M.A. Spycher

Isolation and characterization of rough endoplasmic reticulum associated with mitochondria from normal rat liver

A subfraction of rough endoplasmic reticulum (RER) characterized by its close association with mitochondria (MITO) was isolated from low speed pellets of normal rat liver homogenate under defined ionic conditions. This fraction enriched in MITO-RER complexes contained 20% of cellular RNA, 20% of glucose-6-phosphatase and 47% of cytochrome c oxidase activities. Morphologically, the isolated MITO-RER complexes closely resembled physiological associations between the two organelles commonly seen in intact liver. Partial dissociation of RER from mitochondria of the MITO-RER fraction was achieved by either EDTA (0.5 mM) or by hypotonic/hypertonic treatment of MITO-RER complexes. With the latter procedure approx. 70% of RER (RERmito) with 50% of ribosomes still attached could be separated from the inner compartments of mitochondria. This RERmoto exhibited a higher glucose-6-phosphatase activity than RER isolated as rough microsomes from the postmitochondrial supernatant. Isopycnic centrifugation on linear metrizamide gradients revealed that the mitochondria-associated part of RER corresponds to the high density, ribosome-rich subfraction of rough microsomes isolated in cation-free sucrose solution. The combined data demonstrate that a morphologically and biochemically distinct portion of RER is associated with mitochondria and support the concept of considerable intracellular heterogeneities in distribution of enzymes and enzyme systems along the lateral plane of the endoplasmic reticulum membrane system.

Ultrastructural Changes of Capillaries in Chronic Venous Insufficiency

The ultrastructural changes of cutaneous and subcutaneous capillaries and venules in 6 cases of severe, chronic venous insufficiency were examined. The findings in all cases consisted of numerous and characteristic alterations of the vessel wall structure and of the pericapillary space which are supposed to be due to the increased intravenous pressure. The intercellular spaces are enlarged to wide channels through which erythrocytes pass into the perivascular spaces. Microvesicles occur in great numbers, they are arranged in chain-like formations and seem to come together to form transendothelial channels. Around the capillaries, edematous fluid with proteins and erythrocytes accumulates. Phagocytosis of erythrocytes, siderosomes and collagen fibrils by macrophages is observed. Within the endothelial cells there is an abundance of Weibel-Palade bodies and of multivesicular bodies. The former are frequently seen in contact with the luminal cell membrane. Weibel-Palade bodies are believed to be involved in the clotting mechanism.

Isolation of a subfraction of rough endoplasmic reticulum closely associated with mitochondria: Evidence for its role in cytochrome P450 synthesis

Abstract A subfraction of rough endoplasmic reticulum (RER) structurally associated with mitochondria (mito-RER complexes) was isolated from crude nuclear fractions of rat liver homogenate. When apocytochrome P450 synthesis (which presumably occurs in RER) and mitochondrial heme synthesis was dissociated by concomitant treatment of rats with phenobarbital and cobaltous chloride, apocytochrome P450 accumulated predominantly in mito-RER complexes. These data suggest that cytochrome P450 synthesis requires structural interaction of mitochondria and RER.

Metaplastic lipid‐rich carcinoma of the breast

A case of lipld‐rich mammary carcinoma identified in a lumpectomy specimen from a 56year‐old female is presented. The tumor showed features of poorly differentiated invasive ductal carcinoma of clearcell phenotype. Cytoplasmic lucency was mainly accounted for by the accumulation of neutral fat and, to a lesser degree, glyco‐gen. Tlnctorial properties Included positivity of tumor cells with Sudan iii dye and diastasesensitive periodic acid‐Schiff staining. Ultrastructural examination confirmed the presence of abundant cytoplasmic lipid droplets and some glycogen rosettes. On immunohistochemistty, most tumor cells reacted for cytokeratin, vimentin and S‐100 protein, and there was focal expression of carclnoembryogenic antigen. A minority of tumor cell nuclei expressed progesterone receptors. As an additional feature, part of the leslon exhibited chondroid metaplasia. Lipid‐rich carcinoma of the breast is exceedlngly rare and, to our knowledge, no such example harboring metaplastic elements has been described previously.

