Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Interaction between desialylated hepatitis B virus and asialoglycoprotein receptor on hepatocytes may be indispensable for viral binding and entry.

The cellular receptor for hepatitis B virus (HBV) infection has not yet been identified. The purpose of this study was to address the possibility of participation by desialylated HBV and the asialoglycoprotein receptor (ASGP-R) exclusively expressed on liver parenchymal cells, in infection. Assays for viral binding and entry were performed by culturing a hepatoblastoma cell line, HepG2, and HBV particles derived from the HBV carrier in the presence or absence of neuraminidase (NA). Viral binding and entry were clearly enhanced in the presence of NA, and the enhancement of the binding could be blocked by asialo-fetuin and ethylenediamine-tetraacetic acid (EDTA). In addition, covalently closed circular (CCC)-DNA, as a marker of infectivity, was detected in the presence of NA, but not in its absence. The optimal concentration of NA raised infectivity more than 1000 times. We concluded that this method makes it feasible to evaluate the infectivity of HBV in vitro and that ASGP-R may be a specific HBV receptor once viral particles are desialylated.

Preparation and characterization of spherical polymer packings from polybutadiene for size-exclusion chromatography.

Porous polymer spherical particles for column packings in nonaqueous size-exclusion chromatography (SEC) were prepared from 1,2-syndiotactic polybutadiene by suspension and evaporation method. The polymer microbeads obtained were crosslinked by radical reaction between 2-vinyl groups in polybutadiene with ultraviolet radiation, to render them insoluble. These microbeads have wider chromatographic separation width than polystyrene column packings. In addition, the polybutadiene microbeads did not show the excessive retention observed with commercial polystyrene columns for polycyclic aromatic compounds. Therefore, a close correlation between the elution volume and M, for polycyclic aromatic compounds was observed with polybutadiene microbeads columns.

Comparison of the sensitivity of NAT using pooled donor samples for HBV and that of a serologic HBsAg assay.

BACKGROUND: Studies were conducted using samples from early and late-stage HBV-infected persons to determine the pool size at which PCR had better sensitivity than a sensitive HBsAg chemoluminescence immunoassay (CLIA-HBsAg). STUDY DESIGN AND METHODS: HBV seroconversion panels were tested for HBsAg by CLIA and for HBV DNA by nested PCR (95% hit rate: 100 copies/mL); PCR was carried out at various dilutions. HBV serologically positive samples that were detected from the simultaneous screening of 540,161 routine whole-blood donations using CLIA-HBsAg and agglutination assays were also characterized for additional markers of HBV infection. RESULTS: In 9 of 10 HBV seroconversion panels, PCR had better sensitivity than CLIA-HBsAg at dilutions of 1-in-25 or lower. Of 65 CLIA-only confirmed-positive donor samples (agglutination assay-negative), 8 represented early infection, 2 of which were PCR positive at a 1-in-50 dilution but negative at a 1-in-100 dilution. Only 2 of 47 samples from probable late-stage HBV infection that were positive on CLIA only were PCR positive with 0.1-mL sample volume and the S-region primer; the remaining 45 samples required a 1.0-mL sample input and C-region primer for increased PCR positivity. The remaining 10 CLIA-only confirmed-positive donor samples were from HBV vaccine recipients. None of the 12 CLIA- and HBsAg-negative donor samples that were strongly anti-HBc reactive could be detected by PCR at any dilution; all 12 were PCR positive when undiluted, but 4 required a 1.0-mL input volume for PCR positivity. CONCLUSION: For the detection of samples representing early-stage HBV infection, PCR at dilutions of 1-in-25 or lower (equivalent to a pool of < or =25 members) had greater sensitivity than CLIA-HBsAg. In contrast, samples from late-stage HBV infection were detected by PCR only with undiluted samples (0.1-mL or 1.0-mL input volumes), regardless of CLIA-HBsAg reactivity. Therefore, although NAT using minipools of 25 donations or less may be effective for the detection of early-stage HBV infection, it may not be effective for the detection of persistent HBV infection.

[A case of pheochromocytoma with von Recklinghausen's and review of 67 Japanese cases].

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.

Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in hepG2 cells.

