Biomedical subjects
Publications and source records attributed to J Nishida.
New concepts regarding the diagnosis and treatment of thoracic outlet syndrome, double crush syndrome related to thoracic outlet syndrome, and minor traumatic dystrophy related to thoracic outlet syndrome are explained.
The gene for a testicular cell adhesion protein called Tpx-1, which mediates the binding of spermatogenic cells to Sertoli cells of the rat in primary culture, was previously cloned. Here the characterization of Tpx-1 is reported. Tpx-1 messenger ribonucleic acid (mRNA) became detectable in pachytene spermatocytes and continued to be present throughout development into elongated spermatids, while the amount of Tpx-1 protein seemed to increase some time after the increment of mRNA. Tpx-1 protein was also present, although less abundantly, in spermatozoa prepared from the epididymis. Tpx-1 contains a cluster of hydrophobic amino acid residues near the amino terminus and a cysteine-rich region in the carboxyl-terminal half. Tpx-1 fused with green fluorescence protein was secreted into the medium when expressed in a cultured cell line, depending on the presence of the amino-terminal hydrophobic region. Moreover, Tpx-1 was present in the medium of testicular cell primary culture. Structure-function analysis revealed that the amino-terminal 101 amino acid residues were sufficient for cell adhesion activity, whereas the carboxyl-terminal cysteine-rich region was dispensable. In conclusion, Tpx-1 is produced and secreted from spermatogenic cells at various differentiation stages, and mediates the interaction of those cells with Sertoli cells.
A human cadaver tendon sheath model was used to study the differences in excursion resistance of tendons that might be considered as sources of clinical tendon grafts. The flexor digitorum profundus and superficialis tendons, the extensor indicis proprius tendon used in its normal proximal-distal orientation, the extensor indicis proprius tendon used in a reversed distal-proximal orientation, and the palmaris longus tendon were studied in 7 fingers. The intrasynovial tendons (the flexor digitorum profundus and superficialis tendons and the reversed extensor indicis proprius tendon) produced less excursion resistance (p < .05) than the extrasynovial tendons (the normally oriented extensor indicis proprius tendon and the palmaris longus tendon). In contrast to studies measuring resistance against a single pulley, resistance within a complete tendon sheath may be affected by contact with other structures, particularly in joint extension.
To increase the antisense regulatory effect of oligo(nucleoside phosphorothioate)s (S-Oligo), a photo-crosslinking reagent, 4, 5', 8-trimethylpsoralen, was used in this study. Psoralen-conjugated oligo(nucleoside phosphorothioate) (Ps-S-Oligo) complementary to the human papillomavirus type 18 (HPV18) mRNA drastically inhibited the cellular proliferation of cervical cancer cells only upon UVA-irradiation. In contrast, Ps-S-Oligos with mismatched sequences and scrambled one showed lesser inhibitory effects than that with matched one. These results suggest that psoralen-conjugated antisense S-Oligo has significant potential to regulate gene expression upon UVA-irradiation.
Interleukin-1 (IL-1), which is produced by Kupffer cells and sinusoidal endothelial cells, may play an important role in immunological and microvascular responses to a variety of stimuli in the liver. The responses of the hepatic microvasculature including phagocytic activity of sinusoidal lining cells to IL-1 alpha were examined in C57Bl/6 mice in vivo and using electron microscopy. One hour after recombinant mouse IL-1 alpha was injected at doses of 80 U, the low dose group, and 800 U, the high dose group, the phagocytic activity of sinusoidal lining cells showed significant differences between the two treated groups and between the two groups and the controls. In the low dose group, the numbers of sinusoids containing blood flow and of leukocytes adhering to the sinusoidal lining remained unchanged, but the former decreased and the latter increased significantly in the high dose group. Ultrastructurally, Kupffer cells that phagocytosed latex particles appeared to have decreased in number while the sinusoidal endothelial cells became phagocytic. A considerable number of leukocytes were seen adhering to the sinusoidal endothelium. These findings demonstrate that IL-1 alpha not only elicited sticking and plugging by leukocytes in sinusoids but also activated phagocytic functions in the hepatic sinusoidal endothelial cells. These endothelial responses are similar to those seen following FV3 virus infection, chronic administration of ethanol, or a combination of cocaine and ethanol, or during extracorporal perfusion, suggesting that IL-1 may participate in these responses.
