Biomedical subjects
Publications and source records attributed to M Kumagai.
A case of a 96-year-old male with a foreign body in the larynx is reported. The foreign body was a press-through-pack (PTP), a plastic packing for medicine, 16 mm x 16 mm x 3 mm in size. The PTP was safely removed from the larynx under general anesthesia.
The present study aimed to explain how tinnitus relief following electrical promontory stimulation affects detection of changes in pitch frequency. To determine the effects of tinnitus relief on the auditory system. Japanese words with the same sound but different intonation were used to verify the effects of tinnitus relief on pitch detection in tinnitus patients Eight out of 11 patients experienced relief of tinnitus following treatment. The averaged number of the ratio in 8 patients with relief of tinnitus, 0.58, was significantly higher (p < 0.02) than that in 3 patients without relief, 0.15. In comparison with averaged hearing level, there was no significant difference in averaged hearing level between 8 patients with relief of tinnitus (52.4 dBSL; SD: 11.4) and 3 without relief of tinnitus (58.0 dBSL; SD: 14.7) (p > 0.68). No significant difference in age between patients with and without relief of tinnitus was observed.
The present study showed that there were close relationships between tinnitus relief and improved word perception by means of a grammatically correct but non-sense Japanese word perception test. Fourteen out of 20 patients reported tinnitus relief and improvement in hearing. Nine out of the 14 patients were thought to be significantly improved in word perception. Improved word perception was observed in 7 out of 10 patients whose ears tested were opposite to ears treated while in 2 out of 10 patients whose ears tested were the same as ears treated. Improved word perception was observed in 5 patients at one segment, 2 patients at two segments and 2 patients at three segments. Improved word perception was observed in one patient at the first segment, 5 patients at the second segment, 5 patients at the third segment and 5 patients at the fourth segment. There were no significant differences in hearing level nor age in patients with and without relief of tinnitus.
Improved word perception in hearing-impaired patients following electrical stimulation of ears was shown by means of a grammatically correct but non-sense Japanese 4-segment sentence perception test. Improved word perception was reported in 15 out of 20 patients without tinnitus following electrical stimulation of ears. In 11 out of 15 patients, the number of incorrect words significantly decreased, showing that electrical stimulation of ears improved word perception. Improved word perception was observed in 5 out of 8 patients whose tested ears were contralateral to treated ears while in 8 out of 12 patients whose tested ears were the same as treated ears. The present study suggests that electrical stimulation of ears improves word perception in hearing-impaired patients without tinnitus.
Homologous challenge parasite attrition in gerbils, Meriones unguiculatus, chronically infected with Schistosoma mansoni, was investigated by the recovery technique of retrograde portal perfusion. Whereas the animals vaccinated with gamma- or UV-attenuated cercariae of S. mansoni showed a marginal level of resistance, the chronically infected gerbils exhibited significant parasite attrition against a homologous challenge infection. Our data do not corroborate a previous report suggesting a lack of resistance in gerbils with chronic S. mansoni infection. The gerbil represents an additional experimental host for evaluating acquired resistance to S. mansoni, including that induced by previous exposure to irradiated larvae on chronic infection.
Organ preservation is one of the requirements for maintaining the high quality of life after the treatment of malignant solid tumors in children. We analyze our recent results of renal preservation in the abdominal neuroblastoma and describe 3 cases of successful organ preservation in pelvic malignancy. Between 1982 and 1996, 29 patients with adrenal or retroperitoneal neuroblastoma, that extended into the surrounding tissues and organs and/or to the contralateral side, underwent delayed primary excision. Before 1982, 9 patients were treated and only one ipsilateral kidney was preserved. On the other hand, 13 of 20 kidneys were preserved after 1987. Adoption of cis-platinum deepened our awareness of preserving the kidney. Furthermore, we have altered our strategy since 1987 to continuing preoperative chemotherapy until the size of the tumor becomes as small as it is estimated completely resectable by our own index, which is derived from computed tomography. Kidneys are shielded during intraoperative irradiation, and the tumor relapsed from the shielded area of retroperitoneum in one patient. Four of 14 preserved kidneys became atrophic and lost their function. The bladder and the rectum were left intact at tumor resection after intensive chemotherapy in two patients with pelvic (one retroperitoneal and one vaginal) rhabdomyosarcoma. A yolk sac tumor of the vagina responded completely to chemotherapy with cis-platinum, etoposide and bleomycin. The patient has survived 7.5 years without any local and distant relapse in spite of the fact that surgery, aside from several diagnostic biopsies, was not undertaken.
