Moderate Inflammatory Cell Infiltration Research Articles

Pulpal responses to bacterial contamination following dentin bridging beneath hard‐setting calcium hydroxide and self‐etching adhesive resin system

To evaluate the pulp healing to bacterial contamination beneath a hard-setting calcium hydroxide (DY: Dycal, L.D. Caulk Co.) and a self-etching adhesive resin (2V: Clearfil Liner Bond 2V, Kuraray Medical Inc.) following dentin bridge formation. Class V cavities were prepared on 30 monkey teeth, and the pulps were exposed with a carbide bur through the cavity floor. Each exposed pulp was capped with either DY or 2V. The cavities were restored with a hybrid resin composite. The resin composite was removed at 180 days after capping, and then cavities were left open to the oral environment for 2 weeks to obtain bacteria contamination DY (BDY) and 2V (B2V; n = 10). A non-bacterial-contaminated group capped with DY was used as control. After bacterial challenges, inflammatory cell infiltration, incidence and differentiation of dentin bridges were evaluated histologically. There were significant differences in the presence of inflammatory cell infiltration among all groups (P < 0.05). No moderate or severe inflammatory reaction was found in Group DY. Group BDY showed moderate or severe inflammatory cell infiltration in 50%, and showed four necrotic specimens. Although no statistically significant difference was found in the formation and differentiation of dentin bridges among all groups, tunnel defects in dentin bridges were detected in 70% (DY), 80% (BDY), and 50% (B2V). Group B2V showed a significantly lower presence of inflammatory cell infiltration than Group BDY (P < 0.05). Bonding agent is supposed to seal the exposure site, and the remaining bonding agent on the cavities was effective as the barrier in the dentin bridges after bacterial challenges.

Taurine ameliorates stress-induced degeneration of the urinary bladder

We studied the potential effects of taurine, a free radical scavenger, on chronic water avoidance stress (WAS)-induced degeneration of the mucosa of the urinary bladder in experimental rats. Wistar albino rats were exposed to WAS for 2h/day, for 5 days (WAS group). Before exposing them to WAS, taurine (50mg/kg) (WAS+taurine group) was injected intraperitonally into the animals. Samples of urinary bladder were then investigated by light and scanning electron microscopy. Lipid peroxidation and gluthathione levels were also measured in the urinary bladder. In the WAS-only group, inflammatory cell infiltration, increased number of mast cells in the mucosa and ulcerated areas were observed. In the WAS+taurine group, relatively normal urothelial topography with microvilli, moderate inflammatory cell infiltration and decreased numbers of mast cells in the mucosa were observed. The increased lipid peroxidation and decreased glutathione levels in WAS rats were reversed by taurine treatment. We conclude that taurine protects against WAS-induced oxidant urinary bladder injury, and thus may be a possible therapeutic agent against interstitial cystitis, the symptoms of which are aggravated by stress conditions.

An aqueous garlic extract alleviates water avoidance stress‐induced degeneration of the urinary bladder

To investigate the role of aqueous garlic extract (AGE) on the water-avoidance stress (WAS)-induced degeneration of the urinary bladder in a rat model. Wistar albino rats were exposed to WAS for 2 h/day for 5 days (WAS group), after which, AGE (1 mL/kg) was injected intraperitoneally into the rats (WAS + AGE group). Urinary bladder samples were investigated with both light and scanning electron microscopy, and lipid peroxidation and glutathione levels were also measured in the samples. In the WAS group there was inflammatory cell infiltration, more mast cells and ulcerated areas in the mucosa. In the WAS + AGE group there was relatively normal urothelial alignment, moderate inflammatory cell infiltration and fewer mast cells in the mucosa. The increased lipid peroxidation and decreased glutathione levels in WAS rats were reversed by AGE treatment. These results show that AGE has a protective effect on WAS-induced degenerative changes in the urinary bladder.

Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. The rats were separated randomly into 6 groups: model group I were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/(kg.d) simultaneously, while control group I were fed normal food for 8 weeks; model group II were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/(kg.d) orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group II were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNF-alpha), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed. After 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-alpha were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05) compared with model group I. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group II rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP, FINS and HOMA-IR were significantly increased (P<0.05) in model group II compared with control group II. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-alpha and HOMA-IR were significantly decreased compared with model group II. Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.

Lichenoid tattoo reaction responding to topical tacrolimus ointment

Conflict of interest: none declared. A 51‐year‐old man had four tattoos applied to his skin between 1996 and 2001. The first, on his right anterior chest wall, was drawn by a different artist from the other three, which were sited on the left anterior chest wall, the proximal right lower leg and the distal right lower leg, in 1997, 2000 and 2001, respectively. The constituent parts of the dyes used were not known. Within weeks of shaving the hair overlying the leg tattoos, the patient developed severe itching, irritation and associated thickening of the red‐coloured areas of the tattoos (Fig. 1a). Similar but intermittent symptoms arose in the left chest tattoo, while that on the right, by the other artist, remained quiescent. Patch tests to the European standard series and mercury were negative but the patient reacted to disperse blue dyes 106 and 124 at 96 h. Baseline biopsy showed hyperkeratosis and a dense dermal inflammatory cell infiltrate comprising mainly lymphocytes in keeping with a lichenoid reaction. Potent topical steroid treatment was of limited and short‐lived benefit. A trial of topical tacrolimus ointment (0.1%) dramatically relieved his intense itching and after daily application for 3 months, there was evidence of flattening of the thickened red‐dye areas (Fig. 1b). Repeat biopsy after this interval showed histological improvement, with a normal epidermis and a moderate dermal inflammatory cell infiltrate, in keeping with an ongoing hypersensitivity reaction to the tattoo pigment.

Oral exposure to cadmium chloride triggers an acute inflammatory response in the intestines of mice, initiated by the over-expression of tissue macrophage inflammatory protein-2 mRNA

Intestinal inflammation is an indispensable protective response of the gut immune system to aggressive injury from pathogens and/or chemicals. Although the major route of exposure to cadmium for most people is via food, causing the gastrointestinal tract to become the first target organ, very little information is available on whether cadmium exposure triggers the intestinal inflammatory response. We investigated in the present study the acute inflammatory response in the intestines of mice orally challenged with a single dose of cadmium chloride (CdCl 2) by determining the gene expression of pro-inflammatory mediators with real-time PCR, and by examining the infiltration of inflammatory cells with a myeloperoxidase (MPO) assay and histological analysis of hematoxylin and eosin (H&E)-stained intestinal sections. The results show that CdCl 2 significantly increased the expression of macrophage inflammatory protein-2 mRNA (30–40 times the normal level) 3 h and the activity of MPO (about 2 times the normal level) 24 h after the challenge in the duodenal and proximal jejunal tissue. Furthermore, these increases were dose-dependent over a dosage range of 25–100 mg/kg of body weight. The histological analysis confirmed that CdCl 2 induced mild to moderate villus damage and infiltration of inflammatory cells into the lamina propria. All these results demonstrate that oral exposure to CdCl 2 triggered an acute inflammatory response in the proximal intestine of mice, suggesting that the gut immune system was involved in the toxic effects of Cd on the gastrointestinal tract.

Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor.

