Biomedical subjects
Publications and source records attributed to T Kobayasi.
Lipoid proteinosis (Urbach-Wiethe disease) is a rare, recessively inherited disorder that is characterized by the deposition of hyaline-like material in the skin, oral cavity, and other tissues. It usually appears in infancy with hoarseness. We report a case of lipoid proteinosis in a 10-year-old boy that demonstrates the characteristic clinical, histologic, and ultramicroscopic features of this disease.
The effects of recombinant human erythropoietin (rHuEPO) on improving the anemia associated with autologous blood collection before open heart operations and on improving the postoperative anemia were studied. The study was carried out on 18 patients undergoing coronary artery bypass operations; 400 mL of autologous whole blood was taken from each patient 2 weeks before operation and was subsequently used in the operation, and rHuEPO (100 U.kg-1.day-1) was given intravenously for 2 weeks before operation and for 1 week after operation. The group in which iron preparations were also administered intravenously was designated as group I (10 patients), and the group in which rHuEPO was given alone was designated as group II (8 patients). In group III, as a control group, 11 past patients were used in whom 400 mL of autologous whole blood was collected 2 weeks before operation but neither rHuEPO nor iron preparations were given. After autologous blood collections, the hemoglobin levels improved in group I, group II, and group III, in that order, and with significant differences among them. It was shown that rHuEPO was effective in ameliorating the anemia associated with preoperative autologous blood collection, and the effect was further enhanced with intravenous supplementing iron preparations. After operation, the anemia markedly improved while rHuEPO was administered, but the hemoglobin levels decreased rapidly when the administration was terminated. Further studies are needed regarding the use of rHuEPO after operation.
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A patient suffering from generalized morphea developed blisters in the morpheic plaques on her buttocks. The plaques had an increased concentration of serum aminoterminal propertice of type III procollagen, an echo response and thickened skin on ultrasound scanning, and compact bundles of collagen fibrils with bimodal distribution of the diameters. The blisters appeared as an echo-free band in the subepidermal zone by ultrasound scanning. Electron microscopy revealed blisters in the upper papillary dermis, surrounded by degraded collagen fibrils.
Mucosal biopsies from the pharynx, right main stem bronchus and right lower lobe were obtained during flexible fiberoptic bronchoscopy and were examined with light microscopy (LM) and electron microscopy (EM) in 10 asthmatics after 11 months' (range 7-15 months) treatment with high doses of inhaled budesonide via the Nebuhaler, i.e. 1600 micrograms daily. Results were compared with biopsies from 10 controls suspected of having focal, malignant lung diseases. Visual inspection of the tracheobronchial tree showed no signs of atrophy, ulcerations or thrush patches, and LM and EM showed no specific signs of mucosa and connective tissue atrophy; however, epithelial desquamation was seen in the asthmatics. No complications were observed.
A case of vulvar angiokeratoma studied by electron microscopy is described. The patient, a 51-year-old woman, had noticed eruptions for the last 15 years, though without symptoms. Osmiophilic bodies with myelin-like figures were found in the vascular endothelial cells. The findings support previous opinion that vulvar angiokeratoma is a variant of scrotal angiokeratoma.
Punch biopsies from syphilitic leukoderma lesions and from unaffected skin in 3 patients with secondary syphilis were studies in the transmission electron microscope. In one of the patients the pigment disorder was not preceded by any visible syphilids, and in the biopsy from the leukodermal skin in this patient Treponemata pallidium were demonstrated around vessels and inside nerve fibres in which the myelin sheaths of the axons showed evidence of degeneration. In the other 2 patients the depigmented areas appeared while macular and papular syphilitic lesions were healing. In the biopsies from the leukodermal lesions of these 2 patients and from unaffected skin of all 3 patients, no treponemes were demonstrated. The study indicates that syphilitic leukoderma is not invariably a post-inflammatory phenomenon, but the pigmented skin lesions may themselves represent stigmata of an active syphilitic infection.
