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Biomedical subjects

H R Matthews

Publications and source records attributed to H R Matthews.

At least 91 records · Page 5Linked to original sources
PubMed1990

Light adaptation in cone photoreceptors of the salamander: a role for cytoplasmic calcium.

1. Light adaptation has been studied in isolated red-sensitive cone photoreceptors of the salamander, using suction pipette recordings of circulating current. 2. In the presence of background illumination, the response to incremental dim flashes became desensitized according to the Weber-Fechner law. The recovery phase of the flash response was accelerated significantly, although the time-to-peak was reduced only slightly, and for dim backgrounds the rising phase was unaltered. 3. The role of cytoplasmic calcium concentration, Cai2+, in mediating cone adaptation was investigated by minimizing light-induced changes in Cai2+, either by incorporating calcium buffer into the cytoplasm or by exposing the outer segment to low-Ca2+, 0-Na+ solution. Both treatments appeared to slow dramatically or even to eliminate the onset of light adaptation in the cone. 4. When the low-Ca2+, 0-Na+ solution was presented in darkness, responses to subsequent illumination were affected in a characteristic manner: (i) the response-intensity relation was steepened and shifted to lower intensities, (ii) the response to a step of light could be predicted by integration and compression of the flash response, and (iii) the flash sensitivity declined steeply as a function of background intensity. 5. After extended exposure of the cone to bright backgrounds, the sensitivity in darkness failed to return to its original level. The flash response kinetics were faster and more biphasic than for dark-adapted responses or for responses desensitized to a comparable degree by exposure to steady background illumination. 6. The results indicate that, in cones isolated from the pigment epithelium, the primary factor influencing the adaptational state of the cell is the cytoplasmic concentration of free calcium, but that at high intensities the effects of pigment bleaching are likely to be significant.

Action Potentials↗
PubMed1990

Oesophageal carcinoma: the view from East Birmingham.

Oesophageal carcinoma is a bad, but not a hopeless, disease. Overall survival is poor but a 5-year survival rate in the region of 30% can be obtained with surgical resection in properly selected patients. In this review we outline our overall strategy for the management of patients with both localized and advanced disease, based on more than 1500 cases treated over the past 14 years.

Combined Modality Therapy↗
PubMed1989

Studies of histidine phosphorylation by a nuclear protein histidine kinase show that histidine-75 in histone H4 is masked in nucleosome core particles and in chromatin.

Histone H4 is a good substrate in vitro for the protein histidine kinase activity found both in Physarum polycephalum nuclear extracts and in Saccharomyces cerevisiae cell extracts. However, histone H4 in nucleosome core particles is not a substrate for these kinases. Isolated chromatin was also not a substrate for the protein histidine kinase. The results significantly limit possible interpretations of histidine phosphorylation on histone H4 in vivo and provide a new, sharper focus for future work. In addition, a polynucleotide kinase activity was identified in the Physarum extracts.

Animals↗
PubMed1989

Emergency subtotal oesophagectomy.

From 1981 to 1987 nine patients have undergone resection and reconstruction of the oesophagus as an emergency, using a two-part left-sided approach with oesophagogastric anastomosis in the neck. Five patients had oesophageal perforation with a carcinoma; one had spontaneous perforation of an intrathoracic stomach; two had severe haemorrhage; and one had acute sterile mediastinitis. Following operation there was one postoperative death (11 per cent) and no major complications. Long-term survival was marred only by the development of further malignancy in four patients. Subtotal oesophagectomy has both theoretical and practical advantages over conventional oesophagogastrectomy in oesophageal emergencies and we suggest that it should be considered as the method of choice in the management of these difficult cases.

Adult↗
PubMed1989

Cytoplasmic calcium as the messenger for light adaptation in salamander rods.