We have previously shown that a peptide corresponding to the sequence of the second extracellular loop of the human muscarinic-2 (M2) receptor (M2-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we investigated the effect of M2-antagonist (otenzepad) on M2-peptide-induced cardiomyopathy in rabbits. New Zealand White rabbits were divided into four groups: 1) control group, saline injection; 2) M2-peptide group, M2-peptide injection; 3) M2-antagonist group, otenzepad (30 mg/day) orally and saline injection; and (4) M2-antagonist + M2-peptide group, otenzepad (30 mg/day) orally and M2-peptide injection. The study duration was 1 year. Saline or peptide was injected once a month. All rabbits in both the M2-peptide group and the M2-antagonist + M2-peptide group had high titers of anti-M2-autoantibodies in their sera. Rabbits in the M2-peptide group showed an increase in heart weight, wall thinning and dilatation of the right ventricle. On the contrary, rabbits in the M2-antagonist + M2-peptide group had normal heart weight and shape. All rabbits in the M2-peptide group showed multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells, while four rabbits in the M2-antagonist + M2-peptide group showed slight infiltration of inflammatory cells with normal myocardial cells and interstitium, and another three showed no histological changes in the hearts. In conclusion, M2-antagonist protects the myocardium from injury induced by autoimmune mechanism against M2-muscarinic receptor.

Effects of Iron Overload and Lindane Intoxication in Relation to Oxidative Stress, Kupffer Cell Function, and Liver Injury in the Rat

Parameters related to liver oxidative stress, Kupffer cell function, and hepatocellular injury were assessed in control rats and in animals subjected to lindane (40 mg/kg; 24 h) and/or iron (200 mg/kg; 4 h) administration. Independently of lindane treatment, iron overload enhanced the levels of iron in serum and liver. Biliary efflux of glutathione disulfide increased by 140, 160, or 335% by lindane, iron, or their combined administration, respectively, and the hepatic content of protein carbonyls was elevated by 5.84-, 2.95-, and 10-fold. Colloidal carbon uptake by perfused livers was not modified by lindane and/or iron, whereas gadolinium chloride (GdCl3) pretreatment diminished uptake by 60–72%. Carbon-induced liver O2 uptake was not altered by lindane, whereas iron produced a 61% increase and the combined treatment led to a 72% decrease over control values. Pretreatment with GdCl3 abolished these effects in all groups. Lindane-treated rats showed acidophilic hepatocytes in periportal areas and some hepatic cells with nuclear pyknosis, whereas iron overload led to moderate hyperplasia and hypertrophy of Kupffer cells and moderate inflammatory cell infiltration. Combined lindane–iron treatment led to hepatocytes with pyknotic nuclei, significant acidophilia, and extensive lymphatic and neutrophil infiltration in the portal space. Hepatic myeloperoxidase activity increased by 1.1-, 2.1-, or 6.7-fold by lindane, iron, or their combined administration, respectively. Liver sinusoidal lactate dehydrogenase efflux increased by 2.2-fold (basal conditions) and 9.7-fold (carbon infusion) in the lindane-iron treated rats, effects that were diminished by 35 and 78% by GdCl3 pretreatment, respectively. These data support the contention that lindane sensitizes the liver to the damaging effects of iron overload by providing an added enhancement to the oxidative stress status in the tissue, and this may contribute to the alteration of the respiratory activity of Kupffer cells and the development of an inflammatory response.

A Case of Disappearance of Yamada's Type II Multiple Hyperplatic Polyps of Stomach by Eradication of &lt;i&gt;Helicobacter Pylori&lt;/i&gt;

A 69-year-old woman who had underwent endoscopic polypectomy of stomach before 4 years was admitted to my clinic for endoscopy. In endoscopic examination, five polyps classified Yamada's type II were located on greater curvature of antrum, anterior wall of angulus and greater curvature of upper body. Histological findings of biopsied specimens from these polyps revealed hyperplasia of the foveolar epithelium with moderate infiltration of inflammatory cells which was consistent with hyperplastic polyp. These polyps were unchanged during 2 years and Helicobacter pylori (H. pylori) was found by the CLO test and cultures of biopsied specimens. She was treated with one week course of lansoprazole, amoxicillin and clarithromycin. About 14 months later, all polyps were disappeared and eradication of H. pylori was confirmed by biopsy, cultures and Urea breath test. These result suggests that eradication of H. pylori may be expected as a useful treatment to hyperplastic polyp of stomach.

