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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 541 records · Page 30Linked to original sources

Respiratory muscle weakness during upper respiratory tract infections.

Global respiratory muscle strength was studied in 22 normal healthy volunteers during a 4-month winter period. Twelve subjects developed naturally acquired upper respiratory tract infections. Maximal static expiratory and inspiratory mouth pressures fell significantly during these infections. The greatest falls were documented between the third and seventh days of clinical illness. Full recovery occurred by the fourteenth day. We conclude that significant abnormalities of respiratory muscle function can occur during upper respiratory tract infections in otherwise healthy young adults.

Adult↗

Hypothyroidism presenting with respiratory muscle weakness.

A 58-yr-old woman presented with recurrent chest infections, breathlessness, and orthopnea. She complained of nonspecific tiredness and aching limbs. A chest radiograph showed an elevated right hemidiaphragm. Thyroid function tests showed her to be severely hypothyroid (T4 = 23 nmol/L; TSH greater than 50 mU/L). Measurement of maximal respiratory mouth pressures (expiratory: 50 cm H2O, normal, 94 +/- 33; inspiratory: 15 cm H2O, normal, 71 +/- 27) suggested global respiratory muscle weakness. Severe bilateral diaphragm weakness was demonstrated by a greatly reduced maximal transdiaphragmatic pressure (Pdi) (Pdi Pimax = 0, normal, 65 +/- 31 cm H2O; sniff Pdi = 25 cm H2O, normal, 121 +/- 25). No Pdi was detectable on stimulation of the right phrenic nerve, whereas, on the left, it was 11 cm H2O (normal 7 to 15 cm H2O). Phrenic nerve conduction time was prolonged to both sides (right, 12 ms, left, 10 ms; normal, less than 9.5 ms). The relaxation rate of Pdi after a maximal sniff and after bilateral phrenic nerve stimulation was abnormally slow (7.4%/10 ms, 6.3%/10 ms, respectively). Three months after starting treatment with thyroxine she had become euthyroid, and phrenic nerve conduction times and Pdi relaxation rates had returned to normal. Maximal respiratory pressures, vital capacity, and maximal voluntary ventilation improved progressively on treatment, although maximal respiratory pressures still had not reached the normal range after six months. We conclude that hypothyroidism may present with breathlessness due to respiratory muscle weakness and/or phrenic nerve neuropathy and is reversible with treatment.

Diaphragm↗

The value of sniff esophageal pressures in the assessment of global inspiratory muscle strength.

Esophageal pressure generated during a maximal sniff (sniff Pes) was compared with mouth pressure generated during a maximal inspiration against a closed airway (Pimax) as a measure of global inspiratory muscle strength in 61 patients referred for investigation of respiratory muscle function. Transdiaphragmatic pressure (Pdi) was also measured during both maneuvers to compare maximal diaphragmatic strength. Sniff Pes (males, 68 +/- 27 cm H2O; normal greater than 53; females, 66 +/- 21; normal greater than 48) was greater than Pimax (males, 45 +/- 24 cm H2O; normal greater than 42; females, 42 +/- 24; normal greater than 17) in 55 of the 61 patients, both in absolute values and as a percentage of normal. In 36 patients Pimax and sniff Pes were both normal (mean +/- 2 SD), whereas in 13 patients they were both low. In 11 patients, Pimax was low, but sniff Pes was normal. One patient had a reduced sniff Pes but a Pimax at the lower limit of normal. In the 36 patients in whom both Pimax and sniff Pes were normal, Pdi was also normal or only moderately reduced, and in the 13 patients in whom both Pimax and sniff Pes were reduced, Pdi was very low. However, in the group of 11 patients with a low Pimax but a normal sniff Pes, Pdi was normal or only moderately reduced, suggesting that Pimax was falsely low, perhaps because of difficulties with the technique. Conversely, in the single patient with a low sniff Pes but a Pimax just within the normal range, Pdi was very low. We conclude that measurement of esophageal pressure during a maximal sniff is a useful test of inspiratory muscle strength and overcomes the difficulty some patients have in carrying out the Pimax maneuver.

Adolescent↗

Clinical significance of severe isolated diaphragm weakness.

We studied six patients with isolated bilateral paralysis or severe weakness of the diaphragm, present for 2 to 60 months (mean = 25), to document the clinical and respiratory sequelae of the condition. Severe diaphragm dysfunction was confirmed by the demonstration of the very low maximal transdiaphragmatic pressure (Pdi) generated by either a sniff (13 +/- 6 cm H2O, normal 148 +/- 24) or a static inspiration (11 +/- 8, normal 108 +/- 30) and during bilateral phrenic nerve stimulation (0.8 +/- 2.0, normal 22 +/- 4). Resting arterial blood gases were normal (SaO2 = 95 to 97%) and no oxygen desaturation occurred during maximal exercise on a treadmill. Maximum voluntary ventilation was low and related to PImax (r = 0.89). Overnight sleep monitoring showed that time spent in rapid eye movement sleep was normal (mean 55 +/- 36 min, range 26 to 117 min). Mean maximum increment in transcutaneous CO2 was within normal limits (6 +/- 2 mm Hg, range 3 to 9 mm Hg). Three patients had occasional brief episodes of oxygen desaturation (mean maximal decrease 13 +/- 10%, range 2 to 27%); however, only two of these spent a measurable proportion of total sleep time (TST) with an SaO2 of less than 80% (1% and 3% TST, respectively). No patient has developed any symptoms of nocturnal hypoventilation or chronic respiratory failure during periods of observation of up to five yr. We conclude that bilateral paralysis or very severe weakness of the diaphragm does not of itself lead to respiratory failure unless weakness of other respiratory muscles is present.

