Biomedical subjects

K Gotoh

Publications and source records attributed to K Gotoh.

At least 55 records · Page 3Linked to original sources

PubMed1998

Frequency of MAGE-3 gene expression in HLA-A2 positive patients with non-small cell lung cancer.

Melanoma tumor antigens, MAGE-1 and -3 are presented on HLA-A1 and -Cw*1601, or -A1 and -A2, respectively, to the corresponding cytotoxic T lymphocytes (CTL). If CTL recognizing these antigens were generated in patients, clones of positive tumor cells should be eliminated. To ascertain whether such an immunological response is active in patients with lung cancer and to determine what fraction of lung cancer patients are candidates for MAGE oriented immunotherapy, we assessed the relationship between HLA-A1 or -A2 expression and MAGE-1 or -3 gene expression in their tumors. MAGE-1 and -3 were detected in 18/55 (33%) and 23/55 (42%), respectively, by reverse transcriptase (RT)-polymerase chain reaction (PCR). Allele specific PCR revealed HLA-A1 and -A2 alleles to be expressed in 0/55 (0%) and 22/55 (40%) of our cohort, respectively. Among the 22 patients with HLA-A2 genotype, expression of HLA class I antigens detectable by immunohistochemistry was lost in five (23%) cases. The frequency of MAGE-3 expression in HLA-A2 patients was 5/17 (29%), somewhat lower than that of patients without HLA-A2 expression, 18/38 (47%), although the difference was not statistically significant (P = 0.17). Neither was there a significant association between HLA-A2/MAGE-3 co-expression and survival (P = 0.15, logrank test). We conclude that there is no clear evidence for elimination of lung cancers co-expressing HLA-A2 and MAGE-3 in vivo. Approximately 10% (5/55) of Japanese lung cancer patients are potential candidates for MAGE-3-based immunotherapy.

Adult↗

PubMed1998

An increase of soluble Fas, an inhibitor of apoptosis, associated with progression of COPD.

In chronic obstructive pulmonary disease (COPD) which consists of emphysema and chronic bronchitis, alveolar tissue and/or bronchiolar walls are progressively destroyed. This suggests cell death by necrosis and/or apoptosis although no direct evidence of apoptosis has been reported. It was speculated that the apoptosis-related factors are associated with the progression of COPD. Fas/Apo-1 receptor (Fas), Fas ligand (Fas-L) and soluble Fas ligand (sFas-L) are inducers, while soluble Fas (sFas) is an inhibitor of apoptosis. In this study, plasma sFas and sFas-L were measured in 19 COPD patients receiving supplemental O2 (severe COPD) and 20 COPD patients not receiving supplemental O2 (mild/moderate COPD). Twenty-two age- and sex-matched healthy volunteers (healthy controls) and 20 patients receiving supplemental O2 and with level of hypoxaemia similar to severe COPD due to other pulmonary diseases (disease controls) were also examined. Plasma sFas-L was within normal limits in all groups. Plasma sFas levels were similar among healthy controls, disease controls, and mild/moderate COPD patients, but significantly increased in severe COPD (2.6 +/- 1.1, 2.6 +/- 0.2, 2.8 +/- 0.2 and 4.8 +/- 1.0 ng ml-1, respectively). Although PaO2 was lower in severe COPD than in mild/moderate COPD, and PaCO2 was higher in severe COPD than in mild/moderate COPD, they were close between severe COPD and disease controls. Tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) were increased in patients with COPD, but were similar in both severe and mild/moderate COPD patients. We conclude that increased plasma sFas, which is independent of hypoxaemia, and increases in PaCO2, TNF-alpha, IL-6 and inflammation, may be associated with progression of COPD.

Aged↗

PubMed1998

Nitric oxide synthase immunoreactivity related to cold-induced brain edema.

