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T Gordon

Publications and source records attributed to T Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1997

In vivo exposure to ozone produces an increase in a 72-kDa heat shock protein in guinea pigs.

Although several lines of evidence have suggested that oxidizing agents can induce heat shock proteins (HSPs) in vitro, little is known about the induction of HSPs during in vivo exposure to oxidants. Guinea pigs were exposed to ozone for 6 h and euthanized up to 72 h later. Proteins from lavage cells and lung tissue were characterized by immunoblotting with 72- and 73/72-kDa HSP monoclonal antibodies. Although 73-kDa HSP was expressed constituitively in lung tissue, it was not affected by ozone. In contrast, 72-kDa HSP was significantly increased in lavage cells and lung tissue of animals exposed to 0.4 and 0.66 parts/million of ozone. Both heat treatment and arsenite induced 72-kDa HSP in cultured alveolar macrophages. The increase in 72-kDa HSP in the lavage cell pellet peaked at 24 h after ozone, whereas the influx of polymorphonuclear leukocytes peaked at 4 h. Examination of the induction of HSPs by ozone may provide clues to the development of ozone tolerance in humans and animals.

Air Pollutants↗
PubMed1997

Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats. I. Muscle and motor unit properties.

This study of cat medial gastrocnemius (MG) muscle and motor unit (MU) properties tests the hypothesis that the normal ranges of MU contractile force, endurance, and speed are directly associated with the amount of neuromuscular activity normally experienced by each MU. We synchronously activated all MUs in the MG muscle with the same activity (20 Hz in a 50% duty cycle) and asked whether conversion of whole muscle contractile properties is associated with loss of the normal heterogeneity in MU properties. Chronically implanted cuff electrodes on the nerve to MG muscle were used for 24-h/day stimulation and for monitoring progressive changes in contractile force, endurance, and speed by periodic recording of maximal isometric twitch and tetanic contractions under halothane anesthesia. Chronic low-frequency stimulation slowed muscle contractions and made them weaker, and increased muscle endurance. The most rapid and least variable response to stimulation was a decline in force output of the muscle and constituent MUs. Fatigue resistance increased more slowly, whereas the increase in time to peak force varied most widely between animals and occurred with a longer time course than either force or endurance. Changes in contractile force, endurance, and speed of the whole MG muscle accurately reflected changes in the properties of the constituent MUs both in extent and time course. Normally there is a 100-fold range in tetanic force and a 10-fold range in fatigue indexes and twitch time to peak force. After chronic stimulation, the range in these properties was significantly reduced and, even in MU samples from single animals, the range was shown to correspond with the slow (type S) MUs of the normal MG. In no case was the range reduced to less than the type S range. The same results were obtained when the same chronic stimulation pattern of 20 Hz/50% duty cycle was imposed on paralyzed muscles after hemisection and unilateral deafferentation. The findings that the properties of MUs still varied within the normal range of type S MUs and were still heterogeneous despite a decline in the variance in any one property indicate that the neuromuscular activity can account only in part for the wide range of muscle properties. It is concluded that the normal range of properties within MU types reflects an intrinsic regulation of properties in the multinucleated muscle fibers.

Afferent Pathways↗
PubMed1997

Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats. II. Motoneuron properties.

