Age effects on pupil dilation among Alzheimer's patients.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K Kono.
Explore the source record for details and available documents.
Surgical stress is known to induce immunosuppression of T cell functions, but the mechanism behind this phenomenon is unclear. The purpose of this study was to determine whether surgical stress affects the expression of signal-transducing zeta molecules in peripheral T cells. In the present study, the expression of signal-transducing zeta molecules was studied by flow-cytometric analysis of permeabilized cells in peripheral blood mononuclear cells from 28 patients before and after surgery. The results demonstrate that T cell receptor (TCR) zeta levels in the peripheral T cells were lower on the 2nd or 3rd postoperative days (POD) compared to the preoperative period and recovered on the 7th POD in patients who received major surgery. Surface CD3 epsilon levels were also decreased after surgery but did not recover on the 7th POD. Culturing of T cells from the preoperative period with autologous monocytes from the 2nd POD induced a decreased expression of their TCR zeta. The reduction was prevented by the addition of catalase, a selective scavenger of hydrogen peroxide, indicating that this phenomenon was mediated by hydrogen peroxide. These results suggest that the decreased expression of TCR zeta molecules in peripheral T cells was induced by surgical stress, and was mediated by hydrogen peroxide derived from monocytes.
We investigated characteristics of 72 clients in a geriatric health services facility (hereafter called GHSF), conditions of their family caregivers, and the factors associated with the caregivers choice of discharge destination. Most of the clients were elderly females with a low degree of independence, and dementia was observed in about 60% of them. The clients had children, but many of them lived alone before admission to the GHSF. The rate of admission from hospitals was high (54%), and that of discharge to hospitals was also high (50%). Sixty-seven percent of the clients stayed in for a period of over six months. Most of the family caregivers were daughters or daughters-in-law, and considered themselves to be healthy. Sixty-three percent of them had jobs, and most of the caregivers had no sub-caregiver to assist them. The family caregivers desired the client's home (19.4%), hospital or another GHSF (54.2%), or nursing home (26.4%) as the discharge destination from the GHSF. According to Hayashi's quantification theory type II, the factors related to the home as the discharge destination desired by client's family caregivers are as follows; caregivers used formal home public health nursing visit service before entering the GHSF, the job of the caregiver was a part-time job, the client did not show dementia, the period of care experience was shorter than one year.
Among the clients in a geriatric intermediate care facility located in the suburbs of Osaka and their family caregivers (72 subjects), the characteristics of the clients and their caregivers, and the discharge destination desired by their family caregivers were investigated, and the associated factors were evaluated. 1. Characteristics of the clients. The clients were elderly females with a low degree of independence, and dementia was observed in about 60% of them. The clients had a relatively large number of children, but many of them lived alone before admission. The rate of admission from hospitals was high (54%), and that of discharge to hospitals was also high (50%). Sixty-seven percent of the clients stayed for a long duration of over 6 months. 2. Conditions of the family caregivers. Most of the family caregivers were daughters or daughters-in-law, and considered themselves to be healthy. Sixty-three percent of the caregivers had jobs. However, most of the caregivers did not have sub-caregiver. 3. Factors related to the discharge destination desired by family caregivers. Not many family caregivers (19.4%) wanted them to go back to their homes after discharge, but their preferred discharge destinations were home (19.4%), hospitals (55.5%), and nursing homes (25.1%). The caregivers of single household clients often desired a nursing home as the discharge destination, and those of the clients from a 2- or 3-generation household often desired a hospital. The factors related to the discharge destination desired by client's family caregivers were that the client not show dementia, the job of the caregiver was a part-time job, there was a sub-caregiver, and the client had the experience of home public health nursing visits. This study showed, the percentage of the clients discharged from the geriatric intermediate care facility to their homes was low, and that of the family caregivers who desired their home as the discharge destination was also low. However, the results suggested that leading the discharge destination to the client's home is possible if social resources are provided such as the use of public health nursing services.