Beneficial Effect of Angiotensin-Converting Enzyme Inhibitor on Dilated Cardiomyopathy Induced by Autoimmune Mechanism Against β1-Adrenoceptor

We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1-peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor.

Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing

To evaluate the soft tissue response of calcium phosphate cement (CPC), consisting of an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) under conditions close to those encountered in actual surgical procedures, we implanted three types of CPC [conventional CPC (c-CPC), fast-setting CPC (FSCPC), and antiwashout type FSCPC (aw-FSCPC; formerly called nondecay type FSCPC or nd-FSCPC)] subcutaneously in the abdomens of rats immediately (1 min) after mixing. At 1 week after surgery, histological examination and compositional analysis were performed using light microscopy and powder X-ray diffraction (XRD), respectively. The implanted c-CPC was crumbled completely, whereas FSCPC and aw-FSCPC retained their shape. Large vesicles containing copious inflammatory effusion were subcutaneously formed around the c-CPC. Histologically, many foreign-body giant cells were collected around the c-CPC, and moderate inflammatory cell infiltration was observed at 1 week after surgery. In contrast, the FSCPC and aw-FSCPC were covered with a thin layer of granulation tissue that included few giant cells and presented slight inflammatory cell infiltration, and no effusion was observed. The XRD analysis of the c-CPC revealed the presence of some unreacted DCPA even 1 week after implantation, whereas almost no DCPA was found in the FSCPC or aw-FSCPC. In conclusion, it was found that CPC does not always show excellent tissue response. When c-CPC is implanted subcutaneously in rats immediately after mixing, it fails to set and causes a severe inflammatory response. Therefore, the type of CPC should be chosen according to the clinical particulars. CPC should be used in a manner that assures its setting reaction. We recommend the use of FSCPC and aw-FSCPC for surgical applications, such as orthopedics, plastic and reconstructive surgery, and oral and maxillofacial surgery, where the cement might otherwise crumble due to the pressure before setting.

How to Diagnose Chronic Rejection. A Study in Porcine Intestinal Allografts

Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.

The effect of small bowel transplantation on the morphology and physiology of intestinal muscle: a comparison of autografts versus allografts in dogs.

The effects of acute (AR) and chronic rejection (CR) on intestinal smooth muscle that are responsible for the dysmotility following small bowel transplantation (SBTX) are incompletely understood. Jejunal and ileal specimens from normal control dogs (n=7), and autotransplanted dogs were examined at 7 days (n=6) and 1 (n=7), 3 (n=6), 6 (n=6), and 12 months (n=6). Allotransplanted dogs that developed AR (n=8) and CR (n=5) were examined for gross and microscopic morphology (muscle thickness, the number and size of myocytes, and inflammatory infiltrate), and for contractile and intracellular electrical function in vitro. Auto-SBTX did not alter morphology at any period, but contractile function was impaired at 7 days (73.6%) compared with normal intestine. Acute rejection did not influence myocyte number or size, but was associated with a prominent infiltrate of neutrophils and lymphocytes, and severely impaired contractile function (20.6%) compared with auto-SBTX controls. Acute rejection also significantly inhibited the amplitude of slow waves and of inhibitory junction potentials. Chronic rejection caused thickening of muscularis propria by both hyperplasia (175.5%) and hypertrophy (202.6%) accompanied by moderate inflammatory cell infiltrate compared with auto-SBTX controls. We conclude that the marked inflammatory infiltrate into the muscularis propria indicates that the graft muscle is injured by both acute and chronic rejection; impaired function of intestinal smooth muscle following SBTX results from both rejection and the injury associated with transplantation, and chronic rejection following SBTX is associated with both hyperplasia and hypertrophy of the muscularis propria.

In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats.

