Search PubMed⌕ Search

Biomedical subjects

S E Johnson

Publications and source records attributed to S E Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Correlation of opsonophagocytosis and passive protection assays using human anticapsular antibodies in an infant mouse model of bacteremia for Streptococcus pneumoniae.

An infant mouse assay system for assessment of protective concentrations of human serum pneumococcal anticapsular antibodies is described. Passive immunization of anticapsular antibodies was evaluated for protection of infant mice challenged with Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 18C, and 23A, with bacteremia as an end point. Protection was defined as no detectable bacteremia in 70% of mice 48 h after challenge. Type-specific anticapsular concentrations required for protection varied with serotype (</=0.05 to >0.4 microg/mL). Across serotypes, there was no significant correlation between human IgG concentration in mouse serum and protection from bacteremia or between IgG concentration and opsonophagocytic titer. Significant correlation (r=.84, P<.001) was observed between opsonophagocytic titer of human IgG antibody in mouse sera and protection from bacteremia. Thus, protective concentrations of anticapsular antibodies against bacteremia are serotype dependent. Opsonophagocytosis is a better predictor of in vivo protective capacity of pneumococcal anticapsular antibodies than are ELISA IgG antibody concentrations.

Animals↗
PubMed1998

Positional behavior and vertebral morphology in atelines and cebines.

Atelines are of particular interest to primate evolutionary studies because they converge with hominoids in postcranial anatomy, including the vertebral column. Currently, our understanding of ateline vertebral morphology is limited to mainly qualitative descriptions and functional interpretations based on general categories of positional behavior. Even less is known about the vertebrae of other platyrrhines. This study more closely examines vertebral form and function in atelines and cebines by combining direct field observations of axial postures and movements, assessments of spinal loading regimes, and a detailed vertebral morphometric analysis. Field observations (Corcovado, Costa Rica) on Ateles geoffroyi, Alouatta palliata, Cebus capucinus, and Saimiri oerstedii were quantified in conjunction with a morphometric analysis of ateline and cebine lumbar vertebrae. Hylobates was also included for comparison. Compared to Cebus and Saimiri, atelines engage more frequently in postures and locomotor behaviors that induce pronounced bending loads on the spine. All atelines share lumbar adaptations for resisting bending, including ventrodorsally elongated vertebral bodies and perpendicularly oriented transverse processes. Among atelines, lumbar region lengths and vertebral bodies are shortest in Ateles and Brachyteles, longest in Alouatta (resembling Cebus), and intermediate in Lagothrix. Compared to Cebus and all atelines, Saimiri has a relatively longer lumbar region, longer and less ventrodorsally expanded vertebral bodies, and more ventrally oriented transverse processes. These features accentuate bending loads, but increase the sagittal flexibility required for leaping. Vertebral convergence between hylobatids and atelines is more readily interpretable as a product of shared spinal loading patterns than shared positional behaviors.

Animals↗
PubMed1998

Progressive pseudobulbar paresis, early choreiform movements, and later rigidity: appearance in two sets of dizygotic twins in the same family.

In a family with two sets of dizygotic twins, three, possibly all four, siblings were affected by the same disorder. The parents were unrelated and the illness seemed limited to one generation. Onset was in the early to mid-20s with tics and choreiform movements, dysarthria, and dysphagia. Two twins had epilepsy. There was a marked dyscoordination of bulbar musculature reminiscent of pseudobulbar paresis. Involuntary movements were prominent during the first years, but then disappeared and were replaced by an akinetic-rigid parkinsonian appearance in the late stage. The intellect remained largely intact. Tendon reflexes were reduced. Varying degrees of peripheral nerve changes were seen. Two patients died after 22-24 years from causes indirectly related to the main illness. Marked degenerative changes were found in the caudate nucleus and putamen. Acanthocytes in significant numbers could not be detected in peripheral blood. Lipoproteinelectrophoresis was normal. Creatine kinase levels were moderately raised in one patient, normal in the others. Although certain clinical resemblances exist with neuroacanthocytosis, the exact nosologic status of the disorder has not been determined.

Adult↗
PubMed1998

Immunoreactivity of five monoclonal antibodies against the 37-kilodalton common cell wall protein (PsaA) of Streptococcus pneumoniae.

