[The present state of leukocytes apheresis therapy].
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Clinical Trials as Topic↗
Biomedical subjects
Kenji Kondo
Publications and source records attributed to Kenji Kondo.
[A case of gastric GIST treated preoperatively by imatinib mesylate].
Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the human gastrointestinal tract, is thought to originate from the interstitial cells of Cajal. The mutation of c-kit, cording KIT, is essential in the development of GIST. Imatinib mesylate (IM), an agent for chronic myeloid leukemia, was reported to inhibit tyrosine kinase activity of KIT and to be highly effective for GIST. We report, here, a case of huge gastric GIST who underwent neoadjuvant therapy followed by surgical resection. The patient was a 62-year-old man with GIST in cardia (KIT+, CD34+, mitotic rate 5/50 HPF), whose chief complaint was general fatigue. Because the huge tumor, 7.5 cm in size, directly invaded the pancreas, total gastrectomy with distal pancreatosplenectomy was necessary for curative resection. IM was administered (400 mg/body/day) as a neoadjuvant treatment for down-staging of the tumor. Leucopenia (grade 2) and diarrhea (grade 1) were observed as the adverse effects of IM. Partial response was obtained. He underwent proximal gastrectomy without pancreatosplenectomy since CT no longer showed direct invasion to the pancreas. Histological examination of the resected specimen revealed the extensive degeneration of the tumor, in which tumor cells containing condensed nuclei had decreased remarkably. Interestingly, mitotic rate decreased to 0/50 HPF in the effective area of the resected specimen, indicating that recurrent risk might be decreased. A part of the viable tumor cells, however, had the same feature to that in the biopsied specimen before treatment. The results suggest that the heterogeneity of GIST induces different sensitivity to IM. The postoperative course was uneventful and no sign of recurrence was observed 3 months after surgery. Neoadjuvant therapy with IM may become a useful strategy for GIST, as it reduces the tumor size and decreases the recurrence rate.
Antigens, CD34↗
[Two cases of postoperative recurrence of gastric GIST treated by imatinib].
We report two cases of postoperative recurrence of gastrointestinal stromal tumor (GIST) treated by the tyrosine kinase inhibitor imatinib mesylate (IM), and discuss some important items. Case 1: This 63-year-old Japanese man received a partial gastrectomy for leiomyosarcoma in 1993. Partial hepatectomy and proximal gastrectomy were performed for liver metastasis and local recurrence in 2001. However, 5 months after surgery, a CT scan showed multiple tumors in the liver, lung and thyroid. The patient was treated with 300 mg of IM once daily with transient grade 2 neutropenia and intestinal bleeding. Though the response to treatment was SD-PR initially, a CT scan 15 months after initial treatment demonstrated the regrowth of the tumor in his liver. Case 2: A 63-year-old Japanese woman was treated with 200 mg of IM once daily for multiple liver metastases after gastrectomy for GIST with grade 3 neutropenia and edema of legs. The response to treatment was SD, and continued for 12 months. IM is the treatment of choice for unresectable recurrence of GIST. However, some problems remained. Both basic and clinical research is necessary to increase the therapeutic efficacy of IM.
Antineoplastic Agents↗
Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage.
Cell proliferation in the cochleae of guinea pigs and rats was investigated after systemic application of kanamycin sulfate (KM) and ethacrynic acid (EA). Bromodeoxyuridine (BrdU) was injected daily for 10 days, after which the number of BrdU-positive cells was counted in paraffin sections of the cochlea. Only a few BrdU-positive cells were present in the spiral ligament and among the acoustic nerve fibers in the non-deafened control animals. Animals treated with KM and EA had profound hearing loss and significant increases in the number of BrdU-positive cells in the spiral ligament and among the acoustic nerve fibers. No BrdU-positive cells were found in the auditory sensory epithelium of any animal. These findings suggest that in the mature mammalian cochlea cell proliferation increases in nonsensory regions after ototoxic damage but may not occur in the auditory sensory epithelium.
Aminoglycosides↗
Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx mice.
The ability of aminoglycoside antibiotics to promote read-through of nonsense mutations has attracted interest in these drugs as potential therapeutic agents in genetic diseases. However, the toxicity of aminoglycoside antibiotics may result in severe side effects during long-term treatment. In this paper, we report that negamycin, a dipeptide antibiotic, also restores dystrophin expression in skeletal and cardiac muscles of the mdx mouse, an animal model of Duchenne muscular dystrophy (DMD) with a nonsense mutation in the dystrophin gene, and in cultured mdx myotubes. Dystrophin expression was confirmed by immunohistochemistry and immunoblotting. We also compared the toxicity of negamycin and gentamicin, and found negamycin to be less toxic. Furthermore, we demonstrate that negamycin binds to a partial sequence of the eukaryotic rRNA-decoding A-site. We conclude that negamycin is a promising new therapeutic candidate for DMD and other genetic diseases caused by nonsense mutations.
Amino Acids, Diamino↗
Hoarseness after cardiac surgery: possible contribution of low temperature to the recurrent nerve paralysis.
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Adult↗
[A case of steroid dependent ulcerative colitis (total colitis type) treated by combined use of germinated barley foodstuff].
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Anti-Inflammatory Agents↗
Transgene expression in mature guinea pig cochlear cells in vitro.