To determine the relationship between brain edema and the expression of nitric oxide synthase (NOS), we immunohistochemically studied the distribution and level of NOS in rat brain cold injury model. Vasogenic brain edema was produced by cortical freezing lesion. NOS immunohistochemical studies were performed 4 and 8 h, 1, 3, 5, 7, 14 and 21 days after injury. In control normotensive rats, immunoreactivity for NOS was observed in scattered neuronal cells as reported previously, but there was no reactivity in glial cells. In the present study in the cold injury model, however, fibrinogen staining showed extravasated plasma fluid extending to the white matter contralateral to the site of cold injury. NOS immunoreactivity was observed in most reactive astrocytes and a proportion of the microglial cells and macrophages in the white matter not only just beneath the area of cold injury but also in the contralateral side. The nerve cells in the edematous region scarcely showed additional immunoreactivity for NOS. The distribution of increased NOS relatively corresponded with the sites of extravasated plasma fluid demonstrated by fibrinogen staining. Electron microscopically, NOS was observed in astrocytes along the rough endoplasmic reticulum suggesting that NOS was produced in the cells and not taken up from the surroundings. Based on these findings, we postulate that brain edema and the simultaneously generated free radicals or some extravasated plasma components may induce expression of NOS in the reactive cells, and that the NO thus generated may be involved in the development of diffuse degeneration of the white matter which accompanies brain edema.

Animals↗

PubMed1998

Primary cardiac leiomyosarcoma growing rapidly and causing right ventricular outflow obstruction.

Leiomyosarcomas are extremely rare primary cardiac tumors. We report a rapidly growing primary leiomyosarcoma of the right ventricle, which obstructed the right ventricular outflow tract within one month after symptom onset in a 68-year-old man. Two-dimensional echocardiography was useful in diagnosing the extent and progression of the tumor. The tumor was surgically resected on an emergency basis, and the right ventricle and pulmonary artery were successfully reconstructed. Recurrence of the tumor on the right ventricle was observed, and the patient was overcome by sudden dyspnea and died three months after surgery.

Aged↗

PubMed1998

[An urodynamic study on neobladder function].

OBJECTIVE: To analyze the urodynamic characteristics of neobladders, we conducted a pressure-flow study in patients with orthotopic urinary reservoirs. PATIENTS AND METHODS: From 1986 to 1996, 90 patients underwent bladder replacement following cystectomy, using a right colonic, ileocolic, ileal, or sigmoid colonic segment. The subjects were 38 patients (31 men and 7 women) with stable urination and no evidence of cancer recurrence, urethral stricture, urinary tract infection or vesicoureteral reflux. Their mean age was 60.5 years, with a range of 38 to 77 years. Information on neobladder function, such as desire to void, force of micturition, urinary incontinence and other complaints, was obtained by questionnaire. A pressure-flow study was performed in all patients 3 months to 103 months postoperatively to evaluate total reservoir pressure, abdominal pressure and subtracted reservoir pressure during filling and voiding phases. RESULTS: Ten of 38 patients (26.3%) were dissatisfied with their neobladder function, due to weakness of urinary sensation, loss of urinary force and enuresis. In 6 of the 7 patients with enuresis, the urinary reservoir had been created by Heineke-Mikulicz's procedure of detubularization; 4 of these patients had a high degree (over 40 cmH2O) of phasic contraction during the filling phase. In only 2 of the 38 patients, a pressure-flow study showed an almost same pattern as that obtained with a normal urinary bladder. Twelve patients had increased electromyogram of the external urethral sphincter during the voiding phase, while half of the 38 patients showed a flat electromyogram during both the filling and voiding phases. Thus, 31 of 38 patients revealed a sphincter dyssynergia pattern. Mean total reservoir pressure at maximum cystometric capacity was 65.5 +/- 42.1, 48.4 +/- 19.0, 66.0 +/- 61.0 and 107.0 +/- 43.3 cmH2O in ileal, ileocecal, right colonic and sigmoid neobladders, respectively. The value for sigmoid neobladder was statistically different from that for ileocecal neobladder (p < 0.05). Mean total reservoir pressure at maximal flow was 73.1 +/- 42.4, 56.4 +/- 22.6, 88.9 +/- 69.4 and 94.0 +/- 31.8 cmH2O in ileal, ileocecal, right colonic and sigmoid neobladders, respectively. There were no statistically significant differences among these values. The ratio of subtracted reservoir pressure to total reservoir pressure was lower at maximal flow than at onset. Subtracted reservoir pressure may contribute to total reservoir pressure to a greater extent in sigmoid neobladders than in other types of neobladder. CONCLUSIONS: 1. Enuresis may have various causes such as external sphincter dysfunction and involuntary contraction of the reservoir. 2. Urine is evacuated not only by abdominal pressure but also by subtracted reservoir pressure in neobladders. 3. Sphincter dyssynergia due to absence of the detrusor muscle may be one cause of dysuria.

