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Biomedical subjects

S M Jones

Publications and source records attributed to S M Jones.

At least 109 records · Page 6Linked to original sources
PubMed1995

Neural tuning characteristics of auditory primary afferents in the chicken embryo.

Primary afferent activity was recorded from the cochlear ganglion in chicken embryos (Gallus domesticus) at 19 days of incubation (E19). The ganglion was accessed via the recessus scala tympani and impaled with glass micropipettes. Frequency tuning curves were obtained using a computerized threshold tracking procedure. Tuning curves were evaluated to determine characteristics frequencies (CFs), CF thresholds, slopes of low and high frequency flanks, and tip sharpness (Q10dB). The majority of tuning curves exhibited the typical 'V' shape described for older birds and, on average, appeared relatively mature based on mean values for CF thresholds (59.6 +/- 20.3 dBSPL) and tip sharpness (Q10dB = 5.2 +/- 3). The mean slopes of low (61.9 +/- 37 dB/octave) and high (64.6 +/- 33 dB/octave) frequency flanks although comparable were somewhat less than those reported for 21-day-old chickens. Approximately 14% of the tuning curves displayed an unusual 'saw-tooth' pattern. CFs ranged from 188 to 1623 Hz. The highest CF was well below those reported for post-hatch birds. In addition, a broader range of Q10dB values (1.2 to 16.9) may related to a greater variability in embryonic tuning curves. Overall, these data suggest that an impressive functional maturity exists in the embryo at E19. The most significant sign of immaturity was the limited expression of high frequencies. It is argued that the limited high CF in part may be due to the developing middle ear transfer function and/or to a functionally immature cochlear base.

Action Potentials↗
PubMed1995

The tonotopic map in the embryonic chicken cochlea.

The purpose of the present study was to determine the tonotopic map in the chicken cochlea at 19 days of incubation (E19) by obtaining characteristic frequencies (CFs) for primary afferents, labeling the characterized neurons, and documenting their projections to the papilla. The lowest and highest CFs recorded were 188 and 1623 Hz respectively. The embryonic tonotopic map coincided with maps reported for post-hatch chicks. There were no evidence that neurons selective to low frequencies project inappropriately to more basal locations of the embryonic papilla. Linear regression was used to estimate the frequency gradient (b = 0.037 +/- 0.012 In Hz/% [b +/- SEb]) and intercept (In C, where C = 111 Hz) of the semilog plot of frequency versus cochlear position (in % distance from apex). From these estimates the octave distribution was calculated to be 18.7%/octave or 0.58 mm/octave. These quantities were not significantly different from those found in post hatch chickens. We conclude that the tonotopic map of the avian cochlea for CFs between 100 and 1700 Hz is stable and relatively mature from age E19 to post-hatch day 21 (P21). The most striking sign of immaturity in the E19 embryo is the limited range of high CFs. We offer the hypothesis that, between the ages of E19 and P21, improvements in middle ear admittance alone or in combination with functional maturation of the cochlear base may be the principal factors responsible for the appearance of adult-like high CF limits and not an apically shifting tonotopic map.

Acoustic Stimulation↗
PubMed1995

Neurologic and other disorders in relatives of pediatric patients with CNS tumors.

Abnormalities of embryogenesis and nervous system development may cause or contribute to the development of childhood brain tumors. To identify genetic or environmental factors that may be associated with etiologies of childhood central nervous system tumors, we examined family histories of 165 children with such tumors for the presence of neurologic disorders, including neural tube defects, mental retardation, seizures, and central nervous system tumors, as well as other cancers and birth defects. Only 1 patient, with the neurofibromatosis-Noonan syndrome, was confirmed to have an underlying syndromic diagnosis associated with central nervous system tumorigenesis. Families of 2 probands with posterior fossa primitive neuroectodermal tumors reported relatives with olivopontocerebellar atrophy. Although increased incidences of study disorders were not identified in this population, it is possible that within individual families one or more of these disorders is related to childhood central nervous system tumorigenesis.

Adolescent↗
PubMed1995

Immunologic cross-reactivity among cereal grains and grasses in children with food hypersensitivity.

