Biomedical subjects
Publications and source records attributed to S Tajima.
We report a case of reticular erythematous mucinosis syndrome associated with psoriasis-like eruptions. Although the two skin diseases are clinically distinct, they may be related in some ways.
We report a case of lichen sclerosus et atrophicus (LSA) in a band-like arrangement. The patient had a white atrophic plaque on the left breast which showed the typical histological features of LSA. One month later, the patient had developed multiple, brown-colored plaques from the right breast to the right upper arm following the distribution of the peripheral nerve. These plaques showed the mild histological changes indicative of LSA. This band-like arrangement of LSA appears to be unique.
We report a case of atrophoderma of Pasini and Pierini. We determined the glycosaminoglycan content in the involved skin. Dermatan sulfate content in the involved skin (1.88 micrograms uronic acid/mg dry skin) was greater than that in the uninvolved skin (1.05 micrograms uronic acid/mg dry skin). No significant differences in hyaluronic acid, chondroitin sulfate or heparan sulfate content between involved and uninvolved skin were observed. These results suggest that abnormal metabolism of dermatan sulfate may be involved in the pathogenesis of atrophoderma; this pattern has been observed in systemic or localized scleroderma.
Cardiac manifestations of the CREST syndrome or limited systemic sclerosis (ISSc) are very rare. We report a case of CREST syndrome associated with sick sinus syndrome. Histopathology of cardiac muscle revealed fibrotic changes, suggesting that such changes may be pathogenetically related to CREST syndrome.
We describe two patients with lesions clinically resembling pseudoxanthoma elasticum and histologically exhibiting focal elastosis, with normal-appearing elastic fibres in the mid- and deep dermis. We consider that these skin lesions represent a previously undescribed entity, whose pathogenesis appears to be related to the ageing process.
BACKGROUND: The main clinical symptoms of systemic scleroderma are caused by an accumulation of collagen in the tissues. Familial scleroderma is a very rare disorder in which systemic scleroderma occurs in the members of the same family. OBJECTIVE: To know whether or not the biosynthetic properties of familial scleroderma skin fibroblasts are similar to those of nonfamilial scleroderma fibroblasts, syntheses of extracellular matrix components in the two fibroblast strains obtained from familial scleroderma patients were studied. METHODS: Expression of collagen and glycosaminoglycans by cultured familial scleroderma fibroblasts was determined. RESULTS: Collagen synthesis by patient fibroblasts was elevated 1.4-fold compared with control fibroblasts. Translational activity of type I procollagen mRNA and the level of alpha 1 (I) mRNA in the patient fibroblasts was increased 1.7- and 1.6-fold, respectively. The ratio of hyaluronic acid/dermatan sulfate in the patient fibroblasts was lower than that in control fibroblasts. CONCLUSION: The results indicate that the biosynthetic phenotypes of familial scleroderma fibroblasts are similar to those of nonfamilial scleroderma fibroblasts which have already been reported.
Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene. In the present study, we investigated four Japanese FH homozygotes and identified five point mutations: a splice site mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon 7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a missense mutation in exon 14 (the P664L mutation), and a missense mutation in exon 4 (the E119K mutation). We developed simple methods for detecting these mutations. When we examined the presence of these mutations in 24 unrelated FH homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other four mutations were unique for each proband. We also screened 120 unrelated FH heterozygotes for these mutations and found that the frequencies of the 1845 + 2 T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7% (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These mutations were found in more than 30% of unrelated Japanese FH patients. By using the detection methods developed in this study, the diagnosis of more than 30% of the genetic bases of Japanese FH heterozygotes is expected.