Chronic stimulation (for 2-3 mo) of the medial gastrocnemius (MG) muscle nerve by indwelling electrodes renders the normally heterogeneous MG muscle mechanically and histochemically slow (type SO). We tested the hypothesis that motoneurons of MG muscle thus made type SO by chronic stimulation would also convert to slow phenotype. Properties of all single muscle units became homogeneously type SO (slowly contracting, nonfatiguing, nonsagging contraction during tetanic activation). Motoneuron electrical properties were also modified in the direction of type S, fatigue-resistant motor units. Two separate populations were identified (on the basis of afterhyperpolarization, rheobase, and input resistance) that likely correspond to motoneurons that had been fast (type F) or type S before stimulation. Type F motoneurons, although modified by chronic stimulation, were not converted to the type S phenotype, despite apparent complete conversion of their muscle units to the slow oxidative type (type SO). Muscle units of the former type F motor units were faster and/or more powerful than those of the former type S motor units, indicating some intrinsic regulation of motor unit properties. Experiments in which chronic stimulation was applied to the MG nerve cross-regenerated into skin yielded changes in motoneuron properties similar to those above, suggesting that muscle was not essential for the effects observed. Modulation of group Ia excitatory postsynaptic potential (EPSP) amplitude during high-frequency trains, which in normal MG motoneurons can be either positive or negative, was negative in 48 of 49 chronically stimulated motoneurons. Negative modulation is characteristic of EPSPs in motoneurons of most fatigue-resistant motor units. The general hypothesis of a periphery-to-motoneuron retrograde mechanism was supported, although the degree of control exerted by the periphery may vary: natural type SO muscle appears especially competent to modify motoneuron properties. We speculate that activity-dependent regulation of the neurotrophin-(NT) 4/5 in muscle plays an important role in controlling muscle and motoneuron properties.

Animals↗
PubMed1997

Comparison of USDA quality grade with tendertec for the assessment of beef palatability.

Carcasses (n = 265) selected to differ in USDA yield grade were evaluated by expert graders and assessed for tenderness with the Tendertec Mark III Beef Grading Instrument. Tendertec measurements were collected on longissimus lumborum muscles in both sides of each carcass. During fabrication of each left carcass side, a rib section (later converted into three steaks) was removed for aging and subsequent sensory panel evaluation at 14 d and for Warner-Bratzler shear force measurements at 14 and 28 d. Correlation coefficients for repeatability of Tendertec output variables, between left and right carcass sides, were .57, .44, .70, and .65 for Area-2, Area-2B, Power-2, and Power-2B, respectively. Correlations between Tendertec output variables and Warner-Bratzler shear force evaluations performed on steaks aged 14 or 28 d were not different from zero. Sensory panel ratings for amount of connective tissue were correlated (P < .01) with Tendertec output variables Area-2 and Area-2B (r = -.168 and -.154, respectively), and ratings for overall tenderness were correlated (P < .05) with the Area-2 output variable (r = -.131) but the coefficients were very low. Segregation analysis, using Tendertec output variables Area-2 and Power-2, significantly (P < .05) stratified sensory panel ratings for connective tissue amount and overall tenderness. Even though the Tendertec probe detected some differences in connective tissue contributions to rib steak tenderness, it was not better than USDA quality grade at segmenting A-maturity carcasses into anticipated tenderness outcomes, and thus its applicability as a grading instrument may be limited to use on more mature beef carcasses.

Analysis of Variance↗
PubMed1996

Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 7861 VLBW (401 to 1500 gm) neonates admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991 to 1993). METHODS: The NICHD Neonatal Research Network maintains a prospectively collected registry of all VLBW neonates cared for at participating centers. Data from this registry were analyzed retrospectively. RESULTS: Of 6911 infants who survived beyond 3 days, 1696 (25%) had one or more episodes of blood culture-proven sepsis. The vast majority of infection (73%) were caused by gram-positive organisms, with coagulase-negative staphylococci accounting for 55% of all infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of infection included intubation, respiratory distress syndrome, prolonged ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, severe intraventricular hemorrhage, and necrotizing enterocolitis. Among infants with bronchopulmonary dysplasia, those with late-onset sepsis had a significantly longer duration of mechanical ventilation (45 vs 33 days; p <0.01). Late-onset sepsis prolonged hospital stay: the mean number of days in the hospital for VLBW neonates with and without late-onset sepsis was 86 and 61 days, respectively (p <0.001). Even after adjustment for other complications of prematurity, including intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia, infants with late-onset sepsis had a significantly longer hospitalization (p <0.001). Moreover, neonates in whom late-onset sepsis developed were significantly more likely to die than those who were uninfected (17% vs 7%; p <0.000 1), especially if they were infected with gram-negative organisms (40%) or fungi (28%). Deaths attributed to infection increased with increasing chronologic age. Whereas only 4% of deaths in the first 3 days of life were attributed to infection, 45% of deaths after 2 weeks were related to infection. CONCLUSIONS: Late-onset sepsis is a frequent and important problem among VLBW preterm infants. Successful strategies to decrease late-onset sepsis should decrease VLBW mortality rates, shorten hospital stay, and reduce costs.