The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR gamma activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in HepG2 cells were investigated. Exposure of the cells for 24 hours to either oleic acid or insulin showed no obvious effects on PAI-1 synthesis, whereas the combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis, which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of PAI-1 mRNA. This up-regulation of PAI-1 synthesis was attenuated by bezafibrate in a dose-dependent manner (1-100 microM) with 30% reversal at 100 microM. In contrast, troglitazone further stimulated PAI-1 synthesis to 140% of the level obtained in the presence of both oleic acid and insulin. This attenuation by bezafibrate and enhancement by troglitazone required the presence of both oleic acid and insulin. It is interesting that PAI-1 expression was affected so differently by these two PPAR activators.

Parathyroid hormone-induced bone resorption does not occur in the absence of osteopontin.

Osteopontin is an RGDS-containing protein that acts as a ligand for the alpha(v)beta(3) integrin, which is abundantly expressed in osteoclasts, cells responsible for bone resorption in osteopenic diseases such as osteoporosis and hyperparathyroidism. However, the role of osteopontin in the process of bone resorption has not yet been fully understood. Therefore, we investigated the direct function of osteopontin in bone resorption using an organ culture system. The amount of (45)Ca released from the osteopontin-deficient bones was not significantly different from the basal release from wild type bones. However, in contrast to the parathyroid hormone (PTH) enhancement of the (45)Ca release from wild type bones, PTH had no effect on (45)Ca release from organ cultures of osteopontin-deficient bones. Because PTH is located upstream of receptor activator of NF-kappaB ligand (RANKL), that directly promotes bone resorption, we also examined the effect of RANKL. Soluble RANKL with macrophage-colony stimulating factor enhanced (45)Ca release from the bones of wild type fetal mice but not from the bones of osteopontin-deficient mice. To obtain insight into the cellular mechanism underlying the phenomena observed in osteopontin-deficient bone, we investigated the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the bones subjected to PTH treatment in cultures. The number of TRAP-positive cells was increased significantly by PTH in wild type bone; however, no such PTH-induced increase in TRAP-positive cells was observed in osteopontin-deficient bones. These results indicate that the absence of osteopontin suppressed PTH-induced increase in bone resorption via preventing the increase in the number of osteoclasts in the local milieu of bone.

The addition of bisecting N-acetylglucosamine residues to E-cadherin down-regulates the tyrosine phosphorylation of beta-catenin.

The enzyme GnT-III (beta 1,4-N-acetylglucosaminyltransferase III) catalyzes the addition of a bisecting N-acetylglucosamine (GlcNAc) residue on glycoproteins. Our previous study described that the transfection of GnT-lll into mouse melanoma cells results in the enhanced expression of E-cadherin, which in turn leads to the suppression of lung metastasis. It has recently been proposed that the phosphorylation of a tyrosine residue of beta-catenin is associated with cell migration. The present study reports on the importance of bisecting GlcNAc residues by GnT-lll on tyrosine phosphorylation of beta-catenin using three types of cancer cell lines. An addition of bisecting GlcNAc residues to E-cadherin leads to an alteration in cell morphology and the localization of beta-catenin after epidermal growth factor stimulation. These changes are the result of a down-regulation in the tyrosine phosphorylation of beta-catenin. In addition, tyrosine phosphorylation of beta-catenin by transfection of constitutively active c-src was suppressed in GnT-III transfectants as well as in the case of epidermal growth factor stimulation. Treatment with tunicamycin abolished any differences in beta-catenin phosphorylation for the mock vis à vis the GnT-lll transfectants. Thus, the addition of a specific N-glycan structure, the bisecting GlcNAc to E-cadherin-beta-catenin complex, down-regulates the intracellular signaling pathway, suggesting its implication in cell motility and the suppression of cancer metastasis.

Genomic structure and promoter analysis of the human alpha1, 6-fucosyltransferase gene (FUT8).

GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha1,6-fucosyltransferase (alpha1,6FucT) catalyzes the transfer of a fucosyl moiety from GDP-fucose to the asparagine-linked GlcNAc residue of complex N-glycans via alpha1,6-linkage. We have cloned the genomic DNA which encodes the human alpha1,6FucT gene ( FUT8 ) and analyzed its structure. It was found that the gene consists of at least nine exons spanning more than a 50 kbp genomic region, and the coding sequence is divided into eight exons. The translation initiation codon was located at exon 2, and thus exon 1 encodes only 5'-untranslated sequences. Transcription initiation site of FUT8 was determined by 5'-rapid amplification of the cDNA end and a primer-extension analysis using the total RNA isolated from SK-OV-3 cells, which have a high level of alpha1,6FucT activity. We then characterized the FUT8 promoter region by a reporter gene assay. The luciferase reporter assay indicated that the 5'-flanking region of exon 1, which covered about 1 kbp, conferred the promoter activity in SK-OV-3 cells. This region contains potential binding sites for some transcription factors, such as bHLH, cMyb, GATA-1, as well as a TATA-box, but not a CCAAT motif. 5'-Untranslated sequences found in ESTs and the cDNA for the FUT8 suggest the presence of an additional exon(s) at the upstream of the first exon identified in this study, and therefore, the transcription of the gene would be regulated by multiple promoters.

Differential effects of nicotine against stress-induced changes in dopaminergic system in rat striatum and hippocampus.

A number of studies have shown an increase in nicotine self-administration among smokers when exposed to stress. Since it is well known that nicotine or stress alter the dopaminergic system, we examined the effect of chronic nicotine administration on the dopamine level and its metabolism in the striatum and the hippocampus during stressful conditions in rats. Nicotine (0.4 mg/kg, i.p. for 14 days) increased the dopamine level in the striatum (P<0. 05) and decreased it in the hippocampus (P<0.05) in comparison with the effect of saline. Three hours of water-immersion restraint stress sharply elevated the dopamine level (P<0.05) and reduced the 3-methoxytyramine level (P ranged from 0.05 to 0.001 depending on the area and time point) in both brain regions studied, while dihydroxyphenylacetic acid and homovanilic acid levels were not altered. Nicotine pretreatment attenuated some of these changes in a region- and time-dependent manner. However, stress induced a decrease in dopamine turnover in the hippocampus (P<0.05) but not in the striatum, and nicotine failed to prevent this effect. Stress-induced alterations gradually returned toward normal during the 48-h observation period, and in some cases this was facilitated by nicotine. Thus, we demonstrated differential, region- and time-dependent protective effects of chronic nicotine administration against stress-induced changes in dopamine levels and release in brain regions critically affected by stress.

Clinical and analytical evaluation of the simultaneous HPLC assay of retinol and alpha-tocopherol.

We describe a method for the simultaneous assay of retinol and alpha-tocopherol using normal-phase, high-performance liquid chromatography (HPLC). Our normal-phase HPLC method gave better resolution (Rs) of retinol (Rs= 1.58) and alpha-tocopherol (Rs = 1.40) when compared with the Rs values for a-tocopherol and retinol from literature. Also, the alpha-tocopherol concentrations obtained by our method agreed well with another normal-phase HPLC method that used fluorometric detection (r = 0.951, p<0.001. Sy.x=0.58 mg/L). The concentrations of retinol in our method agreed well with those determined by a reversed-phase HPLC procedure, although the correlation (r=0.646, p<.001, Sy.x=62 microg/L) was not as good as the method proposed. Our procedure gave acceptable precision: the within-run CV was 7.7% for alpha-tocopherol and 5.9% for retinol. The between-day CV was 9.0% for alpha-tocopherol and 6.8% for retinol. The mean recoveries were 97% for alpha-tocopherol and 107% for retinol. Our assays were linear for alpha-tocopherol concentrations from 0.1 to 30 mg/L and for retinol concentrations from 20 to 2,000 microg/L. In children ages 7 to 12 y, and in adolescents ages 14 to 16 y, the alpha-tocopherol and retinol concentrations in the blood were significantly lower than the concentrations in normal adults. Individuals over 70 y old also showed alpha-tocopherol and retinol values that were lower than those of normal adults between ages 30 and 40 y. In female university students, the inter-individual variation of alpha-tocopherol was reduced by dividing the alpha-tocopherol results by their total cholesterol or total lipid concentrations; however, this was not obtained for retinol. In cancer patients undergoing surgery, the ratio of retinol to retinol-binding protein (RBP) remained fairly constant, although the concentrations of both retinol and RBP decreased to about one-half the preoperative values after surgery. We conclude that our normal-phase HPLC method is a stable and reproducible method for alpha-tocopherol and retinol, and is an easy-to-use analytical tool.

