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Biomedical subjects

M Wolman

Publications and source records attributed to M Wolman.

At least 37 records · Page 2Linked to original sources

An attempt to prevent or delay denervation changes in rat muscles.

A number of drugs which are known to affect lysosomes and their enzyme activities were used in an attempt to inhibit or delay the onset of denervation changes in rat muscles. The following parameters were used: the occurrence of fibrillations in electromyographs; diameters of muscle fibers; acid phosphatase activity; acetylcholinesterase activity and distribution in end plates. Differences between denervated and non-denervated limbs were evaluated and compared in the different treatment groups. The various parameters were differently affected by the different drugs. Chloroquin, thiouracil and streptomycin appeared to be more effective than other treatments in the inhibition of denervation changes.

Animals↗

Phagocytic system stimulation in experimental atherosclerosis of chicks.

The effects of activation of the phagocytic system by BCG on the development of diet-induced atherosclerosis was studied in chicken. Injections of BCG had a marked effect on atherogenesis, which was either inhibitory or stimulatory, depending on the route of BCG administration and on the timing. A slight, but significant inhibition was obtained by intraperitoneal injection of BCG administered during the dietary treatment. A more pronounced and significant inhibition was observed in chicks given BCG subcutaneously 8 weeks before the start of the dietary regimen. The findings are consistent with a previously proposed notion that immunization at an early age may affect the course of later life atherosclerosis.

Animals↗

Aging of wound healing in an experimental model in mice.

Healing of incised wounds in the backs of mice was studied to establish criteria that would allow the timing of stages during cutaneous wound healing. Starting from day 4 after the incisions were made, three mice were killed every 3 days until day 40. Sections from wounds were stained with hematoxylin-eosin, a reticulin procedure, and picrosirius red. Unstained sections were used for blue autofluorescence. The significance of the findings from the ultraviolet study was limited, but the picrosirius red-polarized light procedure was found to be useful for estimating the age of the repair process as polarization colors of greater wavelengths progressively increased with the age of the lesion.

Animals↗

Lipid pigments and aging.

It is a short survey of lipid pigment formation in which the role of free radicals in the peroxidation of lipids is particularly stressed. The chemical structure of lipopigments and the role of the chemical moiety in histochemical reactions is shortly overviewed. A new aspect of age in the formation of lipopigments is brought to light. Finally the role of hypoxaemia and no-reflow phenomenon influencing the pigment formation is discussed.

Aging↗

The effects of varying lengths and powers of CO2 laser pulses transmitted through an optical fiber on atherosclerotic plaques.

We have studied the changes induced in atherosclerotic arteries by a CO2 laser beam delivered through a silver halide optical fiber. We found that the crater depth and diameter correlate with the total energy delivered and with the mode of delivery. Short-duration high-power pulses caused shallower and narrower craters and less damage to the arterial wall compared to the same energy delivered as low-power pulses of long duration. Thus, high-power pulses for short periods may be an effective and safe procedure for evaporization of atherosclerotic plaques.

Arteriosclerosis↗

Search for virus nucleic acid sequences in postmortem human brain tissue using in situ hybridization technology with cloned probes: some solutions and results on progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis tissue.

In order to obtain a useful and readily applicable in situ hybridization (ISH) protocol for progressive central nervous system (CNS) diseases of unknown etiology that are possibly due to persistent viral infection, known and well described diseases were studied, namely, progressive multifocal leukoencephalopathy (PML) and subacute sclerosing panencephalitis (SSPE). The procedures described were validated by confirming results obtained by other investigators using histology, immunocytochemistry, electron microscopy, and ISH. A number of frequently encountered problems of tissue preparation are addressed as well as techniques to reduce autoradiography exposure times. A multi-staged specific, sensitive, reliable, and valid procedure for detection of viral genomes, mRNA and proteins is approached. Formalin-fixed and paraffin-embedded (FFPE) brain material from six patients who died with PML and one patient who died from SSPE were studied using ISH with a tritium-labeled cloned JC virus DNA probe and a measles-cloned nucleocapsid (NC) gene cDNA probe, respectively. This report constitutes a methodological framework as well as a detailed neuropathological analysis of identified brain cell populations within which in situ hybridization was detected. In early PML lesions, swollen nuclei or oligodendrocytes were the predominant cells labeled, whereas older lesions revealed increased numbers of reactive and bizarre hypertrophic astrocytes hybridized at the outer periphery of the demyelinated lesions. The hybridization varied greatly in intensity in different cells. Intense hybridization was noted very rarely in microglial cells, including rod cells and rarely in venular pericytes, intravascular mononuclear cells, or in vascular endothelial cells. These results, considered together with previous findings, indicate that in PML the viral infection runs different courses in the various cells: in astrocytes the viral genome persists for a long time inducing pathological changes in some cells. In oligodendrocytes the infection rapidly lyses the cells. There was a good correlation between chromatic changes observable in routinely stained sections and virus presence. In addition, in situ hybridization using a measles-NP-cloned probe in white matter from FFPE SSPE brain is presented confirming earlier results in SSPE cryopreserved brain.

Adult↗

Polarized light microscopy in the study of the molecular structure of collagen and reticulin.

