Concentration gradient of oxalate from cortex to papilla in rat kidney

BACKGROUND: The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. METHODS: At 15-180 min after intravenous injection of 14C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14C-inulin. RESULTS: The radioactivity of 14C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14C-inulin was nine times less in the papilla than in the cortex at the same time. CONCLUSION: Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation.     

Antibodies Against the β-Subunit of Ovine Luteinizing Hormone Can Decrease the Clearance of Human Chorionic Gonadotropin in Rhesus Monkeys*

ABSTRACT: Contraceptive vaccines based on active immunization against gonadotropic hormones are being investigated in humans and other primates. Immunization against the β-subunit of ovine luteinizing hormone (oLHβ) reduces fertility in rhesus monkeys by inducing inadequate luteal phases and preventing corpus luteum rescue by rhesus chorionic gonadotropin (rhCG). These effects result from the cross-reactions of the oLHβ-antibodies with rhCG and rhLH. We used human CG (hCG), which also cross-reacts strongly with anti-oLHβ to examine how the circulating oLHβ-antibodies affect the metabolic clearance rates (MCR) of hCG in rhesus monkeys. ¹²⁵I-hCG was injected into four nonimmunized and seven immunized monkeys and blood was collected at frequent intervals over 7 days. Total and immunoprecipitable radioactivity did not differ significantly, suggesting that the radioactivity in the plasma consisted almost entirely of ¹²⁵I-hCG. This was confirmed by column chromatography. The MCR (mean ± SE) was significantly lower (p < 0.001) in six immunized monkeys (0.35 ± 0.06 liters/day) as compared to controls (1.19 ± 0.09 liters/day). The hCG disappearance curve in control monkeys was best described by a two-compartmental system (slow and fast) while an additional third (intermediate) compartment of distribution was typical for immunized animals. The half-lives of hCG for the two exponentials corresponding to the slow and fast components of distribution were not significantly different between the two groups. One immunized monkey had a MCR (1.44 liters/day) that was much greater than the MCR of the other six. This monkey cleared a significantly smaller proportion of hCG in the slow and a higher proportion in the intermediate compartment and unlike the others, formed a circulating immune complex capable of binding hCG that was significantly larger than the antibody-hCG complexes found in the other six immunized animals. We conclude that circulating antibodies to oLHβ reduced the MCR of hCG in six of seven monkeys. The decreased MCR found in immunized monkeys is associated with a shift in clearance from the “fast” to the “slow” compartment as well as the addition of an intermediate compartment of distribution. Plasma disappearance rates of hCG depend on the size of the antibody hCG complex.     

The novel histamine H2 receptor antagonist FRG-8813 prevents delay of wound repair induced by hydrogen peroxide in a rabbit gastric epithelial cell system

Abstract The effects of a novel histamine H₂ receptor antagonist (FRG-8813) on the restoration process of gastric epithelial wounds were assessed using an in vitro wound healing model. FRG-8813 (1, 10 mol/L) was added to a complete confluent monolayer cell sheet after artificial wounding. The restoration process was analysed by a time-lapse video system and cell migration, proliferation and apoptosis were assessed. Hydrogen peroxide (1, 3 mmol/L) inhibited restoration after wounding by suppressing cell migration and proliferation and induced epithelial cell apoptosis around the wound. The addition of FRG-8813 abolished the hydrogen peroxide-induced retardation and prevented apoptosis, although FRG-8813 itself did not enhance wound healing. FRG-8813 may act as a radical scavenger as well as having an anti-secretory action and may have favourable effects on peptic ulcer healing.     

Anti-ATLA (Antibody to the Adult T-Cell Leukemia Cell-Associated Antigen)-Positive Hematologic Malignancies in the Kanto District

Serum or plasma specimens from 278 patients having various hematologicmalignancies or some other diseases were screened for reactivitywith adult T-cell leukemia cell-associated antigen (ATLA). Antibodiesagainst ATLA in cultured MT-1 cells, a line derived from adultT-cell leukemia (ATL), were found in 18 (6.5%) of the total278 patients, but in 10 (34.5%) of 29 patients born in the ATL-endemicarea. The antibodies were also detected in eight (80%) of 10patients with ATL or adult T-cell leukemia/lymphoma (ATLL),and most of them were born in the ATL-endemic area. The antibodies were detected in only eight (3.2%) of 249 patients whowere born in an ATL nonendemic area, but six of the eight patientswere ones with acute leukemia, and they were found to have hadmassive blood transfusions in cluding platelet or granulocytetransfusions. Generally, the patients who received transfusionswere found to have a higher incidence of anti-ATLA than thosewithout transfusions. In particular, in acute leukemia in anATL-nonendemic area, the antibodies were detected in six (21.4%)of the 28 patients who had previous transfusions, but in noneof the 16 not given transfusions. Further more, ATLA reactivityof the sera from the two patients was found to change from negativeto positive in one to three months. During that period, bothpatients had massive platelet or granulocyte transfusions. Theseresults not only confirm Hinuma's initial report on anti-ATLA,but also indicate the rare existence of anti-ATLA-negative patientswho have ATL or ATLL. These facts also suggest that massiveblood transfusions are one of the possible causes of the generationof anti-ATLA in the patients. However, direct evidence to provethis possibility must be sought.     