The purpose of this study was to analyze the results of initial radiotherapy for bone metastases (BM) from breast cancer and to investigate the prognostic factors. Between 1981 and 1995, 65 women (109 lesions) received initial radiotherapy for BM, aiming at a total dose of 50 Gy/25 Fr. Significant relief of pain was obtained in 61 (88.4%) of 69 estimable lesions according to the RTOG score. The control rates of pain including the prevention of pathological fractures or myelopathy were 80.4% at 5 years and 64.3% at 10 years. The median survival time of all patients was 11 months, and the survival rates were 56% at 1 year, 31.6% at 3 years, 17.9% at 5 years and 10.7% at 10 years, with five long-term survivors. Univariate analysis showed that a normal state of LDH, no other metastatic organs, a disease-free interval longer than two years, good performance status (0 or 1), BM limited to the axial bones, maintenance chemo-hormonal therapy and an age of more than 55 years were good prognostic factors. Multivariate analysis showed that LDH, age and performance status were significant predictors of prognosis. It is important to note the prognostic factors at the initial treatment of BM from breast cancer. We consider that further prospective studies are needed to determine the optimal treatment schedule, including radiotherapy and its combination with chemohormonal therapy, for BM.
We report two cases of intraspinal extradural cysts communicating with an adjacent herniated disk that we term "disk cysts." These cysts were well defined and homogeneous, and were present in the ventrolateral extradural space adjacent to a lumbar herniated disk. They had rim enhancement on contrast-enhanced MR images, and communication with a herniated disk was revealed by diskography.
A 25-year-old woman was admitted to our hospital because of dark red urine in 1993. A diagnosis of hemolytic uremic syndrome (HUS) because of findings of hemolytic anemia with fragmented erythrocytes, thrombocytopenia, and renal dysfunction. The patient achieved remission with steroids and diuretics. In 1998 she caught a cold and happened to take the nonsteroidal anti-inflammatory drug, pranoprofen. Six hours later, she was rehospitalized because of dark red urine. Hemolytic anemia, fragmented erythrocytes, thrombocytopenia and renal dysfunction were observed again, also. A diagnosis of HUS was made. The patient was treated with steroid pulse therapy, infusion of fresh plasma, and plasma exchange transfusion. She recovered completely. In 1993 she had taker pranoprofen just prior to her first HUS episode. This was a recurrent case of HUS induced by pranoprofen.
To investigate optimal thoracic irradiation (TI) for stage IV lung cancer, we retrospectively reviewed 150 patients. In all, 101 patients underwent radiotherapy for the primary lesion, and 130 had radiotherapy for metastasized sites. TI fields were basically divided into two groups; whole thoracic lesion irradiation (WTLI) and partial thoracic lesion irradiation (PTLI). Overall survival rates at 6 months, 1 year and 2 years were 58%, 27% and 11%, respectively, and MST was 7.1 months. There was no difference in survival according to histological type. On univariate analysis, the factors of good prognosis included good PS, free of bone metastasis, metastasis limited to a single organ, TI, chemotherapy, age (less than or equal to 75 years), and TN factors (T0-2 and N0-1). Multivariate analysis showed PS was the predominant factor. Among the patients treated with TI, survival rates of patients with PS 0-1 were superior to those of patients with PS 2-4. Radiation pneumonitis was more frequent in WTLI than in PTLI. The rates of thoracic failure death were 31.7% in patients treated with TI and 63.3% without TI. However, the size of the thoracic radiation field did not affect the rates of thoracic failure death. We concluded that TI for stage IV patients could reduce thoracic symptoms and increase the survival rate in the subgroup with good PS. Furthermore, we considered PTLI was worth while in the subgroup with poor PS.
We and others have shown decreased expression of T-cell receptor-CD3-associated signal transducing zeta molecules (TCRzeta) in tumor infiltrating and peripheral T cells of patients with advanced cancer. In the present study, we performed adoptive immunotherapy (AIT) with tumor-associated lymphocytes (TAL) in patients with gastric (n = 11) and colon (n = 3) cancer with stage IV and investigated whether the alteration of signal transducing molecules was observed with AIT, compared to an untreated control group (n = 13). Autologous TALs isolated from malignant ascites or pleural effusion were cultured with stimulation of autologous tumor in the presence of interleukin-2 (IL-2) and were transferred to the patients. TCR zeta expression in peripheral T cells was measured by flow cytometric analysis of permeabilized cells with anti-zeta monoclonal antibody (MAb) (TIA-2) before and after AIT. We confirmed the down-regulation of TCR zeta expression in peripheral blood lymphocytes (PBL) of patients with gastric and colon cancer with stage IV compared to healthy donors (n = 15). AIT induced up-regulation of TCR zeta expression in 2 of 14 treated patients, caused no significant change of TCR zeta expression in 7 patients and induced further down-regulation in 5 patients. The patients who achieved clinical responses (n = 3) with AIT showed no significant change of TCR zeta expression. On the other hand, in the control group without adoptive transfer, further down-regulation of TCR zeta expression was observed during the corresponding periods, paralleling disease progression. Taken together, TCR zeta expression in the patients was further down-regulated, corresponding to disease progression in individual cancer patients. In some patients, AIT could induce increased or stable TCR zeta expression. The quantitative analysis of TCR zeta expression might provide vital information that can be used to optimize therapy by preserving immune functions within cancer patients.