Scarring Folliculitis in the Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome

Several clinical syndromes are characterized by ectodermal dysplasia (ED) in association with clefting of the lip and/or palate. In these syndromes, alopecia is primarily due to abnormalities of the hair shaft associated with increased hair fragility. Scalp dermatitis is yet another peculiar finding, primarily seen in the ankyloblepharon-ED-clefting (AEC) syndrome. We report on a 16-year-old patient with ectrodactyly-ED-clefting (EEC) syndrome, who exhibited a scarring alopecia due to deep folliculitis. On scanning electron microscopy, irregular torsion and longitudinal grooving of the hair shaft (pili torti et canaliculi) were observed. Quantitative determinations of the elastic and viscous parameters of hair demonstrated a normal viscosity but a significantly reduced hair elasticity, indicating either an abnormal composition or a disordered arrangement of microfibrils within the apparently normal keratin matrix. In contrast to the erosive scalp dermatitis of early onset in the AEC syndrome, alopecia in this case of EEC syndrome demonstrated follicular scarring with onset during puberty. We question a possible role of the anatomical hair abnormality in the pathogenesis of chronic deep folliculitis in this and clinically related syndromes.

Ultrastructural Study of the Normal Rabbit Synovium

The major lining cells of normal rabbit synovium are morphologically classified into two types. One type resembling macrophages or histiocytes (M type) is characterized by dense peripheral nuclear chromatin, many cytoplasmic vacuoles, coated vesicles, poorly developed, rough-surfaced endoplasmic reticulum (RER) and numerous filopodia. Some of the superficially located M cells containing accumulated cytoplasmic filaments are small and less active than the lower M cells. The second type resembling fibroblasts (F type) possesses dispersed nuclear chromatin, distended RER, prominent Golgi apparatus and abundant smooth-surfaced pino-cytotic vesicles. Lysosomal inclusions are commonly seen in both types of cells. In view of the morphological and functional similarities of M cells and regular macrophages or histiocytes, respectively, it seems likely that they are derived from common precursors and these precursor cells differ from those of F cells.

Histopathologic and ultrastructural study of lupus-like skin lesions in a patient with Bloom syndrome

The histopathology of the lupus‐like skin lesions associated with Bloom syndrome has been sporadically described. Skin biopsies from a 2‐year‐old boy with the classical features of Bloom syndrome, including lupus‐like skin lesions, demonstrated marked interface changes with basal liquefaction degeneration, a moderate superficial mononuclear infiltrate, pigmentary incontinence, and capillary dilation in the papillary dermis. Immunophenotyping of the dermal infiltrate revealed predominance of T‐cells. Basement membrane thickening on periodic acid‐Schiff examination was not seen. Direct immunofluorescence failed to demonstrate deposits of immunoglobulin other than nonspecific IgM deposition along the basement membrane zone of lesional skin. Ultrastructurally, the most striking findings were disintegration of basal cell cytoplasm and tubuloreticular inclusions in vascular endothelia. Taken together, the histologic and ultrastructural features of lipus‐like lesions associated with Bloom syndrome mimic those of cutaneous lupus erythematosus, with the exception of paucity of immune deposits at the dermoepidermal Junction.

Acquired Hair Fragility in Pili anulati: Causal Relationship with Androgenetic Alopecia

Pili anulati are defined by characteristic alternating light and dark banding in the hair shaft, due to air-filled spaces between the macrofibrillar units of the hair cortex, and are regarded as a congenital hair shaft disorder without increased hair fragility. Two cases of pili anulati are presented, in which fragility of hair developed in a causal relationship with the onset of androgenetic alopecia. Accordingly, trichorrhexis-nodosa-like hair fracturing was exclusively limited to the androgenetic region. In general, secondary trichorrhexis nodosa is an unspecific finding related to excess stress of hair in relation to its fragility. With onset of hair thinning due to androgenetic alopecia, progressive reduction of hair shaft diameter may cause increased fragility in pili anulati. In this case, hair shaft fracturing occurs within the area of androgenetic alopecia and colocalizes with the air-filled cavities of pili anulati.

