Manabu Kuriyama

Cellular basis of skin allograft rejection in mice : specific lysis of allogeneic skin components by non - T cells

BACKGROUND It has been generally assumed that CD8+ T cells mediate direct lysis of allografts and that their growth, differentiation, and activation are dependent upon cytokine production by CD4+ T cells. However, both the generation of CD4- or CD8-deficient mice and adoptive transfer experiments with CD4+ T cells from CD8-deficient mice demonstrate that noncytotoxic CD4+ T cells alone are sufficient to induce skin or organ allograft rejection. Furthermore, we have reported that the major effector cells responsible for allografted-tumor (e.g., Meth A) rejection are allograft-induced macrophages (AIM) with MHC haplotype specificity. METHODS We characterized the macrophages migrating into the rejection site of allografted skin by immunohistochemical and in situ hybridization analyses using an antibody (K16.5) specific for AIM and a cDNA (pK30) encoding the antigen. To determine the in situ effector cells responsible for the rejection, we prepared both effector cells and target cells from the graft-graft bed border. RESULTS The macrophages seemed to be morphologically (monocytic), phenotypically (K16.5+/pK30+), and functionally (cytotoxic against Meth A cells) AIM. The AIM population in bulk infiltrates taken from the rejection site was cytotoxic against allografted, but not self, skin components (e.g., fibroblasts, myocytes, endothelial cells, and epithelial cells). In contrast, other types of infiltrating cells including lymphocytes and granulocytes were virtually inactive toward these targets, and NK-1.1+ cells hardly infiltrated into the rejection site. CONCLUSIONS These data suggest that the major effector cells mediating allografted skin rejection are AIM and not T cells.

Clinical Evaluation of Serum Prostate‐Specific Antigen‐Alpha1 ‐ Antichymotrypsin Complex Values in Diagnosis of Prostate Cancer: A Cooperative Study

Background We studied the clinical significance of serum prostate‐specific antigen bound to α1‐antichymotrypsin (PSA‐ACT) values determined with a newly developed enzyme immunoassay.

Nucleolar organizer regions in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine

SummaryThe number of nucleolar organizer regions (NORs) stained by the one-step silver colloid method was measured in preneoplastic and neoplastic bladder lesions induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. Male ACI/N rats, 6 weeks of age, were given 0.05% BBN in drinking water for 5, 8, 12, 18 and 30 weeks to induce preneoplastic and neoplastic transitional cell lesions. The mean numbers of silverstained NORs (AgNORs) in such lesions were as follows: untreated transitional epithelium (n = 6), 1.26 ±0.09; transitional cell epithelium outside focal lesions (n= 10), 1.75 ±0.10; simple hyperplasia (n= 10), 2.01 ±0.15; papillary or nodular (PN) hyperplasia (n= 10), 2.15±0.19; transitional cell papilloma (n= 5), 2.37 ±0.12; transitional cell carcinoma (n= 5), 3.52 ±0.23. Thus, the mean number of AgNORs showed a step-wise increase from untreated and treated, histologically normal transitional epithelium through simple hyperplasia and PN hyperplasia to transitional cell papilloma and carcinoma. These results suggest that the mean number of AgNORs may reflect the proliferative nature of bladder lesions induced by BBN, as reported in preneoplastic and neoplastic lesions in other organs. PN hyperplasias were classified into two types based upon the mean number of AgNORs, indicating that they include reversible and irreversible changes in contrast with simple hyperplasia which is reversible change.

Intravesical treatment of bladder cancer with recombinant human interferon-β : intravesical GKT-β chemotherapy research group (Chairman : Tadao Niijima)

SummaryIn order to examine its clinical efficacy, recombinant human interferon-β (rIFN-β) was instilled intravesically into 51 patients with superficial bladder cancer. Ten patients, who received intermittent intravesical instillation at a dose of (3−36) × 106 U rIFN-β on days 1–3 every week, showed no response. Thirty-two patients received intravesical instillation at a dose of (3−36) × 106 U every day for 10–20 days. Eight patients showed partial response, indicating an efficacy rate of 25%. Nine patients received divided doses of 18 × 106 U twice a day every day for 10–20 days. Six patients showed partial response, indicating an efficacy rate of 67%. This value was significantly higher than that obtained by administering divided doses. The response to intravesical instillation therapy with rIFN-β varies with treatment protocol. Frequent and longer exposure to rIFN-β may induce better regression of superficial bladder cancer. Six incidences of side-effects were found in five cases (9.8%): pollakiuria in one, pain on micturition in two, fever in two, and eruption in one case. All of these side-effects were slight and reversible after drug withdrawal. Laboratory tests showed only a few changes with low severity. Thus, rIFN-β is potentially a new drug for instillation therapy of superficial bladder cancer, in view of the absence of adverse effects.