We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor-associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1+, HER2/neu+ gastric cancer cells, HER2/neu-transfected C1R/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected C1R/A2 cells. Our results demonstrate that the HER2/neu-encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9(106)), HER2(9(369)), HER2(9(689))], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ C1R/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.
A simple and rapid method for the determination of urine boron by inductively-coupled plasma argon emission spectrometry (ICPAES) has been developed to establish boron exposure guidelines. After 11-fold dilution in 18.25 M omega cm ultra-pure water and vigorous shaking, urine may be directly injected into the spectrometer, providing accurate and reproducible results. We report the results obtained with urine samples obtained from a group of male Japanese electronic workers (n = 102) who had not been exposed to boron; boron concentrations were corrected with use of a specific gravity of 1.024 g/ml. The frequency distribution resulted in a log-normal distribution diagram for anatomical spread. The geometric mean values for urine boron in the non-exposed workers was 798.0 micrograms/l, while the confidence interval (C.I.) was between 398.1 and 1599.6 micrograms/l. Taking into consideration the short biological half-life of boron and its major excretion route via urine, urine was considered to be a suitable means for monitoring of exposure to this element. We conclude that the guidelines established by determining boron reference values are useful for the protection of individuals exposed to boron in their working environments.
PURPOSE: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS AND METHODS: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. RESULTS: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I) and about half of advanced disease (Stage II-III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.
As the elderly population in Japan increases, senile degenerative aortic valvular disease also tends to increase. These patients often have a small aortic annulus. The problem of "valve-patient-mismatch" occurs when a small prosthesis is inserted into a patient with a small aortic annulus. To avoid annular enlargement after aortic valve replacement (AVR), we tried to use a small-sized St. Jude Medical (SJM) valve. From September 1988 through November 1996, 110 AVR were performed in our institution. In these cases, 30 underwent AVR with a small sized SJM valve (male < or = 21 mm, female < or = 19 mm). Dobutamine stress echocardiography was performed in 19 patients who had undergone AVR with a small-sized SJM valve. Surgical results were also compared between patients with small aortic annulus and those with normal-sized aortic annulus. Using Doppler echocardiography, pressure gradients (PG), cardiac index (CI), effective orifice area (EOA), and performance index (PI) were calculated at rest and during stress. The mean body surface area (BSA) of patient who had undergone AVR with SJM19A, 19HP and 21A was 1.40, 1.42 and 1.56 m2, respectively. With dobutamine stress, heart rates, PG and CI increased significantly. Mean and maximum PG of patients with 19HP (8.0 and 15.4 mmHg at rest, 12.9 and 28.0 mmHg under stress, respectively) and 21A (9.5 and 19.1 mmHg at rest, 16.5 and 35.3 mmHg under stress, respectively) were relatively low. EOA index (EOAI) of patient with 19HP showed the highest values mean 0.93 cm2/m2. PIs tended to be higher with HP models than with standard models. The tests were completed without significant side effects such as frequent ventricular arrhythmias. Among the cases with small aortic annulus, there were no operative deaths or hospital deaths. There were also no late deaths, episodes of hemorrhage or thrombosis. Conclusions. In our institution, AVR was performed safely without any aortic annular enlargement with a small aortic anulus in small BSA patients. Postoperative hemodynamic data obtained by echocardiography were satisfactory for all patients at rest and even during maximum dobutamine stress test.
An excess of sodium fluoride (135 mg F/kg body weight) was given in a single oral dose to male Wistar rats. Effects were investigated of fluoride-induced acute kidney intoxication on the time-dependent variations of urine volume. Also, of urinary fluoride ion (F-), alpha-glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucosaminidase (NAG), and creatinine (CR) concentrations. Fluoride administration strongly affects these urinary biochemical indices. Of the several biomarkers studied, alpha-GST is particularly useful as marker of S3 proximal tubule damage. We found that alpha-GST shows the strongest and more durable changes as a result of the large dose of F- given to the experimental animals. Our results suggest that the toxic effect of F- on the kidney may be more pronounced in the proximal tubule than the glomeruli region, and that the disorder of the proximal tubule is more serious in the S3 segment than S1 or S2 segment. Alpha-GST proved to be a useful marker for the early detection and long-term observation of proximal renal tubular injury resulting from F- intoxication. The animal model should help to establish guidelines for the treatment of industrial workers suffering from acute renal failure resulting from accidental exposure to fluoride.