We tested the hypothesis that chronic hypercapnia contributes to the development of core/targetoid fibers in ventilatory muscles. Five Wistar rats were kept in 5% CO2 in air for 13 weeks. Arterial blood gases (mean +/- SE) were pH 7.402 +/- 0.017, PaCO2 47.4 +/- 2.4 Torr, and PaO2 105.2 +/- 13.2 Torr. While the rats were chronically hypercapnic, their mean minute ventilation was about 1.7 times higher than that of rats that breathed air. This level was maintained throughout the exposure to CO2. Approximately 6% to 12% of the diaphragmatic type-I fibers were replaced by core/targetoid fibers in 3 of 5 chronically hypercapnic rats but not in the 3 control rats. Chronic hypercapnia may have continuously stimulated the respiratory center and resulted in more work done by the ventilatory muscles. Long-term overuse of the ventilatory muscles, which may occur in patients with chronic respiratory failure, can cause morphological changes in type-I fibers in the diaphragm.
Features of Schistosoma mansoni infection in SCID mice, which lack functional T- and B-lymphocytes, were investigated. The retarded development of parasites as well as reduction of liver egg recovery in SCID mice was significantly lower than those in congenic counterpart C.B-17 mice. Furthermore, the rate of parasite recovery from SCID mice with primary infection was always lower than that from C.B-17 mice by 20%, showing the innate resistance to S. mansoni infection. SCID mice vaccinated with UV-attenuated S. mansoni cercariae did not show protective immunity against a homologous challenge infection. The present innate resistance exhibited in SCID mice is discussed in relation to cell mediated immunity of macrophage activation by IFN-gamma which would not involve T-lymphocytes but is initiated by IL-12 and TNF-alpha cytokines. SCID mice may provide novel information on the host-parasite relationship in schistosome infections.
We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.
Ligation of CD38 inhibits proliferation and induces apoptosis of human immature B cells, but the molecular mechanisms underlying this function are unknown. We found that CD38 dimerization with the specific mAbs T16 and IB4 induces rapid and transient tyrosine phosphorylation of several intracellular proteins in the immature B cell lines RS4;11, REH, 380, Nalm6, and OP-1. This effect could be markedly reduced by incubating cells with the tyrosine kinase inhibitors genistein, staurosporine, and herbimycin A. CD38 dimerization induced tyrosine phosphorylation of the protein kinase syk and increased syk kinase activity. CD38 dimerization also induced tyrosine phosphorylation of phospholipase C-gamma and of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-K). The latter was accompanied by a distinct increase in PI 3-kinase activity in the immunoprecipitates obtained with an anti-phosphotyrosine Ab. In contrast to the signaling triggered by surface Ig engagement in B lymphocytes, CD38 ligation did not appear to induce tyrosine phosphorylation of the src-like protein tyrosine kinases lyn, fyn, and btk, or of vav- and ras-GTPase-activating protein, nor did it induce detectable changes in cytosolic CA2+ concentrations. CD38 signaling also differed from cytokine-induced signaling in that it did not cause tyrosine phosphorylation of Jak1 and Jak2. Finally, CD38 ligation did not inhibit IL-3-induced tyrosine phosphorylation of Jak2. These results identify CD38 as a cell surface receptor with signal transduction properties activated by dimerization. Induction of signal transduction by CD38 ligation implies the existence of a yet unidentified natural ligand of CD38.