BACKGROUND: Because of a lack of clinical data from food challenges, allergists often recommend dietary restriction of all cereal grains in patients with sensitivity to at least one grain. OBJECTIVES: The purposes of this study were to assess the degree of intrabotanical cross-reactivity among cereal grains and related grasses, to better define the prevalence of multiple grain hypersensitivity, and to define the protein fractions associated with wheat hypersensitivity. METHODS: One hundred forty-five patients evaluated by food challenges and skin prick tests were divided into three groups: group 1, cereal grain and grass allergies; group 2, wheat allergy alone; and group 3, grass allergy alone. Fifteen patients were further selected from groups 1 to 3. Sodium dodecylsulfate--polyacrylamide gel electrophoresis and immunoblot analyses were performed on six grains and four related grasses with sera from these patients. RESULTS: Only 21% of patients had symptomatic reactivity as determined by food challenge; 80% had reactivity to only one grain. As determined by immunoblot analyses, patients in groups 1 and 2 showed extensive cross-reactivity (within each group) among grains but little cross-reactivity among grasses, whereas patients in group 3 showed cross-reactivity between the grains and grasses. Patients with wheat allergy had specific IgE binding to wheat fractions 47 kd and 20 kd, bands not recognized by patients with grass allergy. CONCLUSIONS: Clinically insignificant cross-reactivity exists among cereal grains and grasses; therefore, elimination of all grains from the diet of a patient with grain allergy is unwarranted. Further purification and characterization of the 47 kd and 20 kd wheat fractions is needed to provide more specific in vitro testing.

Adolescent↗
PubMed1995

Efficacy of portable filtration units in reducing aerosolized particles in the size range of Mycobacterium tuberculosis.

OBJECTIVE: To evaluate engineering control measures to prevent nosocomial transmission of diseases such as tuberculosis, we studied four portable high-efficiency air filtration units, including three high-efficiency particulate air (HEPA) filtration units, for their ability to remove aerosolized particles. DESIGN: Studies were conducted in either a nonventilated aerosol chamber or in a hospital isolation room that met CDC guidelines for TB control (negative pressure, > or = 6 air changes per hour, air exhausted directly to the outside). The rooms were challenged with aerosolized mineral oil in the size range of 0.3 to 5.0 microns at levels 10 to 20 times the normal airborne particle load in the room at baseline. Airborne particles were counted with a laser counter capable of simultaneously measuring sizes > or = 0.3, > or = 0.5, > or = 1.0, and > or = 5.0 microns. Experimental runs were conducted with the filtration units in the center or corner of the chamber or room, and the particle counter in the center of the room or at the exhaust vent. RESULTS: Portable filtration units were effective in accelerating the removal of aerosolized submicron particles. In the nonventilated room, time required by the various portable filtration units for removal of 90% of aerosolized particles (> or = 0.3 microns) ranged from a low of 5 to 6 minutes to a high of 18 to 31 minutes, compared to the control (no filtration unit), > 171 minutes. In the hospital room, individual filtration units removed 90% of aerosolized particles (> or = 0.3 microns) in times ranging from 5 to 8 minutes to 9 to 12 minutes, compared to the control (no filtration unit), 12 to 16 minutes. The location of the portable filtration unit (center versus corner) did not affect the clearance rate of airborne particles. CONCLUSION: Our data indicate that portable filtration units can rapidly reduce levels of airborne particles similar in size to infectious droplet nuclei and, therefore, may aid in reducing the risk of tuberculosis exposure.

Aerosols↗
PubMed1995

Congenital anomalies and genetic disorders in families of children with central nervous system tumours.

Medical genetic histories of 165 children with primary central nervous system (CNS) tumours and 4599 relatives of these probands were examined to identify birth defects or genetic disorders that may be associated with the aetiology of CNS tumours. Twelve primary malignancies were found in 329 (4%) of the parents of probands. Two of 99 half sibs but no full sibs had malignancies. Twenty-four percent of families had histories warranting consultation for an inherited disorder or birth defect. Single instances of malformations or genetic disorders were reported in 36 families and several disorders were reported in more than one family, including familial hypercholesterolaemia (4), olivopontocerebellar atrophy (2), and familial abdominal aortic aneurysm (2). Although recurring abnormalities were not identified in probands, it is possible that one or more of the birth defects or genetic disorders observed in probands or relatives may be associated with CNS tumourigenesis.

Brain Neoplasms↗
PubMed1995

Overexpression of potassium channel RNA: in vivo development rescues neurons from suppression of morphological differentiation in vitro.