Inhibin and activin were initially isolated as regulators of pituitary or gonadal hormone and are now known to be growth factors belonging to the TGF-beta family with diverse influences on the differentiation and proliferation of various tissues. To investigate the role of inhibin and activin in human brain tumors, the expression of inhibin alpha, and beta A mRNA as well as activin type II receptor (ACTR II) mRNA were studied in various human brain tumors. The tumors were divided into the following 4 groups: 3 Rathke's cleft cysts and 2 craniopharyngiomas (group 1), 8 meningiomas (group 2), 8 malignant gliomas (group 3), and various other tumors including 1 each of germinoma, astrocytoma, hemangioblastoma, and osteochondroma as well as 2 malignant lymphomas and 2 metastatic squamous cell carcinomas (group 4). Immediately after resection, tumor tissues were homogenized in guanidine thyiocyanate to extract total RNA. PCR was then performed with reverse-transcribed cDNA and the respective amplification primers. DNA bands were obtained by agarose gel electrophoresis. Messenger RNA for the inhibin beta A subunit was demonstrated in all of the tissues studied. In contrast, inhibin alpha subunit mRNA was expressed in 60%, 50%, 75%, and 75% of the tumors in groups 1, 2, 3 and 4, respectively, whereas ACTR II mRNA was demonstrated in 20%, 37.5%, 62.5% and 50% of the tumors in each group. Coexpression of mRNAs for the inhibin alpha, and beta A subunits and ACTR II occurred in some brain tumors. The levels of inhibin alpha and ACTR II mRNA tended to be higher in the tumors with a higher grade of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibin and activin are known to be involved in the pituitary hormone secretion as well as proliferation of the pituitary. We studied the expression of inhibin alpha, and beta A subunit and activin type II receptor (ACTR 2) mRNAs in human pituitary adenomas to determine the significance of inhibin and activin in pituitary hormone secretion. Tumor tissues were homogenized immediately after resection in guanidinium thiocyanate to extract total RNA. PCR was performed with reversely transcripted cDNA and respective amplification primers. DNA bands obtained for inhibin alpha, beta A and ACTR 2 by agarose gel-electrophoresis were 367, 285, and 389 bp, respectively. Messenger RNAs for inhibin beta A were demonstrated in all of the pituitary tissues studied, namely in 3 GH, 2 ACTH, 6 PRL and 1 FSH producing adenomas and 17 non-functioning adenomas. Inhibin alpha mRNAs were detected in 10 of 12 functioning adenomas and 15 of 17 non-functioning adenomas. ACTR 2 mRNAs were found in 11 out of 17 non-functioning adenomas, but only found in 3 out of 12 functioning adenomas. These results suggested local production of activin, a homodimer of beta-subunits, and inhibin, a heterodimer of alpha and beta subunits, in most of the pituitary adenomas regardless of their hormone secretion. On the other hand, a significantly higher incidence of ACTR 2 in non-functioning adenomas than in functioning adenomas suggested that activin had its main site of action in non-functioning adenomas, which could be potential gonadotropinomas.
Treatment of cultured smooth muscle cells with ascorbic acid resulted in an accumulation of tropoelastin in the culture medium in dose-dependent and exposure time-dependent manner under the condition in which collagen synthesis was stimulated 2-fold. The steady-state level of elastin mRNA was essentially unchanged, whereas collagen mRNA content increased 2-fold by ascorbic acid treatment. Newly synthesized tropoelastin was hydroxylated in the presence of ascorbic acid but was underhydroxylated in a scorbutic condition. Short pulse experiments showed that the secretion rate of tropoelastin was unaltered by ascorbic acid treatment. Pulse-chase experiment demonstrated that the level of fully hydroxylated tropoelastin in the medium of ascorbate-treated cells was greater than that of under-hydroxylated tropoelastin. These results indicate that accumulation of tropoelastin in the medium by ascorbic acid is related to an increased stability of hydroxylated tropoelastin and/or its impaired incorporation into insoluble elastin.
The rate of collagen synthesis in the cell layer fraction of the skin fibroblasts derived from a patient with Marfan syndrome was greater than that in the normal fibroblasts. Neither the relative content of type III collagen nor the level of prolyl and lysyl hydroxylations in type I collagen changed. Intracellular degradation rate of collagen in Marfan syndrome fibroblasts was decreased to one fifth of that in the normal fibroblasts. These results suggest that abnormal collagen metabolism may be related to the pathogenesis of clinical manifestations of Marfan syndrome.