Studies on the Phagocytic function of Urinary Leukocytes

Urine specimens from patients with urinary tract infection (UTI) were examined to determine the rate of phagocytosis and viability of urinary leukocytes. The phagocytic function of urinary leukocytes was also studied in vitro. The mean rate of viable urinary leukocytes was 83 per cent and the phagocytic potency was confirmed by light and electron microscopic studies. In 99 per cent of 113 patients with UTI, urinary leukocytes were shown to have phagocytized bacteria. The rate of phagocytosis in chronic UTI was higher than that in acute UTI. Urinary osmotic pressure and the positive or negative of antibody coated bacteria were supposed to be factors influencing phagocytic potency of urinary leukocytes.

Prostate-specific antigen in prostate cancer.

Prostate-specific antigen (PA) has been evaluated clinically as a tumor marker of prostate cancer with the use of enzyme immunoassay (EIA). For serodetection of prostate cancer, PA was assayed in a total of 1,109 sera. From mean ± 3 S.D. of normal controls, upper cut-off values in males were decided as 2.5 and 1.2 ng/ml in Americans and Japanese, respectively. Serum PA values in prostate cancer patients were positive in 78% of Americans and 62% of Japanese. However, in benign prostatic hypertrophy (BPH) cases, a high false positive rate of 41% was observed in Americans. Simultaneous assays of serum PA and PAP showed high sensitivity and specificity in the detection of prostate cancer. This antigen could be used, as well as PAP, for monitoring prostate cancer patients. Furthermore, serum PA levels prior to treatment may express to some degree the malignant potential of the cancer. These results suggest that PA may be useful as a tumor marker of prostate cancer.

Fluoroquinolone Associated Bladder Stone

Fluoroquinolones have a broad spectrum of antimicrobial activity and they have been shown to be highly effective in curing urinary tract infection. Tosufloxacin is a fluoroquinolone developed in Japan. We report on a patient in whom tosufloxacin was associated with the formation of bladder stones. CASE REPORT

Determination of Serum Prostate-specific Antigen-a1- Antichymotrypsin Complex for Diagnosis of Prostate Cancer in Japanese Cases

OBJECTIVE The clinical utility of the determination of serum prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) for the diagnosis of prostate cancer, especially in cases in the diagnostic gray zone, is still unclear. MATERIAL AND METHODS With the use of a newly approved enzyme immunoassay for the detection of PSA-ACT, 907 sera, including those from non-urological benign and malignant diseases, were analysed. RESULTS Serum values of PSA-ACT in non-prostate cancer males increased according to age from the 40s to 70s. The serum values were high only in the patients with prostatic diseases and, in prostate cancer patients, the values became high as the clinical stage progressed. By receiver-operating characteristic analysis significantly better results in PSA-ACT than total PSA were observed. In the group with a total PSA of 2-20 ng/ml, the detection of PSA-ACT showed better results, although not significantly so, than the free-to-total PSA ratio. CONCLUSIONS The detection of PSA-ACT showed a high clinical utility in the diagnosis of prostate cancer. Therefore, it may replace total PSA determination.Objective:

Serum Prostate‐Specific Antigen Values for the Prediction of Clinical Stage and Prognosis in Patients with Prostate Cancer: An Analysis of 749 Cases

Background: The clinical significance of pretreatment serum prostate‐specific antigen (PSA) values was studied to determine the ability to predict clinical stage and prognosis using a relatively large number of patients with prostate cancer.

Electron microscopic study of acuteretrograde pyelonephritis in mice

Abstract A strain of Escherichia coli 06:H-, which was isolated from a patient with acutepyelonephritis, was used to produce ascending pyelonephritis in mice. The histologic features at the early stage of acute pyelonephritis and the pathways of bacterial invasion and distribution in the infected kidneys were studied by using transmission electron microscope. The histologic changes were characterized by degeneration and destruction of renal pelvic and tubular epithelial cells, and a massive infiltration of polymorphonuclear leukocytes. Bacteria invaded the pelvic surface and spread over the renal medulla and cortex by contiguity twelve hours after infection. It was also shown that bacteria ascended the tubules, multiplied in the tubular lamina, destroyed the tubular epithelial cells, and spread over the renal cortex by twelve hours. In addition, bacteria and leukocytes phagocytizing bacteria were present in the capillaries in the renal interstitium twelve hours after infection.