Comparison of histopathological characteristics of allograft biopsy between responder and non-responder to antiproteinuric effect of angiotensin-converting enzyme inhibitor (ACEI)

Abstract:  Angiotensin-converting enzyme inhibitor (ACEI) has become recognized as agents that have renoprotective effects in the treatment of progressive renal diseases including post-transplant kidneys. Previously we demonstrated the safety and effectiveness of ACEI treatment on the hypertensive proteinuric post-transplant patients ( N  = 10) who had been followed up for 12 months. However, not all patients show good response in urinary protein reduction. We aimed to analyse the histopathological factor(s) affecting the responsiveness of proteinuria to ACEI treatment. Fourteen post-transplant patients with proteinuria who were treated with ACEI and underwent allograft biopsy were analysed. Eight patients showed 50% or more reduction in proteinuria (responder). The other 6 patients showed less (< 50%) reduction in proteinuria (non-responder). There was no difference in clinical characteristics (BP, renal function, donor age, recipient body mass index), dietary sodium or protein intake, and diuretic use between the two groups. As a histopathological characteristic, glomerular size in responder group was significantly larger than that in non-responder group. This suggests that the large glomerular size at least partly contributes to the responsiveness in urinary protein reduction to ACEI treatment in kidney allograft recipients with proteinuria.     

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.     

Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991]

A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years.     

Profile of cytokine production in mixed kidney lymphocyte culture

Abstract Kidney cells are an important source of immunoregulatory molecules that regulate cell-to-cell interactions, which is the key step in the generation of the immunoresponse to alloantigens. In this study we identified the cytokines that are produced by both lymphoid cells and kidney cells when coincubated in mixed kidney lymphocyte cultures (MKLC). The capacity of kidney cells to stimulate the proliferation of effector allogeneic lymphocytes was assayed by incubating irradiated kidney cells and lymphocyte. The cytokine secretion profile in MKLC was investigated by incubating monolayers of kidney cells with effector peripheral blood mononuclear cells (PBMC). The culture supernatants were harvested on days 1, 2, 3, 4, 5, 6, 7, and 8 and assayed for IL-1β, IL-2, IL-6, and TNF alpha using an ELISA. Kidney cells, in comparison to PBMC stimulator cells were poor stimulators of the allo-proliferation even when HLA expression was increased by IFN gamma treatment. Compared to lymphocyte or kidney cells incubated alone, MKLC induced a considerable stimulation of cytokine production. This increase in cytokine production was observed essentially for IL-2 and IL-6 (at day 3, a 10-fold increase in IL-2 and a 5-fold increase in IL-6). This study provided evidence that target kidney cells and effector lymphocyte interactions generate a number of cytokines such as IL-11, IL-2, IL-6, or TNF alpha. These cytokines are known to modulate alloproliferation and generation of cytotoxic J lymphocytes (CTL).     

Hyperbaric oxygenation therapy enhances the protective effect of moderate hypothermia against forebrain ischemia in the gerbil hippocampus.

Moderate hypothermia may have a beneficial effect on the neurological outcome. However, ischemic deterioration such as brain swelling during rewarming has been reported as a notable complication after successful therapeutic cerebral hypothermia. In this study, we investigated the effects of hyperbaric oxygenation during rewarming. Forebrain ischemia was produced in 24 gerbils and sham ischemia in 8 animals. Then ischemia-treated animals were divided into 3 groups, whole-body moderate hypothermia (31 degrees C for 60 min) and hyperbaric oxygenation (HBO2) (2- atmosphere absolute for 60 min using 100% oxygen) during rewarming group (n = 8), moderate hypothermia without HBO2 group (n = 8), and sham treatment without hypothermia and without HBO2 group (n = 8). Both the hypothermia group (77.9 +/- 48.1 neurons per mm, mean +/- SD) and hypothermia + HBO2 group (127.6 +/- 29.7 neurons per mm,) showed significant preservation of CA1 pyramidal neurons in the hippocampus compared to that in the sham treatment group (6.4 +/- 2.7) (p < 0.01). Furthermore, the hypothermia + HBO2 group showed significantly greater preservation of CA1 pyramidal neurons than the hypothermia group (p < 0.05). These results suggest that HBO2 during rewarming preserves the protective effect of hypothermia against ischemic neuronal damage.     

Computational simulation method of intraluminal velocity profile proved by laser Doppler velocimeter

Measurement of the intraluminal velocity profile within an artery may provide insight into predicting the prognosis of arterial reconstruction. To confirm the results of the computer simulation method a laser Doppler velocimeter using an optical fiber was applied to canine femoral arteries with good or poor runoff, and the intraluminal velocity profile was measured directly. Under normal flow conditions, remarkable fluctuation was obtained at the layer adjacent to the wall, whereas under poor runoff conditions, stagnation of flow was seen at the layer adjacent to the wall. These results showed that our computational simulation method which calculates the intraluminal velocity profile was a reliable, valid method of on-line analysis of the intraluminal velocity profile.     

Two cases of Trichosporon beigelii pneumonia in immunocompromised hosts

Two cases of Trichosporon beigelli pneumonia in severely immunocompromised patients are reported. At autopsy, Trichosporon beigelii was detected in all lobes in one patient who had a small cell lung cancer. Polymycotic infection involving Trichosporon beigelii and Aspergillus was proved in the other patient who had a non-Hodgkin's lymphoma. Miconazole therapy was not effective against Trichosporon beigelii infection in both cases. Although diagnosis and management are difficult, Trichosporon beigelii must be considered as a cause of visceral opportunistic fungal infection.