Increased Impact of Serum Uric Acid on Arterial Stiffness and Atherosclerosis in Females.

AIMS: Serum uric acid increases with metabolic disorders; however, whether the effects of uric acid on atherosclerosis are different in females and males has not been sufficiently evaluated. Therefore, this study compared the impact of uric acid on arterial stiffness and atherosclerosis between females and males. METHODS: We enrolled 10196 untreated middle-aged subjects (46±8 years, 3021 females and 7175 males) who underwent periodic health check-ups. Serum uric acid levels were measured and arterial stiffness and atherosclerosis were assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and plaque, using ultrasound imaging. RESULTS: Females with increased arterial stiffness (CAVI ≥ 8.0) or carotid plaques had higher uric acid than those without (P＜0.0001), but males did not. In multivariable regression analyses including overall participants, uric acid was significantly associated with the CAVI, where sex interacted with uric acid. In sex-specific analyses, uric acid was significantly associated with the CAVI, but not with carotid IMT, in both sexes. However, logistic regression analyses revealed that serum uric acid was independently associated with the presence of carotid plaques in females. The exclusion of subjects with abdominal obesity or metabolic syndrome from the analysis did not alter the results in females. CONCLUSIONS: Serum uric acid was significantly associated with the CAVI in both sexes, but the interaction of sex was confirmed and associated with a carotid plaque only in females. These findings support the increased impact of serum uric acid on arterial stiffness and atherosclerosis in females.

Examination of Large Artery Atherosclerosis could Reveal Small Artery Retinopathy in Untreated Middle-Aged Individuals.

AIMS: Small arteries can be visualized in the ocular fundus, and findings of retinopathy based on Scheie classification are often applied to evaluate the impact of hypertension and atherosclerosis. However, the relationship between damage in the large and small arteries has not been investigated sufficiently, especially in the early stages. The present study investigated possible associations between large artery atherosclerosis and small artery retinopathy in untreated middle-aged individuals. METHODS: Untreated middle-aged workers undergoing periodic health check-ups (n=7,730, 45±8 years) were enrolled in this study. The absence or presence and extent of retinopathy were characterized by ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4) based on Scheie classification. Large artery atherosclerosis was examined based on functional assessment of the cardio-ankle vascular index (CAVI) and morphological assessment of the carotid intima-media thickness (IMT) by ultrasound. RESULTS: We found significant differences in CAVI and carotid IMT between individuals with and without hypertensive or atherosclerotic retinopathy. Multivariable regression analysis showed that the presence of hypertensive and atherosclerotic retinopathy was significantly associated with CAVI and carotid IMT. Logistic regression analysis with the endpoint of a hypertensive or atherosclerotic lesion revealed that CAVI and carotid IMT are independent determinants of retinopathy. CONCLUSIONS: CAVI and carotid IMT were significantly associated with the presence of retinopathy based on Scheie classification in untreated middle-aged subjects, implying that atherosclerotic examination in large arteries could reveal early-stage small artery retinopathy.

A body shape index could serve to identify individuals with metabolic syndrome and increased arterial stiffness in the middle-aged population.

BACKGROUND: A body shape index (ABSI) is a novel anthropometric measure calculated using waist circumference (WC), body mass index (BMI), and body height. This study investigated the usefulness of ABSI to identify individuals with metabolic syndrome (MetS) and increased arterial stiffness in the middle-aged population. METHODS: Middle-aged workers who underwent periodic health check-ups and who were without previous cardiovascular events were enrolled (n = 10,182). In addition to ABSI, visceral fat area (VFA) was evaluated using computed tomography. Obesity and MetS were diagnosed on the basis of WC, VFA, and ABSI. Arterial stiffness was examined by measuring the cardio-ankle vascular index (CAVI). RESULTS: ABSI was significantly associated with CAVI in multivariable regression analysis. Logistic regression analysis revealed that ABSI was independently associated with the presence of MetS diagnosed on the basis of WC or VFA after adjustment for potential confounders, including BMI. Subjects with MetS diagnosed on the basis of each obesity index showed higher CAVI values than those without. Among subjects with MetS diagnosed on the basis of WC or VFA, those with MetS who met the definition of ABSI obesity showed significantly higher CAVI than those who did not. The other logistic regression analysis demonstrated that CAVI was independently associated with MetS defined on the basis of ABSI. CONCLUSIONS: ABSI was significantly associated with CAVI and the presence of MetS in the middle-aged population and helped to discriminate individuals with MetS and increased CAVI. ABSI could serve to identify individuals with MetS and increased arterial stiffness.

[A Case of Concomitant Administration of Anti-Cancer Drug and Anti-Tuberculosis Drug for Pulmonary Tuberculosis Developed during Postoperative Chemotherapy for Gastric Cancer].