Treponema pallidum was isolated from various types of secondary syphilitic skin lesions. From moist genital papules and from condylomata lata several treponemes were isolated whereas few were isolated from dry papules of the trunk. One third of the observed treponemes were morphologically different from treponemes isolated from human chancres. Especially the nose-piece structures of the terminal parts of the treponemes were deviating. Some nose-pieces were coated by a fuzzily outlined electron dense substance, whereas others were degenerated or nearly separated from the cytoplasmic body. Other treponemes were missing their nose-piece as avirulent saprophytic treponemes. Recent studies have indicated that the nose-pieces are essential for the tissue attachment of treponemes and the treponemal virulence. The significance of the altered nose-piece structure observed is discussed.
The ultrastructure of biopsies from dry macular and papular secondary syphilitic skin lesions of 10 patients were studied by electron microscopy. In all biopsies few diffusely distributed treponemes were observed. This may explain the difficulties in demonstrating treponemes by darkfield examination of tissue fluid from dry secondary syphilitic skin lesions. The outlines of treponemes were less distinct as compared to those of primary syphilis. The periplastic membranes were almost invariably absent and the cytoplasmic membranes appeared in close contact with an enclosing layer of irregularly demarcated, electron dense amorphous substance. This substance may be a manifestation of the immune reaction of the host cells to the treponemes. Degenerations were noted in both unmyelinated and myelinated nerve tissue. This accounts for the fact that skin lesions in secondary syphilis are usually without symptoms. Also in the vessel walls treponemes were demonstrated. The vascular endothelial cells were proliferating and the basement membranes were multilaminated and split.
In biopsies obtained from syphilitic chancres of varying ages in 10 patients, a total of 766 ultrathin sections of Treponema pallidum were studied by electron microscopy. The course and number of axial filaments observed reveal that one bunch of 3-4 filaments without interruption entwine the whole cytoplasmic body. In 9.2% of the sections a trilaminar or a fragmentary trilaminar periplastic membrane was observed outside the cytoplasmic membrane and the axial filaments. The occurrence of the periplastic membrane decreased with advancing ages of the chancres. A protective function of the membrane is discussed. A peritreponemal fine reticular halo demonstrable in most fragments is supposed to be due to fixation induced shrinkage of treponemal hyaluronidase-influenced semifluid glycosaminoglycans. Peritreponemal reticular halos were also observed in collagen tissue. A destructive effect of the treponemes on collagen fibres could explain how the organisms penetrate through the collagen rich meninges into the central nervous system. A surface associated narrow border of electron dense amorphous substance, probably originating from the host organism, yields to tangentially cut treponemes a spiny caterpillar-like appearance.
Filamentous aggregates of collagen are distinct structures in the pathological dermis. These aggregates are distinguishable from fibrous long-spacing collagen (in vitro and at biopsy) and the Luse body. The aggregates are produced from dermal collagen fibrils by clostridial collagenase and culture-medium extract, which supposedly contains cellular collagenase at a neutral pH, as well as by organ cultures. In vitro experiments showed that carrageenan granuloma contains fibrous long-spacing collagen and segment long-spacing collagen. The granuloma also contains the aggregates. The aggregates were found in skin biopsies from syphilitic chancres, acrosclerotic scleroderma, morphea, mycosis fungoides, myeloid leukemia, mastocytosis and malignant melanoma. These findings indicate that the aggregates are products of the in situ degradation of collagen fibrils by some collagenolytic factor. This factor may originate in fibroblast-like cells, reticulum cells, leukemia cells, mast cells and melanoma cells.
Vascular changes in morphea were studied in skin biopsies from 14 patients. Small vessels with pericytes present the changes in three different patterns. The first was the endothelial cells in a stimulated condition and thickened vascular wall with infiltrating macrophages and mast cells. The second was characterized by thick basal lamina of pericytes and the third by activated pericytes with infiltrating lymphocytes and plasma cells. Otherwise, all patterns showed altered endothelial cells and infiltrating macrophages and mast cells similar to the first pattern. The first pattern was mostly found in uninvolved skin. The second and the third were found in the inflammatory and sclerotic areas. It seems, therefore, that activated pericytes are the most essential changes in vessels of morphea. Probably, muscular vessels are simply involved in the fibrotic process.
The ultrastructure of treponema pallidum obtained directly from human chancres by biopsy was studied by electron microscopy. The treponemes were enveloped by a trilaminar cytoplasmic membrane and a trilaminar periplastic membrane. The central part of the periplastic membrane corresponds to the protective mucoid layer. In undamaged organisms bunches of axial filaments were seen to entwine the whole cytoplasmic body without any disruption or overlapping. The number of axial filaments varied between three and four. Identical nose pieces were demonstrable in both ends of the treponemes. Axial filaments and nose pieces seem to differ from those of Nichols' strain.