BACKGROUND: Creating a "safety zone" during laparoscopic cholecystectomy is defined as dissection of the cystic duct as close as possible to the gallbladder. METHODS: In 29 out of 802 cases in which laparoscopic cholecystectomy was difficult to perform due to uncertainty about the orientation of Calot's triangle, intraoperative cholangiography was performed, using a titanium clip as a marker that designated the safety zone. The distance between the clip and the common hepatic duct or the common bile duct could be determined by evaluation of two intraoperative cholangiograms taken in different orientation. RESULTS: If the clip was located in the safety zone, and was distant from the common hepatic duct or common bile duct, the safety of preparation around the clip was ensured. No complication was encountered in these cases with this method. Eventually, no biliary tract injury was experienced, and the overall conversion rate to open cholecystectomy was only 0.4% (3 of 802 consecutive cases). CONCLUSIONS: This method of confirming the safety zone by intraoperative cholangiography is a useful procedure for avoiding inadvertent injury to the biliary tract.
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BACKGROUND AND STUDY AIMS: Following the recent introduction of laparoscopic cholecystectomy (LC) for cholecystolithiasis, treatment of concomitant common bile duct (CBD) stones has been evaluated by using laparoscopic choledochotomy, a transcystic approach, or by means of endoscopic sphincterotomy (ES) before or after LC. PATIENTS AND METHODS: During laparoscopic cholecystectomy, we attempted lithotripsy of CBD stones using laparoscopic transcystic cholangioscopy with lithotripsy (LTCL), in 70 patients out of 950 laparoscopic cholecystectomies. Preparatory tests included laboratory values, ultrasound, and performance of endoscopic retrograde cholangiography (ERC) with placement of a nasobillary tube (without sphincterotomy). RESULTS: Introduction of the cholangioscope into the CBD was successful in 65 patients (92.9%) and CBD clearance was completely achieved by LTCL alone in 51 (78.5%). The overall success rate was therefore 73%. The remaining 19 cases required postoperative procedures such as extracorporeal shock-wave lithotripsy without ERC or ES (successful in all). The average hospital stay period was 9.4 days for patients in whom CBD clearance was achieved by LTCL alone. This period did not differ significantly from that of patients who underwent LC alone (8.4) days. The operation time was about 70 minutes longer for the LTCL group (total time 174 minutes on average) than for the LC group (107 minutes). We did not observe any series complications during or after LTCL (mean follow-up period: 34 months). CONCLUSION: LTCL in combination with LC allows shortening of the hospital stay and a swift return to work for patients with CBD stones. This procedure also preserves the function of the sphincter of Oddi, so that the longterm prognosis for patients is likely to be very good.
Recently, low dose and long term use of Macrolides (Mls) has been reported to be effective in treatment of chronic lower respiratory tract infections, however its mechanism is still obscure. We evaluated the effect of Mls (EM, AZM, RKM) on cytokine mRNA expressions. We preincubated the whole blood with several concentrations of Mls and removed the Mls and then stimulated human whole blood with LPS as an experimental vivo model. In order to examine cytokine mRNA expressions, we used the RT-PCR method. Cytokine mRNA expressions were suppressed significantly (p < 0.05) by pretreatment with EM, AZM; moreover, the suppression was peaked at low concentrations (0.04 approximately 0.2 microgram/ml). Although, Cytokine mRNA expressions were not suppressed by pretreatment with RKM. These results suggest that EM, AZM have suppression on Cytokine mRNA expressions, and consequently, this suppression has a reasonable effect for DPB patients.
Prophlaxis of CMV-associated disease and/or early initiation of therapy is important in the management of patients with CMV infection. Recently, we developed the CMV antigenemia assay: a rapid and quantitative method based on the detection of CMC antigens in peripheral blood leukocytes by flow cytometry. Heparinized peripheral blood was obtained from healthy donors, bone marrow transplantation patients, patient with collagen disease and patients with adult T cell leukemia. To determine the phenotype of HCMV-infected mononuclear cells, the following phycoerythrin-conjugated mAb were used: CD8, CD15. These mAds were added to the whole blood and incubated. After the hemolysis, the cells were fixed with 4% paraformaldehyde and 0.3% NP-40. To determine the HCMV-infected cells, the following mAb were used in flow cytometry analysis: E13 (Chemicon Inc., Toyo) against HCMV IEA. As a secondary antibody, a FITC-conjugated goat anti-mouse IgG. In the bone marrow transplant patients, CMV-associated antigen was positive in their monocytes and polymorphocytes. In the patient with collagen disease, CMV-antigen was positive in their lymphocytes and monocytes. Our study demonstrates that the detection of CMV antigen-positive blood leukocytes by FACScan is a rapid and quantitative method and useful for the diagnosis and monitoring of CMV-associated CMV-associated disease. The CMV blood antigen assay by FACScan will facilitate the initiation of early treatment with ganciclovir of CMV-associated disease or the administration of prophylactic ganciclovir for preventing the disease.