Adult↗

PubMed1997

Hepatitis C virus is frequently coinfected with serum marker-negative hepatitis B virus: probable replication promotion of the former by the latter as demonstrated by in vitro cotransfection.

Patients with hepatitis C have been reported occasionally to be coinfected with serum marker-negative (silent) hepatitis B virus (HBV). The frequency and significance of such coinfection were investigated. Thirty patients with hepatitis C virus (HCV) infections (10 acute, 10 chronic, 10 cirrhotic) were selected randomly; the acute cases were without serum hepatitis B surface antigen (HBsAg) and anti-hepatitis B core IgM, and the chronic cases were without HBsAg. A nested polymerase chain reaction for the X open reading frame was used to amplify HBV DNA in serum, and immunoperoxidase staining was carried out on liver biopsy specimens. Nucleotide sequencing was carried out to characterize the amplified HBV DNAs. In order to clarify the possibility that the silent HBV mutant promotes HCV replication in the liver, the full-length HCV RNA and the cloned silent HBV DNA dimer were cotransfected into an established cell line, HuH-7, and the amount of secreted HCV RNA was quantified serially. The target HBV DNA was amplified in 26 (86.7%) of the 30 patients. Subsequent direct nucleotide sequencing in 9 selected patients revealed an 8-nucleotide deletion, characteristic of a silent HBV mutant. Immunostaining revealed hepatitis B surface antigen in 15 (50.0%). Cotransfected silent HBV DNA augmented the secretion of HCV RNA by up to 5-fold in comparison with HCV RNA transfection alone. In conclusion, HCV is coinfected frequently with the silent HBV mutant and the latter probably promotes the replication of the former in the liver.

Adult↗

PubMed1997

Histological diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc epitope.

This study evaluates whether immunohistochemical staining using antibody TKH-2 is presented as a sensitive method for the histological diagnosis of amniotic fluid embolism (AFE). TKH-2 is the sensitive antibody clearly directed to sialyl Tn, NeuAc alpha 2-6GalNAc and reacts with meconium- and amniotic fluid-derived mucin-type glycoprotein. Formalin-fixed, paraffin-embedded maternal lung tissue sections were obtained from four cases of patients showing AFE, and four women uninvolved with AFE served as control. Specimens were stained using the streptavidin-biotin-immunoperoxidase method. The results of immunostaining were compared with those of hematoxylin-eosin (H&E) or a conventional Alcian blue stain. Remarkable positive TKH-2 stainings were observed easily within the pulmonary vasculature in patients with AFE syndrome. AFE can be easily missed on H&E sections. Compared with TKH-2 staining, Alcian blue staining also may be insufficient to show intravascular mucin in the maternal lung sections. TKH-2 immunostaining is the sensitive method to detect meconium- and amniotic fluid-derived mucin in the lung sections of patients with AFE syndrome.

Adult↗

PubMed1997

Bony foramina facilitate magnetic stimulation: an experimental cat sciatic nerve model.

We have established an experimental bony foramen model in vivo using a cat sciatic nerve, a section of skull bone and a column made from methylmethacrylate. In each model, a foramen-like slit or fissure was created. Motor responses of the cat right gastrocnemius were elicited with a figure-of-8-shaped magnetic coil. Very high intensities of magnetic stimulation were necessary to evoke motor responses with the coil placed on the thigh. However, when the bone section or methylmethacrylate column was placed under the thigh muscle layer with the sciatic nerve fitted into the foramen-like slit or fissure, motor responses could be elicited with a smaller intensity of magnetic stimulation. Despite changes in stimulation intensity or shifts in the magnetic coil, the latency of the motor responses remained constant. By comparing the latency with the electrical recording, the site of excitation was predicted to be at the exit of the foramen. Our studies have confirmed that bony structures, especially bony foramina, facilitate excitation of the nerve by magnetic stimulation and that the exit of the foramen could be the preferential site for magnetic stimulation.

