The role of TNFalpha and IL-17 in the development of excess IL-1 signaling-induced inflammatory diseases in IL-1 receptor antagonist-deficient mice.

IL-1 receptor antagonist (IL-1Ra)-deficient mice spontaneously develop several inflammatory diseases, resembling rheumatoid arthritis, aortitis, and psoriasis in humans. As adoptive T cell transplantation could induce arthritis and aortitis in recipient mice, it was suggested that an autoimmune process is involved in the development of diseases. In contrast, as dermatitis developed in scid/scid-IL-IRa-deficient mice and could not be induced by T cell transfer, a T cell-independent mechanism was suggested. The expression of proinflammatory cytokines was augmented at the inflammatory sites. The development of arthritis and aortitis was significantly suppressed by the deficiency of TNFalpha or IL-17. The development of dermatitis was also inhibited by the deficiency of TNFalpha. These observations suggest that TNFalpha and IL-17 play a crucial role in the development of autoimmunity downstream of IL-1 signaling, and excess IL-1 signaling-induced TNFalpha also induces skin inflammation in a T cell-independent manner.

Food restriction and spontaneous motor activity in male mice: effects of feeding pattern, far-infrared ray and bamboo grass leaf extract.

The effects on spontaneous motor activity of the pattern of restricted feeding, far-infrared ray (FIR) irradiation or free access in drinking water containing Sasa Health, a bamboo grass leafextract, were examined in SHN male mice at 2-3 months of age. In mice whose diet was restricted to 60% of the control, fed at 9:00 or 17:00 hours, the level of spontaneous behaviour was elevated 1 hour before the respective feeding time (8:00 or 16:00 hours). The activity was stimulated by FIR in both the control and food-restricted mice, but to a much higher degree in the latter. Treatment with Sasa Health in drinking water lowered the elevated activity level in food-restricted mice. Plasma component levels and organ weights were modulated by FIR or Sasa Health. The findings revealed that, not only the restricted feeding itsel, but also its pattern, significantly affected behaviour and that FIR and Sasa Health modified the deleterious effects of restricted feeding.

Multiple sclerosis with secondary syringomyelia. An autopsy report.

We report an elderly woman with multiple sclerosis who showed an extensive cavity formation in the midthoracic cord in addition to multiple abnormal intensity signals in the central nervous system on magnetic resonance imaging (MRI). The cavity decreased in size in response to corticosteroid therapy with an improvement in neurological symptoms. The autopsy demonstrated a slit-like cavity lined with no ependymal cells on the luminal surface in the lower cervical to midthoracic cord, with circumferentially distributed demyelinative lesions, leading to the pathological diagnosis of secondary syringomyelia. In this patient a limited necrosis formed in the spinal cord might have developed into a cavity formation with edematous fluid leading to subsequent episodes of neurological exacerbation.

Myasthenia gravis with membranous nephropathy, successfully treated with extended total thymectomy.

A 46-year-old woman showed proteinuria and hematuria after left blepharoptosis, and revealed a histopathology of membranous nephropathy (MN) at renal biopsy. She was diagnosed as having myasthenia gravis (MG) because of a positive edrophonium test and anti-acetylcholine receptor (AchR) antibodies in serum. We found a decrease in anti-AchR antibodies after extended total thymectomy, in parallel with an improvement in both urinary findings and myasthenic symptoms. In this case, MG preceded MN and the thymectomy was effective for both diseases, suggesting that the thymus might play an important role in the pathogenesis of MN.

Hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA): clinical and neuropathological features of a Japanese family.

We report clinicopathological features of a Japanese family with hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA). Four affected members from a single generation were examined. They shared common clinical features, including insidious onset in teenage, slowly progressive cerebellar ataxia, amyotrophy, sensory disturbance, and dementia. In addition, all the patients showed hypoalbuminemia and hyperlipidemia and a marked atrophy of the cerebellum on magnetic resonance images. Autopsy of the proband revealed a severe loss of Purkinje cells, degeneration of posterior columns and spinocerebellar tracts of the spinal cord, and a marked loss of myelinated and unmyelinated fibers in the peripheral nerves. We consider that HMSNCA is a distinct form of hereditary multisystem neuronal degeneration.

[Cyst of the tunica albuginea associated with intraabdominal testes: a case report].

A case of cyst of the tunica albuginea associated with intraabdominal testes is reported. A 35-year-old man was referred for further examination of azoospermia. Bilateral testes were nonpalpable in the scrotum and inguinal region. Ultrasonography and MR imaging demonstrated a 9 x 8 cm cystic lesion in the median suprapubic area. An open operation showed the cystic lesion to extend to the right spermatic cord and vas deferens. Left intraabdominal testis was also identified. Right orchiectomy and left orchiopexy were performed. Histopathological diagnosis was a cyst of the tunica albuginea. Atrophic seminiferous tubules were recognized at the junction of the cyst and the spermatic cord.

Age-related character of glomerular lesions in IgA nephritis. (2). Histopathological peculiarity in childhood onset.

Histopathological analysis was performed in the first renal biopsy specimens of patients over and under 10 yrs of IgA nephritis. They were divided clinically into two groups, the one with remission and the other with prolonged disease state respectively. Increased mesangial sclerosis, frequent occurrence of segmental glomerular lesions and tubulointerstitial change were significantly evident in the group with prolonged disease state. It is suggested that similar glomerular events are progressing in IgA nephritis which is carried over to adult age.

Influence of subepithelial deposits on permeability of the glomerular capillary wall in serum sickness nephritis in the rat.

