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Biomedical subjects

K Johnson

Publications and source records attributed to K Johnson.

At least 379 records · Page 21Linked to original sources
PubMed1990

The role of perceived speaker identity in F0 normalization of vowels.

In the experiments reported here, perceived speaker identity was controlled by manipulating the fundamental frequency (F0) range of carrier phrases in which speech tokens were embedded. In the first experiment, words from two "hood"-"hud" continua were synthesized with different F0. The words were then embedded in synthetic carrier phrases with intonation contours which reduced perceived speaker identity differences for test items with different F0. The results indicated that when perceived speaker identity differences were reduced, the effect of F0 on vowel identification was also reduced. Experiment 2 indicated that when items presented in carrier phrases are matched for speaker identity and F0 with items in isolation, there is no effect for presentation in a carrier phrase. Experiment 3 involved the presentation of vowels from the "hood"-"hud" continuum in two different intonational contexts which were judged to have been produced by different speakers, even though the F0 of the test word was identical in the two contexts. There was a shift in identification as a result of the intonational context which was interpreted as evidence for the role of perceived identity in vowel normalization. Overall, the experiments suggest that perceived speaker identity is a better predictor of vowel normalization effects than is intrinsic F0. This indicates that the role of F0 in vowel normalization is mediated through perceived speaker identity.

Adult↗
PubMed1990

Unusual features of integrated cDNAs generated by infection with genome-free retroviruses.

We previously demonstrated that when nonretroviral RNAs are encapsidated in retroviral particles they can be reverse transcribed into cDNAs, which are then integrated into the cellular genome. This transfer of genetic information via retroviral infection has been designated retrofection. Further analyses of three genes transferred in this manner (retrogenes) revealed that each was present in a single copy at a different site in the recipient quail cell genome and included a transcriptional promoter encoded by the encapsidated neo RNA. A unique feature of the retrogenes was a common 16-nucleotide sequence at or near a recombination border, which was not present in either recombination partner. The existence of this sequence suggests a common mechanism of retrogene formation and/or integration mediated by retrofection.

Animals↗
PubMed1990

Do voice recordings reveal whether a person is intoxicated? A case study.

In this report we consider the possibility that speech analysis techniques may be used to determine whether an individual was intoxicated at the time that a voice recording was made, and discuss an analysis of the speech produced by the captain of the Exxon Valdez recorded at several points around the time of the accident at Prince William Sound, Alaska. A review of previous research on the effects of alcohol and other effects on speech production suggests that it may be possible to attribute a certain, unique pattern of changes in speech to the influence of alcohol. However, the rate of occurrence of this pattern or the reliability of a decision based on observations such as these is not known. Acoustic-phonetic analysis of a small number of tokens of Captain Hazelwood's speech recorded before, during and after the accident revealed a number of changes in speech behavior which are similar to the pattern of changes observed in previous laboratory-based research on the effects of alcohol on speech production. We conclude with a discussion of the limitations in making inferences concerning the state of the speaker upon the basis of phonetic data and then discuss several possible explanations of the pattern of change found in the recordings of Captain Hazelwood.

Accidents, Occupational↗
PubMed1990

A new polymorphic probe which defines the region of chromosome 19 containing the myotonic dystrophy locus.

The region of human chromosome 19 which includes the myotonic dystrophy locus (DM) has recently been redefined by the tight linkage between it and the gene for muscle-specific creatine kinase (CKMM), which lies just proximal to DM. Utilizing human/hamster hybrid cell lines containing defined breakpoints within this region, we have assigned a number of new probes close to DM. Two of these probes, p134B and p134C, were isolated from a single cosmid clone (D19S51) and detect the same BglI RFLP; p134C detects an additional RFLP with the enzyme PstI. Analysis of these probes in the Centre d'Etude du Polymorphisme Humain families demonstrates tight linkage with a number of markers known to be proximal to DM. A two-point lod score of 6.34 at theta = .025 demonstrates the linkage of this probe to DM. Analysis of a DM individual previously shown to be recombinant for other tightly linked markers indicates that p134C is distal to DM. This result indicates that both the new probe and the existing group of proximal probes including CKMM and ERCC1 probably flank DM and define the genetic interval into which this mutation maps.

Animals↗
PubMed1990

The systematic study of drug therapy in rheumatoid arthritis.

Important advances in therapeutics for rheumatoid arthritis (RA) will probably require coordination of the experience with new developing agents with an ongoing program of systematically collected open data, and formal controlled clinical trials to address key problematic issues. Controlled trials, despite formidable obstacles, not the least of which is the lack of satisfactory end points, are necessary because randomized treatment assignment is the only valid way to obtain results with a defined degree of certainty. A formal test of whether early aggressive intervention can arrest disease appears feasible. On the other hand, it does not now seem desirable to pursue a controlled, blinded study of RA over the longterm.

Anti-Inflammatory Agents↗
PubMed1990

Lupus membranous glomerulonephritis: different prognostic subgroups obscured by imprecise histologic classifications.