Neuronal differentiation often proceeds differently in vitro than it does in vivo. Previous work demonstrated that overexpression of potassium channel RNA reduces the number of morphologically identifiable neurons that appear in cultures prepared from neural plate stage (17-1/2 hr) embryos (Jones and Ribera, 1994). Here, we report that morphological differentiation of neurons in situ is only slightly affected by overexpression of potassium channels. Endogenous factors appear to compensate for the effect of channel overexpression. Consistent with this view, when cultures are prepared from older neural tube embryos (22-24 hr), more neurons containing excess potassium channel RNA differentiate morphologically in vitro. Exposure in situ to a rapid intracellular calcium chelator, but not to tetrodotoxin, omega-conotoxin or a slow calcium chelator, prevents the compensation provided by extended development in vivo. Typically, RNA overexpression is limited to half of the embryo in order to provide an internal control. However, when potassium channel RNA is overexpressed throughout the embryo, few neurons differentiate morphologically in vitro, even if cultures are prepared from older neural tube embryos. Thus, recovery is possible if a minimum of 5 hr of further development in vivo is allowed under conditions in which rapid elevations of intracellular calcium are permitted and half of the nervous system has normal levels of potassium channel RNA. These results suggest that different or additional mechanisms operate in situ than in vitro to promote morphological differentiation of neurons.

Animals↗
PubMed1995

Autosomal dominant familial spastic paraplegia: tight linkage to chromosome 15q.

Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; theta = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder.

Adolescent↗
PubMed1994

Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease.

Subgroups of PsA have been described but their relationship to the mode of onset of arthritis, to DIP joint disease and to nail and skin disease remains controversial. Therefore, the pattern of disease was documented in 100 patients with PsA in whom the mode of onset was known. The patients were divided into six subgroups: monoarthritis; DIP joint disease only; oligoarthritis; polyarthritis; spondyloarthropathy and arthritis mutilans. Sixty-four patients changed pattern. Nail disease (67% of total) was more common in patients with DIP joint disease (27% of total) and was significantly associated with adjacent DIP joint disease. Skin and nail disease severity did not correlate with joint severity, joint activity or functional status, nor differ between subgroups. Therefore, the mode of onset does not predict outcome in the majority. The topographic association of nail disease and involvement of the adjacent DIP joints suggests a common local inflammatory mechanism.

Adolescent↗
PubMed1994

Vaccination with Brucella abortus rough mutant RB51 protects BALB/c mice against virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovis.

Vaccination of BALB/c mice with live Brucella abortus RB51, a stable rough mutant, produced protection against challenge with virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovis. Passive-transfer experiments indicated that vaccinated mice were protected against B. abortus 2308 through cell-mediated immunity, against B. ovis PA through humoral immunity, and against B. melitensis 16M through both forms of immunity. Live bacteria were required for the induction of protective cell-mediated immunity; vaccination with whole killed cells of strain RB51 failed to protect mice against B. abortus 2308 despite development of good delayed-type hypersensitivity reactions. Protective antibodies against the heterologous species were generated in vaccinated mice primarily through anamnestic responses following challenge infections. Growth of the antigenically unrelated bacterium Listeria monocytogenes in the spleens of vaccinated mice indicated that nonspecific killing by residual activated macrophages contributed minimally to protection. These results encourage the continued investigation of strain RB51 as an alternative vaccine against heterologous Brucella species. However, its usefulness against B. ovis would be limited if, as suggested here, epitopes critical for protective cell-mediated immunity are not shared between B. abortus and B. ovis.

Animals↗
PubMed1994

Antibody-mediated protection against Brucella abortus in BALB/c mice at successive periods after infection: variation between virulent strain 2308 and attenuated vaccine strain 19.