Animals↗

PubMed1997

Genetic analysis of a Japanese patient with butyrylcholinesterase deficiency.

A patient (64-year-old, male) with familial cholinesterasemia caused by BChE deficiency was studied. DNA sequence analysis of all exons identified a point mutation, an A-->G transition at codon 128, resulting in a Tyr-->Cys substitution. The propositus showed extremely low BChE activity, but his other family members (three individuals) showed from intermediate to normal BChE activity. An immunological method revealed the absence of BChE protein in serum of the propositus. Both PCR primer introduced restriction analysis (PCR-PIRA) and sequence analysis revealed all three family members to be heterozygotes for this mutation.

Asian People↗

PubMed1997

Second-line chemotherapy for relapsed small cell lung cancer.

Between January 1985 and August 1991, 159 patients with small cell lung cancer received first-line chemotherapy and 123 (77%) were responders. Of these, 88 relapsed, the remainder having died of other or unknown diseases or being alive without carrying cancer. The relapsed patients were examined to evaluate the outcome of the treatment for relapsed small cell lung cancer and to identify the factors that would contribute to the response rates and the survival durations. Forty-eight of 88 relapsed patients received second-line chemotherapy. Of the 48, 3 were evaluated as showing a complete response, 13 as partial response, 9 as no change, 15 as progressive disease and 8 as not evaluable. The response rate was 33% (95% confidence interval 20.4-48.4%). The median survival time was 146 days. The duration and rate of response in first-line chemotherapy affected the response rates of the second-line chemotherapy, but without statistical significance (P = 0.058 and 0.067 respectively). Increased response duration, time off chemotherapy and previous response to first-line chemotherapy all had a positive effect on the survival times (P < 0.01). Relapsed small cell lung cancer still shows a response to second-line chemotherapy without lessening survival time, and thus clinical trials of new drugs or combination chemotherapeutic regimens for relapsed small cell lung cancer cases would be reasonably justified. Randomized comparative studies are warranted for determining the benefits of second-line chemotherapy for relapsed small cell lung cancer cases.

Adult↗

PubMed1997

Antitumor effects of 5'-deoxy-5-fluorouridine in combination with recombinant human interleukin 2 on murine colon carcinoma 26.

The antitumor activity of recombinant human interleukin 2 (rIL-2) in combination with 5'-deoxy-5-fluorouridine (doxifluridine; 5'-DFUR) against marine colon carcinoma 26 (Colon 26) was studied. BALB/c mice were treated daily for 15 days with 5'-DFUR, rIL-2 or both, beginning on day 7 after subcutaneous transplantation of Colon 26. While mice treated with 5'-DFUR or rIL-2 alone died of tumor growth with pulmonary metastases within 9 weeks posttransplantation, the survival time was significantly prolonged in mice treated with both 5'-DFUR and rIL-2. Most of the combination-treated animals showed the regression of local tumors and the inhibition of pulmonary metastasis. Histopathologically, many tumor cells were degenerated and necrotized, with marked infiltration of mononuclear cells including large granular lymphocytes (LGLs) with periodic acid-Schiff-positive cytoplasmic granules. The cells were positive for CD3 epsilon, asialo GM1 and NK1.1. Spleen cells from the combination-treated mice showed high activities of natural killer (NK) cytotoxicity as well as growth inhibition of Colon 26 and Meth A fibrosarcoma in mice. The results suggest that the combination therapy of 5'-DFUR plus rIL-2 enhanced non-specific cytotoxicity of LGL/NK cells for Colon 26 in tumor-bearing mice and was effective in the inhibition of tumor growth.

Animals↗

PubMed1997

Mechanism of posturally induced crackles as predictor of latent congestive heart failure.

