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Biomedical subjects

M Wolman

Publications and source records attributed to M Wolman.

At least 19 recordsLinked to original sources

The pituitary-thyroid axis effects on ocular and orbital tissues: a histological, histochemical, and morphometric study.

This work tests the notion that the effect of thyroid hormone on orbital and ocular tissues is mediated through its action on their lysosomal enzymes. Hyperthyroidism was produced in guinea pigs by thyroxin and TSH; hypothyroidism was induced by thiouracil. After treatment for 10 to 21 days, several ocular and orbital tissues were taken for histological, morphometrical, and histochemical examinations. High acid phosphatase activity was demonstrated in extraocular muscles, optic nerve and the retinal pigment epithelium of thyroxine- and TSH-treated animals. The findings fit the notion that the effects of thyroid hormones are mediated through lysosomes also in ocular and orbital tissues.

Adipose Tissue

Connective tissue nevi collagens. Study with picrosirius red and polarizing microscopy.

Biopsy specimens of five connective tissue nevi were examined under crossed polars after staining with Picrosirius red. One biopsy specimen was from a solitary nevus, another from a Shagreen patch. The other three specimens were of erupted nevi. In all cases, thick (as well as thin) collagen fibers appeared green to yellow. In contrast, thick fibers of normal human dermis appeared orange to red. The findings indicate that the collagen of collagenous connective tissue nevi is less well packed than normal collagen. Examination of the polarization colors of Picrosirius red-stained sections is a useful procedure for diagnosing collagenous connective tissue nevi.

Adult

Reappraisal of the role of macrophages in the pathogenesis of atherosclerosis.

New Zealand rabbits were fed an atherogenic diet, 8 with and 8 without twice weekly intravenous injections of GdCl2. The injections caused a reduction in the phagocytic activity of the reticuloendothelial system by one fourth to one half. No significant differences were found between the two groups in the planimetric extent of atheromata in the aortae. GdCl2 treatment inhibited the deposition of sudanophilic lipids in depth of the arterial wall. The findings indicate that macrophages are the primary foam cells and their uptake of lipoproteins is essential for the deposition of lipids in myocytes. Lipid-laden myocytes and ground substance mucopolysaccharides represent sinks in which lipids are removed from the flow and accumulate locally.

Animals

Are the polarization colors of picrosirius red-stained collagen determined only by the diameter of the fibers?

Polarization colors of various purified collagens were studied in fibers of similar thickness. Three different soluble collagens of type I, insoluble collagen type I, lathyritic collagen type I, two p-N-collagens type I, pepsin extract collagen type II, two soluble collagens type III, p-N-collagen type III, and soluble collagen type V were submitted to a routine histopathologic procedure of fixation, preparation of 5-microns-thick sections, staining with Picrosirius red and examination under crossed polars. Polarization colors were determined for thin fibers (0.8 micron or less) an thick fibers, (1.6-2.4 microns). Most thin fibers of collagens and p-N-collagens showed green to yellowish-green polarization colors with no marked differences between the various samples. Thick fibers of all p-N-collagens, lathyritic and normal 0.15 M NaCl-soluble collagens showed green to greenish-yellow polarization colors, while in all other collagens, polarization colors of longer wavelengths (from yellowish-orange to red) were observed. These data suggested that fiber thickness was not the only factor involved in determining the polarization colors of Picrosirius red-stained collagens. Tightly packed and presumably, better aligned collagen molecules showed polarization colors of longer wavelengths. Thus, packing of collagen molecules and not only fiber thickness plays a role in the pattern of polarization colors of Picrosirius red-stained collagens.

Animals

A histochemical principle bearing on correctness of diagnosis in storage diseases.

A principle is proposed which may help pathologists avoid errors in diagnosis of storage diseases. Tissues from patients in whom a tentative diagnosis of a metabolic disorder has been made often store a number of metabolites in the cells. The presence of these metabolites can occur in single-enzyme or activator defects as a result of the following causes: (a) deposition of metabolites situated near the main substrate of the defective enzyme in the catabolic path, and compounds which were changed after they were deposited; (b) presence of multiple substrates for this enzyme; (c) co-deposition of molecules bound to the main substrates; (d) existence of multiple substrates for a single defective activator molecule. In contrast to these causes, variability in processes not associated with a single-enzyme or activator deficiency may be due to the following: (e) inhibition of multiple hydrolases by drugs or metabolites; (f) localization of substrates and hydrolases in different compartments; (g) multiple enzyme deficiencies; (h) concentration of metabolites beyond the catabolic capacity of cells. According to the proposed principle, diagnosis of storage disease resulting from a single enzyme deficiency can be negated if a wide-range histochemical test shows that the main substrate of a deficient enzyme is not present in some primary storage cells. The validity of the principle and possible pitfalls are discussed.

Enzymes

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