Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

An ultrastructural study on anterior cruciate ligament reconstruction using autogenous patellar tendon grafts in dogs

An ultrastructural study was undertaken concerning morphological changes within the autografted patellar tendon (PT) after being transplanted to the anterior cruciate ligament (ACL) in mongrel dogs. After 4 weeks, the arrangements of both large and small collagen fibrils in the PT graft became disordered, and the number of inflammatory cells increased. However, the same PT grafts revealed postsurgical signs of newly-produced collagen fibrils around activated fibroblasts at 12 to 24 weeks. At 52 weeks after the transplantation, small collagen fibrils increased in both number and density, showing a remarkable morphological similarity to the collagen fibrils of normal ACL. These data indicate that the characteristics of the PT graft eventually resemble those of a normal ACL. This paper was presented in part at the Combined Meeting of the Orthopedic Research Societies of the USA, Japan and Canada in Banff, Alberta, Canada, October, 1991.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Efficacy of continuous cleansing with teicoplanin on post-CABG methicillin-resistant staphylococcus aureus (MRSA) mediastinitis: report of a case.

The patient was a 48-year-old male who was diagnosed with unstable angina. He had worsening cardiogenic shock during coronary angiography. Emergency coronary artery bypass grafting (CABG) was performed. He had a methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis on day 22 after CABG. Drains were placed in the anterior mediastinum, left thoracic cavity, and abscess cavity, and another drain was placed in the mediastinal space for continuous cleansing with povidone iodine, oxydol. For antibiotics, teicoplanin (TEIC) was administered intravenously and to the local site via the cleansing drain for about one month. No MRSA was detected by culture in discharges from the mediastinal drain. Inflammatory findings were improved, and the patient was discharged and resumed everyday life without recurrence of inflammation as of eight months. Although the number of cases of MRSA mediastinitis is small and accumulation of cases is necessary to investigate therapeutic methods and selection of antibiotics, our department will select closed continuous cleansing and TEIC for antibiotics as the first choice for MRSA mediastinitis, and accumulate cases to investigate its efficacy.     

DSM-III-R personality disorders in outpatients with non-bipolar depression: The frequency in a sample of Japanese and the relationship to the 4-month outcome under adequate antidepressant therapy

Summary We investigated the frequency of personality disorders (PDs) and the relationship between the pressence of PD and the 4-month outcome of depression under adequate antidepressant therapy in a Japanese sample of 96 outpatients with non-bipolar major depression. The diagnosis of PD was made using a structured interiew method (the Structured Clinical Interview for DSM-III-R Personality Disorders) and after severe depressive symptoms were reduced. Any one kind of PD was found in 54.2% of the saple. The most frequent was avidant (34–4%), obsessived-compulsive (22.9%), narcisstic (18.8%), and dependent (16.7%) PDs. The frequencies of these PDs in our study except narcisstic PD, were about the same as those reported in previous studies with a matched setting for the PD diagnosis. Compared with patients without PD, a worse outcome was found in patients with PD, especially patients with multiple PDs from multiple PD clussters. There was no evidence that a specific PD or PD cluster especially worsens the outcome of depression.     

Role of β2 integrins in glomerular leucocytes in Henoch-Schoenlein purpura nephritis: an age-matched comparative study with immunoglobulin A nephropathy

SUMMARY: A comparative immunohistological study was performed for the glomerular deposition of complements (C1q and C3c), fibrin/fibrinogen‐related antigen (FRA), the expression of intercellular adhesion molecule‐1 (ICAM‐1), and the infiltration of leucocytes bearing β₂ integrins (leucocyte function associated antigen‐1 (LFA‐1), complement receptor 3 (CR3) and complement receptor 4 (CR4)) on renal biopsy specimens from 49 cases with Henoch‐Schoenlein purpura nephritis (HSPN), and 49 age‐matched cases with immunoglobulin A nephropathy (IgAN). the glomerular expression of ICAM‐1 was signifcantly correlated with the glomerular infiltration of leucocyte function associated antigen (LFA)‐1⁺ leucocytes in both diseases, and with that of CR3⁺ leucocytes in HSPN. the expression of ICAM‐1 was closely localized with the infiltration of LFA‐1⁺ leucocytes in the study with double immunostaining. the incidence and intensity of glomerular deposition of FRA were significantly higher in HSPN than in IgAN (P< 0.001), and those of C3c were significantly lower in HSPN than in IgAN (P< 0.001). the glomerular deposition of FRA was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in HSPN (P<0.05) but not in IgAN. In contrast, the glomerular deposition of C3c was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in IgAN (P<0.05), but not in HSPN. Studies with double immunostaining revealed a close association of CR4⁺ leucocytes with FRA deposition in HSPN and with C3c deposition in IgAN, respectively. the number of glomerular leucocytes bearing β₂ integrins was significantly correlated with urinary protein at the time of renal biopsy in both diseases. These results suggested the differential roles of β₂ integrins in the induction of glomerular injury in HSPN and IgAN. the ICAM‐1/LFA‐1 interaction may commonly be involved in the glomerular infiltration of leucocytes in both diseases. the ICAM‐1/CR3 interaction may be involved only in HSPN. Complement receptor 4 may function as a fibrin/fibrinogen receptor in HSPN, while CR4 may function as a complement receptor in IgAN.     

Clinical studies on the transabdominal resection of esophagocardial cancer and cervical anastomosis using bypass methods. Analysis of data on 76 patients

Transabdominal resection for esophagocardial cancer and reestablishment of alimentary continuity using bypass methods were performed in 76 patients. Thirteen underwent a bypass with a gastric tube and in 30, a colonic segment was prepared. In the remaining 33, a jejunal segment was used as a bypass organ, with considerable success. The 5 year survival rates were 68.8 per cent in those with stages (I+II), 16.5 per cent in those with stage III, 12.6 per cent in those with stage IV and 22.5 per cent in all cases, indicating similar results compared to those with cancer located in the upper third of the stomach with the limited proximal extension within the esophagocardial junction and operated on during the same period.     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.