Five monoclonal antibodies (MAbs) were produced against the Streptococcus pneumoniae pneumococcal surface adhesin A (PsaA) 37-kDa common cell wall protein. These antibodies were used in a dot immunoblot and Western blot study of clinical isolates of S. pneumoniae to detect the presence of the protein. By both assays, the MAbs reacted with clinical isolates representing the 23 type-specific serotypes present in the licensed pneumococcal polysaccharide vaccine. Western blot analysis confirmed the presence of a protein migrating in the gel with a molecular mass of 37 kDa. An extension of the study by using dot immunoblot analysis that included an analysis of the 90 serotypes of S. pneumoniae showed that all five MAbs reacted with 89 of the 90 serotypes tested. MAb 1B6, the exception, did not react with S. pneumoniae serotype 16F. Dot immunoblot analysis of the MAbs with Enterococcus faecalis and viridans streptococci showed varied reactivity patterns, depending on the species. The MAbs against the 37-kDa antigen did not react with Escherichia coli, respiratory pathogens, or nonpathogens representing 22 genera and 29 species of bacteria. All five MAbs also reacted with five multidrug-resistant strains of S. pneumoniae. In summary, these MAbs may be useful for detection of pneumococcal antigen and may lead to the development of diagnostic assays for pneumococcal disease.

Adhesins, Bacterial↗
PubMed1997

Hearing loss associated with neonatal ECMO: a clinical investigation.

To answer the question as to the prevalence of sensori-neural hearing loss (SNHL) among neonates receiving ECMO, a retrospective chart review was conducted on 198 infants having surgery between November 1987 and January 1995. One hundred fifty-seven (79.7%) survived. One hundred thirty infants met our criteria of having a pre-discharge auditory brainstem evoked response (ABR) test and at least one follow-up behavioral audiologic examination. Strict criteria were set for normal hearing on both the ABR and follow-up examinations. Only follow-up results are reported. At the time of the most recent follow-up examination, two children could not be adequately studied, 106 exhibited normal hearing, 21 (16%) exhibited either unilateral or bilateral conductive hearing loss and three (2.3%) exhibited unilateral or bilateral SNHL. Only one child is using amplification. With the largest sample size to date, we found a lower prevalence of SNHL after ECMO than has been previously noted in the literature. Although the prevalence of hearing loss is low, the post-ECMO group of infants must be considered at risk for hearing loss. The prevalence of hearing loss cannot be based solely on a pre-discharge ABR, i.e. ongoing follow-up testing is necessary.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1997

Signaling through mitogen-activated protein kinase and Rac/Rho does not duplicate the effects of activated Ras on skeletal myogenesis.

The ability of basic helix-loop-helix muscle regulatory factors (MRFs), such as MyoD, to convert nonmuscle cells to a myogenic lineage is regulated by numerous growth factor and oncoprotein signaling pathways. Previous studies have shown that H-Ras 12V inhibits differentiation to a skeletal muscle lineage by disrupting MRF function via a mechanism that is independent of the dimerization, DNA binding, and inherent transcriptional activation properties of the proteins. To investigate the intracellular signaling pathway(s) that mediates the inhibition of MRF-induced myogenesis by oncogenic Ras, we tested two transformation-defective H-Ras 12V effector domain variants for their ability to alter terminal differentiation. H-Ras 12V,35S retains the ability to activate the Raf/MEK/mitogen-activated protein (MAP) kinase cascade, whereas H-Ras 12V,40C is unable to interact directly with Raf-1 yet still influences other signaling intermediates, including Rac and Rho. Expression of each H-Ras 12V variant in C3H10T1/2 cells abrogates MyoD-induced activation of the complete myogenic program, suggesting that MAP kinase-dependent and -independent Ras signaling pathways individually block myogenesis in this model system. However, additional studies with constitutively activated Rac1 and RhoA proteins revealed no negative effects on MyoD-induced myogenesis. Similarly, treatment of Ras-inhibited myoblasts with the MEK1 inhibitor PD98059 revealed that elevated MAP kinase activity is not a significant contributor to the H-Ras 12V effect. These data suggest that an additional Ras pathway, distinct from the well-characterized MAP kinase and Rac/Rho pathways known to be important for the transforming function of activated Ras, is primarily responsible for the inhibition of myogenesis by H-Ras 12V.

Animals↗
PubMed1996

Examination of mammalian basic helix-loop-helix transcription factors using a yeast one-hybrid system.

