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Biomedical subjects

J G Morris

Publications and source records attributed to J G Morris.

At least 19 recordsLinked to original sources
PubMed1997

Classification of Vibrio vulnificus strains by the carbohydrate composition of their capsular polysaccharides.

Pathogenic bacteria are often classified on the basis of the complex polysaccharides found on the surface, usually capsular polysaccharides or lipopolysaccharides. It is common in clinical practice to use reactivity with antisera specific to the various cell surface carbohydrates for this purpose. In this work, we describe a chemotyping method for bacterial capsular polysaccharides which is based on a carbohydrate analysis of an acid hydrolysate of the capsule. High-performance anion-exchange chromatography at high pH (HPAE) with electrochemical detection, which is used for analysis of the hydrolysate, shows preferential sensitivity for sugars. A single acid hydrolysis condition is chosen for screening a large collection of bacterial isolates and a computerized autosampler is used to make possible a large number of rapid analyses. This procedure does not yield a quantitative carbohydrate analysis for the sample but produces a fingerprint which can be used to discriminate among isolates which have different capsular polysaccharide structures. The procedure has been applied to a collection of 120 isolates of Vibrio vulnificus, a water-born species common in shellfish which causes septicemia in immunocompromised individuals, most often from eating of raw oysters. The collection of bacterial isolates includes strains from both clinical cases of septicemia and from such environmental sources such as sea water, sediments, and shellfish. Our results show that a number of unusual sugars including many amino sugars are found in these polysaccharides and that a wide variety of capsular carbotypes in V. vulnificus may be readily distinguished by the HPAE fingerprint.

Anion Exchange Resins↗
PubMed1997

Diabetic neuropathy after pancreas transplantation: determinants of recovery.

Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.

Adult↗
PubMed1997

Clonic perseveration following thalamofrontal disconnection: a distinctive movement disorder.

We describe four patients who developed asymmetrical, rhythmic, stereotyped, and repetitive movements of the upper and lower limbs hours to days after infarction that involved the thalamus and/or basal ganglia. The movements appeared to occur spontaneously and were initially labeled as focal motor seizures, ballism, or tremor; they could however, be induced by passive movement of the limbs. The movements most commonly observed were scratching or rubbing movements of the hands that were of such persistence as to cause trauma to the skin; in the lower limbs, the heel was run up and down the bed sheet, often until it bled. The movements were part of a syndrome characterised initially by a reduced level of consciousness and followed by aspontaneity, usually with mutism and frontal release signs. One patient who had relatively preserved cognition and language repeated words or phrases again and again when encouraged to speak, but had no difficulty changing responses appropriately to different cues. In drawing, he overwrote each figure but could change the figure on command. The distinctive movement disorder in these patients was due to clonic perseveration. We suggest that clonic perseveration results from disconnection of prefrontal cortico-basal ganglia-thalamo-cortical loops that are important for the termination of motor plans. Clonic perseveration should be recognised as a movement disorder following thalamic lesions.

Aged↗
PubMed1997

Progressive supranuclear palsy affects both the substantia nigra pars compacta and reticulata.

We have analyzed the neuropathology of the substantia nigra in four cases of progressive supranuclear palsy compared with age-matched controls and patients with Parkinson's disease. Although there are many reports of severe dopaminergic cell loss in progressive supranuclear palsy, the fate of the GABAergic pars reticulata neurones remains unclear. Serial section analysis and fractional counts of pars compacta neurones (identified by their neuromelanin pigment) and pars reticulata neurones (identified using parvalbumin immunohistochemistry) were performed, and the type and distribution of neuropathology were described. Severe neurodegeneration within the dopaminergic pars compacta was seen in all cases of progressive supranuclear palsy and all cases of Parkinson's disease compared with controls. Lewy body pathology was found only in cases of Parkinson's disease, while neurofibrillary tangles were seen only in cases of progressive supranuclear palsy. Tau-positive astrocytes and neuropil threads were occasionally seen in controls and cases of Parkinson's disease (particularly those of advanced age) but were extremely numerous in all cases of progressive supranuclear palsy. There was a similar decrease in parvalbumin immunoreactivity within the pars reticulata in both progressive supranuclear palsy and Parkinson's disease. However, there was a striking 70% reduction in the number of pars reticulata neurones in progressive supranuclear palsy, with no cell loss observed in Parkinson's disease compared with controls. Our results show that both the dopaminergic pars compacta and the GABAergic pars reticulata are significantly damaged in cases of progressive supranuclear palsy. The distribution of neurodegeneration in patients with Parkinson's disease and progressive supranuclear palsy is discussed with respect to the current theories on pathophysiology in basal ganglia circuitry.