Complications of laparoscopic adrenalectomy in 75 patients treated by the same surgeon.

OBJECTIVE: We analyzed the complications of endoscopic adrenalectomy. METHODS: We retrospectively reviewed the operative and postoperative complications among 75 patients with adrenal tumors who underwent endoscopic adrenalectomy by the same surgeon. RESULTS: Five patients (6.7%) were converted to open surgery. Of these, there were 2 with metastatic adrenal carcinoma, and 1 with adrenal tuberculosis. A total of 21 patients (28%) had 24 complications (32%). There was no mortality. As for access and pneumoperitoneum-related complications, 5 cases of subcutaneous emphysema and 3 of radiating shoulder pain occurred. Intraoperative complications included 2 cases of vascular injury, 2 of organ injury, and 4 of massive bleeding (>500 ml). Postoperative complications included 2 cases of mild paralytic ileus, 2 asthma, and 1 each of angina, wound infection, retroperitoneal hematoma, and contralateral atelectasis. Except for the patients with adrenal malignancy and adrenal tuberculosis, 71% of the complications occurred among the initial 25 patients with laparoscopic adrenalectomy and 80% occurred in the initial 10 retroperitoneoscopic patients. CONCLUSION: Although endoscopic adrenalectomy is a valuable alternative to open surgery, it should be done by a skilled laparoscopist in patients with adrenal inflammatory lesions or malignancy. Careful patient selection and correct choice of surgical approach according to the tumor size and the patient's condition are the most important points for avoiding the complications of laparoscopic adrenalectomy.

Efficiency of donor screening for human parvovirus B19 by the receptor-mediated hemagglutination assay method.

BACKGROUND AND OBJECTIVES: Mass screening for parvovirus B19 (B19) by receptor-mediated hemagglutination assay (RHA) may be inadequate to eliminate the virus from plasma pools. We characterized B19 carriers detected in blood donor screening by RHA to explain why some carriers were not detected by RHA. MATERIALS AND METHODS: Donor plasma was screened for B19 by RHA, B19 DNA by nested polymerase chain reaction (PCR) assay, and anti-B19 by enzyme immunoassay. RESULTS: B19 DNA-positive specimens (n = 73) screened from 456,665 donors were divided into group A (n = 41) with high DNA and high RHA titers, group B (n = 16) with low DNA and low RHA titers, and group C (n = 16) RHA-negative. Most (37/41) of the group A samples were without anti-B19, while most (15/16) of the group B samples were positive for anti-B19. Group C specimens were screened by PCR from 3, 042 random RHA-negative specimens. Analysis of samples from early infections revealed that the viremic period, corresponding to group A, lasted only 8-10 days after infection. The RHA reactivity fell rapidly with the appearance of anti-B19 and disappeared 28-30 days after infection, thus corresponding to group B. The RHA reactions of group B specimens were often unstable, probably because of the formation of immune complexes. The B19 DNA-positive, RHA-negative state lasted for several months, which corresponded to group C. CONCLUSION: Only group A specimens are reliably eliminated in donor screening by RHA. Therefore, although donors with high B19 DNA could be screened out by testing for B19 by the RHA, most B19 carriers, with low B19 DNA and RHA-negative, will not be eliminated.

Cancer cells overexpress mRNA of urokinase-type plasminogen activator, its receptor and inhibitors in human non-small-cell lung cancer tissue: analysis by Northern blotting and in situ hybridization.

The transcriptional localizations of urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitors (PAI-1 and PAI-2), which are possibly involved in cancer metastasis, have not been determined in human lung cancer. To identify their regulation in primary non-small-cell lung cancer, we assayed mRNA levels by Northern blot analysis in 25 cases and determined the localizations of mRNA by in situ hybridization in 10 cases. The amounts of uPA and PAI-2 mRNA were significantly higher in cancerous relative to normal lung tissues. However, no significant difference was observed in uPAR and PAI-1 mRNA levels. All transcripts were present in cancer cells and were predominantly located in tumor edges in several cases. In addition, PAI-1 transcripts were more abundant in poorly and moderately differentiated carcinomas relative to well-differentiated carcinomas and PAI-2 transcripts were more abundant in squamous cell carcinomas than in adenocarcinomas. Thus, PAIs may be involved in modulation of malignant potency. Our results indicate that human non-small-cell lung cancer cells can autonomously express the mRNAs of uPA, uPAR and PAIs, which are possibly involved in metastasis.

