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Biomedical subjects

R F Fisher

Publications and source records attributed to R F Fisher.

At least 37 records · Page 2Linked to original sources
PubMed1985

The structure and function of basement membrane (lens capsule) in relation to diabetes and cataract.

The water permeability of the basement membrane (lens capsule) of the crystalline lens of the adult normal and diabetic rat has been investigated. The hydraulic conductivity at low pressure is 51.4 +/- 7.8 X 10(-12) msec-1 Pa-1 in the normal rats and 70.3 +/- 11.1 msec-1 Pa-1 in the diabetic rat. A 37 per cent increase in hydraulic permeability of diabetic membrane was correlated with slit lamp and electron microscopic appearances of oedematous lens fibres in an adult human diabetic lens and the rabbit lens in which the posterior lens capsule had been perforated.

Animals↗
PubMed1984

Ultrastructural appearances of a lens with marked polychromatic lustre: evidence for diffraction as a cause.

A human lens showing polychromatic lustre associated with cortical opacities (Christmas tree cataract) has been examined by slit-lamp photography, thin-section light microscopy, and electron microscopy. Anterior epithelial cells were fibroblast-like, and an area of breakdown of cortical lens fibres was observed in the anterior lens, containing feathery fibres, whorls, and process bodies. Parallel sided stacks of fused cell membranes were found beneath the watery area at the same depth as the polychromatic lustre seen in the slit-lamp. The dimensions of these membrane plates are consistent with the diffraction of light by a parallel thin film to give coloured points of light. Deeper areas of small granules between the lens fibres are associated with the main trunk-like opacity and its branches seen with the slit-lamp.

Aged↗
PubMed1983

Mutations of the beta subunit of RNA polymerase alter both transcription pausing and transcription termination in the trp operon leader region in vitro.

RNA polymerase was purified from rifampicin-resistant mutants of Escherichia coli which exhibit altered transcription termination at the trp operon attenuator in vivo. These mutant polymerases were used to investigate transcription pausing at the trp leader pause site and transcription termination at the trp attenuator. The mutant polymerases examined in vitro mimic their in vivo termination responses; i.e. RNA polymerase isolated from a mutant which displays high transcriptional read-through of the trp operon in vivo allows greater transcriptional read-through in vitro, while RNA polymerase prepared from a mutant which has reduced read-through in vivo exhibits greater termination of transcription in vitro. The observed differences are not due to the presence of--or response to--alternate secondary structures in the trp leader transcript since deletion of the DNA segment corresponding to some of these alternate structures does not affect termination efficiency. The mutant polymerases also have comparable effects on the kinetics of transcription pausing at the trp leader pause site; the termination-deficient polymerase exhibits diminished pausing while the termination-proficient polymerase displays enhanced pausing. We suggest that this correlation reflects polymerase recognition of similar features of RNA secondary structures in the pause and termination events. In addition, since single mutational changes in RNA polymerase affect two activities, pausing and termination, it is likely that a single site or region of the polymerase is involved in both events.

Base Sequence↗
PubMed1982

The water permeability of basement membrane under increasing pressure: evidence for a new theory of permeability.

The water permeability and physical characteristics of the basement membrane (lens capsule) of the crystalline lens of the adult rat have been investigated. The hydraulic conductivity of the basement membrane at low pressure is 50 +/- 9.5 X 10(-12) m s-1 Pa-1 and at high pressure 17 +/- 7.5 X 10(-12) m s-1 Pa-1. This decrease in permeability occurs despite a 75% increase in area of the membrane and a 65% reduction in its thickness. Conventional theories of a membrane possessing pores or of a fibre matrix of filaments of a constant diameter fail to explain the decreasing permeability of the membrane with increasing hydrostatic pressure. The present data suggest that the structure of the membrane is changed by pressure and the coiled filaments of which it is composed are extended as stress is applied to the membrane. If allowance is made both for thinning and for compaction of the membrane and the extension of its area the permeability of the membrane can be predicted satisfactorily at varying pressures. Thus the hydraulic conductivity of basement membrane at a given pressure can be adequately described by the product of a constant and a dimensionless 'deformation coefficient'. This deformation coefficient is equal to the square of the product of the thickness ratio and elongation ratio of the membrane at the given filtration pressure.

Animals↗
PubMed1982

The elastic constants and ultrastructure organization of regenerated basement membrane (lens capsule).