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on alveolar bone resorptive activity in rats were examined. Continuous administration of rhIL-1 beta or phosphate-buffered saline (PBS) was given via osmotic pumps for 3, 7 and 14 days to rats with silk ligatures around second maxillary molars. Other animals without ligatures received insertion of pumps containing rhIL-1 beta or remained untreated. Sections were subject to three different stains:--hematoxylin and eosin (H-E) for histology, acid phosphatase (ACPase) activity for osteoclast detection, and immunohistochemistry using anti-rat monocyte/macrophage monoclonal antibody (ED 1). In addition, body weight, plasma calcium and phosphorus levels were monitored. The mean body weight of rats receiving rhIL-1 beta was significantly lower (P < 0.05 to P < 0.01) compared with untreated rats throughout the experimental period. On Day 7, plasma calcium and phosphorus levels were significantly lower in rats receiving rhIL-1 beta than in rats receiving PBS only (P < 0.05). Sections revealed a moderate inflammatory cell infiltrate reaching near the alveolar crest in both groups with ligatures on Day 3. Only rats receiving rhIL-1 beta exhibited enhancement of inflammatory cell invasion on Days 7 and 14. In rats receiving rhIL-1 beta with ligatures, numerous resorption lacunae containing ACPase-positive multinucleated giant cells (MNGCs), coinciding with ED1-positive cells, were located on the mesial side of the septum where extensive bone resorption had occurred throughout the experimental period. In animals receiving rhIL-1 beta without ligatures, compared with untreated rats, increased ACPase-positive cells were observed on the mesial side of the septum on Day 3. In animals receiving PBS only, a few ACPase-positive cells were observed confined to the mesial regions where slight bone resorption occurred on Days 7 and 14. These results indicate that the administration of rhIL-1 beta accelerated alveolar bone destruction in ligature-induced periodontal tissue inflammation over a two-week period.

智歯歯はいの感染により生じたＧａｒｒｅ骨髄炎の１例

A case of mandibular Garre osteomyelitis caused by a wisdom tooth-germ is reported. The patient was a 10-year-old girl who visited the Department of Dentistry and Oral Surgery of Hakodate Goryoukaku Hospital, complaining of a bony swelling in the right cheek region. Radiographic examination showed a toothgerm of a wisdom tooth, focal overgrowth of bone around the mandibular angle and a radiolucent appearance suggesting a fistula between the toothgerm and the bone mass. The toothgerm was surgically enucleated, and the periosteal bony lesion was curetted. Microscopic examination revealed a toothgerm containing moderate infiltration of chronic inflammatory cells, and new bone with abundent osteoblasts.

Chronic cryptosporidiosis in Australian elapid snakes: control of an outbreak in a captive colony.

An outbreak of chronic cryptosporidiosis resulting in hypertrophic gastritis occurred in a captive colony of Australian elapid snakes. Two species of the genus Notechis were involved: Notechis ater (Black Tiger Snake) and Notechis scutatus (Eastern or Mainland Tiger Snake). The infection was eventually fatal in all 9 affected snakes. Typical histopathological findings of the stomach included mucosal thickening with cystic dilatation of gastric glands, moderate oedema and fibrosis of the lamina propria, and a mild to moderate patchy infiltration of inflammatory cells. Procedures implemented to contain the outbreak included the use of a formaldehyde-based disinfectant, prompt removal of faecal matter, uneaten and regurgitated food from enclosures, and examination of faecal specimens for Cryptosporidium oocytes and other pathogens.

Histologic Changes in Superficial Basal Cell Epithelioma and Bowen's Disease by Intralesional Injection of Recombinant Interleukin 2: Recombinant Interleukin 2 May Induce Redifferentiation of Malignant Tumor Cells In Vivo

