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Biomedical subjects

R Myers

Publications and source records attributed to R Myers.

At least 127 records · Page 7Linked to original sources

Changes in relative biological effectiveness with depth of the Clatterbridge neutron therapy beam.

We have measured the biological equivalence of the Clatterbridge neutron therapy beam [p(62)-Be] and the Hammersmith neutron therapy beam [d(16)-Be] using the mouse intestinal crypt assay. The ratio (NDR) of Clatterbridge neutron (n + gamma) dose relative to Hammersmith neutron dose (n + gamma) was found to be 1.2-1.13 over a dose/fraction range of 1.8-9 Gy at 2 cm deep in a Perspex phantom. It is shown that the effectiveness of the Clatterbridge beam was reduced with penetration into the phantom because of hardening of the beam to a maximum reduction of 11% at 12 cm deep in the phantom. The hardening of the beam with depth of penetration will need to be taken into account by clinicians in assessing the tumour dose and tissue tolerance. Relative biological effectiveness values for the Clatterbridge and Hammersmith neutron beams were also measured. All neutron doses for both Hammersmith and Clatterbridge beams are total doses (n + gamma) which comply with the European protocol for neutron dosimetry and include the gamma-ray component of dose.

Animals↗

Search for the familial Alzheimer's disease gene.

The application of molecular genetic techniques to the study of autosomal dominantly inherited Familial Alzheimer's Disease may provide a means to determine the chromosomal location of the defective gene causing this form of Alzheimer's disease. Knowledge of the chromosomal location of the defective gene will provide a basis for isolating and characterizing this gene. Preliminary investigations indicate that several candidate genes can be excluded as the site of the defect. Current data also indicate that the defective gene does not reside close to random DNA markers on the distal portion of chromosome 21. Additional DNA markers on the proximal portion of chromosome 21 long arm are currently being investigated.

Alzheimer Disease↗

Chronic demyelination in mouse peripheral nerve produced by lysophosphatidyl choline and X-irradiation: ultrastructural observations.

The effects of X-irradiation on demyelination and remyelination were studied in the peripheral nerve of the mouse. Three days after injection of lysophosphatidyl choline into one sciatic nerve, a 20 Gy dose of X-rays was administered to the hind limb. At survival times ranging from 4 days to 6 months after injection, the nerves were examined by light and electron microscopy. Removal of myelin debris was retarded and remyelination delayed or prevented. The myelin sheaths which did form were thin and the configuration of Schmidt-Lanterman incisures and nodes of Ranvier was abnormal. Some of the chronically demyelinated fibres formed focal node-like complexes: patches of finely granular material coated the inner aspect of the axolemma, the external surface was covered by slender processes of Schwann cell cytoplasm, and an electron-dense lamina was present in the enlarged periaxonal space. Elsewhere demyelinated axons and their ensheathing Schwann cells were separated by gap junctions or transverse bands. The present findings indicate that the morphological differentiation of structures thought to be characteristic of nodes of Ranvier can take place in the absence of remyelination.

Animals↗

X-irradiation impairs regeneration of peripheral nerve across a gap.

The effects of X-irradiation on the regeneration of peripheral nerve across a gap were studied in the mouse. The right sciatic nerve was transected and 3 days later a 20-Gy dose of X-rays was administered to the hind limb, which was shielded so that the irradiation affected either the proximal, the distal or both parts of the nerve. Within a few hours of irradiation, the proximal and distal nerve stumps were inserted into a polythene tube within which they were separated by a 5-mm gap. After 1 or 2 months the sciatic nerves were processed for examination by light and electron microscopy. Irradiation affected axonal growth, differentiation of Schwann cells and formation of a perineurium. These effects were most marked when both the proximal and distal stumps had been exposed to X-rays. At 2 months there were fewer axons in the irradiated than in control nerves (P less than 0.01), but all of the larger axons which had regenerated were myelinated, albeit more thinly than in the controls. The changes in the pattern of regeneration in the irradiated nerves are interpreted as being largely due to radiation damage to Schwann cells.

Animals↗

Radiation injury in mouse lung: dependence on oxygen levels in the inspired gas.

The relationship between radiosensitivity and the partial pressure of oxygen (PO2) in the inspired gas has been established for radiation pneumonitis as a measure of lung damage following irradiation of the mouse thorax. The radiosensitivity at low PO2 (0-1 per cent) fitted the linear transformation of the Alper, Howard-Flanders relationship giving a K value for lung tissue of 1.35 per cent oxygen with an oxygen enhancement ratio, m, of 2.13. The radiosensitivity at higher PO2 (5-21 per cent) did not fit the Alper, Howard-Flanders relationship probably because the PO2 of the inspired gas was greater than the PO2 in the alveolus. At the low PO2 levels in the inspired gas, back diffusion of oxygen from blood into the alveolus may lead to errors in the estimated value of K. If the low value of m is due to this 'contaminating' oxygen from blood then by taking a higher value for m, the amount of contaminating oxygen can be calculated (0.23 per cent) and a 'true' value for K(1.1 per cent) determined. Other uncertainties in this estimate of K due to the radiolytic consumption of oxygen and possible inadequacies in equilibration are discussed. Allowing for the uncertainties, it is concluded that the K value for lung damage lies towards the upper end of the range of K values measured for cells in vitro.

Animals↗

Methyl-CCNU and methotrexate therapy in patients with advanced colorectal cancer after failure of 5-fluorouracil chemotherapy.

