbal functions in a case of crossed aphasia: implications for models of functional brain lateralization and localization.

We present a 2-year verbal and nonverbal follow-up of a crossed aphasic patient. The patient had suffered from widespread ischemic damage in the area of right middle cerebral artery, with a parieto-temporal lesion. Three months postonset he showed classical Wernicke's aphasia associated with oral, limb and constructional apraxia and left hemineglect. However, follow-up findings showed a complex, dynamic pattern entirely consistent with cognitive models of language and nonlanguage abilities. Current models of functional brain lateralizations could not satisfactorily account for such longitudinal, fine-grain observations.

Agraphia↗
PubMed2002

Pertubation of beta1 integrin function using anti-sense or function-blocking antibodies on corneal cells grown on fibronectin and tenascin.

During corneal development, neural crest derivatives from the periocular mesenchyme migrate into the cornea and differentiate into corneal fibroblasts. During this time, these cells interact with a variety of extracellular matrices for proper orientation and development. In the present studies, we have examined the interaction of beta(1) integrins on periocular mesenchyme cells (POM) and corneal fibroblasts (CF) with fibronectin and tenascin by perturbing the function of this integrin. POM and CF attached and spread to a much greater extent on fibronectin than on tenascin. An antibody against beta(1) integrin, CSAT, decreased spreading and attachment, and resulted in a lack of immuno-detectable beta(1) integrin in focal adhesions on fibronectin; few beta(1) positive focal adhesions were observed in cells grown on tenascin. An anti-sense retroviral construct decreased endogenous levels of beta(1) integrin protein, and caused decreased attachment and spreading as well as sparse, disorganized focal adhesions. These data indicate that in vitro, both POM and CF have beta(1) integrins that interact with fibronectin and allow them to attach and spread, while tenascin is anti-adhesive. Further studies using both of these experimental paradigms will clarify whether these interactions also occur in vivo.

Animals↗
PubMed1994

Specialized ribosomes allow for the study of mutations in functionally important regions in 16 S rRNA, without affecting cell growth. The identification of functional regions in the central domain of 16S rRNA.

In order to identify the sequences in the central domain of 16 S rRNA of Escherichia coli that are important for ribosome function, we have generated random mutations using a PCR-based mutagenesis technique. We show that the effects of such mutations on ribosomal activity can be analyzed in vivo utilizing the specialized ribosome system. With this system the effect of rRNA mutations on ribosomal activity can be studied by measuring the translation of a modified CAT-mRNA by specialized ribosomes. Specialized ribosomes do not translate the endogenous mRNAs and, therefore, are expected to constitute a non-essential pool of ribosomes within the cell. In total, we have isolated 28 different clones harboring specialized ribosomes with single or multiple point mutations. We demonstrate that for none of these clones was cell growth retarded, even though some of the mutations severely impaired the activity of the specialized ribosomes, to as low as 3% of the wild-type level. For all mutants, their individual activities ranged between 3% and 100% of that of the wild-type activity. Comparison of several mutants indicates that mutations within the hairpin loops 787-795 and 898-901 strongly reduce the ribosomal activity. We also present evidence that the single-stranded region centered around residue A815 may be involved in maintaining translational accuracy.

Base Sequence↗
PubMed1996

Functional domains in protein TrwC of plasmid R388: dissected DNA strand transferase and DNA helicase activities reconstitute protein function.

TrwC is a bifunctional enzyme that displays two biochemical activities essential for plasmid R388 conjugation: oriT-specific DNA strand-transferase and DNA helicase activities. We overproduced and purified different segments of the protein allowing us to map the relaxase and DNA helicase activities to separate regions of the protein. A peptide comprising the N-terminal 275 amino acid residues of the protein was able to catalyze DNA cleavage and strand-transfer reactions when using oligonucleotides encompassing the nic site, although a longer fragment of TrwC (348 amino acid residues) was required to produce the nick on a supercoiled double-stranded DNA substrate. The segment of the protein between amino acid residues 192 and 966 contained the ATPase and DNA helicase activities, while a peptide consisting of amino acid residues 346 to 966 lost both activities. The dimerization region lay in the 495 C-terminal amino acid residues. Two peptides containing the DNA strand-transferase and DNA helicase activities, respectively, could functionally substitute for TrwC in R388 conjugation although at a 10,000-fold lower efficiency. Thus, integrity of the covalent structure of the protein was required for efficient DNA transfer. It can be assumed that the covalent linkage increases the efficiency of conjugation by increasing the effective concentration of one component (presumably the DNA helicase) at its site of action.

Base Sequence↗
PubMed1997

The virion host shutoff function of herpes simplex virus type 1 plays a role in corneal invasion and functions independently of the cell cycle.

A significant restriction was demonstrated in the ability of herpes simplex virus type 1 virion host shutoff (vhs) mutant viruses to invade the corneal epithelium. Viral replication and invasion was confined to the areas of the cornea which were scarified prior to infection. Differences between wild-type and vhs mutant replication in corneas in vivo were 100- to 1000-fold at all timepoints postinfection. Smaller but still significant growth restrictions were observed in cultured corneal cells. This difference between in vitro and in vivo is not likely to be due to differences in cell cycle status since vhs-induced RNA degradation can occur in both cycling and noncycling cells in vitro. The vhs function is therefore important for invasion of the cornea and secondarily the nervous system and is thereby required for efficient establishment of latency.

Animals↗
PubMed1998

Structure-function analysis of the herpes simplex virus type 1 UL12 gene: correlation of deoxyribonuclease activity in vitro with replication function.