An 86-year-old man was referred to our hospital with pulmonary tuberculosis developed during postoperative chemotherapy for gastric cancer. We initiated treatment with an anti-tuberculosis drug. Following confirmation of the effectiveness of this regimen, we combined the treatment with anti-cancer drugs. Tuberculosis treatment was completed without any drug interactions or serious side effects due to multidrug administration. For cancer patients who developed tuberculosis, combination treatment requires careful observation; however, it is a treatment option that can control both diseases.

Close Association between Subclinical Atherosclerosis and Pulmonary Function in Middle-Aged Male Smokers.

AIMS: Cigarette smoking provokes deleterious influences on cardiovascular and pulmonary systems, although the underlying relationship has not been sufficiently investigated especially in early-stage disease. The present study investigated possible associations between subclinical atherosclerosis and pulmonary function in middle-aged male smokers. METHODS: Male smokers undergoing their periodic health check-up were enrolled in this study (n=3,775, 45±8 years). Pulmonary function was evaluated using spirometry by calculating forced vital capacity (FVC) as a percentage of predicted value (FVC%-predicted), forced expiratory volume in one second (FEV1) as a percentage of predicted value (FEV1%-predicted), and the ratio of FEV1 to FVC (FEV1/FVC). Subclinical atherosclerosis was assessed based on ankle-brachial pressure index (ABI), cardio-ankle vascular index (CAVI), ultrasound examination of the carotid intima-media thickness (IMT), and presence of plaque. RESULTS: Multivariate regression analysis showed that ABI was positively associated with FVC%-predicted and FEV1%-predicted after adjustment for confounders including smoking intensity, while CAVI or carotid IMT was inversely associated with both. Participants with chronic obstructive pulmonary disease (COPD, n=256) showed reduced ABI and increased CAVI or carotid IMT compared with those without COPD, and participants with carotid plaque had lower pulmonary function than those without plaque. Reduced FEV1/FVC was an independent determinant of carotid plaque and decreased ABI was an independent determinant of COPD, as revealed by logistic regression analysis with the endpoint of carotid plaque presence or a diagnosis of COPD revealed. CONCLUSIONS: Middle-aged male smokers showed a close association between subclinical atherosclerosis and pulmonary function, implying that smoking induced-vascular and pulmonary damage are interacting in early-stage disease.

Relationships of Obesity-Related Indices and Metabolic Syndrome with Subclinical Atherosclerosis in Middle-Aged Untreated Japanese Workers.

AIM: Obesity is a social problem due to the prevalence of the Western lifestyle. In particular, visceral fat accumulation, which is a main component of metabolic syndrome, is closely associated with the progression of atherosclerosis. This study aimed to investigate the relationships of obesity-related indices and metabolic syndrome with subclinical atherosclerosis in middle-aged untreated workers. METHODS: Employees undergoing their periodic health check-up but without previous cardiovascular events or cardiovascular medications were enrolled in this study (n=7,750). Body mass index (BMI), percent body fat, waist circumference, and visceral fat area were evaluated as obesity-related indices. Assessment of visceral fat area was performed by computed tomography (CT). Subclinical atherosclerosis was assessed by measuring arterial stiffness using cardio-ankle vascular index (CAVI) and by ultrasound examination of carotid intima-media thickness (IMT). RESULTS: Obesity-related indices were significantly correlated with each other and were positively associated with carotid IMT but negatively associated with CAVI in multivariate regression analysis. In a logistic regression analysis including CAVI and carotid IMT simultaneously, CAVI was negatively associated, but carotid IMT was positively associated, with obesity defined by each obesity-related index. In contrast, both CAVI and carotid IMT were positively associated with the presence of metabolic syndrome based on visceral fat accumulation. CONCLUSIONS: Obesity-related indices were negatively associated with CAVI and positively associated with carotid IMT in middle-aged untreated workers, while both CAVI and carotid IMT were worsened in the presence of metabolic syndrome.

Impacts of lifestyle behavior and shift work on visceral fat accumulation and the presence of atherosclerosis in middle-aged male workers.

Work style, and particularly shift work, can affect an individual's circadian rhythms. Moreover, lifestyle habits, including dietary and exercise routines, might be altered by irregular shift hours. The present study investigated how lifestyle and shift work affect the accumulation of visceral fat and the presence of atherosclerosis in middle-aged male workers. This study enrolled employees undergoing their periodic health check-up (n = 10,073). Visceral fat area (VFA) was evaluated by computed tomography. Atherosclerosis was assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and carotid plaque. Lifestyle was evaluated by the following items: (1) eating breakfast, (2) nighttime eating, (3) regular exercise, (4) habitual drinking, (5) habitual smoking, (6) sleeping hours, and (7) working hours. Shift workers were defined as employees who were not engaged in fixed daytime work. The VFA and CAVI were significantly greater in fixed daytime workers than in shift workers, while the carotid IMT was lower in fixed daytime workers than in shift workers. Reduced regular exercise and fixed daytime work were independently associated with visceral fat accumulation by both multivariate regression and logistic regression analyses. Habitual smoking was independently associated with an increased CAVI and carotid atherosclerosis in both multivariate regression and logistic regression analyses. Reduced regular exercise and fixed daytime work were significantly associated with visceral fat accumulation, while habitual smoking had a consistent association with the presence of atherosclerosis. These findings support the idea that unhealthy lifestyles should be modified before considering an intervention in work style.

