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Biomedical subjects

I Johnston

Publications and source records attributed to I Johnston.

At least 55 records · Page 3Linked to original sources

Swimming kinematics of fast starts are altered by temperature acclimation in the marine fish Myoxocephalus scorpius

The swimming kinematics of prey capture was studied in short-horned sculpin (Myoxocephalus scorpius L.) acclimated for 6­8 weeks to either 5 °C or 15 °C (12 h:12 h light:dark) using 15 °C-acclimated shrimps as prey. Fish acclimated to 5 °C remained interested in feeding following an acute rise in temperature to 15 °C over 12 h. Prey capture was a stereotyped behaviour consisting of stalking and stationary phases, followed by an S-shaped fast-start (stage 1), a propulsive stroke (stage 2) and a glide of variable duration during which the mouth was expanded and protruded to suck in the prey (stage 3). The duration of the preparatory stroke (half tail-beat, stage 1) was significantly shorter at 15 °C (48.8 ms) than at 5 °C (108.3 ms) in the 5 °C-acclimated sculpin (Q10=2.2). For 5 °C-acclimated fish, at 5 °C, the maximum values for acceleration and velocity along the path travelled by the fish were 16.2 m s-2 and 0.8 m s-1 respectively. Both variables were relatively independent of acute temperature change (Q10=1.1­1.2; P>0.1). At 15 °C, the maximum velocity was 33 % higher and the tail-beat duration of the propulsive stroke was 37 % shorter in 15 °C-acclimated than in 5 °C-acclimated fish. Both stride length and tail-beat amplitude were significantly higher (28 and 23 % respectively) in 15 °C- compared with 5 °C-acclimated sculpin at 15 °C. The results demonstrate plasticity in the major kinematic variables of fast-starts following warm acclimation sufficient to increase the percentage of successful attacks during prey capture from 23.2 to 73.4 %.

Journal Article↗

Functionally significant allelic variation in myosin light chain composition in a tropical cichlid

Single fast muscle fibres in the tropical fish Oreochromis andersonii were found to contain two myosin light chains (LC1s; LC1f1* or LC1f2*). Breeding experiments confirmed that the different LC1s were of allelic origin and their inheritance patterns conformed to Mendelian expectations (1:2:1). The LC1s differed in apparent relative molecular mass by 800­900. No other differences in myosin subunits were found between the LC1 genotypes. The molar ratios of LC3:LC1(total) in the fast muscle of O. andersonii homozygous for LC1f1* or LC1f2* and heterozygous for both alleles were 2.0:1, 2.1:1 and 2.2:1, respectively, as determined by capillary electrophoresis. The maximum contraction velocity (Vmax) of single skinned muscle fibres was determined at 20 °C by the slack-test method. Vmax values (fibre lengths s-1) for fast muscle fibres from O. andersonii which were homozygous for either LC1f2* or LC1f1* were 5.3 and 3.3, respectively, compared with 3.8 when both alleles were present. Crosses between Oreochromis niloticus and O. andersonii produced F1 hybrids which were heterozygous for either LC1n/LC1f1* or LC1n/LC1f2*, where LC1n is the myosin light chain for O. niloticus. The distribution of myosin light chain genotypes in hybrid offspring was not significantly different from the expected Mendelian 1:1 ratio (47 %: 53 %). The Vmax (fibre lengths s-1) of muscle fibres containing LC1f2* from hybrid Oreochromis was 4.3 compared with 3.1 for the LC1f1* genotype. The results are consistent with a functionally significant allelic variation in myosin LC1 in fast muscle fibres from O. andersonii which is also expressed in hybrid genotypes.

