Biomedical subjects

F N Ghadially

Publications and source records attributed to F N Ghadially.

At least 73 records · Page 4Linked to original sources

PubMed1979

Ultrastructural localization and in situ analysis of iron, bismuth, and gold inclusions.

The purpose of this article is to review ultrastructural and electron probe X-ray analytical studies on metallic deposits in cells. The metals that will be dealt with are iron, bismuth, and gold, mainly because they have been extensively studied in recent years. The nature and chemical composition of endogenously (e.g., from breakdown of autologous blood) and exogenously (e.g., after a transfusion or injection of iron compounds) produced hemosiderin (i.e., iron deposits) has been the subject of time-hallowed controversies. Quite a few of these have now been resolved by ultrastructural studies and the atomic composition of such deposits has been determined by electron probe X-ray analysis. The interest in bismuth centers around the fact that this is one of the two metals (the other being lead) that produces quite large intranuclear inclusions. Here again much has been learned by ultrastructural and X-ray analytical studies. The interest in gold stems from the fact that soluble salts of this metal are used for the treatment of rheumatoid arthritis and current studies with the above-mentioned techniques indicates how gold produces its beneficial and toxic effects.

Animals↗

PubMed1979

The aurosome.

Aurosomes are lysosomal bodies containing gold. Colloidal gold produces aurosomes containing spherical electron-dense granules. Soluble gold salts produce aurosomes containing lamellar, filamentous and rod-like profiles studded with particles and granules. This morphological pattern is quite distinctive, and is not affected or altered by which particular soluble gold salt is administered, by which route it is administered or in which species or cell type the aurosome occurs. In the skin of patients treated with soluble gold salts the characteristics electron-dense formations indicating the presence of gold are often found in compound melanosomes and other lysosomes in the dermal macrophages; while in the synovial membrane these characteristic electron-dense deposits are seen in the numerous lysosomes that develop in the rheumatoid synovial membrane. Thus it would appear that while aurosomes may vary somewhat in morphology, the electron dense contents indicating the presence of gold have a fairly constant morphology.

Animals↗

PubMed1979

The technique of electron probe x-ray analysis and the atomic composition of aurosomes.

Electron probe x-ray analysis is an exciting new method of elemental analysis at the ultrastructural level. This is a relatively non-destructive form of analysis by which elements from Na onwards (i.e. above Z number 10) can be simultaneously detected and displayed as a spectrum. The best spatial resolution that can be achieved is of the order of 20 nm. The sensitivity of detection varies with the elements but about 10-18 g of an element can be detected. With the available computer programs elemental ratios are readily determined without the need of standards. The special appeal of this technique stems from the fact that it is the only way of analyzing minute inclusions in situ within the cell and so correlate morphology with atomic composition. With this method, gold has been demonstrated in aurosomes produced in various sites after the administration of soluble gold salts to experimental animals and man. A more detailed analysis of aurosomes found in the synovial membrane 3 days and 18 months after injection of gold sodium thiomalate into the rabbit knee joint revealed that the aurosome contains gold, phosphorus, and sulphur, and that the atomic ratios of these elements do not alter over the above mentioned time interval.

Animals↗

PubMed1979

Enzyme content of hepatocellular lysosomes in the tumour-bearing rat.

An increase in the number of hepatocellular lysosomes is detectable with the electron microscope in rats bearing a carcinogen-induced sarcoma but not in rats bearing a transplanted Walker tumour. Biochemical studies show an increase in lysosomal enzymes in the liver of both groups of rats, but the increase in the rats bearing a carcinogen-induced sarcoma was greater than that in rats bearing a Walker tumour. This difference is explained by the fact that only gross increases in lysosomal population are likely to be detected in the small samples examined with the electron microscope, but by biochemical methods whereby many grams of tissue are analysed, finer changes may be detected. The collective data to date indicate that an increase in hepatocellular lysosomes and/or lysosomal enzymes occurs in rats and man bearing a variety of tumours and to this there is, as yet, no known exception.

Acid Phosphatase↗

PubMed1978

A mechanism of formation of desmosome-like structures between synovial intimal cells.

Desmosomes or desmosome-like structures do not occur between normal synovial cells but such structures do develop between the synovial cells in cases of traumatic arthritis, rheumatoid arthritis and villonodular synovitis. Morphological evidence is presented suggesting that such structures develop as a result of the interaction of fibrin trapped between synovial cells and the plasmamembrane of these cells.

Arthritis, Rheumatoid↗

PubMed1978

Long term effects of myochrysine in articular cartilage.

