Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A.

In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development.     

The prognostic value of E-cadherin, α-, β- and γ-catenin in bladder cancer patients who underwent radical cystectomy

OBJECTIVES: To determine the value of the loss of expression of E-cadherin and cadherin associated molecules as useful markers for both prognosis and chemosensitivity in bladder cancer patients who have undergone radical cystectomy. PATIENTS AND METHODS: In 55 paraffin embedded specimens of radical cystectomy at our hospital from 1982 to 2000, the expression of E-cadherin, alpha-, beta- and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance of these molecules, Kaplan-Meier survival curves were constructed and a statistical analysis was calculated by a log-rank test. A multivariate test (tumor stage, tumor grade, lymph node metastasis, configuration, the expression of E-cadherin, alpha-, beta- and gamma-catenin) was performed to detect prognostic markers. RESULTS: Normal expression was found in 33 cases (60.0%) for E-cadherin, 29 (52.7%) for alpha-catenin, 31 cases (56.4%) for beta-catenin, and 31 cases (56.4%) for gamma-catenin. The expression patterns for E-cadherin, alpha-, beta- and gamma-catenin were significantly correlated with each other (P < 0.01). Survival analysis showed a significant difference between normal and aberrant expression in each staining. A multivariate analysis revealed that the expression of alpha- catenin was an independent prognostic factor (P = 0.0191). In 23 patients that received adjuvant chemotherapy, there was a significant difference in survival between the normal and aberrant expression of alpha-catenin, but not other molecules. CONCLUSION: Alpha-catenin may not only be a good prognostic marker, but also one of key molecules that determine the chemosensitivities in patients with invasive bladder cancer.     

Resected cases of middle lobe primary cancer

Of 200 lung cancer lesions resected in our hospital, there were 15 cases (7.5%) with middle lobe origin. The histological types were adenocarcinoma in 13 patients (4 patients with alveolar cell carcinoma), squamous cell carcinoma in one and large cell carcinoma in one. These patients were classified into two groups according to the type of operation they received and each group was evaluated. Group I (resection of the middle lobe) included 8 patients. Each one of Stage IIIB and Stage IV received the operation to improve their symptoms. The six patients of Stage I received only middle lobectomy as absolute curable cases. Group II (resection of the middle and lower lobes) included 7 patients, who had preoperative diagnosis of stage III. Two of them were postoperatively found to be cases of Stage I and Stage II. Although it was still short-term, the follow-up evaluation proved that these patients survived without local recurrence and distant metastasis, except for two with pleural dissemination and one with cerebral metastasis, who had received lobectomy as palliative operation. No difference was observed between the two groups receiving different types of operation.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

The present issues to advocate rights of patients with neurological diseases in Japan]

To advocate patient's right is an inevitable assignment of all neurologists who have clinical activities for patients with neurological diseases, though the assignment has very broad fields and is impossible to perform by one. The author summarized present issues of guardianship, the program to protect the social welfare rights in communities, and advance directives for patients with neurological diseases. The new guardianship for adults in Japan started in 2000 and has been increasingly used mainly for the demented. Proxy decision making for a medical care by the guardian is still unsettled. The author raised a possible question on identification of the person who wants medical certification for guardianship and his her intention to obtain such a document, in order to avoid unexpected troubles in the family or involved parties. Replies about the identification from an inspector at a family court, lawyers, judicial scriveners, social workers and Japan National Council of Social Welfare were shown on the table. In May 2007, the Ministry of Health. Labour and Welfare presented the guideline of process to decide the end-of-life-care. But advance directives for medical cares are still controversial in Japan. Multidisciplinary team to advocate patients' rights was stressed in this presentation.     

Clinical study of respiratory infections complicating bronchial asthma]

We conducted a clinical study on respiratory infections complicating bronchial asthma. Transtracheal aspiration (TTA) was performed 37 times in 22 patients. The most frequently isolated organism was H. influenzae. The patients in whom organisms were isolated on TTA had a high incidence of fever and evidence of inflammation. Antimicrobial therapy caused a decrease in indices of inflammation (white blood cell count and ESR), but was less effective against the asthmatic symptoms. Respiratory infection may play a complex role in the clinical picture of bronchial asthma.     

A trial of semiquantitative analysis of whole body bone scintigraphy in renal osteodystrophy

Four color processed whole body bone scintigraphy with 99mTc-methylene diphosphonate was performed in six patients on maintenance hemodialysis, and the results of semiquantitative colorimetric analysis were compared with those of a normal group. The difference between the two (control and patient group) was statistically significant (P less than 0.01). Furthermore, the effect of 1 alpha-hydroxyvitamin D3 treatment on renal osteodystrophy was evaluated by this method. The results indicated that this method provides a useful method for assessing the response of renal osteodystrophy to treatment. Two representative cases of renal osteodystrophy are presented to illustrate the usefulness of this approach to semiquantitative whole body bone scanning.