The regenerated basement membrane of the crystalline lens of the rat has been found to have the following elastic constants: a Young's modulus of elasticity of 0.6 +/- 0.48 X 10(6) N m-2 at low stress and 7.8 +/- 2.0 X 10(6) N m-2 at rupture, an ultimate stress of 19.7 +/- 7.0 X 10(5) N m-2, and a maximum percentage elongation of 33.7 +/- 6.1%. Electron microscopic observations of ultrasonicated fragments of the entire membrane show long filaments in parallel arrays and sheets. The filaments show a periodicity of 3.4 nm and a spacing of 3.2 nm. Electron microscopic observations of regenerated membrane treated with collagenase show a poorly staining matrix with separate short thin and thick non-periodic filaments, their diameters being 1.4 nm and 2.5 nm respectively. In addition, strands project from the ends of filaments with a diameter between 0.5 and 1.0 nm. The reduced ultimate strength and Young's modulus of elasticity at rupture in regenerated membrane as compared with normal membrane is considered to be due to the preponderance of thinner filaments in the former. Normal membrane contains not more than 33% of thin filaments whereas regenerated membrane contains at least 78% of such filaments. A comparison of the diameters of thin and thick filaments indicates that thick filaments are probably composed of five strands while thin ones contain three strands.

Animals↗
PubMed1982

Ultrastructure and elastic changes of regenerated basement membrane in normal and diabetic rats.

Basement membrane of the lens capsule was shown by partial enzymic digestion to be composed of thick (2.5 mn-3.3 nm in diameter) and thin (1.4 nm-2.2 nm) filaments. Much thinner filaments or strands (0.5-1.1 nm) projected from the ends of some of the thicker filaments or were occasionally seen separately. From the measurement of Young's modulus of elasticity the proportion of thick and thin filaments in normal membrane were compared with those seen in regenerated normal membrane, diabetic membrane, and regenerated diabetic membrane. In all these abnormal membranes where growth had been disturbed the percentage of thick filaments was reduced.

Animals↗
PubMed1981

The structure of the lens epithelium and its basement membrane in the diabetic state.

The basement membrane of the crystalline lens of the diabetic rat was found to have a similar elasticity modulus at high stress to that of normal membrane. However, at low stress and extension Young's modulus of elasticity was 0.36 (Mean) +/- 0.15 (SD) X 10(6) Nm-2 and about 30 per cent lower than that of normal membrane. Diabetic membrane was significantly more extensible since it extended a further 7.5% as compared with normal membrane before it ruptured. These changes in the elastic properties of the membrane was accompanied by characteristic changes in the epithelial cells. The cells become round and swollen containing cytoplasm rich in rough and smooth endoplasmic reticulum. The changes suggest increased metabolic activity while the presence of intra-cellular membrane whorls indicate phagocytic activity. Plaques of epithelial cells were sometimes found at the anterior poles of diabetic lenses. Electron microscopic observations of ultrasonicated fragments of diabetic membrane showed that the filaments had no difference in periodicity (3.7 nm) from those found in normal membrane, but their spacing was significantly increased by 0.2 nm. The increased extensibility and decreased Young's modulus of elasticity at low stress, together with the increase spacing of the filaments, were shown to be consistent with the view that the helical macromolecules forming the filaments of diabetic basement membrane may be increased in length.

Animals↗
PubMed1981

Epithelial invasion and secretion of banded collagen in the regenerating lens capsule of the rat.

The invasion of large areas of the anterior lens capsule by epithelial cells occurs during regeneration of this basement membrane, in the 3 to 4 months after the capsule has been thinned by collagenase enzyme. The regenerated capsule in these areas is grossly abnormal; it contains up to 15 alternating layers of banded collagen and apparently normal capsular material. The epithelial cells within the laminated capsule, which may secrete the banded collagen, are fibroblast-like and may migrate from the lens epithelium. Banded collagen in the lens capsule has a much smaller periodicity (approximately 5.3nm) than that found in other parts of the eye and may be composed of the same type of filament as normal lens capsule.

Animals↗
PubMed1981

Toxic shock syndrome in menstruating women.

Eight adult women became severely ill with an acute, toxic erythroderma during menses. The syndrome was characterized by fever, generalized erythema, profound shock, multiple organ dysfunction, and desquamation occurring several days after the rash had faded. Gastrointestinal and cardiovascular abnormalities were present in all patients; three patients required ventilatory support; dialysis was performed on two; and one patient died. Mild relapse occurred in two patients during subsequent menses; the other patients have recovered without sequelae during follow-up of 6 to 42 months. Cervical colonization or local infection with Staphylococcus aureus is associated with this syndrome.

