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Biomedical subjects

R J Lewis

Publications and source records attributed to R J Lewis.

At least 253 records · Page 14Linked to original sources

Ciguatoxin from the flesh and viscera of the barracuda, Sphyraena jello.

Five of six barracuda, Sphyraena jello, captured in the same area of Queensland as toxic Spanish mackerel (Scomberomorus commersoni) were found to be toxic. One major lipid-soluble toxin, present in both the flesh and viscera of a pooled sample of barracuda, was chromatographically indistinguishable from Spanish mackerel flesh ciguatoxin. Signs and symptoms induced by toxic barracuda in humans were typical of ciguatera and cats and mice displayed signs indistinguishable from those induced by Spanish mackerel ciguatoxin. Purified barracuda ciguatoxin had an i.p. LD50 to mice of 55 micrograms/kg. Barracuda ciguatoxin had a narrow range (0.7-1.4 mouse units) of doses between 0% and 100% lethality and its dose vs. death-time relationship was similar to the relationship produced by moray eel and Spanish mackerel ciguatoxin. No water-soluble toxins were detected in the viscera of these barracuda, but a less polar lipid-soluble toxin was found in the viscera. This minor toxin represented 14% of the total viscera lethality and induced signs in mice similar to the major toxin. Barracuda could be an important link in the transfer of ciguatoxin to large Spanish mackerel in southern Queensland waters.

Animals↗

Survival of infective larvae of nematode parasites of cattle during drought.

In a study originally designed to determine the seasonal origin of the high levels of availability of nematode larvae to cattle in winter and spring, plots were serially contaminated with eggs of Ostertagia ostertagi and Cooperia oncophora by naturally-infected calves at monthly intervals from February 1980 to September 1980. The availability of infective larvae was monitored by monthly pasture sampling and larval recovery. Because of the intervention of a 15 month drought, recoveries of larvae from the pastures were very low until March 1981 (autumn in Australia) when large numbers of larvae appeared on pastures contaminated in the preceding spring. Examination of dry dung pats at that time showed that significant numbers of larvae were present in pats deposited up to a year previously, and particularly in pats deposited in May, August and September. Following the resumption of normal rainfall in May 1981, larval numbers in pats rapidly declined and concentrations of larvae on the pastures increased to extremely high levels. It is suggested that survival of infective larvae in dry dung pats was enhanced by the drought, with implications for control of nematode infections of cattle, particularly in winter rainfall environments.

Animals↗

Repeat mediastinoscopy.

Although it has been maintained that a repeat mediastinoscopy results in high morbidity and mortality, it was considered an essential staging procedure in this group of 12 patients. The results of repeat mediastinoscopy were negative in 10 patients and positive in 2. On the basis of negative findings, 6 patients underwent thoracotomy. Five of them had a possible curative resection, and the remaining patient had an unresectable invasive carcinoma. An unnecessary thoracotomy was avoided in 2 patients with positive mediastinal nodes. For various reasons, thoracotomy was not indicated in the other 4 patients. In the evaluation of a patient with a new or recurrent pulmonary lesion, repeat mediastinoscopy can be performed safely. When findings are negative, it would appear to increase the likelihood of a curative resection, whereas when findings are positive, an unnecessary thoracotomy can be avoided.

Aged↗

Urinary catabolites of ribonucleic acid as cancer markers: a preliminary report of their use in patients with lung cancer.

Rats with aflatoxin-B1-induced hepatomas and dimethylnitrosamine-induced nephroblastomas excreted greater than normal amounts of urinary modified nucleosides and bases, catabolites of ribonucleic acid (RNA). Although both neoplasms caused increased excretions of the same catabolites, their quantitative profiles differed, suggesting that it may be possible to distinguish between tumors. Rats with transplanted tumors (e.g., hepatomas and osteogenic sarcomas) did not excrete elevated levels of urinary RNA catabolites until approximately 20 days after transplantation despite rapid growth of the tumor for the first 15 days. These data suggest that the source of the elevated levels of these excretory products may be the host's tissue RNA. Preliminary studies in human beings with lung cancer showed marked elevation of one or more urinary RNA catabolites. Resection of the diseased tissue in 2 patients caused a drop in levels. The measurement of urinary RNA catabolites may be useful in the diagnosis, prognosis, and evaluation of therapy in patients with lung cancer.

Aflatoxin B1↗

Closed intramedullary rodding of pathologic fractures with supplemental cement.

Internal fixation, supplemented with methylmethacrylate to fill bone defects, is the standard treatment for pathologic fractures. Unfortunately, internal fixation procedures often entail substantial blood loss and a not inconsequential risk of infection, problems with which the debilitated patient is poorly able to cope. Techniques such as closed intramedullary rodding entail less operative morbidity but may not produce complete stabilization and immediate pain relief. This report describes a technique that minimizes operative morbidity and produces immediate fracture stabilization by use of closed intramedullary rodding and injection of methylmethacrylate through a cortical drill hole in the long bone.

Bone Cements↗

Mode of action of ciguatoxin from the Spanish Mackerel, Scomberomorus commersoni, on the guinea-pig ileum and vas deferens.