Although collagen structure has been studied by polarized light microscopy since the early 19th century and continued since, modern studies and reviews failed to correlate the conclusions based on data obtained by the techniques with those of polarized light microscopy. Collagen I is intensely positively birefringent in respect to length of the fibres; the positive intrinsic birefringence indicates a quasi-crystalline alignment parallel to the fibre and molecule axis of the amino acid residues of the polypeptide chains. This would not have been compatible with a helical structure but has been achieved by similar tilt angles and opposite directions of the coiling and supercoiling. Birefringence characteristics of collagen are also affected by chemical treatments, extractions and staining procedures. Attachment of chemical groups to the anionic charges present on the surface of collagen molecules results in increased positive birefringence in the case of bipolar molecules attached to two or more anionic residues. Unipolar attachment to the same groups, or to the cationic groups of the associated proteoglycans, as well as sulfation or acetylation of hydroxyls of the protein and/or the carbohydrate, reduced or reversed the sign of birefringence. Increased birefringence caused by stretching cannot be due to intramolecular events and is caused by intermolecular changes. The same applies to changes in collagen during aging. Reticulin is a group of different substances which mostly contain collagen III. The pliability and deformability of this collagen is related to its weakly negative birefringence due to large side chains and presence of different and greater amounts of interstitial proteoglycans and other molecules. The so-called reticulin of healing wounds differs in its constitution from other reticulins but is also rich in intermolecular carbohydrate components.

Birefringence↗

Encephalopathy with astrocytic residual bodies. Report of a case and review of the literature.

Biopsy and autopsy findings in a girl who died at 7 1/2 months after having suffered from progressive axial hypotonia, myoclonus, EEG changes and retarded psychomotor development. Inclusions consisting of lamellar profiles, situated in membrane-bound cytosomes were found mainly in astrocytes, but also in neurones and in axons of peripheral nerves. Lipofuscin bodies were also increased in number. The patient belongs in the same category as cases studied by Towfighi et al. (1975) and Martin et al. (1977). Etiology and pathogenesis of this syndrome remain unknown. It is suggested, however, that the pathological changes observed might have been caused by the administration soon after birth of anti-epileptic drugs (diphenylhydantoin, clonazepam and nitrazepam).

Anticonvulsants↗

Different modes of cell death and related phenomena: a proposal for a meaningful terminology in relation to tests of lethality.

The terms death (as an irreversible occurrence), necrosis and apoptosis are well defined and generally accepted in cell biology. Procedures and terminology related to estimation of different forms of cell mortality are, however, less clear and exact. Evaluation of the rate of mortality is important for numerous biological processes such as growth, atrophy, regeneration and neoplasia. Procedures used for assessing cell mortality include: 1. dye exclusion tests which were shown to be inadequate in apoptosis; 2. release of radioactive markers, also inadequate, as they occur also in life during shedding of membranes and cleavage of cell parts; 3. morphological and histochemical procedures which show only relatively late changes (autolysis) in cells which have not yet been completely obliterated; 4. absence of synthetic activities, which do not necessarily indicate death (e.g. mature erythrocytes); 5. colony forming capacity in cultures, which are considered by most authors as the most useful tests for assessing the effects of cytotoxic treatments. These tests do not, however, assess viability, but rather reproductive capacity. In all these tests, delayed changes in vitality can be determined by repeated or continuous testing. The following new terms are proposed and related to presently available tests. Aposchisis--for cleavage of cell parts not necessarily associated with cell death. N-mortality--for necrosis type of mortality estimated by the dye exclusion tests. A-mortality--for apoptosis type of mortality, which cannot be directly estimated at present. Acarpy--for loss of reproductive capacity of cells which is assessed by the colony forming tests.

Cell Survival↗

The role of nerve lysosomal enzymes in the pathogenesis of denervation atrophy. Electromyographic and histochemical study in rats.

Section of sciatic nerves of rats produced fibrillations within 3 days. Foci of hyalination leading to necrosis corresponded to segments of muscles containing end plates. The electrolyte content, mainly Ca, was increased, NADH2-TR activity was decreased and membrane ATP-ase was increased. The known increase in hydrolytic enzyme activities in denervated muscles was due to spilling of lysosomal enzymes from degenerating axons at the myoneural junction. This explains the discrepancy between morphological studies indicating paucity of lysosomes in normal muscles and the high hydrolytic enzyme activities in denervation. We propose that denervation changes are at least partly due to the effect of lysosomal spillage from degenerating axons.

Adenosine Triphosphatases↗

Can pseudomonas infection in experimental animals mimic Kawasaki's disease?

Experiments aimed at producing a model of Kawasaki's disease by injecting animals intraperitoneally with Pseudomonas bacilli are described. Injection of large numbers of bacilli into mice caused rapidly fatal sepsis. With appropriate numbers of organisms, some mice died within 3 days, most remained healthy, while in some an inapparent chronic disease developed. Positive blood cultures were occasionally obtained 4-17 weeks after the slow infection. An alcohol-precipitable polysaccharide, which could be measured by Roe's procedure for levan, was found in 20% of the experimentally infected mice. We suggest that this substance was partly responsible for the course of the infection. Severe vasculitis with little acute inflammatory reaction and carditis with coronary aneurysms were often obtained by injecting mice and guinea-pigs with supraliminal doses of bacilli at the same time as their immune system was impaired by treatment with either nitrogen-mustard or cyclophosphamide. We suggest that pseudomonas infection in immunologically deficient animals may mimic Kawasaki's disease and that a similar mechanism may operate in the natural form of the disease in children.

Animals↗

Change from inhibition to stimulation by levan of AKR lymphoma following serial transfers.

A progressive increase in malignancy following serial passages of AKR lymphoma is often accompanied by loss in sensitivity to the antitumor agent, levan. In further transfers, stimulation of tumor growth, instead of inhibition, is sometimes observed. It is proposed that the shift from inhibition to stimulation of tumor growth by the immunomodulator levan may be due to a change during tumor progression in the sensitivity of the tumor cells to the reported dual effect of macrophages, inhibitory or stimulatory, on tumor growth.

Adjuvants, Immunologic↗