Basic helix-loop-helix (bHLH) transcription factors play diverse roles in controlling many developmental events. Although a great deal is understood about how bHLH factors activate gene transcription via E-box DNA consensus sequences, studies of bHLH factor function in higher eukaryotes often have been hindered by the presence of multiple family members. As a first step in developing a simplified in vivo system to examine bHLH factor activities, we examined whether the bHLH muscle regulatory factors MRF4 and MyoD function appropriately in yeast. We show that Gal4-MRF4 fusion proteins, or native MRF4 proteins, activate expression of an E-box HIS3 reporter gene whereas MyoD proteins remain inactive. Deletion of the MRF4 transcription activation domain (TAD) or point mutations that abolish MRF4 DNA interactions inhibit HIS3 expression. Substitution of the MRF4 TAD with the Gal4 TAD also produces a functional protein, demonstrating that these transcription activation domains are functionally equivalent in yeast. Replacement of the MRF4 TAD with the related MyoD TAD, however, generates an inactive protein, suggesting that some specificity exists between bHLH family members. Using this experimental system, we also demonstrate that mammalian cDNA libraries can be screened successfully for cDNAs encoding novel bHLH proteins that interact with E-box targets. Thus, this in vivo yeast system provides a novel approach to facilitate functional studies of bHLH factor regulation.

Animals↗
PubMed1996

Casein kinase II increases the transcriptional activities of MRF4 and MyoD independently of their direct phosphorylation.

The myogenic regulatory factors (MRFs) are a subclass of a much larger group of basic helix-loop-helix transcription factors which includes members of the E protein such as E47, E2-2, and HEB. Although the MRFs are unique in their ability to confer a myogenic phenotype on nonmuscle cells, they require E protein partners to form a MRF-E protein heterodimer, which represents the functional myogenesis-inducing complex. The mechanisms controlling homodimer and heterodimer formation in vivo remain largely unknown, although it is likely that posttranslational modification of one or both basic helix-loop-helix partners is critical to this regulatory event. In this respect, MyoD and MRF4, both members of the MRF family, exist in vivo as phosphoproteins and contains multiple consensus phosphorylation sites, including sites for casein kinase II (CKII) phosphorylation. In this study, we demonstrate that overexpression of CKII increases the transcriptional activities of MRF4 and MyoD in vivo. Interestingly, mutation of the individual CKII sites within MRF4 and MyoF does not alter the ability of CKII to enhance MRF transcriptional activity, suggesting that the effect of CKII expression on the MRFs is indirect. Given that the MRFs require dimerization with E protein partners to activate muscle-specific transcription, the effects of CKII expression on E protein function also were examined. Our studies show that E47 serves as an in vitro substrate for CKII and that CKII-phosphorylated E-47 proteins no longer bind to DNA. These observations were confirmed by in vivo experiments showing that overexpressing of CKII produces a dramatic reduction in E47 homodimer-directed transcription. We conclude from these studies that CKII may act as a positive regulator of myogenesis by preventing E protein homodimers from binding to muscle gene regulatory elements.

Amino Acid Sequence↗
PubMed1995

Systemic Mycobacterium smegmatis infection in a dog.

A 3-year-old female Basset Hound was examined because of fever and lameness of 2 months' duration. Physical examination revealed a small cranial abdominal mass, which had an ultrasonographic appearance of a large abdominal lymph node. Cytologic examination of an ultrasound-guided fine-needle aspirate of the mass revealed a few macrophages that contained numerous linear unstained structures consistent with mycobacteria. Intracellular acid-fast bacilli were identified in an aspirate that was stained with modified Ziehl-Neelsen. Exploratory laparotomy revealed wide-spread abdominal lymphadenopathy. Histologic examination of hepatic and lymph node biopsy specimens revealed chronic granulomatous hepatitis and lymphadenitis. Acid-fast organisms isolated after bacteriologic culturing of a mesenteric lymph node specimen were identified as Mycobacterium smegmatis. Because the prognosis was poor, the dog was euthanatized.

Animals↗
PubMed1995

Activation of skeletal muscle satellite cells and the role of fibroblast growth factor receptors.