Age of Onset↗
PubMed1996

Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: Early-onset sepsis (occurring within 72 hours of birth) is included in the differential diagnosis of most very low birth weight (VLBW) neonates. To determine the current incidence of early-onset sepsis, risk factors for disease, and the impact of early-onset sepsis on subsequent hospital course, we studied a cohort of 7861 VLBW neonates (401 to 1500 gm) admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991-1993). METHODS: The NICHD Neonatal Research Network maintains a prospectively collected registry on all VLBW neonates born or cared for at participating centers. Data from this registry were analyzed retrospectively. RESULTS: Blood culture-proven early-onset sepsis was uncommon, occurring in only 1.9% of VLBW neonates. Group B streptococcus was the most frequent pathogen associated with early-onset sepsis (31%), followed by Escherichia coli (16%) and Haemophilus influenzae (12%). Decreasing gestational age was associated with increased rates of infection. Antibiotic therapy for suspected sepsis is frequently initiated at birth in VLBW neonates. Almost half of the infants in this cohort were considered to have clinical sepsis and continued to receive antibiotics for 5 or more days, despite a negative blood culture result in 98% of cases. These findings underscore the difficulty of ruling out sepsis in the symptomatic immature neonate and the special concern for culture-negative clinical sepsis in the face of maternal antibiotic use. Neonates with early-onset sepsis were significantly more likely to have subsequent comorbidities, including severe intraventricular hemorrhage, patent ductus arteriosus, and prolonged assisted ventilation. Although 26% of VLBW neonates with early-onset sepsis died, only 4% of the 950 deaths that occurred in the first 72 hours of life were attributed to infection. For those infants discharged alive, early-onset sepsis was associated with a significantly prolonged hospital stay (86 vs 69 days; p <0.02). CONCLUSIONS: Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants. Improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected VLBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected.

Age of Onset↗
PubMed1996

Alterations in surfactant protein A after acute exposure to ozone.

The surfactant layer covering the gas-exchange region of the lung serves as the initial site of interaction with inhaled oxidant gases. Among the endogenous compounds potentially vulnerable to oxidative injury are surfactant proteins. This study focused on the effect of ozone on surfactant protein A (SP-A) function, content, and gene expression. To determine the time course of response to ozone, guinea pigs were exposed to 0.2-0.8 parts/million (ppm) ozone for 6 h and were killed up to 120 h postexposure. To determine the effect of repeated exposure, animals were exposed to 0.8 ppm ozone for 6 h/day and were killed on days 3 and 5. A significant increase in surfactant's ability to modulate the respiratory burst induced by phorbol 12-myristate 13-acetate in naive macrophages was observed at 24 h after a single 0.8 ppm ozone exposure. Because neutralizing antibodies to SP-A blunted this stimulatory effect, we hypothesized that ozone enhanced the modulatory role of SP-A in macrophage function. This alteration in function was accompanied by an influx of inflammatory cells and only marginal changes in SP-A levels as determined by an enzyme-linked immunosorbent assay. No significant changes in steady-state levels of SP-A mRNA were observed after single or repeated exposure to ozone. Thus the inflammation that accompanies in vivo ozone exposure may result in a change in the structure and thus functional role of SP-A in modulating macrophage activity.

Animals↗
PubMed1996

Self-reinnervated cat medial gastrocnemius muscles. I. comparisons of the capacity for regenerating nerves to form enlarged motor units after extensive peripheral nerve injuries.

