Search PubMed⌕ Search

Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 523 records · Page 29Linked to original sources

An adenovirus E1A protein domain activates transcription in vivo and in vitro in the absence of protein synthesis.

We have shown previously that a synthetic peptide of 49 amino acids, encoding mainly adenovirus E1A protein domain 3 (PD3), functions as an autonomous transcriptional activator. Here we provide two lines of evidence showing that E1A transactivation does not require the induction of cellular protein synthesis. First, PD3 rapidly transactivates E1A-inducible early viral genes in the presence of inhibitors of protein synthesis, as demonstrated by microinjection-in situ hybridization experiments. Second, PD3 greatly stimulates transcription of E1A-inducible genes in vitro. Mutant PD3 peptides with single amino acid substitutions in conserved cysteine residues are defective in transactivation both in vivo and in vitro. Our findings provide compelling evidence that protein synthesis is not required for E1A transactivation, and support a model in which E1A modifies the activity of a preexisting cellular protein(s) involved in the regulation of transcription.

Adenovirus E1A Proteins↗

Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy.

A phase I/II study of granulocyte colony stimulating factor (G-CSF) was undertaken in patients with advanced malignancy receiving melphalan to determine the granulocyte response, side-effects, and pharmacokinetics. Patients received doses of 1-60 micrograms/kg intravenously. There were 3 patients at each dose level. Before chemotherapy the immediate effect of G-CSF was a transient depression in circulating neutrophils followed by a dose-dependent rise. Neutrophil counts up to 80 X 10(9)/l were achieved. G-CSF administration following melphalan reduced the period of neutropenia caused by melphalan. G-CSF was well tolerated and the only clinical observation that appeared related to G-CSF administration was slight bone pain during some infusions. G-CSF was rapidly cleared from the blood with a mean half-life of 110 min for the second phase. Reductions in the number of days of neutropenia following cytotoxic chemotherapy may reduce the morbidity and mortality of chemotherapy.

Aged↗

Phase II trial of 4'-deoxydoxorubicin (DxDx) in non-small cell lung cancer: a Cancer and Leukemia Group B Trial.

Eighty-seven patients with histologically or cytologically proven non-small-cell carcinoma of the lung were treated with 4'-deoxydoxorubicin (DxDx) 30 mg/m2 every 3 weeks. Three responses (4%), all partial, were observed. All responses occurred in patients with large-cell anaplastic lung cancer and none in squamous or adenocarcinoma histologies (P less than 0.01). The durations of partial response for these three responders were 70, 198+ and 209+ days. The side effects noted were predominantly neutropenia, anemia, and weight loss. In three patients, declines in cardiac ejection fraction of 7%, 12%, and 23% occurred after cumulative drug doses of 150 mg/m2, 150 mg/m2, and 233 mg/m2, respectively. 4'-Deoxydoxorubicin had little activity in non-small-cell lung cancer at the dose used in this study.

Carcinoma, Non-Small-Cell Lung↗

Transbronchial aspiration of subcarinal lymph nodes.

Transbronchial needle aspiration of subcarinal lymph nodes has been undertaken in 60 consecutive patients with pulmonary malignancies undergoing routine fibreoptic bronchoscopy. Four aspirates from the subcarinal nodes contained malignant cells; three squamous cell carcinoma and one adenocarcinoma. Four of 40 (10%) of patients with non-small-cell carcinoma of the lung had a positive aspirate. We have not confirmed the high positive rate previously reported, but nevertheless transbronchial needle aspiration provided useful staging information in some patients. The technique is rapid, safe and simple, and can easily be applied in a routine bronchoscopy service for all patients with suspected cancer, or selected patients under active consideration for surgery.

Adenocarcinoma↗

Mineral structure and preferred orientation in the fin bones of the plaice, Pleuronectes platessa.

The technique of collagenase etching of a polished surface of plaice fin bone has been used to reveal the structural detail of the mineral component and hence to explain the preferred orientation previously deduced from X-ray diffraction experiments. High resolution electron micrographs reveal units approximately 20 nm across, which aggregate to form units approximately 100 nm across, which in turn coalesce to produce rods up to approximately 1 micron diameter and of substantial length. These rods show a preferred orientation with their axes parallel to the long axis of the bone, thus demonstrating a preferred orientation of the mineral component. Additionally, collagenase-etched transverse surfaces reveal numbers holes from which collagen fibrils parallel to the long axis of the bone have been removed, whereas similarly treated longitudinal surfaces do not show such holes. This is consistent with a predominance of collagen fibrils running along the bone axis and explains the previously observed preferred orientation of the collagen component of fish fin bones.

Animals↗

Tobacco use prevention and health facilitator effectiveness.

Tobacco prevention programs often use peers to teach refusal skills to other adolescents. College undergraduate health facilitators delivered a tobacco prevention intervention to sixth and seventh grade students in six schools. Outside observers evaluated facilitators in seven categories: being prepared, maintaining class control, keeping students' attention, encouraging participation, communication, relating to students, and working well in a team. Facilitators were rated highly in all categories. Higher rated health facilitators had more effect in reducing tobacco use than poorly rated facilitators. Facilitators who worked well in a team, related well to students, and were well-prepared were especially effective in positively influencing program outcomes.