Subcellular distribution of aspartate aminotransferase isoenzymes in chicken heart: A quantitative study

1. The content of the two aspartate aminotransferase isoenzymes in isolated mitochondria and in the cytosolic fraction from chicken heart was determined by radioimmunoassays. 2. The cationic isoenzyme was found to be associated with the mitochondrial fraction; its content measured in the cytosolic fraction was within the range of that of contaminating mitochondrial marker enzymes. 3. The anionic isoenzyme was found exclusively in the cytosolic fraction, in mitochondria a content of less than 0.05% of the total was measured. 4. Thus, in birds, the anionic and the cationic isoenzyme of aspartate aminotransferase show the same strict intracellular heterotopism as found previously in mammals.

Das Trichorhinophalangealsyndrom Fallbeispiel mit Untersuchung der biophysikalischen Haarschaftparameter

ZusammenfassungDas Trichorhinophalangealsyndrom (TRPS) wurde erstmals 1956 von Klingmüller im Hautarzt beschrieben und 1966 von Giedion aus Zürich als solches bezeichnet. Es umfasst eine Kombination charakteristischer Haar-, Gesichts- und Knochenanomalien variabler Ausprägung, auf deren Grundlage 3 Subtypen unterschieden werden. Bei einer 37-jährigen Patientin mit TRPS Typ I fanden sich neben einem laut anamnestischer Angabe begrenzten Längenwachstum der Haare klinisch feine, spröde Haare. Rasterelektronenmikroskopisch fiel eine Verbreiterung des Abstands der Kutikulaschuppen auf. Die Messung der biomechanischen Eigenschaften ergab einen signifikanten Anstieg des viskösen Parameters als möglichen Ausdruck einer Reduzierung von Disulfid- und Zunahme von Wasserstoffbrücken in der Keratinmatrix des Haares. In der dermatologischen Praxis werden Patienten mit TRPS vorrangig aufgrund der Haarproblematik vorstellig. Aufgrund der Gelenkanomalien sollte mit der Möglichkeit der vorzeitigen Arthrose gerechnet werden und eine entsprechende Patientenaufklärung und Berufsberatung erfolgen. Weitaus seltener kommen kongenitale Herzvitien, Nierenanomalien und endokrinologische Störungen vor, die bei entsprechenden anamnestischen oder klinischen Hinweisen abzuklären sind. Vonseiten der Haare bestehen außer einer schonenden Pflege unter Vermeidung zusätzlicher, exogener, schädigender Einwirkungen, v. a. haarkosmetischer Art, keine weiteren therapeutischen Möglichkeiten.AbstractIn 1956 Klingmüller first described the trichorhinophalangeal syndrome (TRPS), which was named by Giedion ten years later. The syndrome includes a combination of typical hair, facial and bone abnormalities with variable expression allowing the further distinction of three subtypes. In a 37-year old patient with TRPS type I who reportedly had reduced hair growth length, clinically fine and brittle hair were found. Scanning electron microscopy revealed widely spaced cuticular scales. Quantitative measurement of the biomechanical properties of the hair showed a significant increase in the viscous parameter. This could be a result of decreased disulfide bridges and increased halogen bonds in the keratin matrix of the hair. In dermatological practice patients with TRPS often present because of hair abnormalities. Because of premature arthrosis due to skeletal abnormalities, occupational counseling is advised. Congenital heart problems, kidney abnormalities and endocrinological problems are rare, but should be sought in the symptomatic individual. Apart from mild hair care and avoidance of additional physical or chemical injuries due to hair cosmetic procedures, there is no treatment for the hair defects.