1. The aims of this study are to determine 1) whether regenerating motor axons have the capacity to form enlarged motor units (MUs) in muscles reinnervated by few motoneurons and 2) whether the type of nerve injury, repair, and/or growth environment affects this capacity. 2. MU innervation ratio (IR) was estimated by measuring isometric unit tetanic force in reinnervated cat medial gastrocnemius muscles 3-16 mo after denervation by either 1) crushing its nerve, 2) transecting the nerve and suturing the proximal end to the distal stump (N-N suture), or 3) transecting the nerve and suturing the proximal end directly to the muscle fascia (N-M suture). In addition, the number of regenerating axons was experimentally reduced by cutting one of two contributing ventral roots. 3. Muscles were reinnervated by 2-88% of their normal complement of MUs. Mean unit tetanic force increased as the number of reinnervated MUs decreased in reinnervated muscles after nerve crush or N-N suture, but not after N-M suture, even when few axons made functional connections. When the number of MUs was < 20% of normal, mean unit force was significantly higher in reinnervated muscles after nerve crush compared with muscle reinnervated after N-N suture. 4. The cross-sectional areas (CSAs) of all muscle fiber types were similar to normal in reinnervated muscles after nerve crush, but the CSAs of type IIa and IIb fibers were significantly smaller in muscles reinnervated after complete nerve transections (i.e., N-N or N-M sutures). 5. When MU force was normalized to mean muscle fiber CSA, cut motor axons displayed the same capacity to form enlarged MUs as crushed motor axons. The force of the MUs increased by as much as 5-8 times that of normal, provided the axons grew along the distal nerve stump (N-N suture). 6. Tetanic force increased in the normal order slow < fast-fatigue resistant < fast-fatigue intermediate = fast-fatigable. However, the increase in tetanic force of the slow (S) units was significantly larger than the corresponding increase of the more forceful fast (F) units. The disproportional increase in S and not F unit force, was primarily due to a significant decline in CSA of the type IIa and IIb muscle fibers. 7. The technique of glycogen depletion was used to count MU fibers to estimate the IR of MUs in 5 normal and 11 reinnervated muscles (7 N-N sutures, 4 N-M sutures). Unit tetanic force covaried with IR in both normal and reinnervated muscles. 8. These results show that regenerating axons have the same capacity as intact axons in partially denervated muscles to form enlarged MUs to compensate for a reduced number of functioning MUs. Only when axons regenerate in the absence of the distal nerve sheath is this capacity compromised.

Animals↗
PubMed1996

Self-reinnervated cat medial gastrocnemius muscles. II. analysis of the mechanisms and significance of fiber type grouping in reinnervated muscles.

1. The technique of glycogen depletion was used to determine whether regenerating motor axons reestablish the normal regionalization of motor units (MUs) in the cat medial gastrocnemius (MG) muscle, 2) whether the extent of clumping between MU fibers and/or type grouping of muscle fibers progressively increases with a decrease in reinnervated MU numbers, and 3) whether the pattern of innervation can explain why MUs fail to increase significantly in size when the cut nerve is sutured directly to the muscle, even when few axons make functional connections. 2. Distributions of MU fibers were analyzed in 5 normal and 14 reinnervated cat MG muscles 4.5-16 mo after sectioning of its nerve and suturing of the proximal end to the distal nerve sheaths (N-N suture) or directly to the muscle fascia (N-M suture). Muscle unit distributions were quantified according to location, territory size, density, and extent of clumping between fibers from the same MU. 3. Normal MU fibers were regionalized within five regions along the muscle's longitudinal and transverse axes. Reinnervated MUs were located within similar regions, indicating that regenerating axons follow the major proximal nerve branches to restore normal compartmentalization. 4. Muscle unit fibers were diffusely scattered within discrete MU territories in normal muscles. Territory size tended to increase with MU size, whereas density of muscle unit fibers within the territory decreased. 5. Territories increased with MU size after N-N suture but were smaller and showed little size variation after N-M suture. The extent of muscle unit fiber clumping was inversely related to the number of reinnervated MUs. On average, the extent of clumping was substantially higher in muscles reinnervated after N-M suture. These results indicate that distal nerve sheaths facilitate proximal axon branching, which establishes MU territory size. Once the territory is established, motor axons branch distally to increase MU size, which in turn compensates for reduced MU numbers. 6. Muscles reinnervated by < 80% of the MUs exhibited fiber type grouping of type I fibers, and on average the extent of clumping was substantially higher in muscles reinnervated after N-M suture. With less innervation, type grouping increased inversely with the number of reinnervated MUs. However, for a similar number of MUs, type I fiber type grouping was substantially higher in muscle reinnervated after N-M suture. Type grouping therefore reflects muscle unit fiber clumping under conditions where MU size increased (N-N suture) or MU territory size decreased (N-M suture).