Intra-articularly administered sodium aurothiomalate (Myochrysine) produced aurosomes containing characteristic electron dense contents (indicating the presence of gold), in the chondrocytes of rabbit articular cartilage. At first the aurosomes were bounded by a membrane but later the electron dense contents were seen lying free in the cytoplasmic matrix. Such deposits were detectable up to 14 months after injection of Myochrysine but none were found at later time intervals (18 months and 2 years). There was a reduction in the population of superficial chondrocytes (Zone I) while those in deeper zones (Zones II and III) showed an increased content of intracytoplasmic filaments. It is thought that these are regressive or degenerative changes produced by gold.

Animals↗

PubMed1978

Ultrastructure of the skin of patients treated with sodium aurothiomalate.

Skin biopsies from cases of rheumatoid arthritis treated with sodium aurothiomalate were examined with the electron microscope. Intralysosomal gold deposits were found in the macrophages of both normal-looking skin and from areas of erythematous rash that had developed as a toxic manifestation of gold therapy. The main difference between affected and normal-looking skin was the presence of numerous mast cells in the former. It is hence suggested that the dermatologic side-effects of gold are probably mediated by the release of vasoactive substances from mast cells and that vigorous administration of antihistamines to neutralise the liberated products of mast cells or an agent that interferes with degranulation of mast cells might have a palliative effect on the skin rash that sometimes develops during chrysotherapy.

Adult↗

PubMed1978

Ultrastructure of intramuscular haematomas and electron-probe x-ray analysis of extracellular and intracellular iron deposits.

Haematomas were produced in rabbits by intramuscular injections of autologous blood. Clotting and marked lysis of erythrocytes was noted in these haematomas but there was no evidence of fragmentation of erythrocytes, prior to, during, or after ingestion by macrophages as has been reported in other sites such as spleen, peritoneal cavity or joint cavity. The phagocytosis of intact erythrocytes, lysed erythrocytes and haemoglobin led to the formation of three main types of lysosomal bodies, (1) myelinosomes, (2) siderosomes and (3) myelinosidersomes. Electron-probe X-ray analysis of siderosomes has yielded further data supporting the idea that haemosiderin is essentially an inorganic iron compound; presumably a hydrated ferric oxide. An unusual and hitherto unreported finding was the occurrence of electron-dense granules in the connective tissue matrix in two animals. The granules were shown to contain iron, calcium, potassium and phosphorus. It is thought they might represent an attempt at pathological calcification in damaged tissue.

Animals↗

PubMed1978

Long-term effects of myochrysine on the synovial membrane and aurosomes.

Mysochrysine injected into the rabbit knee joint produced regressive and destructive changes in the synovial membrane, ultimately leading to fibrosis. Aurosomes, containing characteristic electron-dense deposits indicating the presence of gold, formed in the synovial intimal cells and subsynovial macrophages. The number of aurosomes decreased with the passage of time but some were found even 2 yr after the injection of Myochrysine. Electron-probe X-ray analysis showed that the aurosomes contain gold, sulphur and phosphorus. A comparison was made between the atomic ratios of these elements in 3-day and 18-mth-old aurosomes but no significant difference was detected.

Animals↗

PubMed1978

Ultrastructure of rabbit semilunar cartilages.

A light and transmission electron microscopical study of 6 to 8 months old rabbit semilunar cartilages has shown that the cells in this tissue resemble chondrocytes more than fibroblasts. The prominent organelles in these cells were rough endoplasmic reticulum and the Golgi complex. An unusual finding was the occurrence of filamentous material in Golgi sacs and vesicles, and collagen fibrils within smooth membrane-bound tubular structures, apparently within the cells. Collagen fibrils forming fibres, fibre bundles and lamellae constituted the major component of the menisci. Protein-polysaccharide particles and associated fine filaments were found in the interfibrillary matrix and in the sparse territorial matrix adjacent to the chondrocytes. Numerous immature elastic fibrils, and rare mature elastic fibres with an electorn-lucent amorphous core, were also found in the general matrix amongst the collagen fibrils.

Animals↗

PubMed1978

A maturation change in the surface of cat articular cartilage detected by the scanning electron microscope.

The articular surface of the femoral condyle of kittens (2 days to 2 months old) and cats (6 months to 20 months old) was studied by examining air dried and critical point dried specimens in the scanning electron microscope. The surface of kitten cartilage was found to be populated by innumerable humps which were more prominent in air dried than in critical point dried specimens. Undulations and ridges were seen on air dried kitten cartilage, which was markedly shrunken and distorted, but undulations and ridges were absent from critical point dried specimens where shrinkage was more modest or even undetectable. The surface of the articular cartilage of 12 months and 20 months old cats was populated by innumerable pits. A rare hump in a pit was seen in specimens from the 12 months old cat, but not from the 20 months old animal. In 6--8 months old cats an intermediate situation prevails, for in some specimens pits were present on the posterior part of the condyle but humps and humps in pits were present on the anterior aspect. This study shows that the surface of young articular cartilage is populated by humps, but as the cartilage matures these formations are either transformed into pits or replaced by pits.

