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Biomedical subjects

S Koga

Publications and source records attributed to S Koga.

At least 73 records · Page 4Linked to original sources
PubMed1999

T cell infiltration into class II MHC-disparate allografts and acute rejection is dependent on the IFN-gamma-induced chemokine Mig.

Direct evidence that cytokines with chemoattractant properties for leukocytes, chemokines, recruit alloantigen-primed T cells into transplanted allografts has been lacking. We present evidence that neutralization of a single chemokine inhibits T cell infiltration into class II MHC-disparate murine allografts and acute rejection. The chemokines IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma (Mig) are expressed in allogeneic skin grafts during the late stages of acute rejection. Survival of class II MHC-disparate B6.H-2bm12 allografts is prolonged from day 14 to day 55 posttransplant when C57BL/6 recipients are given a short course treatment with an antiserum to Mig. This treatment also inhibits T cell and macrophage infiltration into the allografts. B6.H-2bm12 allografts are also not rejected by IFN-gamma-/- C57BL/6 recipients. Injection of Mig directly into B6.H-2bm12 grafts on IFN-gamma-deficient recipients restores T cell infiltration and rejection. Therefore, the inability of IFN-gamma-deficient recipients to reject the class II MHC-disparate allografts is due to the lack of intraallograft Mig production and alloantigen-primed T cell recruitment to the graft. These results indicate for the first time the potential utility of chemokine neutralization strategies in preventing T cell infiltration into allografts and abrogating acute rejection.

Acute Disease↗
PubMed1999

CD8+ T cells produce RANTES during acute rejection of murine allogeneic skin grafts.

BACKGROUND: Based on their chemoattractant properties, it is likely that chemokines play a role in recruiting alloantigen-primed T cells to allografts and in amplifying inflammation within the graft. The graft-infiltrating leukocytes producing specific chemokines remain largely unknown. METHODS: We tested the intragraft RNA expression of the chemokine RANTES (regulated on activation normal T expressed and secreted) and granzyme B during rejection of full thickness, allogeneic skin grafts by C57BL/6 mice. Grafts with different immunogenetic disparities were chosen to test expression when rejection was mediated by CD4+, CD8+, or both CD4+ and CD8+ T cells. RNA expression was also tested in purified CD4+ and CD8+ T cell populations from skin graft recipients. Immunohistology was performed on graft sections to test colocalization of RANTES protein and graft-infiltrating CD4+ and CD8+ T cells. RESULTS: Intra-allograft RANTES RNA expression was not observed during CD4+ T cell-mediated rejection. Expression of RANTES and granzyme B RNA was observed at low levels in purified populations of CD8+, but not CD4+, T cells from the spleen and lymph nodes of graft recipients beginning at day 7 after transplantation and increased thereafter. Intra-allograft RANTES protein was associated with a small number of graft-infiltrating CD8+ T cells but was also associated with endothelial cells and with many graft-infiltrating CD4+ T cells. CONCLUSIONS: CD8+ T cells produce RANTES during allogeneic skin graft rejection. In the allograft, the chemokine also colocalizes with CD4+ T cells that do not produce RANTES.

Acute Disease↗
PubMed1999

Modulation of the thermoregulatory sweating response to mild hyperthermia during activation of the muscle metaboreflex in humans.

1. To investigate the effect of the muscle metaboreflex on the thermoregulatory sweating response in humans, eight healthy male subjects performed sustained isometric handgrip exercise in an environmental chamber (35 C and 50 % relative humidity) at 30 or 45 % maximal voluntary contraction (MVC), at the end of which the blood circulation to the forearm was occluded for 120 s. The environmental conditions were such as to produce sweating by increase in skin temperature without a marked change in oesophageal temperature. 2. During circulatory occlusion after handgrip exercise at 30 % MVC for 120 s or at 45 % MVC for 60 s, the sweating rate (SR) on the chest and forearm (hairy regions), and the mean arterial blood pressure were significantly above baseline values (P < 0.05). There were no changes from baseline values in the oesophageal temperature, mean skin temperature, or SR on the palm (hairless regions). 3. During the occlusion after handgrip exercise at 30 % MVC for 60 s and during the occlusion alone, none of the measured parameters differed from baseline values. 4. It is concluded that, under mildly hyperthermic conditions, the thermoregulatory sweating response on the hairy regions is modulated by afferent signals from muscle metaboreceptors.

Adult↗
PubMed1999

Evaluation of asialoglycoprotein receptor imaging agent as a marker of hepatic ischemia-reperfusion injury and recovery.