Serum sickness nephritis was induced in male Fisher rats by immunization with egg albumin (EA). Correlations of subepithelial deposits (SD) with size and charge barriers of the glomerular filter were investigated using native (NF) and cationized (CF) ferritin as tracer probes. In proteinuric animals large numbers of NF molecules perfused from the abdominal aorta were observed to cross the glomerular basement membrane (GBM) and enter SD. The concentration of NF molecules was higher in GBM segments with SD than in GBM segments without SD, and the concentration of these molecules was higher within SD than in the intervening GBM. In contrast, CF clusters were fewer in number in the lamina rara externa (LRE) of GBM segments with SD than in the GBM segments without SD. CF particles could not be observed within SD, even in the areas of podocyte detachment. It is suggested that permeability in GBM segments with SD increases and that the development of proteinuria in this model can be attributed to alterations in both charge- and size-selective barriers to glomerular filtration.

Small cell carcinoma of the gallbladder combined with adenocarcinoma.

A rare case of small cell carcinoma (SCC) of the gallbladder combined with adenocarcinoma is reported. The patient was a 70-year-old Japanese man, who died of the disease shortly after the onset of symptoms. Autopsy disclosed a small tumor (1.0 cm in longest diameter) in the fundus of the gallbladder, with widespread metastasis. Histochemically, the tumor cells showed negative reactions for argyrophilic and argentaffin stainings, a weak immunohistochemical reaction only for neuron-specific enolase, and negative reactions for all of the other neurosecretory markers used, including neurofilament, chromogranin, somatostatin, gastrin and leu-7. However, electron microscopic examination revealed a few typical neurosecretory granules (NSG) in the cytoplasm of some tumor cells. We suggest that: 1. The presence of NSG in the cytoplasm of tumor cells is the most reliable diagnostic criterion for SCC. 2. SCC, at least the combined type, arises from a multipotential stem cell.

[Arthus-type nephritis and glomerular clearing system].

Glomerular clearing system was histologically studied to see what role it played in the flourishing, resolving and healing stages of Arthus-type nephritis in rabbits with intravenously injected colloidal carbon or ligation of thoracic duct. In the glomerulus, poorly soluble immune complexes were found within mesangial channels, a route for the egress of macromolecules from the peripheral mesangium through the hilus into the juxtaglomerular apparatus, other than phagocytosed by polymorphonuclear leukocytes. However, in the flourishing stage the immune deposits supplied to the external mesangial matrix seemed to originate in that made in the periglomerular blood capillary. Severer glomerulitis was observed under the condition of lymph stasis and juxta-glomerulitis, which was composed of inactive monocytes and plasmocytes, appeared late from the resolving stage. Coincidentally, stagnant amorphous, electron dense material was seen around the border between the external and internal mesangium or the wall of the efferent arteriole at the reflection site of Bowman's capsule. These features of juxta-glomerulitis may be explained by stagnant deposits transported upstream through mesangial channels. Carbon particles within mesangial channels were finally taken up by mesangial cells, whose endocytotic phagosome settled down until three weeks of the healing stage. Mesangial blebs or pseudopods protruding in the capillary lumen were observed in the resolving stage, the injection of colloidal carbon and the ligation of thoracic duct. The endothelium was lifted by mesangial blebs from the juxta-mesangial portion and seemed to interrupt the capillary blood stream. Mesangial influx was increased because of partly desquamation of the endothelium and macromolecules tended to accumulate in the sub-basement membrane of the para-mesangium. It's suggested that focal segmental sclerotic and adhesive lesions in the healing stage are correlated with the degree of juxta-glomerulitis and the peripheral mesangial blebs.

Masking of anionic sites by deposits in lamina rara externa in immune complex nephritis in rats.

Alterations in glomerular basement membrane (GBM) anionic sites associated with immune deposits (ID) were observed using polyethyleneimine (PEI) as a cationic probe in serum sickness nephritis induced by egg albumin (EA). The anionic sites were fewer in number than in other GBM segments and were irregular in distribution in most, but not all, of the segments of the GBM with ID on the epithelial side of the lamina densa (LD). The disappearance of anionic sites was obvious in areas where the internal aspects of the lamina rara externa (LRE) of the GBM were occupied by ID, even if the ID were very small. In contrast, the disappearance of anionic sites was not evident, even though no change in anionic sites was found in some areas, where the ID had departed from the internal aspects of the LRE and a pale band was seen between the ID and the LD. Further, PEI aggregates, showing localization of anionic sites, were seen within the low density ID, but no PEI aggregates were seen within the high density ID. The results suggest that: 1) whether or not ID induce the disappearance of anionic sites is independent of the size of the ID, but is dependent on the density of and the place occupied by the ID, and 2) the ID seem to induce the disappearance of anionic sites by masking rather than destroying them.

Size of normal hilar lymph nodes measured in autopsy specimens.

The normal size of lymph nodes for each region of the hilum was determined by direct measurement of the short and long diameters of each node in the transverse plane of the node and the longitudinal diameter in the vertical plane of the node in 30 adult cadavers. The mean short transverse diameters ranged from 3.2 to 6.4 mm, the mean long transverse diameters ranged from 4.9 to 10.0 mm, and the mean longitudinal diameters ranged from 5.7 to 11.3 mm. The largest mean transverse diameters were found in the anterior upper lobe (AUL) and the inferior interlobar (IIL) regions. We noted a different maximum normal size for lymph nodes in each region of the hilum and determined the standard maximum normal short transverse diameters to be as follows: 12 mm for nodes in the right AUL and IIL regions, 10 mm for nodes in the right superior interlobar region and the left AUL and IIL regions, and 8 mm for nodes in other regions. Both the maximum normal long transverse diameters and the longitudinal diameters showed a wider variation, ranging from 18 to 10 mm and from 20 to 12 mm, respectively.