Journal Article↗

Temperature and myogenesis in embryos of the Atlantic herring Clupea harengus

The development of axial muscles has been investigated in spring-spawning Atlantic herring (Clupea harengus L.) reared at 5, 8, 12 and 15 &deg;C. In 1994, around 90 % of embryos hatched after 28 days at 5 &deg;C, 16 days at 8 &deg;C, 9 days at 12 &deg;C and 8 days at 15 &deg;C. The somites were formed from cells of the paraxial mesoderm in a rostral to caudal direction, starting at the neural plate stage. Somites were added at rates ranging from one every 3 h at 5 &deg;C to one every 52 min at 15 &deg;C. A small number of myoblasts, located adjacent and lateral to the notochord, elongated to span the somite to form mononuclear myotubes. The majority of muscle fibres were formed by the fusion of 2&shy;5 myoblasts to produce multinucleated myotubes that subsequently differentiated into either superficial or inner fibre types. The timing of myogenesis with respect to somite stage and the initial appearance of the gut, pectoral fin buds and pronephric tubules was found to vary with development temperature. For rostral myotomes, the synthesis of contractile filaments and myofibril assembly were first observed at the 42-, 38- and 27-somite stages at 5, 8 and 12 &deg;C, respectively. The differentiation of myotubes into morphologically recognisable muscle fibre types first occurred at the 62-somite stage at 5 &deg;C, at the 48-somite stage at 8 &deg;C and as early as the 40-somite stage at 12 &deg;C. Cell proliferation experiments with 5-bromo-2'-deoxyuridine showed that another population of myoblasts was activated on the surface of muscle fibres just prior to hatching. Development temperature also affected muscle cellularity; there were 43 % more inner muscle fibres in the myotomes of 1-day-old larvae reared at 12 &deg;C than at 5 &deg;C (P<0.02).

Journal Article↗

How fish power predation fast-starts

Short-horned sculpin (Myoxocephalus scorpius L.) were acclimated for 6&shy;8 weeks to either 5 &deg;C or 15 &deg;C (12 h dark: 12 h light). Fast-starts elicited by prey capture were filmed from above in silhouette using a high-speed video camera (200 frames s-1). Outlines of the body in successive frames were digitised and changes in strain for the dorsal fast muscle calculated from a knowledge of backbone curvature and the geometrical arrangement of fibres. For 15 &deg;C-acclimated fish at 15 &deg;C, muscle strain amplitude (peak-to-peak) during the first tail-beat was approximately 0.16 at 0.32L, 0.19 at 0.52L and 0.15 at 0.77L, where L is the total length of the fish. Fast muscle fibres were isolated and subjected to the strains calculated for the first tail-beat of the fast-start (abstracted cycle). Preparations were electrically stimulated at various times after the initiation of the fast-start using an in vivo value of duty cycle (27 %). Prior to shortening, muscle fibres at 0.52L and 0.77L were subjected to a pre-stretch of 0.055l0 and 0.085l0 respectively (where l0 is resting muscle length). The net work per cycle was calculated from plots of fibre length and tensile stress. For realistic values of stimulus onset, the average power output per abstracted cycle was similar at different points along the body and was in the range 24&shy;31 W kg-1 wet muscle mass. During shortening, the instantaneous power output reached 175&shy;265 W kg-1 wet muscle mass in middle and caudal myotomes. At the most posterior position examined, the muscle fibres produced significant tensile stresses whilst being stretched, resulting in an initially negative power output. The fibres half-way down the trunk produced their maximum power at around the same time that caudal muscle fibres generated significant tensile stress. Fast muscle fibres at 0.37&shy;0.66L produced 76 % of the total work done during the first tail-beat compared with only 14 % for fibres at 0.67&shy;0.86L, largely reflecting differences in muscle mass. The effect of temperature acclimation on muscle power was determined using the strain fluctuations calculated for 0.52L. For 5 &deg;C-acclimated fish, the average power per cycle (&plusmn; s.e.m.; W kg-1 wet muscle mass) was 21.8&plusmn;3.4 at 5 &deg;C, falling to 6.3&plusmn;1.8 at 15 &deg;C. Following acclimation to 15 &deg;C, average power per cycle increased to 23.8&plusmn;2.8 W kg-1 wet muscle mass at 15 &deg;C. The results indicate near-perfect compensation of muscle performance with temperature acclimation.

Journal Article↗

Hydrocephalus and pseudotumour cerebri in the mucopolysaccharidoses.

This paper reports two cases of cerebrospinal fluid circulation disorder in children with mucopolysaccharidosis. One patient developed pseudotumour cerebri and the other communicating hydrocephalus. It is suggested that both have a similar underlying abnormality of cerebrospinal fluid absorption with different modes of presentation.

Animals↗

Atopy as a risk factor for cryptogenic fibrosing alveolitis.