Although the product of the UL12 gene of herpes simplex virus type 1 (HSV-1) has been shown to possess both exonuclease and endonuclease activities in vitro, and deletion of most of the gene within the viral genome results in inefficient production and maturation of infectious virions, the function of the deoxyribonuclease (DNase) activity per se in virus replication remains unclear. In order to correlate the in vitro and in vivo activities of the protein encoded by UL12, mutant proteins were tested for nuclease activity in vitro by a novel hypersensitivity cleavage assay and for their ability to complement the replication of a DNase null mutant, AN-1. Rabbit reticulocyte lysates programmed with wild-type UL12 RNA cleaved at the same sites cleaved by purified HSV-1 DNase, but distinct from those cleaved by DNase 1 or micrococcal nuclease. All mutants which lacked DNase activity in vitro also failed to complement the replication of AN-1 in nonpermissive cells. Likewise, all mutants which contained HSV-1 DNase activity, as detected by the hypersensitivity cleavage assay, were capable of complementing the replication of the DNase null mutant, though to varying extents. Of particular note was the d1-126 mutant protein, which, despite having the same specific activity as the wild-type enzyme in vitro, complemented the replication of AN-1 significantly less than the wild-type protein. The results suggest that DNase activity per se is required for efficient replication of HSV-1 in vivo. However, residues, including the N-terminal 126 amino acids, which are dispensable for enzymatic activity in vitro may facilitate the accessibility or activity of the protein in vivo.

Animals↗
PubMed1985

Link between functional and morphological changes in the inner ear--functional changes produced by ototoxic agents and their interactions.

Common potentials used to evaluate cochlear function are the ac cochlear potential (ACCP), N1 and the positive dc endocochlear potential (EP). The ACCP is an electrical analogue of the sound stimulus; its source is the electrical activity of the cochlear hair cells. N1 is a volume conductor recorded action potential of the auditory nerve. The EP is the positive polarization of the middle compartment of the cochlea (scala media) with respect to the other compartments (the scalae tympani and vestibuli); the stria vascularis is apparently responsible for the EP. Generally, ototoxic drugs and very intense broad-band noise affect the basal portion of the cochlea first and, because of tonotopic organization, the ACCP responses to high frequency pure tones are affected before those to the low frequencies. However, the correlation between the effect of an ototraumatic agent on the ACCP and its effect on cochlear morphology is not always reliable. The correlations between changes in N1 and EP and in cochlear morphology are even less precise. Also discussed will be the cochlear effects of noise and the ototoxic interactions between drug/drug, noise/drug, and noise/drug/otitis media.

Acetylcysteine↗
PubMed1980

A dnaB analog function specified by bacteriophage P7 and its comparison to the similar function specified by bacteriophage P1.

Evidence is presented that bacteriophage P7 specifies an analog of the E. coli DNA replication protein, dnaB. As in the related bacteriophage P1 (D'Ari et al., 1975; Ogawa, 1975), in lysogens of P7, the production of the analog protein is repressed and constitutive mutants could be isolated. Such constitutive mutants could suppress efficiently the thermosensitivity of several dnaB(ts) mutations and also rescue a strain carrying a dnaB amber mutation. While neither P7 nor the mutant P1bacban (defective in the structural gene ban) could suppress dnaB(ts) mutations efficiently, recombinants between these two phages could do so, indicating the presence of a functional dnaB analog gene (called sdb) on P7. In a dnaB amber strain suppressed by the presence of the constitutive mutant P7csb, bacteriophage lambda failed to replicate which is a further similarity between P7 and P1. P7csb mutants or P7-P1bacban recombinants were found to be less thermoresistant than P1bac1 suggesting that the P7-specified dnaB analog protein or its production is relatively less tolerant of temperatures above 37 degrees C.

Coliphages↗
PubMed1993

Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic rats and nerve function.

We examined the effect of the angiotensin II receptor blocker, ZD 8731, on nerve function, capillary density, and blood flow in streptozotocin-diabetic rats. Deficits in sciatic motor and saphenous sensory nerve conduction velocity of 21% and 15%, respectively, were observed after 1 month of diabetes mellitus (p < 0.001). These were completely ameliorated by a further month of ZD 8731 treatment (p < 0.001). Treatment of non-diabetic rats for 1 month with ZD 8731 had no effect on motor or sensory conduction velocity. Sciatic nerve capillary density was not significantly affected by 1- or 2-month untreated diabetes, however, there was a 15% increase in density with ZD 8731 treatment (p < 0.001). Treatment of non-diabetic rats for 1 month had no effect on capillary density. Diabetes prolonged the time taken for 80% conduction failure by 19% (p < 0.05) and 49% (p < 0.001) for 1 and 2 months of diabetes, respectively, when sciatic nerve was exposed to hypoxia in vitro. ZD 8731 treatment during the second month of diabetes limited the prolongation to 22%, not significantly different from 1 month of untreated diabetes but less than for the 2-month diabetic group (p < 0.001). Concentrations of sciatic nerve polyol pathway metabolites were elevated six-fold and myo-inositol was reduced 40% by diabetes; ZD 8731 treatment was without effect. Acute experiments examined the effect of ZD 8731 on sciatic nerve blood flow using laser-Doppler flowmetry. In non-diabetic rats, blood flow changes followed the dose-dependent reductions in systemic arterial pressure and there were no significant variations in sciatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1975

Experimental investigation of the bound dissipation function: change of the psi u-function during the growth of yeast.

By means of a microcalorimeter (direct calorimetry) and a Warburg-apparatus (indirect calorimetry) that part of the dissipation of a growing culture of yeast cells which remains irreversible in the cells is determined (psi u). The course of the psi u-function with time correlates with the increase of the specific cell concentration being conditioned by the growth phase of the culture but similar for fermentative and respirative metabolism.

Aerobiosis↗