Eighteen patients with lupus membranous nephritis were retrospective identified by reviewing the renal biopsy records of an active renal pathology service. Seven had minimally proliferative membranous nephropathy (World Health Organization (WHO) classes Va and b). Eleven had membranous nephropathy with superimposed changes of focal or diffuse proliferative glomerulonephritis (WHO Vc and d). After mean follow-up periods of 73 +/- 6 and 74 +/- 15 mo, respectively, one patient of seven from WHO Va and b and seven of 11 from WHO Vc and d reached end stage renal disease. The latter patients were distinguishable from the former only by the degree of superimposed proliferation on renal biopsy and not by blood pressure, antinuclear antibody, anti-double stranded DNA, or complement levels. These data stand in contrast to the widely held belief that lupus membranous nephropathy is relatively benign. The belatedness of this observation is partially due to imprecision in nosology for patients with lupus who have renal biopsies with "overlap" characteristics.

Biopsy↗
PubMed1989

Effects of distal point-site mutations on the binding and catalysis of dihydrofolate reductase from Escherichia coli.

The importance of salt bridge interactions at the NADPH binding site of dihydrofolate reductase has been studied by using site-directed mutagenesis. The mutations R44L and H45Q respectively disrupt the ionic contacts made between the 2'-phosphate and pyrophosphoryl moiety of the coenzyme and the N-terminal region of helix C. Equilibrium fluorescence experiments indicate that while the overall binding of NADPH to both free mutants is weakened by 1.1 and 1.5 kcal/mol (H45Q and R44L, respectively), the binding of dihydrofolate and tetrahydrofolate is unaffected. Despite the similar binding energies for both mutants, the transition state for the chemical hydride step is differentially destabilized relative to wild type (0.6 and 1.8 kcal/mol for H45Q and R44L, respectively). Both stopped-flow and pre-steady-state experiments suggest that the root of this effect may lie in multiple conformations for the E-NADPH complex of R44L. The ability of both mutants to transmit their effects beyond the local environment of the NADPH pocket is manifested in several details: (1) the pKa of Asp-27 (25 A away from the sites of mutation) is elevated from 6.5 in the wild type to 7.5 and 8.4 in H45Q and R44L, respectively; (2) NADPH elevates the off rates for tetrahydrofolate from 12 s-1 in the wild type to greater than 45 s-1 in R44L; and (3) bound tetrahydrofolate decreases the affinity of the enzymes for NADPH as reflected in the Km from 2 to 40 microM for H45Q (similar to wild type) but from 8 to 5000 microM for R44L.

Binding Sites↗
PubMed1989

Tumor necrosis factor identified in multiple sclerosis brain.

Frozen brain specimens from patients with multiple sclerosis (MS) and other neurologic diseases were analyzed using immunocytochemical techniques for the presence of TNF. In brain lesions in MS, and subacute sclerosing panencephalitis, TNF+ cells were demonstrated. At the lesion site in MS, TNF+ staining is associated with both astrocytes and macrophages. These observations were not made in Alzheimer's disease or normal brain tissue. The presence of TNF in MS lesions suggests a significant role for cytokines and the immune response in disease progression.

Astrocytes↗
PubMed1989

Islet amyloid polypeptide (IAPP):cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus.

We have cloned and sequenced a human islet amyloid polypeptide (IAPP) cDNA. A secretory 89 amino acid IAPP protein precursor is predicted from which the 37 amino acid IAPP molecule is formed by amino- and carboxyterminal proteolytic processing. The IAPP peptide is 43-46% identical in amino acid sequence to the two members of the calcitonin gene-related peptide (CGRP) family. Evolutionary conserved proteolytic processing sites indicate that similar proteases are involved in the maturation of IAPP and CGRP and that the IAPP amyloid polypeptide is identical to the normal proteolytic product of the IAPP precursor. A synthetic peptide corresponding to a carboxyteminal fragment of human IAPP is shown to spontaneously form amyloid-like fibrils in vitro. Antibodies against this peptide cross-react with IAPP from species that develop amyloid in pancreatic islets in conjunction with age-related diabetes mellitus (human, cat, racoon), but do not cross-react with IAPP from other tested species (mouse, rat, guinea pig, dog). Thus, a species-specific structural motif in the putative amyloidogenic region of IAPP is associated with both amyloid formation and the development of age-related diabetes mellitus. This provides a new molecular clue to the pathogenesis of this disease.

Amino Acid Sequence↗
PubMed1989

Recombination events that locate myotonic dystrophy distal to APOC2 on 19q.