In a case-control study of occupational and environmental causes of cryptogenic fibrosing alveolitis we recently observed a higher prevalence of self-reported symptoms of wheeze, rhinitis or conjunctivitis in cases than in controls. To determine objectively whether this was due to a higher prevalence of atopy amongst cases of CFA, we have measured skin sensitivity to common allergens (D. Pteronyssinus, grass pollen, and cat fur), eosinophil counts and total Immunoglobulin E (IgE) in venous blood in the 22 surviving CFA cases from that study who were willing to provide a blood sample, and in one matched control per case. At least one positive skin test was recorded in 13 cases and six controls, the matched odds of one or more positive test being significantly increased in cases by a ratio of 8.0 (95% confidence interval 1.01-64, P = 0.05). Geometric mean eosinophil counts and IgE levels were also increased amongst cases by factors of 1.6 (95% CI 0.96-2.6) and 1.9 (0.9-3.8) respectively, although these differences were not significant. Differences in skin sensitivity, eosinophil counts, and IgE levels all tended to be more obvious in the 13 case control pairs in which the case was not taking steroids or other immunosuppressive treatment. We conclude that cases of CFA showed increased skin sensitivity to common allergens, and had evidence of increased IgE and eosinophilia in peripheral blood. These findings suggest that atopy may be an important determinant of susceptibility to CFA.

Aged↗

Heterogeneity of calcium channel autoantibodies detected using a small-cell lung cancer line derived from a Lambert-Eaton myasthenic syndrome patient.

We investigated the heterogeneity of anti-voltage-gated calcium channel (VGCC) antibodies in the Lambert-Eaton myasthenic syndrome (LEMS) using a small-cell lung carcinoma line (MB) derived from an LEMS patient. Four of 13 LEMS patients had raised titers of anti-125I-omega-conotoxin-labeled (N-type) VGCCs, measured by radioimmunoassay using line MB as the source of antigen. Antagonists for L-type (nitrendipine and nifedipine) and N-type (omega-conotoxin) VGCCs inhibited K(+)-stimulated (voltage-dependent) Ca2+ flux into this line--by 22% for L-type and 2% for N-type at maximum concentration. Inhibition by the LEMS IgGs, by contrast, ranged from 46 to 78% at a concentration of 2 mg/ml. These differing effects on Ca2+ flux inhibition by LEMS IgGs on the one hand and by L- and N-type channel antagonists on the other, taken together with the observation that many of the sera failed to react with omega-conotoxin-labeled (N-type) channels in the immunoprecipitation assay, suggest that in many LEMS patients the autoantibodies target other VGCC subtypes besides L- or N-types, and that these are important in inducing the myasthenic disorder.

Autoantibodies↗

ARE MITOCHONDRIA SUBJECT TO EVOLUTIONARY TEMPERATURE ADAPTATION?

Thermal tolerance and the respiratory properties of isolated red muscle mitochondria were investigated in Oreochromis alcalicus grahami from the alkaline hot-springs, Lake Magadi, Kenya. Populations of O. a. grahami were resident in pools at 42.8 &deg;C and migrated into water reaching temperatures of 44.8 &deg;C for short periods. The maximum respiration rates of mitochondria with pyruvate as substrate were 217 and 284 natom O mg-1 mitochondrial protein min-1 at 37 &deg;C and 42 &deg;C, respectively (Q10=1.71). Fatty acyl carnitines (chain lengths C8, C12 and C16), malate and glutamate were oxidised at 70&shy;80 % of the rate for pyruvate. In order to assess evolutionary temperature adaptation of maximum mitochondrial oxidative capacities, the rates of pyruvate and palmitoyl carnitine utilisation in red muscle mitochondria were measured from species living at other temperatures: Notothenia coriiceps from Antarctica (-1.5 to +1 &deg;C); summer-caught Myoxocephalus scorpius from the North Sea (10&shy;15 &deg;C); and Oreochromis andersoni from African lakes and rivers (22&shy;30 &deg;C). State 3 respiration rates had Q10 values in the range 1.8&shy;2.7. At the lower lethal temperature of O. andersoni (12.5 &deg;C), isolated mitochondria utilised pyruvate at a similar rate to mitochondria from N. coriiceps at 2.5 &deg;C (30 natom O mg-1 mitochondrial protein min-1). Rates of pyruvate oxidation by mitochondria from M. scorpius and N. coriiceps were similar and were higher at a given temperature than for O. andersoni. At their normal body temperature (-1.2 &deg;C), mitochondria from the Antarctic fish oxidised pyruvate at 5.5 % and palmitoyl-dl-carnitine at 8.8 % of the rates of mitochondria from the hot-spring species at 42 &deg;C. The results indicate only modest evolutionary adjustments in the maximal rates of mitochondrial respiration in fish living at different temperatures.