The development of a percutaneous artificial internal organ system requires a reliable biocompatible connection between the external environment and the inside of the human body. Such is necessary for the success of a permanent left ventricular assist device. However, the search for a satisfactory interface at the epidermal level has proven to be difficult. Carbon has been proposed for this application, but its texture does not typically promote ingrowth from surrounding tissue. We have therefore employed a new processing method to produce a fine trabecularized carbon implant. The method for preparing the implant involves infiltrating low temperature pyrolytic carbon into the surface of a carbon core which is wrapped with carbon fabric. This results in a tightly woven porous structure of carbon (carbon fiber diameter: 35-50 microm, maximal pore size >200 microm) with gradually increasing porosity from 15-75%. We implanted test samples percutaneously in a calf for in vivo histological evaluation. Thirty days after implantation epidermal downgrowth was minimal. Microscopic analysis revealed that a thin fibrous capsule surrounded the implant, and mature connective tissue with accompanying blood vessels filled the pores of the fine trabecularized carbon layer. From these results we suggest that fine trabecularized carbon is ideally suited for a percutaneous device system in a permanent left ventricular assist device.
A compact centrifugal blood pump has been developed as an implantable left ventricular assist system. The impeller diameter is 40 mm, and pump dimensions are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in a pump weight of 400 g including a brushless DC motor. The weight of a second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal system, the seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. Purge fluid is continuously purified and sterilized by an ultrafiltration unit which is incorporated in the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular (LV) apex descending aorta bypass was performed utilizing an expanded polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5-9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb levels were measured at less than 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (<0.5 ml/day). In both calves, the pumps demonstrated trouble free continuous function over 6 month (200 days and 222 days).
We have been developing centrifugal pumps for an implantable left ventricular assist device. We manufactured 2 prototype centrifugal pumps (PI, PII). These two have similar designs except for the PII having a volute casing and a large output port. To determine the differences in the hydraulic characteristics between the PI and PII, we carried out in vitro and in vivo experiments. In vitro study showed that the PII had a shallower H-Q curve than that of the PI, and the PII required a pump speed faster than the PI for the same flow rate and pressure head. On the other hand, in vivo study showed that the PII demonstrated a flow pulsatility greater than that of the PI at 1,900 rpm and 8 L/min although no significant change was observed at low pump speeds (< or = 1,500 rpm). This greater pulsatility consisted of a large discharge according to the small differential pressure during the systolic phase and a small discharge according to the large differential pressure during the diastolic phase. In contrast, the PI, having the steeper H-Q curve, showed a small discharge in the systolic phase and a large discharge in the diastolic phase. These results showed that pulsatility synchronized with the native heart beating depended on the slope of the H-Q curve. As a result, the slope of the H-Q curve is important to determine the component of pulsatility synchronized with native cardiac output. Regarding the slope of the H-Q curve, a pump having a volute casing and a large outlet port demonstrates a shallow slope in the H-Q curve. In conclusion, we suggest that a centrifugal pump for use in left ventricular aortic bypass should be designed considering the effect on the native heart pulsatility.
Peripheral blood lymphocytes (PBLs) of patients with cervical intraepithelial neoplasia (CIN), cervical carcinoma, or early breast carcinoma were tested for the expression of T cell receptor zeta chain (TCR zeta) and CD16 zeta chain and production of interferon-gamma (IFN gamma) and interleukin (IL) 10. We found that in all patients with CIN and invasive cervical carcinoma, PBLs showed a reduced TCR zeta and CD16 zeta expression and a significant down-regulation in IFN gamma production (a T helper 1 cytokine) after anti-CD3 stimulation. However, the IL 10 secretion (a T helper 2 cytokine) was not diminished after anti-CD3 stimulation. This indicates that only T helper 1 cells are affected by the down-regulation of the TCR zeta chain expression. We also analyzed PBLs of 12 patients with early breast carcinoma. In these patients, we found TCR zeta and CD16 zeta expression down-regulation in 2 of 12 patients. Six of 12 patients had an enhanced TCR zeta expression. The enhanced TCR zeta expression correlated with a reduced IFN gamma expression after anti-CD3 stimulation. These data show that in general PBLs of early breast carcinoma patients, unlike those of cervical carcinoma patients, do not show a decreased TCR zeta expression. However, a functional impairment of T cells was observed in the subgroup of early breast carcinoma patients with a high nuclear grade of their tumor.