The transverse rectus abdominis musculocutaneous (TRAM) flap cannot be used successfully in a patient with a pre-existing midline abdominal scar because the area distal to the scar undergoes circulatory failure leading to necrosis. To investigate the usefulness of various procedures to improve the circulation in such a flap, we studied the percentage area survival of experimental abdominal island flaps in five groups of rats with pre-existing midline scar treated by different procedures which depended on the source of blood used to supply the flap (control, arterial, venous, arteriovenous shunt, and delayed, n = 5 in each group). All flaps in the arterial group survived completely. The mean (SEM) percentages of the flaps that survived in the control (17(2)%) and venous (17(1)%) groups were significantly lower than those in the delayed (31(2)%) and arteriovenous shunt (67(6)%) groups (all, p < 0.01). These results indicate that preservation of arterial inflow by arterial anastomosis or arteriovenous shunt on the opposite side is important if the flap is to survive across the midline scar. Preservation of the vein in the opposite flap is not essential, because venous outflow is supposed to drain through the midline scar into the epigastric vein of the pedicle without any signs of congestion.
Minoxidil was found to inhibit the proliferation of smooth muscle cells in the proliferating phase, but not in the quiescent phase. Treatment of proliferating or quiescent cells with minoxidil resulted in a dose- and time-dependent stimulation of elastin synthesis specifically. Maximum stimulation (fourfold) occurred in cells treated with 1 mM minoxidil for 48 h. The stimulation of elastin synthesis was accompanied by a proportional increase in elastin mRNA level, and it was partially prevented by a K+ channel blocker (tetraethylammonium) and completely prevented by high K+ salt (0.1 M). Minoxidil had no significant effect on the extent of prolyl hydroxylation in newly synthesized elastin. These results indicate that minoxidil stimulates elastin synthesis at a pretranslational level by a mechanism unrelated to cell proliferation but one that may involve K+ efflux. As a pharmacological agent capable of stimulating elastin expression, minoxidil would be a useful drug for the treatment of abnormal elastin metabolism.
Mouse B16 melanoma cells are of heterogenous populations and consist of melanotic and amelanotic cells. Two clones, M3 (melanotic) and A7 (amelanotic), were screened from B16 melanoma cells using a microscope, and gelatinolytic activities in these clones were studied with zymography. Gelatinolytic enzyme was found in the cultured medium of A7 cells, but not in M3 cells. The enzymes with apparent molecular weights of 70, 140 and 280 kDa were detected and found to form complexes: a dimer or more than dimer. Their enzyme activities were not inhibited by ethylenediaminetetraacetic acid. The optimal pH of this enzyme was found to be at neutral pH. Preferential expression of this novel gelatinolytic enzyme in amelanotic melanoma will be related to tumorigenic and metastatic phenotype of amelanotic melanoma.
Effects of two major potent vasoconstrictors, angiotensin II and platelet-derived growth factor, on elastin expression in cultured chick embryonic arterial smooth muscle cells were studied. Platelet-derived growth factor exhibited no effect on elastin synthesis nor its mRNA level but stimulated (1.5-fold) cell proliferation slightly. Angiotensin II inhibited elastin synthesis dose- and time-dependent manner with a maximum suppression of sixty percent of control at a concentration of 10 microM for 18 h treatment. The suppression was accompanied with a comparable decrease in elastin mRNA level. The inhibition was blocked by addition of Sar1,Ala8-angiotensin II and 8-bromo-cGMP. It showed no effect on cell proliferation. Angiotensin II appears to inhibit elastin synthesis through the interaction with its receptor and the modulation of intracellular Ca2+ level. Thus angiotensin II, not platelet-derived growth factor, can exert a profound effect on the extracellular matrix composition in arterial walls, leading to an arterial change in hypertension or atherosclerosis.
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We have screened several chinese medicinal herbs for the presence of antifibrotic agents. An aqueous extract of Salviae miltorrhizae Radix was found to inhibit collagen secretion by human skin fibroblasts without affecting DNA or noncollagen protein synthesis. We have subsequently purified the material exhibiting the inhibitory activity and identified it as magnesium lithospermate. From its chemical structure this compound was predicted to be an inhibitor of the post-translational modifying enzymes prolyl and lysyl hydroxylases in collagen biosynthesis. Accordingly, it decreased the extent of prolyl and lysyl hydroxylations in collagen by approx. 50%. Added to cell extracts it inhibited both prolyl and lysyl hydroxylase activities, but only lysyl hydroxylase activity when added to intact cells. Oral administration of this compound to mice led to a significant reduction of prolyl hydroxylation in newly-synthesized skin collagen. This naturally-occurring compound thus offers a potential means for treating fibrotic diseases, such as systemic scleroderma and keloid.