[Prostatic cancer with cystic formation: a case report].

An 82-year-old man presented with a huge hypogastric tumor. A pelvic computed tomographic scan and magnetic resonance imaging revealed a multiple cystic mass 14 x 10 x 15 cm in diameter. The prostate specific antigen (PSA) value was elevated to 903 ng/ml. Histological examination of the needle biopsy specimens of the prostate revealed moderately differentiated adenocarcinoma. Bone scintigraphy showed a hot area in part of the costa. No other abnormalities were found. The tumor origin was suspected to be the prostate, but the possibility that it was another organ could not be denied completely since the tumor was located in the anterior portion above the bladder. Treatment with luteinizing hormone-releasing hormone agonist and diethylstilbestrol was initiated considering the patient's age. The PSA value returned to normal and the tumor size was reduced markedly after 28 weeks of therapy. Thirty-seven case of prostatic cancer with cystic formation in the Japanese literature are reviewed.

[Blood amino acid levels in sarin poisoning patients].

Since plasma is generally employed for amino acid analysis, we compared amino acid levels in plasma with those in serum for healthy individuals and examined the influence of separation and storage conditions on the stability of the samples. Then, we determined the amino acid levels of frozen serum samples obtained from sarin poisoned patients. A. Comparison of Amino Acid Levels in Plasma and Those in Serum Blood was collected from 5 healthy individuals. Then, heparinated plasma and serum were separated by centrifugation immediately after blood collection. Serum was also separated by centrifugation after standing whole blood at room temperature for 1 hour. Frozen plasma and serum were store at -40 degrees C for 5 months. All were subjected to analysis in an amino acid analyzer. It was found that the cystine (Cys) and 3-methyl-histidine (3-M-His) levels in serum and plasma were affected when stored in a frozen state, that the aspartate (Asp) level was changed according to the method of collecting serum, and that the taurine (Tau) and ornithine (Orn) levels were affected by standing blood. B. Analysis of Blood Taken from Sarin Poisoned Patients Twelve sarin poisoned patients were selected as subjects, and serum cholinesterase (Ch-E) and serum albumin (Alb) levels were determined. Amino acid analysis was conducted using an amino acid analyzer. Serum samples which had been obtained from the 6 patients and frozen and stored at -40 degrees C from 5 months were used for amino acid analysis. As a result, the serum Ch-E level decreased and the Alb level tended to rise. Since the Ch-E/Alb ratio was reduced in the sarin poisoned patients, it is considered useful for discrimination from liver cirrhosis in which both Ch-E and Alb levels decreased. Amino acid levels in the serum obtained from the sarin poisoned patients were compared with those of healthy individuals, both of which had been stored under the same conditions. There were significant differences in Asp, glutamate (Glu), phenylalanine (Phe), 3-M-His, glutamine (Gln), and Cys levels. The Glu, Phe, and Gln levels were not affected by storage of serum in a frozen state, while the Glu and Phe levels were elevated and the Gln level was reduced. Although Cys exhibited lower values in frozen serum samples, the Cys level was elevated with a rise in the serum Ch-E levels. Therefore, we deduced that Cys metabolism disorders also occur in sarin poisoning. As stated above, the Glu and Phe levels were elevated and the Gln and Cys levels were reduced, suggesting the presence of abnormal amino acid metabolism, in patients with sarin-poisoning.

MRI of anterior cruciate ligament healing.

OBJECTIVE: The purpose of this study was to evaluate using MRI the natural healing of the anterior cruciate ligament (ACL) when treated conservatively by early protective motion. MATERIALS AND METHODS: Consecutive acute complete intraligamentous ruptures of the ACL in 50 cases that were allowed to heal without surgery were evaluated before and after 3 month treatment by MRI, arthroscopy, and stress radiographs. Twenty-nine of the 50 patients were also reevaluated 11 months from the initial injury, of which 7 were reevaluated again 24 months from the initial injury by MRI. The MR appearance of the treated ACL was categorized into four grades depending on homogeneity, straight band, and size. RESULTS: MR assessment of the ACL after 3 month treatment demonstrated a well defined normal-sized straight band in 37 cases (74%). There was a significant relationship between the 3 and 11 month MR evaluations (rs = 0.801, p <0.0001). There were also significant relationships between the MR and arthroscopic evaluations (rs = 0.455, p <0.005) and between the MR stress radiographic evaluations (rs = 0.348, p <0.025) after the 3 month treatment. CONCLUSION: MRI can demonstrate ACL healing when treated conservatively with early protective mobilization.