Grammatically correct but nonsense twenty 4-segment sentences mixed with multiple talk recorded on CD were delivered to ears tested in 47 tinnitus patients at a comfortable level via a headphone. The signal-to-noise ratios were 0dB, 5dB and 10dBSPL. Patients were requested to repeat what they heard before and after electrical treatment. A sinusoidal wave of 10kHz at the intensity of about 200mA was delivered to ears for 30 minutes by using a plate electrode for ECG at the tragus or a stimulating Pt-Ir electrode on the middle ear. Alternatively, 0.5mA DC was delivered to patients using a iontophoretic instrument. Improved word perception under noises was observed in most patients with tinnitus relief following electrical stimulation of the ear, demonstrating that electrical stimulation improved auditory selective attention. There may be a relationship between tinnitus relief and improved selective attention. It may be electrical stimulation of the ears that produced improved selective attention, inducing tinnitus relief and improved word perception according to our previous reports.
Apoptosis of normal and leukemic immature B-cells in vitro is suppressed by contact with bone marrow-derived stromal layers. In stroma-supported cultures of immature B-cells, we found that ligation of CD38, a type II transmembrane protein, inhibited the cell growth and induced apoptosis. CD38 ligation also induced tyrosine phosphorylation and activation of intracellular substrates, including syk, phospholipase C-gamma, c-cbl, and phosphatidylinositol 3-kinase (PI 3-K). Wortmannin and LY294002, two potent inhibitors of PI 3K, rescued immature B cells from CD38-mediated growth suppression. In vitro culture of leukemic lymphoblasts may have potentially important clinical application. First, stroma-supported cultures of acute lymphoblastic leukemia (ALL) cells can determine the growth potential of leukemic cells. In a series of 70 children enrolled in a single program of chemotherapy, cell growth on stroma was a powerful and independent prognostic indicator. Second, a culture system capable of maintaining the majority of ALL blast cells at high levels of viability is also ideally suited for testing antileukemic drugs. Promising results were obtained with 2-chloro-deoxyadenosine and interleukin-4, leading to clinical trials of these two compounds in children with refractory ALL. In addition, we compared the direct antileukemic activities of dexamethasone and prednisolone and found that dexamethasone is five to six times more cytotoxic (on a molar basis) than prednisolone, in agreement with the anti-inflammatory activities of these drugs. This finding may serve to guide the selection of dexamethasone dosage in the treatment of ALL.
A number of antiherpesviral 5-substituted derivatives of 1-beta-D-arabinofuranosyluracil (araU) were significantly resistant to phosphorolysis by rat liver extract (S-9), but were gradually deglycosylated in a 2% enterobacteria cell suspension. The relative order of the resistance conferred by the different C-5 substituents was: 5-propynyl > 5-(E)-2-bromovinyl > 5-(E)-2-chlorovinyl > 5-methyl > 5-iodo. The 2'-fluoro derivatives of araU were completely resistant to phosphorolysis by both liver extract and enterobacteria, whereas the corresponding ribofuranosyl and 2'-deoxyribofuranosyl nucleosides were easily phosphorolysed by S-9, and were immediately cleaved in a 1% enterobacteria cell suspension. These findings suggest that antiherpesviral 5-substituted araU analogues can be relatively stable in vivo, when injected intravenously, and that degradation of 1-beta-D-arabinofuranosyl-5-(E-2-bromovinyl)uracil (sorivudine) following oral administration is due primarily to the action of enterobacteria.