Ciguatoxin causes a sustained contraction of the guinea-pig ileum at all doses tested. The contraction was dose dependent and at a high dose of 0.25 mouse units/ml the contraction lasted for approximately 24 min. Associated with this sustained contraction were bursts of contractile activity. The ileum was refractory to repeated doses of ciguatoxin. The response to ciguatoxin was completely blocked by atropine, tetrodotoxin and low Na+ Ringer but was unaffected by hexamethonium or mepyramine. Ciguatoxin did not alter ileal responses to histamine, acetylcholine and 5-hydroxytryptamine. The ileal response to nicotine was, however, irreversibly reduced by prior exposure to ciguatoxin. Eserine potentiated the ileal response to ciguatoxin. It is proposed that the contractile action of ciguatoxin on the guinea-pig ileum is the result of a release of acetylcholine from cholinergic nerve terminals. This release is via nerve excitation produced by a Na+-dependent depolarization of postganglionic neural elements. The tachyphylactic nature of the action of ciguatoxin indicates that nerve stimulation is followed by nerve blockade, probably as the result of further nerve depolarization caused by ciguatoxin. The action of ciguatoxin isolated here is not different from the action of ciguatoxin isolated from moray eel viscera when tested on guinea-pig vas deferens. Ciguatoxin has a similar indirect action on the ileum and vas deferens. The action of ciguatoxin is compared with the action of other marine toxins on the guinea-pig ileum and vas deferens, particularly okadaick acid, a toxin chemically similar to ciguatoxin.

Animals↗

Respiration-dependent proton translocation in alkalophilic Bacillus firmus RAB and its non-alkalophilic mutant derivative.

Obligately alkalophilic Bacillus firmus RAB had a higher molar growth yield on L-malate (Ymal = 38 mg, dry weight/mmol of L-malate) than its non-alkalophilic mutant derivative, strain RABN (Ymal = 12 mg, dry weight/mmol of L-malate). Measurements of respiration dependent proton translocation by the two strains in the presence of K+ and valinomycin showed that the alkalophile also has much higher H+/O stoichiometries (at pH 9.0) than does the mutant (at pH 7.0). H+/O ratios for B. firmus RAB at pH 9.0 were as high as 13, with a frequently observed value of 9. These high values were observed in the first phase of a set of biphasic curves for both oxygen consumption and proton ejection. At pH 7.0, both the wild type and the mutant exhibited H+/O ratios near 4 in a single phase of oxygen consumption and proton ejection. The results are consistent with suggestions that the alkalophilic respiratory chain is especially well adapted for effective energy transduction at alkaline but not neutral pH.

Bacillus↗

Occurrence of a ciguatoxin-like substance in the Spanish mackerel (Scomberomorus commersoni).

A lipid-soluble toxin, similar to ciguatoxin as isolated by Scheuer et al. (1967), has been found in the flesh of the Spanish mackerel, Scomberomorus commersoni, caught in Queensland. The ciguatoxin-like substance was experimentally characterized by examination of specific biological and chromatographic properties of the lipid-soluble extract from a pooled sample of flesh from Spanish mackerel. Flesh from specimens known to have caused S. commersoni poisoning in humans was confirmed as toxic by cat bioassay. A toxin was extracted from S. commersoni which yielded, on partial purification, a clear, oily substance with an LD50 i.p. to mice of 0.72 mg/kg, and which had chromatographic properties similar to those of classical ciguatoxin. However, the Rf value on thin-layer chromatography plates was lower for S. commersoni toxin than for classical ciguatoxin. This is the first record of a ciguatoxin-like substance experimentally identified in S. commersoni, a pelagic fish that occurs throughout Queensland coastal waters. The majority of toxic S. commersoni are caught between latitudes 24 degrees and 26 degrees S.

Animals↗

Respiratory chain of the alkalophilic bacterium Bacillus firmus RAB and its non-alkalophilic mutant derivative.

The membrane-bound respiratory chain components of alkalophilic Bacillus firmus RAB were studied by difference spectroscopy and oxidation-reduction potentiometric titrations. Cytochromes with the following midpoint potentials were identified at pH 9.0: a-type cytochromes, +110 and +210 mV; b-type cytochromes, +20, -120, -280, and -400 mV; and cytochrome c, +60 mV. Only the higher-potential cytochrome a showed an upward shift in midpoint potential when titrated at pH 7.0. Parallel studies of a non-alkalophilic mutant derivative of B. firmus RAB, strain RABN, revealed the presence of only one species each of a-, b-, and c-type cytochromes which exhibited midpoint potentials of +110, -150, and +160 mV, respectively, at pH 7.0. Membranes of both strains were found to contain menaquinone. At pH 9.0, NADH caused the reduction of essentially all of the cytochromes that were seen in fully reduced preparations of wild-type B. firmus RAB membranes. By contrast, at pH 7.0, NADH failed to appreciably reduce the b-type cytochromes. These findings may relate to our recent proposal that an inadequacy in energy transduction (production of a proton motive force) by the alkalophilic respiratory chain at pH 7.0 is what precludes the growth of B. firmus RAB at a neutral pH.