Protection of hepatocytes from ischemia-reperfusion injury is a clinically important issue. The purpose of this study was to evaluate changes in acute liver damage and recovery after ischemia-reperfusion in rats with asialoglycoprotein receptor (ASGP-R) ligand. Ischemia was induced by clamping the hepatoduodenal ligament for 90 min. At 1, 3, 24, 48 hr, 1 and 2 wk after reperfusion, I-125-GSA was injected. Five min after injection, blood samples were obtained and the liver was removed. Several regions from each lobe were dissected, weighed and counted. Mean uptakes (% dose/g) in the liver and blood samples were calculated. Histologic sections stained with hematoxylin-eosin (H-E) stain showed ischemic damage at 1 and 3 hr, and focal hepatocyte necrosis at 24 hr. Predominant massive necrosis was not seen. The mitotic index with H-E stain and proliferating cell nuclear antigen (PCNA) labeling index were highest at 1 wk, indicating liver regeneration. At 1 and 3 hr, liver uptake was significantly decreased, and blood uptake was significantly increased, indicating decreased tissue blood flow and ischemic damage. Liver uptake showed significant increases at 48 hr and 1 wk, and was the highest at 1 wk, indicating liver regeneration during the convalescence stage. ASGP-R binding may provide valuable information on ischemia-reperfusion injury and recovery.

Animals↗
PubMed1999

Systemic immune response after intravesical instillation of bacille Calmette-Guérin (BCG) for superficial bladder cancer.

The mechanism of anti-tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for superficial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL-1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and macrophage colony-stimulating factor (M-CSF) after BCG instillation. Levels of IL-2 and IFN-gamma in the serum also increased after BCG instillation, but IL-1beta, IL-6, TNF-alpha and M-CSF were not detectable. Maximal levels of IL-2 and IFN-gamma in the urine or serum were shown after the fourth instillation. BCG-induced killer cell activity in PBMC increased significantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour-free patients produced higher BCG-induced killer cell activity than tumour recurrence patients. BCG-induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.

Administration, Intravesical↗
PubMed1999

Laparoscope-assisted minimally invasive treatment for choledochal cyst.

The principle of treatment of choledochal cysts is total cyst excision with hepaticojejunostomy because of the high rate of associated malignancy of the biliary system. The authors used a minimally invasive laparoscopic procedure to treat a patient with nonmalignant choledochal cyst. Although a large median laparotomy is usually used for cyst excision and hepaticoenterostomy, laparoscope-assisted total cystectomy and hepaticojejunostomy were performed with minimal skin incision. To avoid gas embolism during dissection around the hepatic hilus the surgical procedure was divided into two stages: CO2 insufflation and abdominal lifting without pneumoperitoneum. This combination of procedures was as safe and technically adequate as conventional surgery. No abnormalities were observed in liver function, and the patient could sit up in bed the first day postoperatively. Thirteen days after surgery, he was discharged from the hospital uneventfully.

Adult↗
PubMed1999

Interspecies transmission of feline immunodeficiency virus from the domestic cat to the Tsushima cat (Felis bengalensis euptilura) in the wild.

Feline immunodeficiency virus (FIV) was isolated from a wild-caught Tsushima cat (Felis bengalensis euptilura), an endangered Japanese nondomestic subspecies of leopard cat (F. bengalensis). Phylogenetic analysis of the env gene sequences indicated that the FIV from the Tsushima cat belonged to a cluster of subtype D FIVs from domestic cats. FIVs from both the Tsushima cat and the domestic cat showed similar levels of replication and cytopathicity in lymphoid cell lines derived from these two species. The results indicated the occurrence of interspecies transmission of FIV from the domestic cat to the Tsushima cat in the wild.

Amino Acid Sequence↗
PubMed1999

Kinetics of oxygen uptake during supine and upright heavy exercise.