We investigated the role of changes in pulmonary function in posturally induced crackles (PIC) in 76 patients with various heart diseases. Regional ventilation was evaluated by spirometric gated ventilation scanning using 133Xe in 23 of these patients and its relationship to PIC was analyzed. A change from the sitting to the supine position was associated with a significant decrease in the percent functional residual capacity (FRC, p < 0.01) and significant increases in closing volume (CV), CV/vital capacity (VC) and closing capacity (CC)/FRC (p < 0.01) in the PIC-positive subjects. CV, CV/VC and CC/FRC did not differ significantly between PIC-positive (n = 37) and PIC-negative (n = 39) subjects in the sitting position, but in the supine position, these values were significantly higher in the PIC-positive group than in the PIC-negative group (CV: p < 0.05, CV/VC and CC/FRC: p < 0.01). These results suggest that airway closure was markedly increased in PIC-positive subjects in the supine position compared with PIC-negative subjects. Regional ventilation (V) was assessed in the sitting and the supine position from right lateral images divided into 9 segments from the base to the apex of the lung using spirometric gated ventilation scanning. There was no significant difference in regional ventilation in the sitting position between PIC-negative (n = 11) and PIC-positive (n = 12) subjects; in the supine position, regional ventilation decreased significantly at the base in the PIC-positive group. Findings suggest that PIC at the base of the lungs may be related to airway closure at the base of the lungs in the supine position in PIC-positive subjects.

Adult↗

PubMed1997

Serial histopathologic myocardial findings in a patient with ectopic atrial tachycardia-induced cardiomyopathy.

A 17-year-old woman was found to have ectopic atrial tachycardia by her physician. Echocardiography and cardiac catheterization revealed findings resembling dilated cardiomyopathy at the time of initial presentation. The tachycardia was controlled with atenolol only at a dose of 50 mg/day. However, at the age of 22, the presence of ectopic atrial tachycardia was once again confirmed. We successfully performed catheter ablation for persistent ectopic atrial tachycardia. Serial echocardiographic findings showed the left ventricular dimension and function appeared to return to normal 1 year postablation. However, despite pharmacologic control and catheter ablation therapy, histopathology revealed myocardial fibrosis presumably representing permanent damage of the heart secondary to tachycardia 1 year postablation.

Adolescent↗

PubMed1997

Assessment of right ventricular contractile function in patients with left ventricular dysfunction by a simplified echocardiographic subtraction method.

A simplified version of the modified echocardiographic subtraction method for measuring right ventricular (RV) volume was used to assess the indices of RV contractile function, the end-systolic pressure-volume (RV Emax) ratio and the +dP/dt(max)-end-diastolic volume (EDV) relationship. RV volumes determined by the simplified subtraction method and the modified subtraction method were compared in 18 patients. Subsequently, RV contractile function was assessed in 13 patients with normal left ventricular (LV) function (control group: ejection fraction > 56%, as determined by left ventriculography), and 10 patients (group F; five with myocardial infarction, three with dilated cardiomyopathy, two with ischemic cardiomyopathy) with depressed LV function (ejection fraction < or = 55% by left ventriculography). During the application of lower body negative pressure of -20 mmHg, B-mode echocardiograms (apical four-chamber view) and RV or pulmonary artery pressure were recorded simultaneously. The regression equation between RV volumes obtained by the simplified subtraction method and the modified subtraction method was y = 0.99x + 4.5, and the correlation coefficient (r) was 0.985 (p < 0.001). The RV Emax of group F was not significantly less than that of the control group (0.40 +/- 0.16 vs 0.44 +/- 0.17 mmHg/ml, not significant). The correlation coefficients of RV Emax in each group were large (control group 0.92 +/- 0.09, group F 0.90 +/- 0.07). The +dP/dtmax-EDV ratio of group F was significantly less than that of the control group (2.05 +/- 0.74 vs 3.40 +/- 1.85 mmHg/ml.sec, p < 0.05). The correlation coefficient of the +dP/dtmax-EDV ratio was 0.91 +/- 0.06 in the control group and 0.85 +/- 0.15 in group F. The indices of RV contractile function could be assessed using the simplified subtraction method. RV function in patients with LV dysfunction appeared to be depressed.