To the Editor.— We describe the antineoplastic effect of recombinant interleukin 2 on malignant tumors of the epidermis by intralesional injection. Report of Cases.— Case1.—A 44-year-old woman had a 31 × 22 mm, sharply defined plaque on her right waist, whose biopsy specimen was histologically diagnosed as superficial basal cell epithelioma. The lesion was treated by intralesional injection of recombinant interleukin 2 (TGP-3, Takeda Chemical Industries Co, Osaka, Japan). The recombinant interleukin 2 was given at a dose of 1000 U once daily for 13 consecutive days. In the second biopsy performed the day after the last injection, the epidermis had moderate inflammatory cell infiltration, without any necrotic cells or cell debris. Particularly, all basalioma cells were replaced by nearly normal epidermal cells showing orthokeratinization. In the upper aspect of the dermis there were numerous inflammatory cells, including scattered eosinophils. Immunohistochemically, OKT8— positive cells were scattered in considerable numbers

A sequential light microscopic study of the pulmonary lesions in porcine dermatosis vegetans

The sequential pulmonary changes in dermatosis vegetans were studied in pigs aged one, seven, 14, 17, 21 and 28 days, and two and a half, four and 12 months. At one day old the lung tissues appeared normal. At seven days old there was a moderate infiltration of mononuclear inflammatory cells in the alveolar structures, and proliferation of type II pneumocytes was also observed. At 14 and 17 days old the alveolar structures were intensely infiltrated with mononuclear inflammatory cells. At 21 days old, loosely arranged epithelioid and multinucleate giant cell granulomas appeared, and there was a proliferation of alveolar epithelial cells. By four and 12 months old the inflammatory changes diminished, and small granulomas and moderate alveolar fibrosis were present. The initial lesions were characterised by an alveolitis, developing into loosely arranged granulomas by four months old, and persisting to the age of 12 months. These observations suggest that the interpretation of the lung changes and the disease in general should be revised.

Clinical and immunopathological studies of pars planitis in a family.

We examined a family in which two brothers with identical HLA typing have pars planitis with snowbanking. Immunopathological studies of one of their eyes showed that in the area of snowbanking over the pars plana there was mild to moderate inflammatory cell infiltration, consisting of mostly Pan T (Leu 4+) lymphocytes. The ratio of T helper/inducer to T suppressor/cytotoxic cells was approximately 10:1. Few macrophages (OKM1+) were identified. Very few B cells and no NK cells were observed. Some retinal vessels had a perivascular infiltration consisting of mostly T lymphocytes. Most of the inflammatory cells bore class II antigens (HLA-DR+), while T cells bore few IL-2 receptors (anti-TAC+). The snowbank consisted mainly of glial elements (GFAP+) and basement membrane components (type IV collagen and laminin) with the predominant cell the Müller cell (Mü+). A site of inflammation at the iris-ciliary body junction also stained for B cells (Leu 14+). These findings suggest that the snowbank could be formed by the glial elements of the peripheral retina. The chronic inflammation in pars planitis appears to consist of helper T cells, both in the pars plana, and the retinal vasculature.

Bile ductal and ductular changes of the livers in the renal allografted patients.

Nine liver biopsies from six renal allografted patients suffering from liver injury were examined by light and electron microscope and immunostaining. The patients had never been on liver dysfunction prior to renal transplantation and after renal transplantation had been administered azathioprine continuously. These patients had shown HBs antigen negative sera. Three of these patients restored normal liver function after withdrawal of azathioprine. Accordingly, the liver diseases of the three were supposedly caused by azathioprine. The liver biopsies of six patients were histologically diagnosed as follows: chronic active hepatitis with severe cholestasis (1 patient), liver cirrhosis with cholestasis (1 patient), acute hepatitis (1 patient), and mild hepatitis (3 patients). The common pathological findings of six patients were degeneration of interlobular bile ducts and ductules, as well as degeneration of liver cells, and mild to moderate inflammatory cell infiltration of portal tracts and sinusoids. The degeneration of bile ductal and ductular cells were classified into two types: light microscopical finding showed vacuolar or eosinophilic cytoplasm and electron microscopic compatible findings showed hydropic cytoplasm scant of free ribosome and organelles, or dense cytoplasm rich in free ribosome and degenerated organelles. The basement membranes of interlobular bile ducts and ductules were always preserved.