Thirty-six patients with advanced colorectal cancer whose disease progressed during treatment with 5-fluorouracil (5-FU) chemotherapy were treated with methyl-CCNU and methotrexate. Five patients (14%) achieved a partial response (PR), three (8%) showed disease regression less than that required for a PR, and three (8%) showed evidence of stable disease. Twenty-five patients (69%) progressed on treatment. Tumor regression was seen only in patients with good performance status (ECOG 0.1). The median survival time of patients achieving a PR was 31 weeks. Those patients with stable disease or disease regression less than a PR had median survival times of 49 and 32 weeks, respectively. The comparable figure for those patients with disease progression was 17 weeks. Myelosuppression, principally in the form of leukopenia and thrombocytopenia, was common. Nausea and vomiting were universal with methyl-CCNU, and mucositis and diarrhea occurred commonly due to methotrexate. These results demonstrate the limited activity of chemotherapy in refractory colorectal cancer. They also reaffirm that poor pretreatment performance status should exclude patients from futile attempts at palliative therapy or phase II clinical trials, as these patients derive little or no benefit from them.

Adult↗

The nucleotide sequence of the Escherichia coli K12 nusB (groNB) gene.

The nusB (groNB) gene product of Escherichia coli plays a pivotal role in allowing bacteriophage lambda N protein to function as an antiterminator of mRNA transcription and in modulating host gene expression. In addition it is essential for bacterial viability since mutations in it result in a cold-sensitivity phenotype for growth. We have previously cloned the nusB gene and shown it to code for a 14,500-Mr protein. Here we present the primary DNA sequence of the nusB gene. From the sequence we deduce that it codes for a slightly basic protein (21 basic as opposed to 20 acidic amino acids) composed of 139 amino acids with a cumulative 15,689-Mr. The predicted N-terminal amino acid sequence as well as the overall amino acid composition agrees well with that of the purified protein.

Amino Acid Sequence↗

Elimination of germ-line tandemly repeated sequences from the somatic genome of the ciliate Oxytricha fallax.

The ciliated protozoa exhibit nuclear dimorphism. The genome of the somatic macronucleus arises from the germ-line genome of the micronucleus following conjugation. We have studied the fates of highly repetitious sequences in this process. Two cloned, tandemly repeated sequences from the micronucleus of Oxytricha fallax were used as probes in hybridizations to micronuclear and macronuclear DNA. The results of these experiments show: (1) the cloned repeats are members of two apparently unrelated repetitious sequence families, which each appear to comprise a few percent of the micronuclear genome, and (2) the amount of either family in the macronuclei from which our DNA was prepared is about 1/15 that found in an equal number of diploid micronuclei. Most, if not all, of the apparent macronuclear copies of these repeats can be accounted for by micronuclear contamination, which strongly suggests that these sequences are eliminated from the macronuclei and have no vegetative function.

Cell Nucleus↗

The pharyngeo-tracheal lumen airway: preliminary investigation of a new adjunct.

The technique of prehospital airway management is determined largely by the level of training and expertise of the prehospital care provider. We report preliminary observations and data in experimental animals and patients using a new airway adjunct--the pharyngeo-tracheal lumen (PTL) airway. The PTL airway employs a two-tube, two-cuff system that is inserted in a "blind" fashion. The airway's design allows it to function as an endotracheal tube if the trachea is entered or as an esophageal obturator airway (EOA) if the esophagus is intubated. In the esophageal position, a face-to-mask seal is not required. Preliminary data in 23 experimental animals suggest that the PTL (in the esophageal position) is as effective as a conventional cuffed endotracheal tube. Volumetric efficiency at optimal cuff inflation pressures was 100%, and arterial blood gas values obtained during PTL ventilation were not significantly different from those measured during ventilation with an endotracheal tube at comparable minute ventilations. In six arrest patients undergoing cardiopulmonary resuscitation, arterial PO2 and PCO2 using the PTL airway (176 +/- 105 mm Hg and 36 +/- 12 mm Hg, respectively) were not significantly different from those measured during artificial ventilation with an endotracheal tube (PO2, 162 +/- 124 mm Hg; PCO2, 34 +/- 10 mm Hg). Although the numbers are small, the data suggest that the PTL airway may be an alternative method of emergency airway management when endotracheal intubation cannot be performed.

Aged↗

Protection of hepatocytes with hyperoxia against carbon tetrachloride-induced injury.

Hyperbaric oxygen (HPO) was administered to rats (100% O2 at 2.8 atm for 90 min) immediately or 1 hr after severe carbon tetrachloride (CCl4) intoxication in order to study the mechanisms of protection against hepatocellular injury by hyperoxia. Slight to moderate hepatocellular injury was observed, particularly by morphologic criteria, 4 hr after CCl4 intoxication. Little cell death was observed; 24 hr after CCl4, 20% of the untreated animals died. In the survivors, the following typical changes occurred in the liver: extensive hepatocellular swelling, vacuolization and necrosis; severe ultrastructural alterations; binding of CCl4 to microsomal lipids; elevation of lipid peroxidation products (conjugated dienes); little decrease in cytochrome b5 and severe decrease in cytochrome P-450 levels. Serum transaminase (alanine aminotransferase and aspartate aminotransferase) levels were elevated. Immediate treatment with HPO prevented the mortality and markedly decreased the hepatocellular necrosis 24 hr after intoxication. Immediate HPO treatment did not lower the levels of free CCl4 in the liver. However, the rise in lipid peroxidation products caused by CCl4 intoxication at 4 hr was reduced. Delayed treatment with HPO (1 hr after CCl4) prevented the mortality but was less effective in preventing necrosis. Some hepatocellular protection was still demonstrable. In particular, the rise in lipid peroxidation products was reduced. Hyperoxia protects hepatocytes against CCl4 toxicity. The rapid decline in protective effect within 60 min of intoxication suggests that hyperoxia inhibits CCl4 activation and/or damage from molecular intermediates. Hyperoxia has little effect on the progression of sublethal injury to cell death in the livers of CCl4-intoxicated rats.

Alanine Transaminase↗