Journal Article↗

Cross-linking of presynaptic calcium channels: a mechanism of action for Lambert-Eaton myasthenic syndrome antibodies at the mouse neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Immunoglobulin G (IgG) autoantibodies act presynaptically to cause functional loss of Ca2+ channels by down-regulation. This in turn causes reduced release of acetylcholine in response to nerve stimulation (i.e. reduced quantal content). We show here that in vitro application of LEMS IgG for 24 h was as effective in causing reduced quantal content in mice as injecting animals with the antibody for 2 days. Furthermore, incubation with divalent (F(ab')2) fragments also significantly reduced quantal content. However, monovalent (Fab) fragments were without significant effect. No antibody or antibody fragment preparation affected spontaneous release. Whole LEMS IgG and F(ab')2 (but not Fab) fragments also inhibited K(+)-evoked 45Ca2+ flux in a small cell carcinoma cell line. These findings present functional evidence that LEMS IgG-induced down-regulation of nerve terminal Ca2+ channels arises due to antibody cross-linking of these channels.

Acetylcholine↗

SCM4, a gene that suppresses mutant cdc4 function in budding yeast.

The gene SCM4 encodes a protein which suppresses a temperature-sensitive allele of the cell division cycle gene CDC4 in Saccharomyces cerevisiae. SCM4 was cloned on a 1.8 kb BamHI fragment of yeast genomic DNA in the high copy-number vector pJDB207, which results in a 50- to 100-fold increase in the level of the 700 nucleotide SCM4 transcript in vivo. The SCM4 gene encodes a 20.2 kDa protein of 187 amino-acids with a clear tripartite domain structure in which a region rich in charged residues separates two domains of largely uncharged amino acids. Although the apparent allele specificity of cdc4 suppression suggests that the CDC4 and SCM4 proteins interact, disruption of SCM4 demonstrates that the gene product is not essential for mitosis or meiosis; however, it may be a member of a family of related, functionally redundant proteins.

Alleles↗

Pituitary gigantism.

A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment.

Adenoma↗

Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

Aged↗

Action to reduce road casualties.

Progress in road safety is reviewed with particular reference to radical measures that have proved beneficial in Australia. Community involvement in decision-making is vital if gains are to be made and sustained in this field.

Accidents, Traffic↗

Heterotopic pregnancy associated with gamete intra-fallopian transfer.

Recent reports in the literature have focused on the increased risk of heterotopic pregnancy after the transfer of multiple concepti or oocytes. In an international collaborative patient registry between 1985 and 1989, 601 clinical pregnancies resulted from 2092 gamete intra-Fallopian transfer (GIFT) retrieval cycles. Five of the pregnancies were heterotopic (0.83%). After surgical intervention, all five cases of combined gestation resulted in live birth from intrauterine pregnancies. Routine vaginal ultrasonographic examination of the adnexa in patients who conceive after GIFT may help early diagnosis of heterotopic pregnancy. If the diagnosis is made early, conservative treatment may preserve the future fecundity of the patient and more intrauterine pregnancies may be salvaged.

Female↗

The pseudotumor syndrome. Disorders of cerebrospinal fluid circulation causing intracranial hypertension without ventriculomegaly.

We report a series of eight cases that show a close resemblance to, but are not identical with, pseudotumor cerebri (PTC) as normally defined. The majority of these cases are characterized by raised intracranial pressure without ventriculomegaly. They include two cases of cranial venous outflow obstruction in which clinical or radiologic abnormalities precluded the diagnosis of PTC proper (cases 1 and 2); one case of chronic meningitis in which an abnormal cerebrospinal fluid (CSF) composition precluded the diagnosis of PTC (case 3); two cases without either papilledema or a measured increase of CSF pressure, which in other respects, particularly in response to treatment, resembled PTC (cases 4 and 5); and three cases of what is thought to represent an infantile form of PTC (cases 6 through 8). The purpose of the analysis of these cases is twofold. First, it is argued that these cases throw light on the mechanism of PTC itself, supporting a concept of a disturbance of CSF circulation in this condition, and that they are themselves illuminated by considerations of typical PTC. Second, the cases are used to frame a proposed classification of the pseudotumor syndrome aimed at broadening the diagnostic criteria applied currently to PTC. It is suggested that the pseudotumor syndrome has a single underlying mechanism (disturbed CSF circulation) and that recognition of this mechanism not only clarifies the pathophysiologic processes of PTC but also has important diagnostic and therapeutic implications.

Adolescent↗