Specific, high-affinity binding of FGF2 was evaluated in cultured skeletal muscle satellite cells from young (3- to 4-week-old) and adult (9- to 12-month-old) rats prior to the first division in culture. Specific binding of FGF2 was detected on satellite cells from young rats at 18 h postplating, the earliest time examined, but specific binding was not detectable until 42 h on satellite cells from old rats. This correlates well with the delayed entry into the cell cycle exhibited by adult satellite cells and with the ability of satellite cells from rats of these ages to proliferate in response to FGF2. Patterns of tyrosine phosphorylation in whole cell extracts, following stimulation by FGF2, indicated specific FGF2 phosphorylation of proteins of 150/145, 90, 42, and 35 kDa in cells from both age groups. Several growth factors were evaluated for their ability to stimulate early entry of adult satellite cells into the cell cycle, and none of the following growth factors were able to activate proliferation of these cells: FGF2, IGF-1, IGF-2, PDGF-BB, TGF-beta 1, or TGF-beta 2. In addition, specific binding of FGF2 to 48-h cultures of adult satellite cells was not stimulated by FGF2, IGF-1, IGF-2, PDGF-BB, or TGF-beta 2, and specific binding was significantly decreased (P < 0.05) by FGF2 and TGF-beta 2. Specific binding was significantly lower in cells treated with PDGF-BB than in cells treated with either form of IGF but was greater than in cells treated with FGF2 or TGF-beta 2. The results of these experiments suggest that expression of functional FGF receptors on the surface of satellite cells may represent an important step in the activation of quiescent satellite cells.

Age Factors↗
PubMed1995

The cosmid CSSM25 assigns syntenic group U2 to bovine chromosome 9 and is localized to ovine chromosome 8.

The cosmid-derived microsatellite CSSM 25 has previously been shown to map to bovine syntenic group U2 by linkage and hybrid somatic cell analysis. We have mapped the cosmid by fluorescent in situ hybridization to bovine Chromosome (Chr) 9q17-21 and ovine Chr 8q17-21 and hence assign U2 to Chr 9 in cattle. Bovine Chr 9 and ovine Chr 8 show strong banding pattern homology, and the localization of CSSM 25 to the same region confirms the strong conservation of gene locations on these chromosomes.

Animals↗
PubMed1995

Ras p21Val inhibits myogenesis without altering the DNA binding or transcriptional activities of the myogenic basic helix-loop-helix factors.

MRF4, MyoD, myogenin, and Myf-5 are muscle-specific basic helix-loop-helix transcription factors that share the ability to activate the expression of skeletal muscle genes such as those encoding alpha-actin, myosin heavy chain, and the acetylcholine receptor subunits. The muscle regulatory factors (MRFs) also exhibit the unique capacity to initiate the myogenic program when ectopically expressed in a variety of nonmuscle cell types, most notably C3H10T1/2 fibroblasts (10T1/2 cells). The commitment of myoblasts to terminal differentiation, although positively regulated by the MRFs, also is controlled negatively by a variety of agents, including several growth factors and oncoproteins such as fibroblast growth factor (FGF-2), transforming growth factor beta 1 (TGF-beta 1), and Ras p21Val. The molecular mechanisms by which these varied agents alter myogenic terminal differentiation events remain unclear. In an effort to establish whether Ras p21Val represses MRF activity by directly targeting the MRF proteins, we examined the DNA binding and transcription activation potentials of MRF4 and MyoD when expressed in 10T1/2 cells or in 10T1/2 cells expressing Ras p21Val. Our results demonstrate that Ras p21Val inhibits terminal differentiation events by targeting the basic domain of the MRFs, and yet the mechanism underlying this inhibition does not involve altering the DNA binding or the inherent transcriptional activity of these regulatory factors. In contrast, FGF-2 and TGF-beta 1 block terminal differentiation by repressing the transcriptional activity of the MRFs. We conclude that the Ras p21Val block in differentiation operates via an intracellular signaling pathway that is distinct from the FGF-2 and TGF-beta 1 pathways.

Cell Differentiation↗
PubMed1994

Hypodipsic hypernatremia in a dog with defective osmoregulation of antidiuretic hormone.

Hypernatremia was detected in a dog that was evaluated because of seizures. During hospitalization, the dog was fully conscious and remained hypernatremic when drinking voluntarily and when water was added to the food. Urine volume increased and urine osmolality decreased during an infusion of hypertonic saline (2.5% NaCl) solution, despite development of progressive hyperosmolality. There was no correlation between plasma antidiuretic hormone concentration and osmolality during the infusion study. The dog released antidiuretic hormone normally after nonosmotic stimulation (ie, apomorphine administration). These findings allowed a diagnosis of hypodipsic hypernatremia caused by destruction of hypothalamic osmoreceptors. At necropsy, there was hydrocephalus, atrophy of the septum pellucidum, and neuraxonal dystrophy of the cuneate nuclei. The underlying neurologic disease responsible for the CNS lesions could not be determined, but hydrocephalus may have led to pressure atrophy in the region of the hypothalamus that contains osmoreceptors.