Animals↗
PubMed1996

Biomarkers of lung inflammation in recreational joggers exposed to ozone.

Humans exhibit an acute inflammatory response in the lungs after controlled laboratory exposure to ozone. The present study was designed to test whether biomarkers of inflammation are detectable in humans exposed to ozone and associated copollutants under natural conditions outdoors. Bronchoscopy with bronchoalveolar lavage (BAL) was carried out on 19 normal volunteer joggers from Governors Island, NY, who exercised in the afternoon during the 1992 summer (S1) season. Fifteen subjects were retested during the following, low ozone, winter season (W). The BAL protocol involved an initial instillation of 20 ml saline followed by four sequential 50-ml saline washes carried out in both the right middle lobe and the lingula. The eight 50-ml samples were pooled as the 'alveolar' sample. Analyses performed on the alveolar lavage samples included cell differentials, release of IL-8, TNF-alpha, and reactive oxygen species (ROS) by pooled cells, and levels of IL-8, protein, LDH, fibronectin, alpha1-antitrypsin (alpha1-AT), complement fragment 3a (C3a), and prostaglandin E2 (PGE2) in lavage fluids. Release of ROS by stimulated BAL cells was lower in S1 than in W (p = 0.03). In contrast, LDH levels in BAL fluids were 2-fold higher in S1 than in W (p = 0.02), as were IL-8 (p = 0.12) and PGE2 (p = 0.06). These results suggest a possible ongoing inflammatory response in the lungs of recreational joggers exposed to ozone and associated copollutants during the summer months.

Adult↗
PubMed1995

Intra- and intermolecular spreading of autoimmunity involving the nuclear self-antigens La (SS-B) and Ro (SS-A).

We have tested the extent of immune self-tolerance to the ubiquitously expressed nuclear/cytoplasmic autoantigens La (SS-B) and Ro (SS-A) in healthy, nonautoimmune mice. Immunization of mice with recombinant mouse La resulted in a specific, isotype-switched autoantibody response, which was initially directed toward the La C subfragment (aa 111-242) but rapidly spread to involve the La A (aa 1-107) and La F (aa 243-345) regions of the La antigen. Intramolecular spreading of the anti-La antibody response was further demonstrated by the appearance of autoantibodies to multiple, nonoverlapping antigenic regions of La, after immunization of mice with the 107-aa La A subfragment. Moreover, immunization of mice with recombinant mouse or human La also elicited specific anti-60-kDa Ro IgG antibodies in all strains tested. Mice immunized with 60-kDa Ro produced a high titer anti-Ro antibody response, which was also associated with intermolecular spreading, resulting in the specific appearance of anti-La autoantibodies. These findings show that the development of autoantibodies to multiple components of the La/Ro ribonucleoprotein complex may follow initiation of immunity to a single component. In addition, the data reveal the incomplete nature of immune tolerance to La and Ro despite their endogenous expression in all nucleated cells. These observations are likely to account for the coexistence of anti-La/Ro antibodies in autoimmune disease and suggest a general explanation for the appearance of mixed autoantibody patterns in systemic autoimmune disorders.

Animals↗
PubMed1995

Mucous cell metaplasia in the airways of rats exposed to machining fluids.