Biopsies from a 5-year-old girl with dermatomyositis and universal calcinosis were studied histopathologically and by means of electron optical techniques. The dermis was infiltrated by fibroblasts, lymphocytes and plasma cells. In the lower part of the dermis, dense basophilic areas were present. In the vicinity of these areas irregular elastic fibers appeared. In the electron microscope these elastic fibers appeared mineralized to varying degrees. The mineral part was identified as calcium apatite (either calcium-hydroxy-apatite or calcium fluoroapatite) by X-ray microanalysis and selected area diffraction. No calcification was observed outside the elastic fibers.
Dermatological conditions characterized by dermo-epidermal separation, basal lamina discontinuity, multiplication, and thickness variability, and/or irregularity of the subepidermal space are discribed. Pathological changes of the dermo-epidermal junction are considered to be destructive or reproductive. Both may appear in combination. Destructive processes may be relfected by dermo-epidermal separation. Epidermal cells and/or dermal connective tissue appear degenerated. Thickening of the lamina may occur by reactive hyperproduction or by precipitation of pathological materials. Reproductive processes of the junction originate in the epidermal cells and are reflected in multilayering of the basal lamina. Interruption of the lamina and irregularity of the subepidermal space often precede these phenomena.
Collagenolytic enzymes are produced by cultured skin explants. During cultivation the acellular compartment of the dermal connective tissues is digested away. The ultrastructure of the connective tissue resorption has been studied in human skin maintained in organ culture for 2--10 weeks. The connective tissue changes are: (1) Collagen fibrils with normal axial periodicity but decreasing diameters. On cross sections these fibrils have irregular outlines, while the longitudinal sections show fibrils separated into thin bundles of filaments 40--80 A thick with preserved normal axial periodicity. (2) Cross-banded filamentous aggregations (CBFA) consisting of fine parallel filaments 25 A thick and without axial periodicity. The CBFA has 350 A thick bands at 525 A intervals. At the end of the cultivation, the CBFA are replaced by solitary filaments 25 A thick. (3) The elastic fibres show no marked changes of the amorphous matrix, while the fibrils disappear. The loss of collagen and elastic fibrils during cultivation of the skin gives direct evidence of connective tissue degradation. The described changes are discussed in relation to previous ultrastructural studies on connective tissue resorption of various tissues.
Amyloid masses were found in the dermis of two brothers suffering from primary amyloidosis. The masses consisted of fibrils, composed in turn of twin hollow filaments of amyloid. An amyloid filament appeared as a 3 nm thick lucent core with a 2 nm thick wall. Occasionally 4--6 filaments were packed together in one fibril. The twin filaments were slightly twisted, with a twisting angle of 2.5 degrees and a coiling pitch of 1 160 nm. Wavy shapes of amyloid fibrils were also seen in elastic fibres. Amyloid fibrils were found in elastic fibres, under the basal lamina of the epidermis, sweat gland epithelium and Schwann cells; also around perineural cells, perivascular cells and, in one of the brothers, in collagen fibril bundles. No amyloid fibrils were found under the endothelial basal lamina. It would appear that amyloid fibrils are pathological fibrils belonging to the elastic fibre-basal lamina system.
During cultivation, the collagen fibrils of skin explants are broken down. The cells of the explants participate in this resorption. The ultrastructure of the intracellular degradation of collagen fibrils of cultured human skin has been examined. Intracellular collagen fibrils occur in fibroblasts, macrophages, smooth muscle cells and unidentifiable cells. Normal collagen fibrils are engulfed and appear within membrane-bounded tubes of the cytoplasm. Primary lysosomes fuse with the tubes. Degraded intracellular collagen fibrils are frequently present in secondary lysosomes and show decreasing diameters, filamentous splitting, loss of axial periodicity, variable stainability and cross-banded filamentous aggregates. The changes in the intracellular collagen fibrils are identical with those seen in the extracellular space. The present study demonstrates that various cell types in dermis are involved in collagen fibril degradation and that the lysosomes play an important part in the intracellular resorption.