A thymic hormone protects mice from enteropathy during acute graft-versus-host disease.

We have previously reported that a nonapeptide thymic hormone, facteur thymique serique (FTS), is involved in the differentiation and activation of intestinal intraepithelial lymphocytes (i-IEL) in mice. In this study, we examined the effect of FTS treatment on enteropathy in a murine model for acute graft-vs.-host disease (GVHD) induced by injection of parental C57BL/6 splenocytes into unirradiated (C57BL/6 x DBA/2) F1 hybrids. FTS treatment significantly protected mice from developing acute GVHD as assessed by mortality rate, splenomegaly and enteropathy. The infiltration of donor-derived TCR alpha beta i-IEL bearing CD8 alpha beta was significantly inhibited in the small intestine of FTS-treated mice, and the frequencies of apoptosis of crypt cells in the intestinal mucosa were decreased in these mice during acute GVHD. These results suggest that FTS treatment contributes to protection against enteropathy of acute GVHD. Thus, FTS may provide a useful approach to control acute GVHD after blood transfusion or bone marrow transplantation.

Decreased beta-amyloid and increased abnormal Tau deposition in the brain of aged patients with leprosy.

We examined the brains of 37 leprosy patients (mean age, 76.3 +/- 7.8 years), 5 patients with Alzheimer-type dementia (mean age, 79.0 +/- 9.5 years), and 23 age-matched non-dementia controls (mean age, 77.6 +/- 5.4 years). The frequency of beta-amyloid (A beta)-positive cases was lower (27.0%) in leprosy patients (n = 37) than in controls (47.8%; P = 0.05, Z = 1.49). When senile plaque subtypes were examined, type III (classical) plaques were significantly fewer (P < 0.05) in leprosy subjects compared with controls. Interestingly, neurofibrillary tangles in the temporal cortex were much more frequent in leprosy patients than in controls (P < 0.05). However, hippocampal CA3 pyramidal neurons in leprosy patients were well preserved. These data indicate that 1) leprosy patients have a low risk of A beta deposition but a high risk of abnormal tau deposition, 2) abnormal tau deposition is unrelated to A beta deposition in leprosy, and 3) neuronal loss is unrelated to abnormal tau deposition. It is not clear at present whether the result is related to the disease process itself, antileprosy treatment, environmental factors, or the genetic background in leprosy patients.

[Is a false image of the senile plaque in elderly Japanese with leprosy?--pathological findings on the immunohistology].

By the advance of chemotherapy and aging of the inpatients with leprosy (mean age: 75.7 years), geriatric disease are becoming major problems in Japanese National Leprosarium. Dementia is not diagnosed inpatient with leprosy. After autopsy Alzheimer fibrillary tangle and senile plaques in the brain of aged leprosy is not easy demonstrated by routine stains. However, these is easy demonstrable a different senile plaque with accretion to the Alzheimer fibrillary tangle, if it employed the specific immunohistochemical method on these brain. We employed both tau protein and the divided beta protein, and each of protein is able to divide dementia and non-dementia into aged groups in leprosy. Low prevalence in Japanese leprosy patients is demonstrable in dementia of what happened was accurate in alzheimer disease with subtype of senile plaque.

Development of GFAP-positive cells and reactive changes associated with cystic lesions in HTX rat brain.

HTX rat, a congenital hydrocephalic strain, develops ventricular dilatation and cystic cavities in the cerebral white matter after birth. To investigate the reactive changes in glial cells around these cavities, immunohistochemical staining for glial fibrillary acidic protein (GFAP), a specific marker protein of astrocytes, and bromodeoxyuridine (BrdU), a thymidine analogue, was carried out on 107 Wistar and HTX rat brains from birth to postnatal day (P) 26. Animals were divided into three groups: Group A, Wistar rats as normal controls; Group B, HTX rats with a normal structure or only mild ventricular dilatation without any lesion in the white matter; and Group C, HTX rats with severe ventricular dilatation and cyst formation in the white matter. Group B rats showed similar development of GFAP-positive (GFAP+) cells to that in Group A rats, both morphologically and quantitatively. On the other hand, Group C rats showed definite structural changes in GFAP+ cells around the cystic cavities from P5. These included enriched cytoplasm and thickened cell processes with increased GFAP expression, and enveloped most cyst walls from P10. However, quantitative examination of the percentage of GFAP+ cells in Group C rats showed a similar developmental profile to those in Group A and B rats. Furthermore, the labeling index of BrdU-positive cells, indicating S-phase cells, in the white matter in Group C rats showed a similar decreasing pattern to that in Group A and B rats from P1 to P26.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathology of cystic cavities in the cerebral white matter of HTX rats with inherited hydrocephalus.

To investigate the mechanism of cystic cavity formation in the cerebral white matter of the HTX rat, a strain with inherited hydrocephalus, the authors carried out a histopathological study of the brain in pups from birth to postnatal day (P) 26. Cystic cavities were formed in the cerebral white matter on the lateral side of the basal ganglia of all HTX rats with moderate to severe ventricular dilatation and, additionally, in the white matter beneath the paramedian cortex in advanced cases at P10-26. In the initial stage of cyst formation, disarrangement of the ependymal cell layer and spongy alteration of the white matter took place in pups between P1 and P7. The ependymal disarrangement involved disruption and flattening of the ependymal cells, which were often devoid of microvilli, cilia and intercellular junctional complexes. The spongy state was due to expansion of the extracellular space and multiple microcyst formation with fluid accumulation in the early stage, and large cystic cavities in the advanced stage. The cerebrospinal fluid (CSF) in the ventricle communicated with the fluid in the cystic cavities via the disarranged ependymal cell layer. The ependymal damage was more prominent at the lateral wall of the posterior horn than at the anterior horn of the lateral ventricles. These cavities were demarcated by reactive glial cells in the advanced stage. However, the cavities enlarged in accordance with progressive dilatation of the lateral ventricles during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological study on the motility of the human colon.