Blood Gas Analysis↗

Respiratory muscle function in myasthenia gravis.

Global respiratory muscle function and diaphragmatic strength were assessed and compared with quadriceps femoris muscle strength in 17 patients with generalized mild-to-moderate myasthenia gravis and breathlessness. Initial measurements, made 10 h after the last dose of oral anticholinesterase therapy, demonstrated reduced maximal static expiratory (52.4 +/- 26.8% predicted) and inspiratory (54.0 +/- 23.5% predicted) mouth pressures in 16 patients, and reduced quadriceps femoris muscle strength in all cases. Vital capacity (VC) (70.9 +/- 19.0% predicted) was abnormal in 12 patients. Transdiaphragmatic pressure recorded during maximal sniffs (sniff Pdl) was reduced in eight patients, whereas pressure recorded during bilateral phrenic nerve stimulation at 1 Hz (twitch Pdi) was reduced in only three. There was no relationship between the grade of myasthenia or the severity of dyspnea and any of the measurements of respiratory muscle strength. After the administration of edrophonium hydrochloride (Tensilon), there was a significant increase in maximal static expiratory and inspiratory mouth pressures in quadriceps muscle strength and in sniff Pdi. The small increase in VC was not significant, and twitch Pdi increased in only one patient. Phrenic nerve conduction time was normal before and after Tensilon. Two patients with severe long-standing myasthenia showed no improvement in any measurement after Tensilon. We conclude that expiratory and inspiratory muscle weakness was not uncommon in patients with myasthenia gravis. Respiratory muscle strength improved after Tensilon. Vital capacity was a less sensitive measure of respiratory muscle strength than were respiratory mouth pressures and sniff Pdi. Diaphragmatic involvement was not detected by twitch Pdi unless the weakness was severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endogenous substrates for UDP-glucuronosyltransferases.

1. Multiple forms of UDP-glucuronosyltransferase (UDPGTs) have been demonstrated in the livers of all mammalian species that have been studied. Rat liver possesses at least eight different isozymes and human liver has at least five different forms which have been identified. 2. Endogenous substrates (e.g., steroids) are helpful in distinguishing UDPGTs as they generally react with only a single form, whereas xenobiotic substrates (e.g., 4-methyl-umbelliferone, p-nitrophenol) react with several forms of the enzyme. 3. Human liver UDPGTs differ in physical properties and substrate specificity from these enzymes obtained from laboratory animals. Hence, it is necessary to study human liver UDPGTs to elucidate substrate specificity and to understand drug-endogenous substrate interaction in humans.

Animals↗

Comparison of two different mouthpieces for the measurement of Pimax and Pemax in normal and weak subjects.

We investigated the effect of mouthpiece design on maximum static expiratory (PEmax) and inspiratory (PImax) mouth pressures. We measured PEmax from total lung capacity (TLC) and PImax from residual volume (RV) in 21 healthy volunteers, and in 40 patients referred for respiratory muscle testing. We compared two different mouthpieces, a semi-rigid plastic flanged type fitting inside the lips, and a 4 cm diameter rubber tube held against the lips. The tube mouthpiece gave significantly higher values for PEmax (p less than 0.02) in all subjects. PImax was also significantly higher (p less than 0.005) with the tube mouthpiece in subjects who recorded normal pressures. We conclude that maximum pressures are obtained in all normal subjects with the rubber tube mouthpiece, and that differences in quoted normal ranges of maximum static respiratory pressures reflect in part the design of the mouthpiece and the way in which it was used.

Equipment Design↗

Demonstration that a chemically synthesized BPV1 oncoprotein and its C-terminal domain function to induce cellular DNA synthesis.

Bovine papillomavirus type 1 contains the smallest known oncogene (ORF E5), encoding a hydrophobic 44 amino acid protein. To study the biochemical functions of the E5 oncoprotein, we have chemically synthesized it and several deletion mutant peptides. We demonstrate induction of cellular DNA synthesis in growth-arrested cells by microinjection of E5 oncoprotein. This activity can be broken down into two functionally distinguishable domains. Remarkably, the first domain, which alone is sufficient to induce cellular DNA synthesis, contains only the C-terminal 13 amino acids. This is the smallest known protein fragment that can autonomously activate cellular DNA synthesis. The second domain is the hydrophobic middle region, which by itself fails to induce cellular DNA synthesis but confers a 1000-fold increase in specific activity. The N-terminal one-third of the molecule is dispensable for induction of DNA synthesis.

Amino Acid Sequence↗

Functional domains of adenovirus type 5 E1a proteins.

Adenovirus E1a proteins function in transcriptional activation, transcriptional repression, cellular DNA synthesis induction, and cellular transformation. Here we examine the role of the previously undefined E1a region 1, the last of three conserved E1a regions to be characterized. Region 1 is required for transcriptional repression, transformation, and DNA synthesis induction, but not transcriptional activation. These results support our previous suggestion that transcriptional repression is the basis of E1a-mediated transformation. Two conserved regions (regions 1 and 2), present in both early E1a proteins, are essential for transcriptional repression, transformation, and induction of DNA synthesis. In contrast, mutagenesis suggests that transcriptional activation requires only 49 amino acids (region 3) unique to the 289 amino acid E1a protein. This we prove by demonstrating that a 49 amino acid region 3 synthetic peptide efficiently activates an E1a-inducible promoter. This peptide is the smallest known protein fragment functioning as a transcriptional activator.

Adenovirus Early Proteins↗