Aged↗
PubMed1997

The minimum sodium requirement of growing kittens defined on the basis of plasma aldosterone concentration.

The minimum sodium requirement of growing kittens was measured using a 6 x 6 Latin square design. Twelve specific-pathogen-free short-hair growing kittens (six males, six females) were fed casein and lactalbumin-based purified diets supplemented with various levels of sodium (NaCI). Using six growing kittens (four males, two females), a sodium depletion and repletion study was conducted to define the variables associated with sodium deficiency. Sodium-deficient kittens exhibited anorexia, impaired growth, polydypsia, polyuria, hemoconcentration, reduced urinary sodium output and specific gravity, and elevated aldosterone concentration in plasma and output in urine. Plasma sodium concentration was not affected by dietary sodium intake. Urinary sodium output was positively related to (r = 0.818, P < 0.001), but fecal sodium loss was independent of sodium intake. These results suggest that sodium balance in kittens is essentially regulated by renal excretion. The recommended minimum sodium requirement of kittens for growth is 1.6 g Na/kg diet (energy density, 22 kJ ME/g diet), or 0.07 mg Na/kJ ME, or 34 mg Na x kg body wt(-1) x d(-1). A sodium requirement of adult cats for maintenance was estimated to be 21 mg Na x kg body wt(-1) x d(-1). These requirements are considerably greater than those recommended by the National Research Council in 1986.

Aldosterone↗
PubMed1997

The subthalamic nucleus in Parkinson's disease and progressive supranuclear palsy.

The subthalamus has become a promising target for the neurosurgical treatment of parkinsonian symptoms. We have used unbiased counting techniques to quantify the neuronal populations of the subthalamic nucleus in patients with idiopathic Parkinson's disease and progressive supranuclear palsy. In addition, the type of calcium binding proteins contained within these subthalamic neurons was established using immunohistochemistry. Most of the 550,000 subthalamic neurons contain either parvalbumin or calretinin calcium binding proteins, and patients with idiopathic Parkinson's disease sustained no damage to this nucleus. This is consistent with current theories of basal ganglia circuitry, which postulate that overstimulation of this excitatory nucleus contributes to the inhibition of the motor thalamus via the activation of inhibitory relays. In contrast, we found that there was substantial cell loss in the subthalamus in progressive supranuclear palsy (45 to 85% neuronal reduction) and that both cell types were equally affected. Extracellular neurofibrillary tangles as well as tau-positive glia were observed in the subthalamus of these cases. As the patients with Parkinson's disease and progressive supranuclear palsy all had overlapping parkinsonian symptoms, the loss of subthalamic stimulation within the basal ganglia of progressive supranuclear palsy cases is puzzling, unless their parkinsonian symptoms were generated by an alternate mechanism.

Aged↗
PubMed1997

Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity.

The emergence of a new agent of cholera, Vibrio cholerae O139, has prompted a reevaluation of the vibriocidal antibody assay. This assay, primarily directed to lipopolysaccharide, is an important correlate of O1 immunity. V. cholerae O139 strains are encapsulated, rendering them relatively resistant to killing by serum. Recent reports suggest that there is strain-to-strain variability in the sensitivity of the vibriocidal assay to fully encapsulated O139 strains. We have assessed a modified vibriocidal assay for fully encapsulated O139 strain AI-1837 and its unencapsulated mutant 2L in sera from 53 volunteers given wild-type AI-1837 or its attenuated derivative CVD 112 and from 48 controls challenged with V. cholerae O1 or strains of the family Enterobacteriaceae. Vibriocidal responses to the AI-1837 and 2L strains were seen in 67 and 89% of volunteers, respectively, following a single exposure to the wild-type strain. However, >50% of all controls had low-level vibriocidal responses to both strains. These nonspecific responses were transient and of the immunoglobulin G isotype. No binding activity against purified O139 lipopolysaccharide (LPS) by immunoblotting was seen in control sera. In contrast, vibriocidal assay and strain 2L LPS responses by immunoblotting were detectable in 91% of tested volunteers following a single exposure to O139. The presence of vibriocidal antibody to AI-1837 or 2L was not associated with protection in rechallenge studies with O139 strain AI-1837. The vibriocidal assay with unencapsulated strain 2L may be used to detect exposure to O139 strain AI-1837 in controlled research trials. However, its lack of specificity does not make it useful for determining exposure to V. cholerae O139 in the field.