The significant effect of HLA-DRB1 matching on acute rejection in kidney transplants.

The object of the present study was to confirm the HLA-DRB1 matching effect on rejection crisis, its severity, and kidney graft survival based on genotyping. Ninety-four renal allografts were included in this study. DNA typing of HLA-DRB1 was performed by the polymerase chain reaction sequence-specific oligonucleotide method. The incidence of acute rejection within 6 months following transplantation, the frequency of OKT3 administration for steroid-resistant rejection, histopathological findings, and graft survival rate were compared between the DRB1-matched (n = 23) and DRB1-mismatched (n = 71) groups. Four acute rejections occurred in the DRB1-matched group (incidence; 17%) and 40 in the DRB1-mismatched group (56%). In the DRB1-matched group, the incidence of acute rejection was significantly less frequent than that of the DRB1-mismatched group (P < 0.005). In the DRB1-matched group, only one patient received OKT3 administration (4%), in contrast to 16 of 71 patients in the DRB1-mismatched group (23%). The use of OKT3 was significantly less frequent in the DRB1-matched group (P < 0.05). Histopathological findings from biopsy specimens showed no constant distribution of pathological grades of acute rejection according to DRB1 matching in the present study. The graft survival rate in the two groups did not differ significantly, but the graft survival rate in the DRB1-mismatched group had a tendency to decrease as the grafts survived longer. In conclusion, the results of the present study confirm that HLA-DRB1 matching has marked beneficial effects on kidney transplants through reduction of the acute rejection rate and decrease of the severity of rejection, and suggest that improvement of graft survival will be obtained through kidney allocation to a DRB1-matched recipient.

[Clinical study of pediatric kidney transplantation at Kansai].

BACKGROUND: The clinical study of pediatric kidney transplantation in Kansai area is reported in this paper. METHODS: Seventy six children, 0-15 years old, received renal transplants at 8 transplant centers of Kansai area up to December, 1993. Clinical study was carried out about the etiology of renal failure causes, the graft survival and the complications. RESULTS: End-stage renal failure was due to a variety of diseases. The 3 most common causes were chronic glomerulonephritis, chronic pyelonephritis including of reflux nephropathy and focal segmental glomerulosclerosis (FSGS). The graft rates at 3, 5 and 8 years were 75%, 71% and 53% for children receiving azathioprine (AZ), compared to 77%, 59% and 52% for ones receiving ciclosporin (Cs). Cs has led no improvement of the graft survival. Adult had the better graft survival rate than children in Cs immunosuppressive protocol. In 12 children transplanted kidneys for FSGS, only 3 cases had recurrent FSGS. Neoplasia was found in two case. They were acute leukemia and liposarcoma. CONCLUSION: Kidney transplantation is recommended as the treatment for end-stage FSGS. Even the children should be carefully followed up after transplantation for malignant tumors.

[Clinical study of primary carcinoma in situ of the bladder].

In our department 14 patients with primary carcinoma in situ of the bladder were treated. Thirteen patients were male and 1 patient was female. Most of the patients complained of irritative vesical symptoms such as painful urination and/or pollakisuria. Cystoscopic examination revealed no overt tumor but some abnormal findings like localized or diffuse hyperemia or fine granular changes were noted. In 4 patients, total cystectomy was performed primarily and 10 other patients were treated at first with intravesical chemotherapy or intravesical BCG. Five of those 10 patients (50%) developed invasive cancer and total cystectomy was performed secondarily in them. Invasive cancer occurred in the bladder wall in 2 patients, in the prostate in 2 patients and in both bladder and prostate in 1 patient. Five-year and 10-year survival rates of 14 patients in this study were 66.7% and 44.4%, respectively.