Adult↗

PubMed1996

Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters.

The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.

Animals↗

PubMed1996

Relationship of ultrasonic and histologic findings in benign prostatic hyperplasia.

We compared the ultrasonic and histologic findings in 25 patients with benign prostatic hyperplasia (BPH) who underwent retropubic subcapsular prostatectomy. Preoperative ultrasonograms showed a fine echogenic pattern in one case, a rough echopenic pattern in four cases, and a combination of these patterns in 20 cases. In cases exhibiting a mixed pattern, we analyzed each region individually. Ultrasonic and histologic findings were compared in a total of 45 regions. In the 21 regions with a fine echogenic pattern, 14 regions corresponded to those with complicated hyperplastic glands, one region with small cystic atrophic glands, and six regions with a mixture of the two types on histology in observation. In the 24 regions with a rough echopenic pattern, 20 regions corresponded to those with large cystic atrophic glands and an equal volume of large and small cystic atrophic glands were found in the other four. Thus, the echogenic structures observed in patients with BPH were determined by the presence of complicated hyperplastic glands and small cystic atrophic glands.

Aged↗

PubMed1996

Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation.

The testicular toxicities of two compound semiconductor materials, gallium arsenide (GaAs) and indium arsenide (InAs), and arsenic oxide (As2O3) were examined in rats by repetitive intratracheal instillation of these substances in suspension twice a week, a total of 16 times. A single instillation dose was 7.7 mg/kg in the GaAs and the InAs groups and 1.3 mg/kg in the As2O3 group. A significant decrease in sperm count and significant increase in the proportion of morphologically abnormal sperm were found in the epididymis in the GaAs group. Especially, abnormal sperm with a straight head increased markedly in this group. In the GaAs-treated rats, there was 40-fold increase in the degenerating late elongated spermatids at the postspermiation stages, stages IX, XI, and XI. From these results, it is indicated that GaAs disturbed the spermatid head transformation at the late spermiogenic phases and caused spermiation failure. InAs caused a sperm count decrease in the epididymis, though its testicular toxicity was relatively weak compared with that of GaAs. As2O3, a probable dissolution arsenic product of GaAs and InAs in vivo, did not show any testicular toxicities in this study. It seems likely that, along with arsenics, gallium and indium play a role in the testicular toxicities of GaAs and InAs.

Animals↗

PubMed1996

Electrophysiological investigation of hemifacial spasm: F-waves of the facial muscles.

In patients with hemifacial spasm (HFS), the spasm is due to cross-compression of the facial nerve by a blood vessel. There are currently two hypotheses for the mechanism of HFS: 1) the spasm is caused by ephaptic transmission and an increase in excitability at the site of compression; and 2) the spasm is caused by hyperexcitability in the facial nerve nucleus. In peripheral nerves, F-waves, which result from the backfiring of antidromically activated anterior horn cells, have been proposed as indices of proximal motoneuron conduction and anterior horn cell excitability. Enhancement of the F-waves indicates increased anterior horn cell excitability. We have therefore measured F-waves in the facial muscle of HFS patients in order to investigate the excitability of the facial nerve nucleus. The authors obtained facial nerve evoked responses from 20 HFS patients before microvascular decompression (MVD), 10 HFS patients after MVD and 10 healthy controls. The F-waves, obtained with surface electrodes from the mentalis muscle, were the second response after the M-wave. On the patient's spasm side, the F-wave duration, F/M amplitude ratio and frequency of F-wave appearance significantly increased compared with those of the normal side or healthy controls; minimum latency and chronodispersion did not significantly differ between these groups. In patients whose spasm disappeared completely following MVD, the abnormal muscle response (lateral spread), which is a characteristic sign of HFS, and the enhancement of the F-wave eventually also disappeared. Because of the correlation between HFS and F-waves, the authors' study supports the hypothesis that the cause of HFS is hyperexcitability of the facial motonucleus.

Adult↗