We previously reported a recombination in an individual with myotonic dystrophy (DM) which placed the markers D19S19 and APOC2 on the same side of the DM locus. Haplotyping of this family with more recently characterized probes which are either tightly linked to DM or distal to the linkage group at q13.2 shows that the DM locus is distal to APOC2. This is confirmed by other recombinants where DM segregates with distal probes. Additional marker to marker recombinations in unaffected individuals are reported and support the order and orientation of the DM linkage group as pter-(INSR, LDLR,S9)-(S19,BCL3,APOC2)-(CKMM,DM)-(S22,+ ++PRKCG)-qter. The data presented here cannot determine whether DM is proximal or distal to CKMM. The consequences of this probe order for antenatal diagnosis and future research aiming to isolate the gene which is affected in DM are discussed.

Chromosome Mapping↗
PubMed1989

Purification of a putative brain somatostatin receptor.

The brain somatostatin (somatotropin release-inhibiting factor; SRIF) receptor was purified by affinity chromatographic techniques. A protein of 60 kDa could be purified from rat brain. The protein was eluted from a [D-Trp8]SRIF affinity column with either sodium acetate (pH 5.5) or free [D-Trp8]SRIF. The binding of the protein to the affinity column was prevented by free [D-Trp8]SRIF or the stable SRIF analogue SMS 201-996 but not by the inactive somatostatin 28-(1-14). The purified receptor could be covalently labeled by the 125I-labeled SRIF analogue CGP 23996. Excess [D-Trp8]SRIF blocked the binding of 125I-labeled CGP 23996 to the purified receptor, but somatostatin 28-(1-14) did not affect the binding. A 60-kDa protein was also purified from the anterior pituitary cell line AtT-20, which has a high expression of SRIF receptors. In contrast, no 60-kDa protein could be purified from CHO cells, which have no detectable SRIF receptors. These findings present evidence for the purification of the SRIF receptor.

Affinity Labels↗
PubMed1989

An addendum to "Effects of Noise on Speech Production: Acoustic and Perceptual Analyses" [J. Acoust. Soc. Am. 84, 917-928 (1988)].

The authors respond to Fitch's comments [H. Fitch, J. Acoust. Soc. Am. 86, 2017-2019 (1989)] on an earlier paper. New analyses are presented to address the question of whether F1 differences observed in the original report are an artifact of linear predictive coding (LPC) analysis techniques. Contrary to Fitch's claims, the results suggest that the F1 differences originally reported are, in fact, due to changes in vocal tract resonance characteristics. It is concluded that there are important acoustic-phonetic differences in speech when talkers speak in noise. These differences reflect changes in both glottal and supraglottal events that are designed to maintain speech intelligibility under adverse conditions.

Humans↗
PubMed1989

Isolation of orally attenuated Salmonella typhimurium following TnphoA mutagenesis.

One hundred fifty Tn5 IS50L::phoA (TnphoA) mutants of a mouse-virulent, nalidixic acid-resistant (Nalr), prototrophic Salmonella typhimurium strain, C5 Nalr, were isolated. None of the mutants were auxotrophs. Groups of 8 to 10 BALB/c mice were infected orally with each of 95 mutants with a dose equivalent to 20-fold the 50% lethal dose of the wild-type C5 Nalr strain, and deaths were counted over the next 28 days. Fifteen of the mutants failed to kill any mice, whereas all mice died following challenge with the other mutants. Nine of the 15 attenuated mutants exhibited a defect in lipopolysaccharide biosynthesis. The remaining six mutants were smooth. The TnphoA transposon of each of the smooth attenuated mutants was moved, using P22-mediated transduction, into a fresh C5 background, and all retransductants were still attenuated. Analysis of the membrane proteins of the attenuated mutants failed to reveal any alterations in detectable major outer membrane proteins, although colonies of two of the mutants exhibited a mucoid phenotype following growth on L-agar plates. Individual attenuated mutants differed in their abilities to translocate to livers and spleens of mice following oral infection. All of the smooth TnphoA mutants exhibited increased 50% lethal doses with respect to the wild type following intravenous infection of BALB/c mice. Southern analysis of DNA prepared from each of the mutants suggested that TnphoA had inserted into a number of different sites in the S. typhimurium genome. None of the TnphoA mutants had inserts in the virulence-associated plasmid.

Administration, Oral↗
PubMed1989

Characterization of degP, a gene required for proteolysis in the cell envelope and essential for growth of Escherichia coli at high temperature.

The degP gene, required for proteolysis in the cell envelope of Escherichia coli, maps at approximately 3.5 min on the chromosome. Null mutations in degP result in temperature-sensitive growth. In certain genetic backgrounds, expression of abnormal periplasmic or inner membrane proteins (protein fusions or proteins with internal deletions) enhances the temperature-sensitive phenotype. Such growth defects were used as a selection for cloning the degP gene into Mud4042 and pACYC184 plasmid vectors, and a restriction map was determined. Analysis of deletion and insertion mutations on one of these plasmids showed that the degP gene is approximately 1.5 kilobases in size. The plasmid-encoded DegP protein had an apparent molecular weight of 50,000, as determined by maxicell analysis. Protein fusions between DegP and alkaline phosphatase had high alkaline phosphatase enzymatic activity, indicating that DegP is a periplasmic or membrane protein.

Alkaline Phosphatase↗