1. In order to study the role of cytoplasmic calcium concentration (Ca2+i) in rod photoreceptor light adaptation, we have attempted to prevent light-induced changes in Ca2+i by minimizing calcium fluxes across the outer segment plasma membrane. This was achieved by exposing the outer segment to a low-Ca2+, 0-Na+ solution, in which sodium was replaced with either guanidinium or lithium and the external calcium concentration (Ca2+o) was reduced to micromolar levels. 2. With guanidinium and 1-3 microM-Ca2+o, the circulating current in darkness was maintained for a period of at least 15 s, consistent with approximate stability of Ca2+i. With Li+ rather than guanidinium most of the initial current was suppressed, but the residual current was again relatively stable. 3. During prolonged exposures (greater than 30 s) to low-Ca2+, 0-Na+ solution followed by dim illumination, the circulating current did not remain constant but slowly increased. Incorporation of calcium buffer into the cytoplasm greatly reduced the rate of change of current, consistent with the idea that the increase arose from a gradual decrease in Ca2+i. 4. Light responses of rods exposed to low-Ca2+, 0-Na+ solution in darkness were altered in a characteristic manner. Although the initial rising phase of the light response was little changed, the peak amplitude of the response was larger and occurred later, and the response decayed more slowly than in control. The response-intensity relation was steepened and was shifted towards lower intensities both for flashes and for steps of light. The normal sag in the response to steps disappeared, and the waveform of the step response could be predicted to a close approximation from the integral of the dim flash response. 5. Presentation of background illumination in Ringer solution produced a marked acceleration of the response to a subsequent bright flash. No such acceleration was observed if the background was given in low-Ca2+, 0-Na+ solution. 6. The results described in paragraphs 4 and 5 indicate that, under conditions expected to minimize changes in Ca2+i, all manifestations of light adaptation disappear, and the rod simply sums the effects of incident photons with an invariant integration time. 7. Exposure of a light-adapted rod to low-Ca2+, 0-Na+ solution altered the responses to superimposed test flashes in much the same way as for rods in darkness. The initial rising phases in low-Ca2+, 0-Na+ solution were unchanged, but the responses were larger, reached peak later and decayed more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Ocular↗
PubMed1989

Origin and behaviour of emphysematous bullae.

Giant emphysematous bullae are believed to produce symptoms of pulmonary compression and collapse by containing gas under pressure that has been generated through valvular feeding airways. To examine this hypothesis, we have measured oxygen and carbon dioxide tensions (PO2, PCO2) in four patients and pressure within the bullae in three patients immediately before surgery. During spontaneous tidal respiration PO2 in the bulla was higher than arterial PO2 but did not rise as fast during the breathing of oxygen. The intra-bulla pressure during inspiration was negative (-5.5 to -19 cm H2O) and similar to pleural pressure in phase and degree. During intermittent positive pressure ventilation in two patients airway pressures were transmitted to the bulla with the development of a positive end expiratory pressure within the bulla. Histological examination of the walls of the bullae in the four patients and adjacent lung tissue in an additional patient failed to identify any valvular mechanism. The available information suggests that bullae develop after retraction and collapse of surrounding lung away from a region of weakness.

Adult↗
PubMed1989

Malignant carcinoid tumour of the oesophagus.

A patient with a carcinoid tumour of the oesophagus developed widespread metastases within three years of a successful local resection. Of the seven patients with oesophageal carcinoid tumours so far reported, four have died with widespread metastases.

Aged↗
PubMed1989

Colopleural fistula due to strangulated Bochdalek hernia in an adult.

An elderly patient presented with a right sided pneumothorax due to strangulation of part of the colon through a congenital Bochdalek hernia. Congenital posterolateral diaphragmatic hernia of Bochdalek is rare in an adult and strangulation with pneumothorax has not been reported before.

Aged↗
PubMed1989

Chemotherapy plus adjuvant surgery for local small cell lung cancer.

Eight patients with local Stage II (T2N1) and III (T3N0, T3N1, T2N2) small cell lung cancer received combination chemotherapy prior to elective surgery to assess the effectiveness of such a regimen in improving operability, preventing local relapse and extending survival. The regimen was well tolerated and prevented local relapse. However, the median time to recurrence of disease was 10 months and the median survival time 13 months, results which are similar to those achieved with chemotherapy and radiotherapy. Distant metastases, particularly in the brain, occurred predictably indicating that successful adjuvant surgery, despite preventing local relapse, may not afford additional survival benefit with currently available drug regimens.

Adult↗
PubMed1988

Phosphohistidine is found in basic nuclear proteins of Physarum polycephalum.

Nuclear extracts of the true slime mold, Physarum polycephalum, show protein histidine kinase activity towards exogenous histones [(1985) J. Biol. Chem. 260, 16106-16113]. Physarum microplasmodia were labeled with [32P]phosphate in vivo and two basic proteins containing alkali-stable phosphate were detected. The labeled proteins comigrated with Physarum histones H1 (approximately) and H2A and phosphoamino acid analysis showed that each protein contained [32P]-phosphohistidine. The H2A-like protein was also labeled in isolated nuclei incubated with [35S]thio-ATP. We conclude that some Physarum nuclear proteins contain phosphohistidine.

Histidine↗
PubMed1988

Photoreceptor light adaptation is mediated by cytoplasmic calcium concentration.