Age Factors↗

PubMed1978

A maturation change detected in the semilunar cartilages with the scanning electron microscope.

The surface of rabbit, cat, monkey and human semilunar cartilages was examined with the scanning electron microscope. A common feature was the occurrence of numerous ridges, undulations and furrows on the surface, but this was thought to be due to marked shrinkage and distortion of cartilage not firmly attached to bone. Humps were seen on the semilunar cartilages of young animals, but pits occurred in adults. This is thought to reflect a maturation change. Humps were seen in a young human semilunar cartilage, but pits were not seen in adult specimens. It is not clear whether pits are truly absent or just masked by the severe ridging produced during the preparation of large human specimens.

Aging↗

PubMed1977

Aurosomes produced in the synovial membrane by the oral administration of a gold compound SK & F 36914.

Chlorotriethylphosphine gold (SK & F 36914) administered orally to rabbits produced aurosomes in the synovial membrane. These aurosomes were similar to aurosomes produced by parenteral or intra-articular injections of soluble gold salts such as sodium aurothiomalate and aurothioglucose. This study shows, (1) that an orally administered gold compound is capable of producing gold deposits in the synovial membrane, and (2) that such compounds may have a future in the treatment of rheumatoid arthritis.

Administration, Oral↗

PubMed1977

Satellite heterophagosomes.

An incidental observation made during a recent ultrastructural study shows that after ingestion of an erythrocyte by a Kupffer cell surface budding occurred from the heterophagosome leading to the formation of smaller satellite or daughter heterophagosomes. It is suggested that an entire erythrocyte may be too large to digest in a single heterolysosome and that fragmentation into smaller units facilitates digestion by bringing about better contact between the enzymes and substrates.

Erythrocytes↗

PubMed1977

Ultrastructure of experimentally produced subcutaneous haematomas in the rabbit.

Haematomas were produced in rabbits by subcutaneous injection of autologous blood. Clotting and marked lysis of erythrocytes was noted in these haematomas, but there was no evidence of fragmentation of erythrocytes prior to or after ingestion by macrophages as has been reported in other sites such as the peritoneal cavity and the joint cavity. The phagocytosis of intact erythrocytes, lysed erythrocytes and haemoglobin led to the formation of three main types of lysosomal bodies; (1) myelinosomes containing whorled osmiophilic membranes, (2) siderosomes containing haemosiderin, and (3) myelinosiderosomes containing a mixture of osmiophilic membranes and haemosiderin.

Animals↗

PubMed1977

Long-term results of deep defects in articular cartilage. A scanning electron microscope study.

Core defects produced in the medial femoral condyle of the rabbit were studied by scanning electron microscopy and light microscopy over a period of 2 years. In some cases the defect was filled by hyaline articular cartilage with a fairly smooth surface, but in others the tissue was markedly fibrillated and resembled fibrous tissue and fibrocartilage. Appearances suggesting disintegration of the newly formed cartilage were seen in some cases. It would appear that a continuation of this process can lead to the exposure of subchondral bone. In one instance no repair tissue or new cartilage could be identified but the surrounding old cartilage had formed a shelf over the defect. The cartilage surrounding the defect was either normal or showed superficial fibrillation, and/or flow formation, and/or fissures.

Animals↗

PubMed1977

Long-term results of superficial defects in articular cartilage: a scanning electron-microscope study.

Superficial defects produced in rabbit articular cartilage were studied with the scanning electron microscope over a period of 2 yr. It would appear that at first a new layer of matrix forms on the injured surface but that this is abraded away by joint movement so that even after 2 yr the defect does not heal. In some instances the general articular surface developed superficial fissures, deep ravines, and foci of fibrillation.

Animals↗

PubMed1977

Atypical glycogen deposits in a plasmacytoma: an ultrastructural study.

A solitary, benign plasmacytoma, arising from the gum of the lower jaw of a dog, was studied by light and electron microscopy. Some of the tumour cell nuclei showed the characteristic clockface or cartwheel pattern of heterochromatin distribution similar to that found in normal plasma cells. Like normal plasma cells the tumour cells were endowed with rough endoplasmic reticulum but this was invariably dilated or visiculated. Glycogen deposits were found within mitochondria and within the dilated and vesiculated rough endoplasmic reticulum. The idea that these deposits were derived secondarily from glycogen deposits in the cytoplasm seems untenable because no glycogen particles were found in the cytoplasmic matrix. It would therefore appear that most, perhaps all, stages of glycogen synthesis occurred within the mitochondria and rough endoplasmic reticulum of some of these tumour cells.

Animals↗