Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.     

Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

Skull metastasis of thyroid papillary carcinoma.

Skull metastasis of thyroid carcinoma is rare. The majority of skull metastases of thyroid carcinoma are of the follicular subtype, rather than thyroid papillary carcinoma. In this report, a 55-year-old woman with skull metastasis from thyroid papillary carcinoma is presented. The metastatic lesion of the skull was hypervascular and osteolytic, and the bleeding was profuse during resection. There have been only four reports of skull metastasis from thyroid papillary carcinoma. The mean period from the initial diagnosis of thyroid carcinoma until the detection of skull metastasis is 23.3 years, whereas in this patient, it was about 2 years. Therefore, in the clinical course of thyroid papillary carcinoma, skull metastasis should be considered, and the patient should be meticulously followed up.     

Familial spontaneous pneumothorax in three generations and its HLA

We experienced a case of familial spontaneous pneumothorax in three generations. Six of 13 family members had episodes of spontaneous pneumothorax. It is well established that there are some diseases associated with human leukocyte antigen (HLA). We performed HLA phenotyping for HLA of A, B and C. In our study, we detected the HLA haplotype A2, B61 in three of 4 who had episodes of spontaneous pneumothorax. The HLA haplotype A2, B70 were also detected in three of 4 who had episodes. This suggests that familial spontaneous pneumothorax might have hereditary factors.     

Regional vascular responses to thromboxane A2 analogue and their blockade with vapiprost, a selective thromboxane receptor blocking drug, in anesthetized dogs.

Regional vascular responses to the thromboxane A2 analogue U46619 and effects of the selective thromboxane receptor blocking drug vapiprost on these responses were examined in anesthetized dogs. Hemodynamic responses to U46619 (0.5 micrograms/kg into the left atrium), norepinephrine (NE, 0.3 microgram/kg, i.v.) and angiotensin II (AII, 30 or 60 ng/kg, i.v.) were periodically tested before and after administration of vapiprost (10, 30 or 100 micrograms/kg, i.v.) or its vehicle. In the absence of vapiprost, U46619 increased total peripheral (TPR), vertebral (VR), coronary (CR) and renal (RR) vascular resistance by 60.1 +/- 4.7%, 33.6 +/- 4.9%, 15.3 +/- 1.3% and 120.8 +/- 17.4%, respectively, indicating that vasoconstrictor responses to U46619 were most prominent in the renal vascular bed as compared to those in the vertebral or coronary vasculatures. Vapiprost as well as the vehicle did not affect the base-line hemodynamics. However, vapiprost apparently inhibited the U46619-induced vasoconstriction in all measured vascular beds in a dose-related manner without attenuating vasoconstrictor responses to NE compared to the inhibitions of VR and CR. These results demonstrate that there was a regional difference both in the vasoconstrictor responses to U46619 and in the blocking effects of vapiprost, and indicate that vapiprost is a potent and selective antagonist for thromboxane receptors in vivo.     

A case of acute focal bacterial nephritis

Acute focal bacterial nephritis refers to a renal mass caused by acute focal infection. We report a case of acute focal bacterial nephritis, herein. The case was in a 56-year-old woman, who was hospitalized with the chief complaint of left flank pain, chills and fever. Intravenous pyelography suggested the presence of a mass in the upper pole of the left kidney. Ultrasonography showed a hypoechoic mass, CT scan revealed a round, low density mass. Antibiotic therapy resulted in resolution of symptoms, and a follow-up CT scan and ultrasonography showed complete resolution of the renal mass.     

Coagulation changes during liver resection]

Thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor (PAI) were measured during liver resection surgery in 8 patients. TAT and PAI activities of patients under liver resection were compared with those of 11 patients under resection of esophageal carcinoma. TAT activity increased during liver resection (P < 0.001) and reached 14 times (P < 0.001) of its control value in the recovery room. PAI activity was very stable during operation, but increased to twice (P < 0.01) of its control value in the recovery room. TAT activity of patients after liver surgery in the recovery room was (P < 0.05) more than twice of that of patients after esophageal surgery. We conclude that hypercoagulable state occurred during liver resection to a greater degree compared with that observed with esophageal surgery, and that its cause might be liver resection itself.     

Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

Modification of the Na,K-pump of glial cells within cobalt-induced epileptogenic cortex of rat

The characteristics of a glial Na⁺,K⁺-pump dependent on extracellular K⁺ within epileptogenic cortex were studied electrophysiologically, biochemically and histochemically in vitro using slices from cobalt-induced epileptogenic cortex of rat. When the extracellular K⁺ concentration ([K⁺]_o) was varied between 4 and 40 mM, the mean slope of membrane potential plotted against [K⁺]_o was about 57 mV in glia from the normal cortex (tissue A) and about 44 mV in glia from the epileptogenic cortex (tissue B); whereas no significant difference in the resting membrane potential of these tissues was observed. In glia from tissue B, a marked transient hyperpolarization above control level was caused by replacement of elevated [K⁺]_o with the normal medium. Ouabain abolished these phenomena observed in glia from tissue B, but had no effect on the membrane potential during normal [K⁺]_o. Reduction of extracellular Na⁺, Ca²⁺ and Cl⁻ did not significantly affect the membrane potential of glia from either tissue. In tissue A, the cells marked by intracellular injection of horseradish peroxidase after intracellular recording were protoplasmic astrocytes; in tissue B, fibrous astrocytes with abnormal processes predominated. K⁺-dependent stimulation of Na⁺,K⁺-ATPase activity of the astrocyte-enriched fraction and its membrane preparation from tissue B was much larger than that from tissue A. A certain amount of the reaction product of K⁺-pNPPase activity was seen on glial plasma membrane within tissue B but not on that from tissue A. The above findings suggest that a glial Na⁺,K⁺-pump within actively firing epileptogenic cortex may be modified to increase in its activity.     

The effects of long term Tranilast administration on bronchial hypersensitivity in asthmatics

Tranilast is an oral antiallergic agent developed in Japan. This study investigated the effect of prolonged administration of Tranilast on the bronchial sensitivity of 18 asthmatic subjects. They were treated for either less than 3 months or more than 3 months continuously. Methacholine loading testing was used to assess bronchial reactivity, and the respiratory parameters were recorded on an Astograph. Patients treated for longer than 3 months showed a significant decrease in bronchial sensitivity (p less than 0.05). The anticholinergic and bronchodilatory properties of Tranilast were also investigated in 8 subjects. No significant anticholinergic or bronchodilatory effects were observed following a single oral dose of 100 mg of Tranilast.