The carcinogenicity of thiamphenicol (TAP), an antibiotic drug, was examined in Fischer 344 rats of both sexes. TAP was given ad lib. in drinking water at levels of 0 (control), 125 or 250 ppm to groups of 50 male and 50 female rats for 2 yr. The treatment did not affect mortality and no toxic lesions were specifically induced. Furthermore, the incidence of tumours in the treated groups did not show any significant dose-related increase as compared with the control group. The results thus indicate that TAP is neither toxic nor carcinogenic, for any organs or tissues of F344 rats when given continuously at levels of 125 or 250 ppm in drinking water for 2 yr.

Administration, Oral↗

PubMedDate not supplied

Activation mechanism of brain microglia in patients with diffuse neurofibrillary tangles with calcification: a comparison with Alzheimer disease.

Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles (NFTs) without senile plaques (SPs). In this study, we investigated the distribution of human leukocyte antigen (HLA)-DR-positive activated microglia in postmortem brain tissue of six patients with DNTC and six patients with Alzheimer disease (AD). HLA-DR-positive activated microglia were observed to associate with SPs in AD. In the DNTC brain, which lacks SPs, HLA-DR-positive microglia were mainly accumulated around weakly tau-positive NFTs, which were also positive for anti-amyloid-P and anti-C3d antibodies. The results of this study suggest that the complement pathway is also activated in the DNTC brain and that immune and inflammatory responses, including microglia activation, may occur around extracellular NFTs in DNTC patients.

Aged↗

PubMedDate not supplied

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings.

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease (HD) accompanied with minimal non-specific neuropathological features was reported. When the patient was 45 years old, he had faulty memory, mood swing, personality change and agitation. Neurological and psychiatric examinations revealed choreoathetoid movements in limbs and trunk, generalized hyperreflexia and mental deterioration. However, cerebellar ataxia and muscle rigidity were not disclosed. Neuroimaging study did not show a definite atrophy of heads of caudate nuclei. Neuroacanthocytosis and Wilson's disease were ruled out by the peripheral blood examination and serum Cu and ceruloplasmin examination. At the age of 55 he died of pneumonia. Post-mortem examination revealed minimal non-specific neuropathological features for HD (Vonsattel's grade 0), that is, no visible fibrillary gliosis in the striatum, and few neuronal loss and only proliferation of astrocytes (astrocytosis) in the striatum. Molecular-genetic study the patient's brain tissues and his youngest son's blood was performed. These studies revealed 40 CAG repeats in the patient, 56 CAG repeats in his youngest son. These results suggest they may be HD. Vonsattel et al. [ 1998] insist that grade 0 comprises 1% of all HD brains, and grade 1 comprises 4% of all HD brains. But we could not find any reports in which the clinical and neuropathological features were described in detail on the cases with clinically and molecular genetically diagnosed HD without specific pathological findings. Therefore, we present in detail the clinical and neuropathological features of such case.

Brain↗

PubMedDate not supplied

Non-Alzheimer non-Pick dementia with Fahr's syndrome.

Five patients with non-Alzheimer non-Pick dementia combined with Fahr's syndrome were studied. Atypical clinical pictures emerged from an evaluation of these cases. Their symptoms and signs could be attributed neither to Alzheimer's disease nor to Pick's disease but to a partial mixture of both. The neuropathological changes were characteristic, and the common findings were as follows: 1) the absence of senile (neuritic) plaques, 2) the widespread presence of numerous neurofibrillary tangles throughout the neocortex, 3) a calcareous deposition of Fahr's type, 4) a circumscribed cerebral atrophy in the temporal or/and frontal lobes, 5) a moderate or severe demyelination and fibrous gliosis in the white matter of the atrophied areas and 6) a mild or moderate neuronal loss in the nucleus basalis of Meynert. These neuropathological changes were not due to Alzheimer's disease nor to Pick's disease. Similar cases reported previously were reviewed.

Aged↗

PubMedDate not supplied

Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine.

Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was examined. Female Donryu rats were divided into four groups at 7 weeks of age. Rats in Croup 1 were controls under a 12-h light/12-h dark regimen while Groups 2-4 were persistent estrous animals maintained under 24-h light conditions. At 10 weeks of age, rats in Group 1 and 2 were given a single intra-uterine administration of polyethylene glycol(PEG), and those in Groups 3 and 4 received ENNG(20 mg/kg body weight), dissolved in PEG, in the same manner. Group 4 rats also received an s.c. 17 beta-estradiol(E2) implant one week thereafter. At the termination of the experiment (week 42 after the ENNG-treatment), all surviving rats were killed and the development of uterine proliferative lesions assessed. All groups demonstrated hyperplasias, the incidence and severity being higher in ENNG-treated animals. The incidence of uterine adenocarcinomas in Group 2(2/20, 10%) was slightly higher than that in Group 1(0/16, 0%), although this difference was not significant. In Groups 3(7/19, 37%) and 4(6/20, 30%) statistically significant induction of adenocarcinomas was noted, two lesions in the latter case being very large with prominent invasion of tumor cells into the perimetrium. At 10 and 25 weeks after ENNG-treatment, the E2-progesterone(E2:P) ratios in Groups 2, 3 and 4 were significantly higher than in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMedDate not supplied

Effect of age on the induction of endometrial lesions by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine in F344 rats.

A total of 54 10-week-old or 49 10-month-old female F344 rats were given a single intrauterine administration of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina using a non-laparotomy approach. Control animals (32 10-week-old or 29 10-month-old rats) were given PEG alone in the same manner. The animals were killed at 15 and 18 months of age, respectively. One animal in the young treated group presented an endometrial adenocarcinoma (incidence: 2.1%), although the incidence and degree of endometrial hyperplasias were significantly increased in both groups of treated animals, as compared to corresponding controls. Histologically, many of these lesions were polypous glandular hyperplasias (adenomatous polyps) with stromal proliferation. The incidence and grade of proliferative lesions in the young treated group were slightly higher than those in the old treated group. ENNG administration did not appear to affect the hormonal situation in treated animals. These results indicate that young animals may be more sensitive to ENNG than aged ones for induction of endometrial lesions, although ENNG-treatment alone is not sufficient for early and high induction of carcinomas even in young rats of this strain.

Adenocarcinoma↗