Occupational exposure to microbial-contaminated machining fluids is associated with a variety of adverse pulmonary effects including chronic bronchitis and increased sputum production. We have previously demonstrated in F344 rats that inhaled endotoxin can increase the amount of stored intraepithelial mucosubstances (Vs) in the respiratory tract. The purpose of the present study was to examine the effect of endotoxin-contaminated machining fluid aerosols on mucous production. Rats were exposed to aerosols of pyrogen-free water, 1 or 10 mg/m3 used machining fluid, or 10 mg/m3 unused machining fluid for 3 hr/day for 3 days. Twenty-four hours after the final exposure, right lung lobes were lavaged and the nasal cavity and left lung were fixed in formalin. The amount of Alcian blue/periodic acid-Schiff-stained mucosubstances was determined by morphometry. Exposure to 10 mg/m3 used machining fluid (equivalent to 0.8 micrograms/m3 endotoxin) produced a significant increase in Vs in the epithelial lining of both the nasal septum and intrapulmonary airways. These changes in Vs were accompanied by a significant increase in total cells and neutrophils in the lavage fluid. No changes in stored mucosubstances or lavage parameters were found in animals exposed to 1 mg/m3 used machining fluid aerosols. A significant increase in Vs was observed in the nasal septum but not in the intrapulmonary airways of animals exposed to 10 mg/m3 unused machining fluids (no measurable endotoxin). These results suggest that in addition to endotoxin, nonendotoxin components of machining fluids may contribute to the increase in sputum and chronic bronchitis reported for workers exposed to machining fluid aerosols.

Administration, Inhalation↗
PubMed1995

Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: We conducted a large clinical trial to evaluate the effect of low-dose aspirin on the frequency of preeclampsia in nulliparous women. A secondary objective of the trial was to identify those clinical characteristics that might be predictive for the development of preeclampsia. STUDY DESIGN: A total of 2947 healthy women with a single fetus were prospectively followed up from randomization at 13 to 27 weeks' gestation to the end of pregnancy. Of these, 1465 women were assigned to low-dose aspirin and 1482 to placebo. Baseline maternal blood pressure and demographic characteristics were examined for the prediction of preeclampsia. RESULTS: Preeclampsia developed in 156 women (5.3%). Four characteristics predicted the development of preeclampsia: in order of importance, systolic blood pressure at entry, prepregnancy obesity (weight as a percentage of desirable weight), number of previous abortions or miscarriages, and smoking history. Contrary to previous reports, black race was not a risk factor for preeclampsia. Systolic blood pressure was a better predictor of preeclampsia than either diastolic or mean arterial blood pressure. The greater the blood pressure or prepregnancy weight, the greater was the risk for preeclampsia. If the woman had never smoked or had never been previously pregnant, her risk was also higher than average. A multivariate logistic regression equation based on these four factors was able to define a tenth of the population at very high risk and another tenth at very low risk; the ratio of risk between these two groups was 12:1. The p value for each of the multivariate coefficients of the risk equation was systolic blood pressure (p < 0.001), prepregnancy weight (p < 0.01), smoking history (p < 0.01), and gravidity (p < 0.05). There were no statistically significant differences in the predictive values of these risk factors between women receiving low-dose aspirin or placebo. CONCLUSIONS: These risk factors should be of value to practitioners counseling women regarding preeclampsia. Moreover, such risk factors should be considered in the design of future studies dealing with preeclampsia.

Abortion, Induced↗
PubMed1995

Human autoantibodies directed against the RNA recognition motif of La (SS-B) bind to a conformational epitope present on the intact La (SS-B)/Ro (SS-A) ribonucleoprotein particle.