Bacillus↗

Ligation of oligonucleotides by pyrimidine dimers--a missing 'link' in the origin of life?

One of the principal photochemical reactions of DNA on exposure to UV is the formation of intrastrand cyclobutane-type pyrimidine dimers. The efficiency of this reaction depends on both the wavelength of the UV2 and the specific nucleotide sequence in the DNA. The formation of the pyrimidine dimer and its repair in living cells have been studied extensively. We have examined the possibility that pyrimidines at the ends of DNA strands may be adequately juxtaposed for dimer formation by the presence of a complementary strand, even when no phosphodiester linkage joins their sugars. In these conditions the formation of a dimer will 'ligate' two DNA strands end-to-end. We report here that thymidine oligonucleotides annealed to polydeoxyadenylate can be ligated end-to-end by UV irradiation, via thymine dimerization of the terminal nucleotides in adjacent oligonucleotides. The linkages are susceptible to direct photoreversal by 254 nm UV, as expected for cyclobutane-type thymine dimers, but they are not cleaved by the bacteriophage T4 endonuclease V, a dimer-specific DNA repair enzyme. We demonstrate that the ligating dimers are also resistant to photolyase from Escherichia coli. Although the phosphodiester backbone is not required for dimer formation, it is required for recognition of dimers by these DNA repair enzymes. We discuss the possibility that high molecular weight polynucleotides in primordial seas might have been generated from oligonucleotides by pyrimidine dimerization under the intense solar UV flux unattenuated by an ozone layer.

Endonucleases↗

The antispasmogenic action on guinea-pig ileum of a fraction obtained from the toxic skin secretion of the stonefish, Synanceia trachynis.

The toxic skin tubercle gland secretion of the stonefish, Synanceia trachynis, contains a smooth muscle antispasmogen that is readily distinguished from papaverine, verapamil and both alpha and beta adrenoreceptor agonists. At 15 micrograms/ml, the toxin containing fraction markedly inhibited the phasic response and had a lesser inhibitory effect on the tonic response of acetylcholine-and KCl-induced contractures of guinea-pig ileum, while at 50 micrograms/ml, the toxin markedly inhibited both responses. Over the same dose range the toxin fraction markedly inhibited BaCl2-induced contractile responses but did not distinguish between the phasic and tonic components. Whereas the toxin fraction markedly reduced the tone of previously induced supramaximal KCl and acetylcholine responses of guinea-pig ileum, it had little effect on the tone of previously induced BaCl2 responses. The toxin non-competitively inhibited acetylcholine-induced contractions of guinea-pig ileum and similarly non-competitively inhibited the response induced by Ca2+ in high-[K+] Ringer. The toxin is not a chelating agent for Ca2+ or Mg2+ and it does not affect ATP-induced contracture of glycerinated guinea-pig ileum. The antispasmogenic effect of the toxin contained in the fraction does not result from inhibition of cAMP phosphodiesterase activity.

Acetylcholine↗

Diffuse, mixed malignant pleural mesothelioma.

Forty-six patients with diffuse, mixed malignant pleural mesothelioma were treated between January, 1970, and May, 1979. All had a history of exposure to asbestos. The diagnosis was established by thoracentesis in 3 patients, thoracoscopy in 28, thoracotomy in 5, and minithoracotomy in 9. Mediastinoscopy was performed in 31 patients and bronchoscopy in 32. Mediastinoscopy was positive in only 1 patient, and in no patient was bronchoscopy positive. Ten patients received no definitive therapy and survived an average of 9.1 months (1 lived for 16 months). Thirty-one patients received chemotherapy and survived an average of 9.6 months, the 2 longest survivors each lived for 24 months. Five patients appeared to have early disease and therefore underwent thoracotomy. In only 2 of these patients did resection of all gross disease appear possible. One patient with incomplete removal is still alive after 9 months. The other 4 are all dead, having survived an average of only 6.75 months. We believe that pleural mesothelioma should be considered an unresectable neoplasm because of its multicentric origin and its diffusely invasive nature, and that attempts at partial or complete resection are not indicated. Until prospective, controlled studies demonstrate otherwise, patients with diffuse, mixed malignant mesothelioma should have the most benign surgical procedure necessary to establish a diagnosis.

Adult↗

Mediastinoscopy in advanced superior vena cava obstruction.

Superior vena cava syndrome can be a rapidly progressive, lethal process that is caused by a malignancy in 92 to 94% of cases. Since all effective therapy is inherently harmful, it would be reassuring to have a definitive tissue diagnosis before initiating treatment. Because easily accessible tissue is not always available, mediastinoscopy must be relied on to confirm the diagnosis in some patients. Twenty-nine patients with advanced superior vena cava syndrome were reviewed. Fifteen of them required mediastinoscopy to confirm the diagnosis, since lesser procedures, i.e., bronchoscopy, needle biopsy, and sputum cytology, were negative for malignant tissue. Contrary to reports in the literature, mediastinoscopy can be performed safely in patients with advanced superior vena cava syndrome and can yield a definitive diagnosis in each.

Aged↗