Animals↗
PubMed1994

Isolation and mapping of a single-locus minisatellite sequence marker to 1q36-qter and synteny group 10 in cattle and to 1q36-qter in sheep.

A minisatellite sequence (RD1613) was isolated from a bovine cosmid genomic library and its chromosomal location determined in cattle and sheep. In cattle, somatic cell hybrid panel analysis assigned RD1613 to the syntenic group U10 with a concordancy of 100%. In situ hybridization placed RD1613 onto bovine chromosome 1 in the region of bands q36-qter. This is the first in situ localization to chromosome 1 in cattle and allows the provisional assignment of syntenic group U10 to this chromosome. It was also found that RD1613 hybridized strongly to sheep genomic DNA. In situ hybridization localized RD1613 to sheep chromosome 1q36-qter, which is consistent with homology between cattle chromosome 1 and sheep chromosome 1q. The RD1613 probe detects a polymorphic single locus marker (designated D1S1) in both cattle and sheep and will be very useful in linkage studies.

Animals↗
PubMed1994

Expression of epidermal growth factor family gene members in early mouse development.

Transcription of four members of the epidermal growth factor (EGF) family, EGF, TGF-alpha, Amphiregulin, and Cripto, was investigated in the ovulated unfertilized egg and preimplantation embryo using cDNA libraries. EGF was present as a maternal message only, TGF-alpha was present at low levels in each library, Amphiregulin was not detected, and Cripto transcripts were first detected in the blastocyst cDNA library. In situ hybridization studies of the implanting embryo revealed Cripto expression localized to the entire ectoderm and then to the rapidly growing ectoplacental cone. At gastrulation, Cripto was detected in the primitive streak and developing mesoderm. During organogenesis, Cripto localized to the developing heart. Two Cripto transcripts were detected: one is confined to the early embryo and teratocarcinoma cells, and the other, first found in the fetus, is the major form detected in adult organs.

Amphiregulin↗
PubMed1994

Acid-base status at birth and subsequent neurosensory impairment in surviving 500 to 1000 gm infants.

OBJECTIVE: The purpose of this study was to assess, in infants born weighing < or = 1000 gm, if umbilical cord blood acid-base measures at birth are associated with an additional increase in neurosensory impairment. STUDY DESIGN: Of 289 surviving infants with a birth weight of 500 to 1000 gm born from 1979 to 1989, 219 had umbilical cord acid-base status measured at birth and were followed prospectively for > or = 1 year. Measures of neurologic impairment used in this study included mental retardation, cerebral palsy, and major neurosensory impairment. RESULTS: Gestational age was inversely associated with all neurosensory impairments and was a better predictor of subsequent impairment in this population than was birth weight. Very low umbilical cord pH values were also significantly related to adverse outcomes. There was also an inverse relationship between cord blood bicarbonate levels and major neurosensory impairment. The highly significant relationship between cord blood bicarbonate and pH values and the development of neurosensory impairments persisted in spite of adjustment for gestational age, birth weight, plurality, use of general anesthesia, maternal race, and presence of hypertension. CONCLUSION: An adverse acid-base status at birth is additive to the effect of gestational age in predicting neurosensory impairment in infants weighing < or = 1000 gm.

Acid-Base Equilibrium↗
PubMed1994

Evaluation of total serum bile acids concentration and bile acid profiles in healthy cats after oral administration of ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA; 10 mg/kg of body weight) was administered orally to 5 healthy cats for 3 months. Signs of illness were not apparent in any cat during treatment with UDCA. Results of monthly CBC, serum biochemical analysis, and urinalysis were unchanged during drug administration. There was a decrease in serum cholesterol concentration in 4 cats. Total postprandial serum bile acids (PPSBA) concentration was significantly (P = 0.0003) increased over total preprandial serum bile acids (PRSBA) concentration at all sample collection periods. The PRSBA and PPSBA concentrations were significantly (P < 0.05) increased at all sample collection periods after administration of UDCA, compared with baseline values. Ursodeoxycholic and tauroursodeoxycholic acids were not detected in serum prior to initiating administration of UDCA. Both bile acids were detected in the serum of all cats 1 and 2 months after UDCA administration and were detected in the serum of 2 cats 3 months after initiating UCDA administration. Hepatic ultrasonographic findings were normal before and after completion of UDCA administration. A mild, focal lymphocytic infiltrate was observed in 3 cats 3 months after initiating UDCA administration. Results of the study indicate that UDCA is absorbed into the systemic circulation of cats after oral administration, undergoes hepatic conjugation, and appears to be safe.

Administration, Oral↗