Acute Kidney Injury↗
PubMed1980

A comparison of the local and remote effects of basement-membrane regeneration in normal and diabetic rats.

If the capsule basement membrane of the lens is partially removed, the underlying epithelial cells of the normal rat, as the animal ages, continue to produce basement membrane as if the membrane had not been disturbed. The response of the diabetic animal is quite different and basement membrane synthesis is increased by about 60%. Furthermore, this increase also occurs although at a reduced rate in the opposite eye where basement membrane was undisturbed. This might be termed a "sympathetic effect" and appears to be due to a substance or substances dissolved in the aqueous humour of the sympathizing eye and arising from increased activity of cells producing basement membrane in the other eye.

Animals↗
PubMed1980

Comparison of the size of pericytes of the retinal capillaries in the normal and diabetic state.

The sizes of pericytes and aneurysms were measured in washed and unfixed flat autodigest preparations of retinae from normal and diabetic Wistar albino rats kept under observation for up to 12 months. The weight of the lens and lens basement membrane (capsule) was also measured at the time animals were killed. It was found that a very significant increase in the numbers of larger pericytes occurred in the diabetic animals. However, the overall number of pericytes plus aneurysms in the diabetic animal was not greater than the number of pericytes seen in normal animals. No dilatations greater than the diameter of a retinal were seen in normal vessels, so anything greater was considered to be an aneurysm. A very significant correlation exists between the size of the lens and the size of the pericytes in each animal and suggests a common growth relationship. These significant correlations occur in both the normal and diabetic state. Moreover, for a given size of lens, the number of larger pericytes is much increased in the diabetic state. It is suggested that this may be due to the increased extensibility of basement membrane which occurs in the diabetic state with weakening of the capillary wall. This is compensated for by an increase in the size of the surrounding pericyte.

Animals↗
PubMed1979

Thickness and volume constants and ultrastructural organization of basement membrane (lens capsule).

1. The basement membrane of the crystalline lens of the rat has been found to have the following elastic constants: a Young's Modulus of elasticity of 0.56 +/- 0.38 x 10(6) Nm-2 at low stress and 11.3 +/- 1.9 x 10(6) Nm-2 at rupture, an ultimate stress of 28.8 +/- 4.5 x 10(5) Nm-2, and a maximum percentage elongation of 41.3 +/- 5.8. 2. The ratio of initial thickness of the membrane to the thickness at the point of rupture is 0.271 +/- 0.02 while the similar ratio for volume is 0.461 +/- 0.031. 3. Electron microscopic observations of ultrasonicated fragments of the entire membrane show long filaments in parallel arrays and sheets. The filaments show a periodicity of 3.7 nm and a spacing of 3.5 nm. 4. Electron microscopic observations of collagenase-treated membrane show a poorly staining matrix associated with separate short straight non-periodic filaments some 2.5 nm in diameter. In addition strands project from the ends of the filaments with a diameter of between 0.5 and 1.0 nm. 5. A model is proposed which consists of these filaments, composed of between three and five parallel strands, some 0.8 nm in diameter, wound in a superhelix. 6. The model predicts satisfactorily thickness and volume changes in the membrane when subjected to stress, and also indicates that the filaments would have a similar Young's Modulus of elasticity and ultimate stress to those of collagen. 7. If the basement membrane of the smallest retinal capillaries is subjected to a change of pressure of only 5 mmHg within the vessel lumen, then the membrane is likely to undergo some 30% reduction in thickness.

Animals↗
PubMed1979

Influence of a prolonged period of low-dosage x-rays on the optic and ultrastructural appearances of cataract of the human lens.

Human lenses extracted for cataract 26 years after long-term exposure to an imperfectly shielded radium source were examined by slit-lamp photography, thin-section light microscopy, and electron microscopy. Anterior epithelial cells were fibroblast-like, and germinal epithelium and vacuolated cortical fibres had accumulated at the equator. A zone of light scatter at the anterior pole corresponded to an area of breakdown of cortical lens fibres, where unusual feathery fibres were orientated perpendicular to the lens surface. Two zones of light scatter separated by a 250-microM clear interval were seen in the posterior cortex. The zone at the posterior pole corresponded to an area of fibre liquefaction and large rounded membrane whorls, while the deeper zone comprised small flattened membrane whorls. The characteristic plaques of swollen abnormal cells described in previous histological studies of x-ray cataract were not present. This and other differences probably reflect the extremely long time course and repeated subliminal doses to which the patient was exposed.

Cataract↗