We tried to make a clear three-dimensional picture of the autonomic nerves in the wall of the human colon, using a Golgi method rarely applied to human materials. At autopsy, sigmoid colon without mucosal lesions were collected from 16 males after sudden death from apoplexy, head injury, or myocardial infarction. These materials were fixed in 10% formalin, impregnated with a modified Golgi method and embedded in celloidin. Then three-dimensional serial sections were made and observed with a light microscope. Many fine nerve fibers formed a plexus in the subserosa, muscular layer, submucosa, and mucosa. The myenteric plexus was made up of rectangular meshes of nerve fiber bundles. However, unlike myenteric plexus, no regular mesh was found in the submucosal plexus. Further, nerve fibers connecting myenteric and submucosal plexus were observed. It may be concluded from these findings that there exist nerve pathways regulating intestinal motility between myenteric and submucosal plexus.

[Emulsifiers which reduce the latency of the development of colonic cancer--sodium lauryl sulfate and methylazoxymethanol].

The effect of emulsifier (nonionic surfactant) on the production of adenocarcinoma by methylazoxymethanol acetate in the large intestine of rats was studied. Following emulsifier, sodium lauryl sulfate administration, many cases of undifferentiated adenocarcinoma consisting of anaplastic glandular cells were induced in the experimental groups. Lymphatic invasion by cancer cells was found in 3 cases and metastasized to other organs in 6 cases. On the contrary, the control group (administered methylazoxymethanol acetate only) revealed well-differentiated adenocarcinoma in many cases. This fact may be due to an emulsifier used as a vehicle for the chemical, and the emulsifier might activate the character of promotion to carcinogenisity as a secondary agent. By virtue of the strong penetrating property of the emulsifier, colonial carcinogenesis seems to be enhanced.

Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

1 Plasma levels of isoniazid (INH) and acetyl INH in plasma were measured with a spectrofluorometric method, and INH and its metabolites (acetyl INH, mono-acetylhydrazine, diacetylhydrazine and free hydrazine) excreted in urine were measured with a gas chromatography-mass spectrometry, respectively, after an oral dose of INH 10 mg/kg in 19 Japanese patients with idiopathic systemic lupus erythematosus (SLE) and in the same number of healthy controls. 2 When phenotyped according to various methods previously reported, 16 to 18 of the SLE and 17 to 19 of the control group were rapid acetylators. Regardless of the phenotyping methods applied, the distribution of acetylator phenotype of SLE patients was not significantly different from the control group or from the data previously reported among normal Japanese population. 3 By phenotyping our subjects with an INH T 1/2 of 110 min or less as rapid acetylators, and more slow acetylators, 3 of SLE patients and 2 of the controls were slow, while the remainder were all rapid. When this antimode was used, the mean apparent kinetic variables of INH and acetyl INH estimated from the plasma concentration-time data and the mean values for the 24-h urinary amount of INH and its metabolites, except for monoacetylhydrazine (P less than 0.05), did not significantly differ between the rapid acetylators of SLE and control groups. 4 The distribution of INH T 1/2, acetyl INH to INH ratios in plasma and urine, values in urine for log10 (diacetylhydrazine to monoacetylhydrazine) and for diacetylhydrazine to INH or acetyl INH was similar between the two groups except for one patient who was definitely classified as a slow acetylator regardless of whichever phenotyping methods were used. The excretory patterns of hydrazine compounds reflect, in general, the inactivating ability of INH in each individual. 5 The data suggest that phenotyping by using plasma samples is, in general, better than by using urine samples. The plasma T 1/2 alone is the most satisfactory criterion. 6 We conclude that neither INH disposition nor phenotype distribution assessed by the reported methods using INH as the test compound are altered in idiopathic SLE, and that a search for racial and/or geographical factor(s) likely to result in autoimmune disease may give a clue to the pathogenesis in addition to further exploration for the possible interrelation between idiopathic SLE and genetic slow acetylation.

Acetylator phenotype and metabolic disposition of isoniazid in Japanese patients with systemic lupus erythematosus.

Acetylator phenotype and metabolic disposition of isoniazid (INH) were studied in 19 Japanese (a population shown to be 11.5% slow acetylators) patients with spontaneous systemic lupus erythematosus (SLE) and 19 healthy controls. Subjects with the elimination half-life (t1/2) of INH of 2.0 hours or less were considered rapid and those of 2.2 hours or more were slow acetylators. Results of phenotyping showed that 17 of 19 SLE patients were rapid, 1 slow, and 1 indeterminate, whereas 18 of the controls were rapid and 1 indeterminate. When phenotyped according to another reported antimode (107 or 110 minutes), 3 of the patients and 2 of the controls were slow and the remainder were all rapid acetylators. The distribution of INH t1/2, acetyl INH to INH ratios in urine and plasma, and hydrazine compounds in urine measured with gas chromatography mass spectrometry was similar between the two groups, except for 1 patient who was definitely classified as a slow acetylator. The relationship between phenotype distribution and possible pathoetiologic factors is discussed.