Inoculation of adenovirus vectors in vivo has induced transgene expression in a variety of cochlear cells, but not hair cells or supporting cells in most previous studies. Specific hair cell inoculation by viral vectors has not been demonstrated in the mature guinea pig cochlea in vitro. We injected an Adex1CAlacZ into the mature guinea pig cochlear explants, which were incubated for 24-72 h. We found many lacZ-positive cells in a variety of tissues including the spiral ganglion and stria vascularis. Transgene expression was also found in the outer hair cells and supporting cells, such as the Deiters cells and pillar cells. These findings indicate that adenovirus vectors can be transfected into mature guinea pig hair cells and supporting cells in culture.
Adenoviridae↗
Hair cell development in vivo and in vitro: analysis by using a monoclonal antibody specific to hair cells in the chick inner ear.
The purpose of this study was to establish a hair cell-specific marker and a convenient explant culture system for developing chick otocysts to facilitate in vivo and in vitro studies focusing on hair cell genesis in the inner ear. To achieve this, a hair cell-specific monoclonal antibody, 2A7, was generated by immunizing chick inner ear tissues to a mouse. Through the use of immunofluorescence and immunoelectron microscopy, it was shown that 2A7 immunoreactivity (2A7-IR) was primarily restricted to the apical region of inner ear hair cells, including stereocilia, kinocilia, apical membrane amongst the extending cilia, and superficial layer of the cuticular plate. Although the 2A7 antibody immunolabeled basically all of the hair cells in the posthatch chick inner ear, two different patterns of 2A7-IR were observed; hair cells located in the striolar region of the utricular macula, which consist of two distinct cell types identifiable on the basis of the type of nerve ending, Type I and II hair cells, showed labeling restricted to the basal end of the hair bundles. On the other hand, hair cells in the extrastriolar region, which are exclusively of Type II, showed labeling extending over virtually the entire length of the bundles. These findings raised the possibility that chick vestibular Type II hair cells, characterized by their bouton-type afferent nerve endings, can be divided into two subpopulations. Analysis of developing inner ear by using the 2A7 antibody revealed that this antibody also recognizes newly differentiated immature hair cells. Thus, the 2A7 antibody is able to recognize both immature and mature hair cells in vivo. The developmental potential of embryonic otocysts in vitro was then assessed by using explant cultures as a model. In this study, conventional otocyst explant cultures were modified by placing the tissues on floating polycarbonate filters on culture media, thereby allowing the easy manipulation of explants. In these cultures, 2A7-positive hair cells were differentiated from dividing precursor cells in vitro on the same schedule as in vivo. Furthermore, it was found that hair cells with both types of 2A7-IR were generated in culture as in vivo, indicating that a maturational process of hair cells also occurred. All these results as presented here suggest that the 2A7 monoclonal antibody as a hair cell-specific marker together with the culture system could be a potential tool in analysis of mechanisms underlying hair cell development.
Animals↗
The present status and the recent development of the treatment for inflammatory bowel diseases: desirable effect of extracorporeal immunomodulation.
The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well elucidated in the recent years. The pharmacologic treatment of IBDs accordingly becomes to focus upon the individual pathologic step (targeting therapy), whereas the therapeutic action is not yet a pinpoint one. It has been known recently that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than the conventional drugs, and they might alter the treatment strategy of IBDs in the near future. The limitation of pharmacologic treatments mainly results from adverse effects of the drugs, i.e. infection susceptibility, oncogenesis, teratogenesis and so forth. The extracorporeal therapy such as leukocytapheresis and photopheresis is reportedly effective for IBDs probably through immunomodulation such as decrease in circulating activated T-lymphocytes and activated granulocytes that play a central role in the pathogenesis of IBD. It can be said that these extracorporeal treatment methods have advantage of rapid action and lack of serious adverse effects to drug therapy.
Adjuvants, Immunologic↗
Vocal cord paralysis after surgery for thoracic aortic aneurysm.
OBJECTIVE: To determine the incidence, etiology, prognosis, and treatment of vocal cord paralysis (VCP) after surgery for thoracic aortic aneurysm (TAA). STUDY DESIGN: Retrospective study performed between 1989 and 1995. SETTING: Academic, tertiary care, referral medical center. PATIENTS: Seventy-one TAA patients underwent surgery at the Kameda Medical Center between 1989 and 1995. RESULTS: Sixty-two of 71 patients were examined postoperatively for voice quality. Twenty patients (32%) had hoarseness develop caused by VCP, as confirmed by laryngoscopy. The left recurrent laryngeal nerve had been sacrificed in 1 patient during surgery, but it was preserved in the remaining 19 patients. Unilateral left VCP was noted in 19 patients, and bilateral VCP occurred in 1 patient. The incidence of VCP was higher in those patients who underwent surgery for type I aneurysms (9 of 14 patients, 64%). In 16 of the 19 patients (84%) who received follow-up for > 6 months, vocal cord movement did not return to normal. Surgery to improve voice quality, arytenoid adduction in five patients and intracordal injection in two patients, was performed with success. CONCLUSIONS: Our results indicate that surgery for TAA is associated with a relatively high incidence of VCP. VCP occurred despite preservation of the recurrent laryngeal nerve, and the paralysis did not show a spontaneous recovery even 6 months after surgery.
Adult↗