Histological Evaluation of Effects of Radiotherapy and Chemotherapy for carcinomas

Based on the histological observation of tumors of the headand neck region serially biopsied during radiotherapy, thehealingprocess of irradiated tumors was described. Healing processof the tumors treated with chemotherapeutic agents such as MitomycinC and Bleomycin was found to be quite similar to that of theirradiated tumors. And histological gradings of effects of radiotherapyand chemotherapy for carcinomas have been set, which have beenused at National Cancer Center Hospital for the past severalyears and found to be useful. With this grading, effects of radiotherapy were evaluated on83 carcinomas of the lung and 97 of esophagus, all of whichhad been irradiated preoperatively, and on autopsy cases, 49eacof lung and esophageal carcinomas, all of which had beenirradiated 5000 rad or more. Also evaluated were the effectsof Mitomycin C infused into the bronchial artery on 29 carcinomasof the lung according to the histological types of the tumor.Relationship between doses and histological effects was investigatedin each group, and some problems of the radiotherapy and chemotherapyfor the tumors were discussed on the histological basis.     

T cell subsets In peripheral blood and cerebrospinal fluid from children with aseptic meningitis

T cell subsets in peripheral blood (PB) and cerebrospinal fluid (CSF) obtained from patients with aseptic meningitis were studied using quantitative two-color fluorescence analysis with a flow cytometer. The percentage of HLA-DR⁺/CD3⁺ lymphocytes (activated T cells) in CSF was significantly increased in the recovery phase when compared to the acute phase, while no significant change in the activated T cells in PB was observed. More interestingly, CD4⁺ T lymphocytes in CSF were increased in the acute phase and subsequently decreased in the recovery phase. Instead, CD8⁺ T lymphocytes gradually accumulated into the CSF in the recovery phase, resulting in a successive decrease in the CD4/CD8 ratio. On the other hand, the CD4/CD8 ratio in PB remained normal during the course of aseptic meningitis. The present results suggest that T lymphocytes (CD4⁺ subset in the acute phase and CD8⁺ in the recovery phase) could be infiltrated and further activated at the site of inflammation, possibly in the subarachnoid space in the patients with aseptic meningitis.     

Chemical modification of superoxide dismutase Extension of plasma half life of the enzyme through its reversible binding to the circulating albumin

Protection of organisms from oxidative stress is one of the major prerequisites for aerobic life. Since intravenously injected Cu⁺⁺/Zn⁺⁺ -type superoxide dismutase (SOD) rapidly undergoes renal glomerular filtration and appears in urine in its intact form, its clinical use as a scavenger for superoxide radicals has been highly limited. To test whether reversible interaction of SOD with plasma albumin might decrease the rate of disappearance of the enzyme from the circulation, the lysyl residues of the human erythrocyte-type enzyme were covalently linked with poly-(styrene-co-maleic acid) butyl ester (SMA) via amide linkage. Affinity chromatographic analysis by an albumin-Sepharose column revealed that the enzyme samples labeled with SMA (SMA-SOD) tightly bound to the column, while unmodified SOD was eluted in the unbound fractions. SMA-SOD bound to the column could be eluted by the buffer solution containing 0.1% sodium dodecylsulfate. In vivo analysis revealed that intravenously administered SMA-SOD circulated bound to albumin with an extremely long half-life (6 h), while unmodified SOD rapidly underwent renal glomerular filtration with a plasma half-life of 4min. Thus, SMA-SOD may effectively dismutate superoxide radicals in the circulation.     

Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma

Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and the development of pathological scarring. In this study, we demonstrate that keloid fibroblasts can be identified as apoptotic cells because of their highly condensed chromatin and discrete nuclear fragments. To further reveal the phenomenon of apoptosis, we quantified the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in surgically resected tissues of keloids (N = 10), hypertrophic scars (N = 10), normal healed flat scars (N = 10), and dermatofibroma (N = 10). The number of TUNEL-positive cells was relatively low, but was significantly higher for the keloid group compared with the normally healed flat scar group (p = 0.004), suggesting reduced cell survival and increased apoptotic cell death in a subpopulation of keloid fibroblasts. Furthermore, the number of TUNEL-positive cells was significantly higher for the keloid group compared with the dermatofibroma group (p = 0.044), suggesting that a subpopulation of keloid fibroblasts may suppress tumorgenicity at a greater rate than dermatofibroma by undergoing cell death. Hypertrophic scars had significantly higher levels of apoptosis than normally healed flat scars (p = 0.033). Therefore, these results suggest that selected fibroblasts in keloids and hypertrophic scars undergo apoptosis, which may play a role in the process of pathological scarring.