It is presently unclear how the fast and slow components of pulmonary oxygen uptake (VO(2)) kinetics would be altered by body posture during heavy exercise [i.e., above the lactate threshold (LT)]. Nine subjects performed transitions from unloaded cycling to work rates representing moderate (below the estimated LT) and heavy exercise (VO(2) equal to 50% of the difference between LT and peak VO(2)) under conditions of upright and supine positions. During moderate exercise, the steady-state increase in VO(2) was similar in the two positions, but VO(2) kinetics were slower in the supine position. During heavy exercise, the rate of adjustment of VO(2) to the 6-min value was also slower in the supine position but was characterized by a significant reduction in the amplitude of the fast component of VO(2), without a significant slowing of the phase 2 time constant. However, the amplitude of the slow component was significantly increased, such that the end-exercise VO(2) was the same in the two positions. The changes in VO(2) kinetics for the supine vs. upright position were paralleled by a blunted response of heart rate at 2 min into exercise during supine compared with upright heavy exercise. Thus the supine position was associated with not only a greater amplitude of the slow component for VO(2) but also, concomitantly, with a reduced amplitude of the fast component; this latter effect may be due, at least in part, to an attenuated early rise in heart rate in the supine position.

Adult↗
PubMed1999

Renal transplantation in systemic amyloidosis.

Renal transplantation was performed in a 24-yr-old woman with type AA systemic amyloidosis. Renal biopsy at 11 yr post-transplantation showed no amyloid recurrence, but the presence of mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Renal function was satisfactory with the exception of mild proteinuria. Symptoms related to systemic amyloidosis including goiter and cardiac deposition, improved post-transplantation. Renal transplantation is the recommended therapy for type AA systemic amyloidosis.

Adult↗
PubMed1998

Long-term renal function in on-heart-beating donor kidney transplantation: a single-center experience.

BACKGROUND: One of the most serious problems facing major transplant programs is the severe shortage of organs. Expansion of the donor pool to include nontraditional donors, such as non-heart-beating donors (NHBDs), would considerably expand the availability of organs. METHODS: Between 1983 and 1996, we performed a total of 125 non-heart-beating cadaveric renal transplantations under cyclosporine-based or tacrolimus-based immunosuppression. Thirty-nine recipients were females and 86 were males. Total ischemic time (TIT) and warm ischemic time (WIT) were an average of 761+/-347 min (322-2027 min) and 7.4+/-13.1 min (0-45 min), respectively. RESULTS: Of the 125 transplanted kidneys from NHBDs, 98 (78.4%) developed delayed graft function (DGF), which lasted a mean of 16+/-21 days (range 3-37 days). One hundred and eight patients (86.4%) were off dialysis by the time of discharge. Of the 125 grafts, 11 (8.8%) were primary nonfunction. The average of the nadir of serum creatinine levels, which was evaluated using 108 patients who were off dialysis by the time of discharge, was 1.4+/-0.5 mg/dl. The lowest creatinine levels (nadir) were under 2.0 mg/dl in 98 (78.4%) of the 125 patients. Acute rejection occurred in 64 (51.2%) of the 125 recipients. Patient survival rates were 90% at 5 years and 88% at 10 years. Graft survival rates were 65% at 5 years and 46% at 10 years. We tried to find the risk factors that affected graft survival. We examined the various possible risk factors, including harvesting condition (controlled versus uncontrolled), HLA-AB mismatches, HLA-DR mismatches, graft weight, donor age and sex, recipient age and sex, posttransplant DGF, acute rejection, WIT, and TIT. However, no significant risk factor was identified except acute rejection. We tried to discover the risk factors that caused primary nonfunction. Possible risk factors, including donor age, TIT, WIT, graft weight, and harvesting condition were compared, but no significant risk factor was identified. Long-term renal function was evaluated by serum creatinine levels. Serum creatinine levels at 1, 5, and 10 years were 1.76+/-0.7 mg/dl, 1.7+/-0.96 mg/dl, and 1.53-/+0.6 mg/dl, respectively. CONCLUSIONS: In conclusion, our data demonstrated that the procurement of kidneys from NHBDs leads to acceptable long-term graft survival and renal function, despite a high incidence of DGF.

Adult↗
PubMed1998

Long-term results of ABO-incompatible living kidney transplantation: a single-center experience.

BACKGROUND: Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. METHODS: Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. RESULTS: Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa

ABO Blood-Group System↗
PubMed1998

Characterization of neuronal damage by iomazenil binding and cerebral blood flow in an ischemic rat model.