Antibodies, Bacterial↗
PubMed1996

Cloning and characterization of dnaE, encoding the catalytic subunit of replicative DNA polymerase III, from Vibrio cholerae strain C6706.

We report that Vibrio cholerae (Vc) contains a gene homologous to Escherichia coli dnaE, the structural gene for the alpha (catalytic) subunit of replicative DNA polymerase III (PolIII). Despite 24% amino acid (aa) differences in the encoded proteins, the Vc gene strongly complements an E. coli dnaE temperature sensitive (ts) mutant, indicating that all functional features essential for replication are conserved.

Amino Acid Sequence↗
PubMed1996

Brainstem myoclonus in a patient with non-dopa-responsive parkinsonism.

In the few reports where electrophysiologic techniques have been used to characterise stimulus-sensitive myoclonus in the setting of a parkinsonian syndrome, the origin of the myoclonus has usually been found to be cortical. We describe a patient with parkinsonism unresponsive to levodopa who had myoclonus that was both spontaneous and induced by somatosensory stimuli. In addition, autonomic symptoms and a marked sleep disturbance were present early in his illness. Results of electrophysiologic investigations including electromyography (EMG) studies, routine electroencephalography (EEG) recording, jerked locked back-averaging of EEG, and somatosensory evoked potentials were consistent with a brainstem origin for the myoclonic jerks. Following ipsilateral digital and supraorbital electrical stimulation, the earliest muscle activation occurred in the trapezius. An all-night sleep study showed frequent myoclonic jerks during sleep and markedly abnormal sleep architecture. We believe that this patient's myoclonus was related to pathologic changes in brainstem reticular nuclei that occurred as part of his disease process. To our knowledge, brainstem myoclonus has not been described as a feature of parkinsonian syndromes.

Brain Stem↗
PubMed1996

Acid-base balance affects dietary choice in cats.

The effect of acid-base status on self-selection of dietary protein was examined in three groups of adult male cats fed 20% soybean-protein and lactalbumin diets formulated to produce acidic, neutral or alkaline status. In two experiments, cats were offered a choice between the 20% protein diets or (1) the same diet with additional protein as casein (49% total crude protein) or (2) the same diet with added soybean-protein and lactalbumin (43% crude protein). Casein contained 0.63 mmol H+/g and caused all three groups to avoid the high casein diets by day 4. The high soybean-protein-lactalbumin diets did not contain added acid but would produce some extra acid upon catabolism of the sulfur-containing amino acids. Again, all three groups avoided the high protein diets by day 4. In a third choice trial, cats adapted to three low protein diets containing appropriate electrolytes to cause neutrality, acidemia or alkalemia, were offered a choice between: neutral vs. acidic; acidic vs. neutral or basic vs. acidic. The cats chose the neutral, neutral and basic diet respectively, restoring or maintaining acid-base homeostasis for each situation. The diets producing acidosis lowered serum sodium and potassium concentrations. We conclude that cats select appropriate diets in an attempt to maintain acid-base homeostasis.

Acid-Base Equilibrium↗
PubMed1996

Substantia nigra pars reticulata neurons in Parkinson's disease.

We have examined by immunohistochemistry the parvalbumin-containing neurons of the substantia nigra in patients with Parkinson's disease and in age-matched controls. Parvalbumin, a calcium binding protein, is involved in buffering intracellular calcium and in this study was localized within the majority of non-pigmented neurons of the human pars reticulata. Previous studies have shown that the parvalbumin-immunoreactive pars reticulata neurons are GABAergic and project to the motor thalamus and tectum. Their increased output, due to the loss of dopaminergic inhibition in Parkinson's disease, decreases cortical activation via thalamic pathways, causing parkinsonian symptoms. In Parkinson's disease there was a significant loss of parvalbumin-immunoreactivity from these neurons, though there was no evidence of actual cell loss. This loss of parvalbumin-immunoreactivity was detected only in those cases with end-stage Parkinson's disease.

Age of Onset↗
PubMed1996

Apomorphine can increase cutaneous inhibition of motor activity in Parkinson's disease.