In BALB/c mice antibodies specific for the O polysaccharide (OPS) as well as T lymphocytes mediate protective immunity to Brucella abortus. We performed quantitative analyses of isotypes of OPS antibodies generated during primary infections, and tested the protective qualities of antisera at successive stages of infection against B. abortus strain 2308, representative of the wild type, and attenuated vaccine strain 19. IgM antibodies predominated during the first 3-4 weeks of infection. IgG3 antibodies increased slowly for the first 3 weeks but then rose rapidly and persisted at high levels (> 300 micrograms/ml). IgG1, IgG2a and IgG2b antibodies had increased slightly by week 4 and then remained at low to moderate levels (< 70 micrograms/ml). Week 2 serum pools (IgM high, IgG3 low or undetectable) transferred substantial protection against 2308 (> or = 1 log unit) which increased relatively little (to 1.2-1.5 log units) with later sera that were high in IgG antibodies. In contrast, week 2 sera conferred low levels of protection against 19 (< 0.6 log units), but protection was dramatically increased (to > or = 2.3 log units) with sera obtained 1 week later that had slightly increased IgG antibodies. Monoclonal IgM antibodies also provided better protection against 2308 than 19, while monoclonal IgG3 antibodies protected much better against 19. Strain 19 opsonized with antibodies taken at any stage of infection was killed within normal macrophages, whereas comparably opsonized 2308 underwent intracellular replication. Phagocytosis of 2308 was better than of 19 when brucellae were opsonized with either polyclonal IgM or IgG3 antibodies, and the difference between strains was more extreme following IgM opsonization. The data suggest an explanation for differences in the growth curves of 2308 and 19 in spleens of BALB/c mice. Higher numbers achieved by 19 at week 2 could result from extracellular replication owing to ineffectual opsonization by IgM antibodies, while the precipitous decline of 19 beginning at week 3 could be caused by the increase in more effective IgG3 opsonins that facilitate its rapid intracellular destruction.

Animals↗
PubMed1994

Overexpression of a potassium channel gene perturbs neural differentiation.

Functional regulation of potassium currents in developing neurons is pivotal for changes in excitability and action potential waveform. Here, we test whether an excess of potassium channel transcripts is sufficient to drive functional expression of potassium current and shortening of the duration of the action potential. Injection of Shaker-like potassium channel transcripts into two-cell stage embryos achieves increases in RNA levels. The elevated levels of potassium channel RNA produce larger delayed-rectifier currents. Action potential durations are briefer, indicating that larger potassium currents are not compensated by changes in inward currents. Strikingly, overexpression of potassium current RNA leads to a reduction in the number of morphologically differentiated neurons in culture. We suggest that, by prematurely reducing the duration of the impulse, early overexpression of potassium channel activity suppresses normal developmental cues.

Action Potentials↗
PubMed1993

Topographic mapping of human motor cortex with transcranial magnetic stimulation: Homunculus revisited.

The purpose of this study was to non-invasively evaluate the homuncular organization of the motor cortex in man. We used transcranial magnetic stimulation to induce motor evoked potentials (MEP's) in Abductor Pollicis Brevis (APB) and Biceps Brachii (BB) muscles of 10 healthy volunteers. The practicality and accuracy of magnetic stimulation to scalp sites one cm apart was increased by the application to the scalp of a flexible nylon grid with grid size of 1x1 cm. Responsive scalp sites collectively contributed to distinct but overlapping muscle representational areas for the two muscles. The topography of these motor maps along and slightly anterior to the central fissure corresponds to the homuncular configuration as described by Penfield and Boldrey in 1937.

Adult↗
PubMed1993

A cytosolic complex of p62 and rab6 associates with TGN38/41 and is involved in budding of exocytic vesicles from the trans-Golgi network.

TGN38/41, an integral membrane protein predominantly localized to the trans-Golgi network, has been shown to cycle to the plasma membrane and return to the TGN within 30 min. (Ladinsky, M. S., and K. E. Howell. 1992. Eur. J. Cell Biol. 59:92-105). In characterizing the proteins which associate with TGN38/41, a peripheral 62-kD protein, two forms of rab6 and two other small GTP-binding proteins were identified by coimmunoprecipitation. However, approximately 90% of the 62-kD protein is cytosolic and is associated with the same subset of small GTP-binding proteins. Both the membrane and cytoplasmic complexes were characterized by sizing column fractionation and velocity sedimentation. The membrane complex was approximately 250 kD (11.6 S) consisting of the cytosolic complex and a heterodimer of TGN38/41 (160 kD). The cytosolic complex was approximately 86 kD (6.1 S) consisting of p62 and one small GTP-binding protein. Preliminary evidence indicates that phosphorylation of the p62 molecule regulates the dissociation of the cytosolic complex from TGN38/41. Functionally the cytosolic p62 complex must bind to TGN38/41 for the budding of exocytic transport vesicles from the TGN as assayed in a cell-free system (Salamero, J., E. S. Sztul, and K. E. Howell. 1990. Proc. Natl. Acad. Sci. USA. 87:7717-7721). Interference with p62, rab6 or TGN38, and TGN41 cytoplasmic domains by immunodepletion or competing peptides completely inhibited the budding of exocytic transport vesicles. These results support an essential role for interaction of the cytosolic p62/rab6 complex with TGN38/41 in budding of exocytic vesicles from the TGN.

Amino Acid Sequence↗