It is known that tissue factor (TF) activity depends on cell membrane phospholipids. However, the mechanism involved in the regulation of TF activity by the modulation of the phospholipids has not yet been described in detail. To determine whether some mediators regulate TF activity by such a mechanism, we investigated the effect of platelet activating factor (PAF). Addition of PAF to TF-expressed monocytes caused a rapid and marked increase in the activity, but no increase in the antigen. Kinetic analyses were performed on TF-expressed monocytes with or without the addition of PAF, and on purified TF. The former revealed that the activity enhancement by PAF was associated with reduced Km, with Vmax remaining unaltered. The latter showed that the additional phosphatidylserine produced greater TF activity in purified TF, with an alteration pattern of kinetic parameters similar to that observed in the addition of PAF. From these results, we conclude that PAF regulates TF activity at the cell surface by alteration of the phospholipid composition of the membrane, and not by fresh production of TF apoprotein. The role of PAF as described in this paper must be one of the major regulatory systems in TF activity.
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To investigate regulation mechanisms of G2/M phase transition, we studied the association of cell cycle progression with p53-dependent p21/waf-1 and cyclinG expression. We used doxorubicin (DOX) and sodium butyrate (NaB) to accumulate p53 protein. DOX treatment resulted in an apparent increase of cells in the G2/M fraction, whereas NaB arrested cells at G1. P53 protein induction in response to DOX accompanied up-regulation of p21/waf-1 and cyclinG expression. However, cyclinG was undetectable in NaB-treated cells. These results implied a putative association between increases in the proportion of cells accumulating in the G2/M fraction and enhanced cyclinG expression. Antisense oligo DNAs (AS) complementary to cyclinG mRNA inhibited the cyclinG protein expression induced by DOX treatment. This inhibition resulted in a marked reduction in the number of cells arrested at G2/M and accumulating at G1. A role for cyclinG in G2/M phase transition control is implied.
Lipomas are common benign soft tissue tumors which tend to be indolent, and symptoms caused by nerve compression are unusual. However, a parosteal lipoma, occurring adjacent to the proximal radius may easily cause paralysis of the posterior interosseous nerve because of a specific anatomical relationship of these structures in that area. Two cases of parosteal lipoma of the proximal radius causing paralysis of the posterior interosseous nerve are reported. CT and MR imaging demonstrate the characteristic fatty mass around the radius and are specific in making the diagnosis. Surgical excision should be promptly performed to ensure optimal recovery from the nerve paralysis.
Ten cadaver digits were used to evaluate excursion resistance between a tendon and pulley after completing 4 methods of pulley reconstruction (Bunnell's, Kleinert's, Lister's, and Karev's techniques). Five tissues (palmaris longus tendon, extensor digitorum tendon, flexor digitorum superficialis tendon, extensor retinaculum, and volar plate) were used to reconstruct the A2 pulley. Intrasynovial tissue sources (extensor retinaculum, volar plate, and flexor digitorum superficialis tendon) produced less excursion resistance than extrasynovial tissue sources (extensor digitorum tendon and palmaris longus tendon). The models using the extensor retinaculum and volar plate as reconstructive materials produced less excursion resistance than the normal A2 pulley, whereas the models using the palmaris longus tendon produced the highest excursion resistance. Bunnell's technique of pulley reconstruction produced less excursion resistance than Kleinert's technique with all 3 tissues tested. The results of the in vitro study of excursion resistance between the tendon and reconstructed pulley demonstrated that Lister's technique of pulley reconstruction using the extensor retinaculum produced the least resistance to tendon gliding.