Adult↗

Diaphragm strength in patients with recent hemidiaphragm paralysis.

Eleven patients with unilateral diaphragm paralysis of recent onset were studied to investigate the effect of the paralysis on inspiratory muscle function. Nine of the patients had noticed a decrease in exercise tolerance, which was not explained by any other pathological condition. Hemidiaphragm dysfunction was confirmed by the demonstration of a greatly reduced or absent transdiaphragmatic pressure on stimulation of the phrenic nerve in the neck, by means of surface bipolar electrodes (unilateral twitch Pdi), compared with normal values on the contralateral side. Transdiaphragmatic pressure was 44.6% (9.4%) predicted during a maximal sniff and 30.3% (16.8%) predicted during a maximal static inspiration against a closed airway, confirming diaphragm weakness. Maximum static inspiratory mouth pressures were also low (61.7% (12.7%) predicted), consistent with a reduction in inspiratory muscle capacity. Phrenic nerve conduction time was prolonged on the affected side in nine patients, consistent with phrenic nerve dysfunction, whereas on the unaffected side it was normal. It is concluded that recent hemidiaphragm paralysis causes a reduction in transdiaphragmatic pressure that is associated with a reduction in maximum inspiratory mouth pressure. Phrenic nerve stimulation is a useful technique with which to confirm and quantify hemidiaphragm dysfunction. Measurement of phrenic nerve conduction time provides useful information about the underlying pathology.

Diaphragm↗

Diaphragm weakness in Charcot-Marie-Tooth disease.

Two patients are described with Charcot-Marie-Tooth disease and chronic peripheral neuropathy. Both had dyspnoea, orthopnoea, and evidence of severe diaphragm weakness. Expiratory muscle function was well preserved and abnormalities of gas exchange during sleep were only minor.

Charcot-Marie-Tooth Disease↗

Effects of amoxapine and imipramine on evoked potentials in the Continuous Performance Test in patients with affective disorder.

Twenty patients with major depressive disorder were studied with evoked potential (EP) topographic mapping after receiving placebo, imipramine, or amoxapine for 2 days in a random-assignment, double-blind design. Patients performed the Continuous Performance Test (CPT), a visual vigilance test. The stimuli were the digits 0-9, with 0 a target to be responded to with a button press. EPs were recorded from 32 channels and were averaged separately for detected and undetected targets and for false positives and correctly identified nontargets (no button press). Twenty-one normal controls were also tested. Amoxapine enhanced N120 amplitude in midline parietal and right parietal cortex where selective attention effects have been found to be greatest in studies of normal controls. Both amoxapine and imipramine enhanced differences in P200 between target and nontarget stimuli in comparison to placebo, with amoxapine differences again being greatest over midline parietal locations. CPT performance was significantly better on amoxapine than placebo.

Adult↗

Respiratory muscle weakness associated with cerebellar atrophy.

Transdiaphragmatic pressures were measured in 3 patients with cerebellar atrophy. Recordings were made during 3 types of voluntary maneuver--maximal sniffs, full inspirations, and maximal static inspiratory efforts, and during bilateral supramaximal phrenic nerve stimulation at 1 Hz. Although diaphragmatic weakness was demonstrated during the voluntary maneuvers, transdiaphragmatic pressures recorded during phrenic nerve stimulation were normal. These findings indicate that diaphragmatic dysfunction, probably caused by ataxia during voluntary maneuvers, may occur in association with cerebellar atrophy. In the presence of diaphragmatic weakness, normal values of transdiaphragmatic pressure during phrenic nerve stimulation may suggest an upper motor neuron lesion affecting the diaphragm.

Adult↗

Assessment of diaphragm weakness.

Thirty patients with breathlessness and diaphragm weakness were studied by measuring transdiaphragmatic pressures during maximal inspirations to total lung capacity, maximal static inspiratory efforts from residual volume, and maximal sniffs from functional residual capacity. Maximal static respiratory mouth pressures were also recorded, and rib cage and abdominal movements were monitored with pairs of magnetometers. Sniff transdiaphragmatic pressure was abnormally low in all patients and was correlated with transdiaphragmatic pressure during other maneuvers, and with maximal static inspiratory mouth pressures. There was no relationship between the severity of dyspnea and transdiaphragmatic pressure in the group as a whole. The weakest patients had orthopnea and paradoxical inward inspiratory motion of the anterior abdominal wall; measurements suggested that at least 30 cm H2O transdiaphragmatic pressure was required to overcome the hydrostatic pressure of the abdominal contents. By contrast, patients with mild diaphragm weakness had neither orthopnea nor abdominal paradox. Thus, patients with breathlessness and diaphragm dysfunction may have varying degrees of diaphragm weakness that may be difficult to detect clinically; the diagnosis and quantification of diaphragm weakness requires the measurement of transdiaphragmatic pressure.

Adolescent↗