In systemic autoimmunity, the human B cell response to the La (SS-B) autoantigen is polyclonal and directed to both conserved and human-specific epitopes. This study has further characterized the B cell epitope(s) present within the conserved central region of the La protein, LaC (amino acids 111-242) containing the RNA recognition motif (RRM, aa 111-187). Ten overlapping and non-overlapping protein fragments spanning LaC were expressed in bacteria as NH2-terminal fusions with glutathione-S-transferase. The fusion proteins were tested by ELISA for reactivity with a panel of human anti-La sera in order to define the nature of the epitopes. Ninety-two percent of patient sera containing anti-La antibodies reacted with the region of La containing the RRM. Fine mapping of this reactivity using deletion mutants indicated that the deletion of 19 amino acids from either the NH2-terminal or COOH-terminal region of the RRM was associated with loss of antibody reactivity, suggesting that the immunodominant epitope expressed in this region is discontinuous. Autoantibodies affinity-purified from the La RRM fragment to remove other specificities immunoprecipitated newly synthesized native La (SS-B)/Ro (SS-A) complexes, providing additional evidence that autoantibodies were recognizing a conformational epitope. The findings indicate that the human autoantibody response to La involves recognition of a conformational determinant involving the conserved RRM region without necessarily interfering with the RNA-dependent association of the La/Ro ribonucleoprotein.

Autoantibodies↗
PubMed1995

Cotton dust produces an increase in intraepithelial mucosubstances in rat airways.

Occupational exposure to endotoxin-contaminated organic dusts is associated with a variety of adverse pulmonary effects, including chronic bronchitis and sputum production. We have previously demonstrated in F344 rats that inhaled endotoxin rapidly induces an increase in the volume of stored intraepithelial mucosubstances (Vs) in the respiratory tract. The present study examined whether endotoxin-contaminated cotton dust can produce a similar increase in Vs in this animal model. Rats were exposed to air or 1.5 to 15.0 mg/m3 cotton dust for 2 h/d for 3 d. Twenty-four hours after the final exposure, the nasal cavity and lungs were fixed in formalin and the presence of Alcian blue/periodic acid-Schiff-staining mucosubstances determined by morphometry. Exposure to cotton dust produced concentration-dependent changes in Vs in the nasal septum and intrapulmonary airways. Statistically significant increases in Vs were observed in the epithelial lining of the nasal septum of animals exposed to 5.3 and 14.5 mg/m3 cotton dust (equivalent to 2.8 and 8.9 micrograms/m3 endotoxin). Vs in the intrapulmonary airways was also significantly increased at these concentrations. No significant changes were observed in the nasal septum or intrapulmonary airways after exposure to 1.8 mg/m3 cotton dust. These results are consistent with the hypothesis that endotoxin may contribute to the increase in human cases of chronic bronchitis reported in occupational settings in which endotoxin-contaminated dusts are encountered.

Animals↗
PubMed1995

Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy.

The contribution of prolonged motoneuron axotomy to the poor functional recovery after delayed nerve repair was determined by means of a nerve cross-anastomosis paradigm in the rat. The tibial nerve was axotomized up to 12 months before it was cross-sutured to the distal stump of the freshly cut common peroneal nerve to innervate the freshly denervated tibialis anterior muscle. Three to 17 months later, muscle and motor unit (MU) forces were measured to quantify the number of axons that had successfully regenerated and reinnervated the muscle. The extent of axonal branching was estimated by the innervation ratio (IR) (i.e., the number of muscle fibers innervated by each axon), which was obtained directly by counting muscle fibers in a single glycogen-depleted MU in each muscle and indirectly by calculation. The total number of MUs in each muscle significantly decreased with progression of axotomy and was only 35% of the control when axotomy was prolonged more than 3 months. Concurrently, MU force and IR increased exponentially, with a mean increase of threefold when axotomy was more than 3 months, which largely compensated for the reduction in the number of axons that reinnervated the muscle. Consequently, muscles reinnervated by tibial motor axons that had been axotomized up to 12 months produced as much force as those reinnervated by freshly axotomized tibial motor axons. Muscle weight, size, and muscle fiber size were similar to those after immediate nerve suture. Although prolonged axotomy does not compromise the number of muscle fibers innervated by each axon, it does reduce the capacity of motor axons to regenerate and thus is an important contributing factor to the poor functional recovery in delayed nerve repair.

Anastomosis, Surgical↗