We measured excursion resistance of 4 different tendons (flexor digitorum superficialis, the portion of the extensor indicis proprius tendon beneath the extensor retinaculum, the portion of the extensor indicis proprius tendon distal to the extensor retinaculum, and palmaris longus) beneath the A2 pulley. Intrasynovial tendons (i.e., flexor digitorum superficialis and the portion of the extensor indicis proprius beneath the extensor retinaculum) produced less excursion resistance than extrasynovial tendons (i.e., the portion of the extensor indicis proprius distal to the extensor retinaculum and palmaris longus). The excursion resistance of the intrasynovial portion of the extensor indicis proprius tendon was significantly lower than that of the extrasynovial portion of the same tendon. Intrasynovial tendons may be preferred to extrasynovial tendons when choosing a tendon graft source and graft gliding under a pulley is a consideration.
The excursion resistance between the canine flexor digitorum profundus tendon and A2 pulley was compared after pulley reconstruction using tendon grafts of either intrasynovial or extrasynovial origin at 10 days, 3 weeks, and 6 weeks after surgery. The changes over time in the underlying flexor digitorum profundus tendon after pulley reconstruction were also evaluated. The excursion resistance for both types of pulley reconstruction was significantly greater than that of the control group at all time periods. The excursion resistance of the extrasynovial tendon graft reconstruction was greater than that of intrasynovial pulley reconstruction at all time periods. In conclusion, pulley reconstruction with intrasynovial tendon grafts may facilitate tendon gliding after surgery.
Since the majority of endometrial carcinomas do not contain any detectable ras mutations, the precise contribution of aberrant Ras function, if any, to endometrial carcinoma development remains to be determined. Since there is considerable evidence that Ras transformation is associated with a decreased requirement for growth factors, we compared the growth response of endometrial carcinoma cells harbouring wild-type (Ishikawa cells) or mutated (HHUA cells) K-ras to epidermal growth factor (EGF). K-ras mutation did not significantly affect the level of the EGF receptor (EGFR) expressed in these carcinoma cells. EGF could stimulate the growth of Ishikawa, but not HHUA cells. Furthermore, EGF caused elevation of Ras-GTP levels in Ishikawa, but not HHUA cells. However, the introduction of mutated, but not normal, K-ras into Ishikawa cells rendered them non-responsive to EGF growth stimulation. Thus, the presence of mutated K-ras alone modulated the growth response of endometrial carcinoma cells to EGF. An inhibitor of the EGFR tyrosine kinase activity could prevent soft agar colony formation of Ishikawa cells, but not HHUA or mutant K-ras(12V)-transfected Ishikawa cells. Taken together, these results suggest that mutated K-ras causes a loss of responsiveness to EGF stimulation and that EGFR function is dispensable for the growth of mutant Ras-positive endometrial carcinoma cells.
We investigated the biological significance of estrogen receptors (ER) in NIH3T3 cell transformation by the [12Val] K-Ras mutant. This mutant enhanced the steady state level of ER. Cells expressing mutant K-Ras (K12V cell) were tumorigenic. To determine the role of ER accumulation in Ras-transformed cells, we developed cells (KwtER cells) that overexpressed both wild-type (wt) K-Ras and ER, and found these cells were also tumorigenic. E2 stimulated the transcriptional activity by ER dominantly in K12V cells. However, only partial activation of ER by E2 was seen in KwtER cells. In the presence of 10% serum in media, the activation of ER appeared only in transformed KtwER and K12V cells, suggesting that two independently transmitted signals, the E2-ER binding and the ER-AF1 activation, are necessary for ER activation and that the dominant activation of ER might be involved in Ras-mediated cell transformation. Co-expression of progesterone receptor (PR) with mutant K-Ras led to suppression of tumorigenicity and inhibition of the activation of ER. The antisense oligomers complementary to the ER suppressed proliferation and transformed phenotypes of K12V cells. These observations support the importance of ER in Ras-mediated cell transformation.