We studied the effect of non-nociceptive ipsilateral digital stimulation on EMG recorded from a small hand muscle before and after the administration of subcutaneous apomorphine in 6 patients with Parkinson's disease. All were receiving the drug to control ¿on-off¿ fluctuations in motor performance. Averaged rectified EMG was recorded from tonically contracted abductor pollicis brevis (APB) following index finger stimulation using a brief stimulus train. In 5 patients motor evoked potentials (MEPs) were also recorded from APB during tonic contraction. A conditioning stimulus train was applied to the index finger at intervals between 15 and 65 msec prior to the transcranial magnetic stimulus. After apomorphine administration the patient group showed a significant increase in both EMG and MEP inhibition induced by digital stimulation. In patients with Parkinson's disease who have marked motor fluctuations, the inhibitory response of upper limb motor neurones to low level digital cutaneous stimulation can be altered by dopamine agonists.

Aged↗
PubMed1996

Antibodies that react with the capsular polysaccharide of Vibrio vulnificus are detectable in infected patients, and in persons without known exposure to the organism.

In serious infections with Vibrio vulnificus, IgG antibodies to the capsular polysaccharide of the infecting strain were demonstrable in patient serum. It was not possible to show that persons with probable increased exposure to V. vulnificus (shellfish industry workers) had increased levels of antibodies to any one of three capsular types tested when compared with persons who would be expected to have had minimal exposure to the organism (Seventh Day Adventists). Antibodies that reacted with the capsular polysaccharides were demonstrable in persons without a history of V. vulnificus infection, suggesting that cross-reacting antibodies are present in the general population.

Antibodies, Bacterial↗
PubMed1996

Cloning and sequence of a region encoding a surface polysaccharide of Vibrio cholerae O139 and characterization of the insertion site in the chromosome of Vibrio cholerae O1.

Vibrio cholerae serogroup O139 Bengal is the first documented serogroup other than O1 to cause epidemic cholera. The O139 Bengal strains are very similar to V. cholerae serogroup O1 biotype El Tor strains. The major differences between the two serogroups are that O139 Bengal contains a distinct O antigen and produces a polysaccharide capsule. We previously described three TnphoA mutants of O139 strain AI1837 which abolish both O antigen and capsule production. These TnphoA insertions were mapped to a 21.5 kb EcoRI fragment of the O139 chromosome. We describe here the cloning and mapping of this 21.5 kb EcoRI fragment and it was shown to complement each of the mutants in trans to produce O antigen and capsule. The EcoRI fragment contains 13 kb of DNA that is specific to O139 and 8.5 kb of DNA that is common to O1 and O139. Sequence analysis of the 13 kb of O139-specific DNA revealed that it contains 11 open reading frames all of which are transcribed in the same direction. Eight of the 11 open reading frames are homologous to sugar biosynthesis genes from other organisms. Using extended polymerase chain reactions, we show that the extent of the DNA region in O139 that is not present in O1 is approximately 35 kb. The site of insertion of this O139-specific DNA in the O1 chromosome was mapped to the rfbO1 region. We also demonstrate that O139 Bengal strain AI1837 contains a deletion of 22 kb that in serogroup O1 strains contains the rfb region. Therefore, O139 Bengal probably arose from an O1 strain that had undergone genetic rearrangements including deletion of the O1 rfb region and acquisition of a 35 kb region of DNA which encodes O139 surface polysaccharide.

Bacterial Capsules↗
PubMed1996

Vibrio cholerae O1 can assume a chlorine-resistant rugose survival form that is virulent for humans.

Vibrio cholerae can shift to a "rugose" colonial morphology associated with expression of an amorphous exopolysaccharide that promotes cell aggregation. Flow cytometric studies indicated that up to 3% of particles in rugose cultures represented aggregates of >5 bacterial cells. Rugose variants of our test strains displayed resistance to killing by chlorine, with viable cells persisting for >30 min in 2 mg/L free chlorine; strains also showed resistance to killing by complement-mediated serum bactericidal activity. Six volunteers fed 10(6) cfu of a rugose variant of V. cholerae O1 El Tor Inaba N16961 developed symptoms typical of cholera, with a mean diarrheal stool volume of 2.2 L (range, 1.4-4.3). Isolates recovered from the stool of infected volunteers retained the rugose phenotype. The data suggest that rugose strains cause human disease. The role of these strains in the epidemiology of cholera remains to be determined.

Adult↗