The vertebrate visual system can operate over a large range of light intensities. This is possible in part because the sensitivity of photoreceptors decreases approximately in inverse proportion to the background light intensity. This process, called photoreceptor light adaptation, is known to be mediated by a diffusible intracellular messenger, but the identity of the messenger is still unclear. There has been considerable speculation that decreased cytoplasmic Ca2+ concentration (Cai2+) may play a role in light adaptation, and recent experiments in which Ca2+ buffer was incorporated into rod-cells have supported this notion. The extent of the contribution of calcium, however, remains unresolved. We now show that light-dependent changes in sensitivity in amphibian photoreceptors can be abolished by preventing movements of Ca2+ across the outer-segment plasma membrane. These experiments demonstrate that light adaptation in photoreceptors is mediated in cones primarily, and in rods perhaps exclusively, by changes in Cai2+.

Adaptation, Ocular↗
PubMed1988

External and internal actions in the response of salamander retinal rods to altered external calcium concentration.

1. The membrane current was recorded from retinal rods isolated from Ambystoma tigrinum using the suction pipette and whole-cell patch pipette techniques, while the concentration of calcium bathing the outer segment was rapidly reduced. 2. The increase in outer segment current induced by lowered external calcium in darkness could be resolved into two components, one as rapid as the time course of the solution change (as judged by the junction current) and the other somewhat slower. 3. Introduction of the calcium buffer BAPTA (1,2-bis(o-aminophenoxy)ethane-N ,N ,N' ,N'-tetraacetic acid) into the cell from a patch pipette led to a progressive slowing of the second component of current increase. 4. When several minutes had elapsed following rupture of the patch, to allow a substantial amount of BAPTA into the cell (ca. 10 mM in the patch pipette), the second component was slowed by a factor of about 20-fold, while the first component continued to have the same rapid time course as the solution change. 5. The rapid component is attributed to a direct effect of external calcium, Ca2+o, and the delayed component to an indirect effect mediated by a reduction in internal calcium, Ca2+i. 6. These results confirm that, in previous experiments in which BAPTA was introduced into photoreceptors, the internal calcium concentration was very significantly buffered. 7. When Ca2+o drops from 1 mM to less than 10(-8) M, the rapid external component corresponds to an increase in circulating current of 3- to 4-fold, and the internal component corresponds to an increase of at least 4- to 5-fold. However, the total current at late times is limited by electrical factors, so that the size of the internal effect is bound to be considerably greater.

Action Potentials↗
PubMed1988

Incorporation of analogues of GTP and GDP into rod photoreceptors isolated from the tiger salamander.

1. Analogues of GTP and GDP were introduced into isolated rod photoreceptors using the whole-cell patch clamp technique, while simultaneously recording the photocurrent with a suction pipette. After several minutes of whole-cell recording the patch pipette was disengaged, thus trapping the analogue inside the cell. 2. During the introduction of the hydrolysis-resistant GTP analogues guanosine-5'-O-(3-thio-triphosphate) (GTP-gamma-S) and guanylyl-imidodiphosphate (GMP-PNP) the dark current progressively declined, and the duration of responses to flashes of light which had previously been just-saturating increased slightly. The form of the rising phases of the responses to dim or bright flashes was little affected. 3. Following the incorporation of these GTP analogues the response to an intense flash was prolonged by a factor of up to 300, and the circulating current remained suppressed for up to 1 h. Ultimately the circulating current recovered and the duration of the flash response returned to near its control value. 4. Superfusion of the outer segment with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX) during the extended period of saturation resulted in a rapid increase in the circulating current, suggesting that the analogues had their major effect on the duration of phosphodiesterase activation by light. 5. Introduction of the phosphorylation-resistant GDP analogue guanosine-5'-O-(2-thio-diphosphate) (GDP-beta-S) resulted in a decrease in light sensitivity and a reduction in the slope of the rising phase of the flash response. 6. The response to an intense flash was also prolonged in cells containing GDP-beta-S, recovery becoming progressively slower on successive presentations of the flash following the withdrawal of the patch pipette. This observation suggests that GDP-beta-S may be slowly converted within the cell to form a hydrolysis-resistant product. 7. These results indicate that the presence of a hydrolysis-resistant analogue of GTP within the cell causes light activation of the transduction mechanism for an extended period. Our interpretation of this finding is that hydrolysis of the bound guanosine nucleotide is necessary for the quenching of activated GTP-binding protein.

1-Methyl-3-isobutylxanthine↗