The localization of parvalbumin was determined in skeletal muscles with different fiber type compositions from quails (Coturnix japonica) and pigeons (Columba livia) by sandwich ELISA. The biochemical profiles of these muscles were evaluated by the assay of total lactate dehydrogenase (LDH) activity as well as the LDH isozymes for anaerobic metabolism, and by the analysis of myoglobin for aerobic metabolism. The quail fast posterior latissimus dorsi (PLD) with a lower myoglobin content and higher LDH activity or M-type isozyme pattern was assessed as containing primarily fast-twitch glycolytic and oxidative-glycolytic (FG/FOG) fibers, and the mixed sartorius (SA) in quails and pigeons was shown to be composed mostly of FOG fibers because of the intermediate myoglobin content and LDH activity or H/M-type isozyme pattern. Parvalbumin, which functions as a relaxing factor in the fast-twitch fibers, was present in PLD and SA in significant amounts, whereas it was undetectable in quail anterior latissimus dorsi (ALD) and pigeon latissimus dorsi (LD) which contain exclusively slow-tonic (ST) fibers with the lowest LDH activity or predominant H-type isozyme characteristics. The pectoralis superficialis (PS) and pectoralis profundus (PP) muscles from quails and pigeons seem to consist mostly of FG/FOG fibers because of the highest myoglobin contents and LDH activities or M-type and H/M-type isozyme patterns. Despite fast-twitch fiber compositions, parvalbumin was absent from these pectoralis muscles. The tetanic contraction induced in avian fast-twitch pectoralis fibers during flapping flight might be independent of a function of parvalbumin as a relaxing factor.
BACKGROUND: Malignant fibrous histiocytoma of bone, a relatively rare primary malignant neoplasm occurring in bone, is a distinct clinicopathologic entity formerly included in the category of osteosarcoma or fibrosarcoma. A series of patients treated at the Mayo Clinic for malignant fibrous histiocytoma of bone was studied to determine whether the prognosis for this disease is different from that of osteosarcoma and whether treatment should be different. METHODS: The bone tumor files of the Mayo Clinic were reviewed for examples of malignant fibrous histiocytoma of bone. Clinical records and histologic slides were reviewed for 81 patients. Roentgenograms of 13 patients were available for review. RESULTS: Patients with malignant fibrous histiocytoma of bone ranged in age from 6 to 81 years. The region most commonly affected was the knee. Seventy-eight percent of the lesions arose de novo and 22% in preexisting conditions. Histologically, most of the tumors were classified as the storiform pleomorphic type, although other histologic subtypes were identified. The prognosis depended on the types of surgical margins involved. Patients with wide or radical margins had a better prognosis than patients in whom the margins were contaminated. Some patients who received radiation therapy alone became long term survivors. CONCLUSIONS: The overall prognosis for patients with malignant fibrous histiocytoma was not found to be significantly different from that described for patients with osteosarcoma in recent series. However, at least in this small series, some patients with malignant fibrous histiocytoma had a good response to radiation therapy. Osteosarcoma is generally considered radioresistant.
The p16INK4A gene, which encodes the cell-cycle regulatory protein cyclin-dependent kinase 4 inhibitor, is a putative tumor-suppressor gene. We examined p16 gene alterations in 30 primary ovarian cancers and 11 ovarian cancer cell lines. Five of the primary cancers (16.7%) had lost both p16INK4A genes. In addition, four cancers (13.3%) contained five kinds of missense mutations and a one-base deletion. Three cell lines had homozygous deletions of p16 genes, and one cell line had multiple intragenic mutations. There was also suppressed transcription of the p16 gene in one cell line. Some point mutations occurred in the conserved ankylin consensus region. These observations suggest that p16 is a functional target for ovarian carcinogenesis and that p16 alterations occurred in the primary cancers.
The case of a 14-year-old girl with rhabdomyosarcoma of the right foot is reported. Plain radiography showed a large nonspecific soft tissue tumor between the metatarsals with bowing of the metatarsals away from the mass. MR imaging showed a large soft tissue mass involving the metatarsals. The findings were conflicting, because the tumor had an infiltrative soft tissue mass and bowing of the metatarsals more suggestive of slow expansive growth. Bowing of short tubular bones may be a process similar to cortical saucerization, which is typically seen in Ewing's sarcoma, and it can be one of the findings of high grade neoplasms, such as embryonal rhabdomyosarcoma.