I-123-iomazenil is a SPECT probe for central benzodiazepine receptors (BZR) which may reflect intact cortical neuron density after ischemic insults. We evaluated whether neuronal damage in rats could be characterized by iomazenil as compared with cerebral blood flow (CBF). Serial changes in I-125-iomazenil for BZR and I-123-IMP for CBF were analyzed after the unilateral middle cerebral artery occlusion in rats by using an in vivo dualtracer technique. Uptake ratios of affected to contralateral regions were calculated. The iomazenil as well as IMP were decreased in all regions except for the cerebellum (remote area). Both iomazenil and IMP increased over time except in the temporal region (ischemic core). The iomazenil uptake was higher than IMP except in the ischemic core between 1 and 3-4 wk when iomazenil was lower than IMP. Iomazenil showed a moderate decrease in the proximal and middle parietal regions (peri-infarct areas) at 3-4 wk. The triphenyl-tetrazolium-chloride (TTC) stain at 1 wk demonstrated unstained tissue in the temporal region indicating tissue necrosis. With hematoxylin-eosin (HE) stain at 1 wk, widespread neuronal necrosis with occasional intact neurons were found in the proximal parietal region, and isolated necrotic neurons were represented in the distal parietal region. Iomazenil correlated well with the neuron distribution and the finding of a discrepancy between iomazenil and IMP might be useful in evaluating the neuronal damage.

Animals↗
PubMed1998

A novel glycerol kinase from Flavobacterium meningosepticum: characterization, gene cloning and primary structure.

A thermostable glycerol kinase (FGK) was purified 34-fold to homogeneity from Flavobacterium meningosepticum. The molecular masses of the enzyme were 200 kDa by gel filtration and 50 kDa by SDS-PAGE. The Km for glycerol and ATP were 0.088 and 0.030 mM, respectively. The enzyme was stable at 65 degrees C for 10 min and at 37 degrees C for two weeks. The enzyme gene was cloned into Escherichia coli and its complete DNA was sequenced. The FGK gene consists of an open reading frame of 1494-bp encoding a protein of 498 amino acids. The deduced amino acid sequence of the gene had 40-60% similarity to those of glycerol kinases from other origins and the amino acid sequence of the putative active site residue reported for E. coli GK is identical to the corresponding sequence of FGK except for one amino acid residue.

Amino Acid Sequence↗
PubMed1998

[Paraurethral cyst in a female neonate: a case report].

A seven-hour-old female neonate visited our hospital because of the anormaly of external urethral meatus. An interlabial cystic mass, the diameter of which was about 1 cm, was observed and an external urethral meatus could not be found. Direct needle aspiration of the cystic mass showed a small quantity of milky fluid and an urethral meatus was then identified.

Cysts↗
PubMed1998

[Study on urinary levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in patients with renal cell carcinoma].

We examined the preoperative and postoperative, urinary levels of the cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in 14 patients with renal cell carcinoma (RCC), and 9 patients who underwent nephrectomy as donors (controls). Although urinary IL-1 beta was measurable in every subject, both IL-6 and TNF-alpha were undetectable in 12 of the 14 patients. None of the urinary cytokines showed levels significantly different from the controls preoperatively. Urinary levels of IL-1 beta showed no correlation with clinical stage or histological grade. Only urinary IL-1 beta was significantly elevated after nephrectomy, when compared with the controls (P < 0.05). However, urinary IL-1 beta showed no correlation with operative blood loss or postoperative infection. These findings suggest that measurement of urinary cytokines is not useful for diagnosis or monitoring of therapy in RCC patients.

Adult↗
PubMed1997

Comparative study of cytomegalovirus (CMV) antigenemia assay, polymerase chain reaction, serology, and shell vial assay in the early diagnosis and monitoring of CMV infection after renal transplantation.

BACKGROUND: Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay. METHODS: Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay. RESULTS: Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation. CONCLUSIONS: Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.

Adolescent↗
PubMed1997

Effects of reduced muscle temperature on the oxygen uptake kinetics at the start of exercise.

The purpose of this study was to examine the effects of reduced muscle temperature (Tm) on gas exchange kinetics and haemodynamics at the start of exercise. Six male subjects performed moderate cycle exercise under reduced (C) and normal (N) Tm conditions. Tm and rectal temperature were significantly reduced by immersion in cold water (by 6.6 degrees C and 1.8 degrees C, respectively). The increases in oxygen uptake (Vo2) and oxygen pulse (Vo2/HR) during phase 1 (abrupt increase after the start of exercise) were significantly lower under C than under N. The time constant for O2 under C (36.0 +/- 7.7 (SD)s) was significantly greater than under N (27.5 +/- 4.4 s); however, the time constants of cardiac output under C (38.3 +/- 16.6 s) and N (33.7 +/- 18.5 s) were similar. These results suggest that the slower Vo2 on-response under reduced Tm conditions is caused by decreased O2 extraction in working muscle and/or by impairment of oxidative reactions by reduced muscle temperature.

Adult↗