Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384) on learning and memory were studied using four different experimental rat models. In electroconvulsive shock- or scopolamine-induced amnesia in the step-through passive avoidance task, DM-9384 improved both types of amnesia when administered before the training trial. Aniracetam also showed similar but somewhat weaker effects. Furthermore, in the scopolamine amnesia model, an improvement was confirmed with arecoline. The dose-response curves for these compounds were bell-shaped. In the shuttle box active avoidance task, DM-9384 administered daily 1 hr before each training session facilitated the acquisition process of the avoidance response. In addition, the experiment of light-dark discrimination task with positive reinforcement showed that this compound administered daily after each session slightly accelerated the acquisition process of the correct response. These results suggest an ability of DM-9384 to enhance cognitive functions.     

Embolic myocardial infarction and left ventricular rupture due to mitral valve endocarditis.

A left ventricular rupture due to embolic myocardial infarction is extremely rare. A 72-year-old woman developed an acute embolic myocardial infarction and mitral regurgitation due to infective endocarditis. Two days after the infarction, a left ventricular free wall rupture occurred after transesophageal echo examination. She received an epicardial patch and mitral valve replacement. Perioperatively, an intra-aortic balloon pump and long-term antibiotics were used. The postoperative course was uneventful, and she is doing well 10 months after surgery.     

Combined operation for renovascular hypertension and ischemic heart disease

We have experienced two patients of ischemic heart disease associated with renovascular hypertension. Patient 1 (60-year-old man) underwent LV aneurysmectomy and triple aortocoronary bypass grafting (saphenous vein to diagonal branch, left internal mammary artery to obtuse marginal branch, and right gastroepiploic artery to right coronary artery). Seventy five days after the initial cardiac surgery endarterectomy for the left renal artery and bifurcated Dacron graft implantation for the iliac artery obstruction were performed. Patient 2 (62-year-old woman) underwent simultaneous operation of both right nephrectomy and triple aortocoronary bypass grafting (saphenous vein grafts to obtuse marginal branch and right coronary artery, and left internal mammary artery to left anterior descending artery). Their postoperative courses were uneventful except unstable and high blood pressure for four to seven days after the operation. It appears that it should be decided to achieve either simultaneous or two stage approach for ischemic heart disease associated with renovascular hypertension based on the preoperative cardiac function. And both postoperative cardiac function and hypertension should be carefully managed until the blood pressure becomes stable after the surgery.     

An experimental study on the pathogenesis of congenital hand malformation--with reference to local disturbance in the limb bud and congenital constriction band syndrome

In order to study congenital constriction band syndrome, we performed local cauterization of the lower limb buds of embryos in fertilized white leghorn eggs between hour 0 on day 4 (day 4-0) and day 7-0 of incubation. Constriction bands, acrosyndactyly, and amputation of digits, malformations characteristic of this syndrome, were all induced by intervention after day 5-0, when digital ray formation was first observed, indicating that they all develop after ray formation. Histological examination showed that encapsulation and shedding of the lesion containing hematoma and necrotic tissue at the distal end of a digital ray led to digit amputation. When the cells encapsulating this lesion extend over another digital ray, moreover, the ray tips fuse, while the rest of the two digits involved remain discrete-resulting in acrosyndactyly.     

Glued Carbon Fiber Electrodes for Diaphragm Pacing

Carbon fibers with fibrin glue were used as electrodes for diaphragm pacing. The electrodes were applied to three mongrel dogs and the effectiveness was tested. The carbon leads were glued to phrenic nerves by means of the fibrinogen and thrombin bilaterally. The tidal volumes and threshold current level for stimulation were measured at various time up to 9 weeks after implantation. Effective contraction of diaphragm were observed for 9 weeks. By using this electrode, the exfoliation of the nerve is not necessary, the nerve can be maintained in an intact state, and the risk of the implanting operation can be minimized.     

Antiulcer effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl] carbamoyl]methyl]-amino-N-methylbenzamide in experimental gastric and duodenal ulcers

Effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl] methyl]-amino-N-methylbenzamide (DQ-2511), a newly synthesized compound, were evaluated using various types of experimental gastric and duodenal ulcers in rats. Pretreatment with DQ-2511, over the dose range 30-300 mg/kg p.o., resulted in a dose-related inhibition of water-immersion stress-, serotonin-, acetylsalicylic acid (ASA)-, indometacin-, ethanol-, and 2-deoxy-D-glucose(2DG) plus indometacin-induced gastric ulcers as well as cysteamine-induced duodenal ulcers. The antiulcer potencies of DQ-2511 were equal to or greater than those of H2-receptor antagonist cimetidine in these ulcer models except for ASA- and 2DG plus indometacin-induced ulcers. The rate of healing of chronic gastric ulcers induced by acetic acid was significantly accelerated by DQ-2511 (100 and 300 mg/kg p.o.) but not by the same doses of cimetidine. DQ-2511, at doses of 30 mg/kg p.o. and above, produced a significant decrease in gastric acid and pepsin output in pylorus-ligated rats. In anesthetized rats with acute gastric fistulae, 30 mg/kg i.v. of DQ-2511 significantly inhibited gastric acid secretion stimulated by 2DG, whereas it did not affect gastric hyperacidity evoked by either carbachol, histamine or pentagastrin. At effective antiulcer doses, this compound produced a sustained increase in gastric mucosal blood flow in conscious, restrained rats. Based on these observations, DQ-2511 is characterized as a new antiulcer compound with beneficial effects on both gastric aggressive and defensive factors. Furthermore, these results indicate a possible superiority of DQ2511 over cimetidine in regard to its antiulcer potency and spectrum.     

Jejunal carcinoma with adenoma —Report of a case and review of the Japanese literature—

A rare case of jejunal carcinoma coexisting with adenoma, situated 120 cm distal to the ligament of Treitz in a 53 year old male, is reported herein. We also review cases of adenoma and carcinoma in the jejunum and ileum from the Japanese literature, and discuss the histogenesis of carcinoma of the jejunum and ileum.