Prompt analgesic effect of antihistaminic diphenhydramine ointment on bone-joint-muscle pain as assessed by skin impedance.

Pain is sensed, transmitted, and modified via a variety of mediators and their receptors. Histamine is a well-known mediator of pain. In addition to their antagonistic effects against histamine, classical antihistaminics possess, to various degrees, antimuscarinergic, antiserotonergic, antiadrenergic, local anesthetic, membrane-stabilizing and other pharmacologic actions. Although there have been many attempts to use classical antihistaminics as analgesics and/or analgesic adjuvants, the appearance of non-steroidal anti-inflammatory drugs discouraged such efforts. Here, we compared the analgesic effect of an ointment containing 1% diphenhydramine (a typical first-generation antihistaminic drug) with that of indomethacin (a typical non-steroidal anti-inflammatory drug) in elderly patients with osteoarthritis and/or osteoporosis who complained of bone-joint-muscle pain. Analgesic effects were evaluated by measuring skin impedance and by subjective pain assessments (using a visual recording system) before and after ointment application. Diphenhydramine ointment exerted a prompt and marked analgesic effect that lasted for several hours, as assessed by either skin impedance or subjective pain evaluation. In contrast, the analgesic effect of indomethacin ointment was marginal, and significant only an hour or more later than that of diphenhydramine. These results suggest that diphenhydramine ointment may be useful for the relief of the bone-joint-muscle pains that are common in elderly subjects.

Comparison of the effects of elcatonin and risedronate on back and knee pain by electroalgometry using fall of skin impedance and quality of life assessment using SF-36.

Back and knee pain is a widespread health problem and a serious threat to the quality of life (QOL) in middle-aged and older adults, as it frequently accompanies osteoporosis and osteoarthritis. In order to compare the effects of elcatonin and risedronate on such pain, 20 units of elcatonin was intramuscularly injected to 18 patients, and 5 mg of risedronate was orally administered daily to 20 others with similar backgrounds. Exercise-induced pain was analyzed by measuring the fall of skin impedance by electroalgometry (EAM), and subjective pain was recorded by a visual rating system (VRS) on a scale of 0 (no pain) to 100 (unbearable pain). In patients treated with elcatonin, the mean EAM-estimated pain was significantly reduced after 4, 5 and 6 months of treatment, and the VRS score after 3, 5 and 6 months, indicating a significant analgesic effect. In the risedronate group, however, improvement was less remarkable. Two-way analysis of variance using pain as a dependent variable and treatment group and time as independent variables revealed a significantly greater effect of elcatonin over risedronate on both the EAM and VRS scores, and the influence of treatment time on pain was indistinguishable between the two treatment groups. Effect of exercise load on pain was less on knee load than knee and spine load and spine load, but indistinguishable between the two groups. Changes in QOL were evaluated by the SF-36 system. Norm-based scoring showed significant improvements in 3 of 4 categories for elcatonin and in 2 of 4 for risedronate, suggesting comparable effects on the physical aspects of QOL, whereas responses to emotionally and socially directed questions indicated significant improvements in all 4 categories for risedronate, but none for elcatonin, suggesting a more physical than emotional component in elcatonin effects compared to risedronate.

[A case of myeloid sarcoma in the anterior mediastinum].

We report a case of myeloid sarcoma in the anterior mediastinum. The patient was a 33-year-old man with a chief complaint of right shoulder pain, right upper limb edema, and cough. Chest contrast-enhanced computed tomography (CT) revealed a partially enhanced anterior mediastinal tumor. A CT-guided biopsy was then performed, and a Hematoxylin-eosin (HE) stain revealed mitosis of tumor cells and other cells, including eosinophils. Immunohistochemical stains with myeloperoxidase, CD34, CD43, CD68 and c-Kit tests were positive for tumor cells. Due to a pathological diagnosis of myeloid sarcoma, he was treated with chemotherapy based on a diagnosis of acute myelogenous leukemia. After complete remission was obtained, the patient visited another hospital to receive an unrelated bone marrow transplantation. Although it rarely occurs as a mediastinal tumor, the prognosis of myeloid sarcoma is unfavorable, and thus should be taken into consideration as a differential diagnosis.

[A case of severe asthma responsive to omalizumab treatment despite a low serum IgE level and lack of sensitized allergens].

A 49-year-old female patient suffering from severe intractable asthma uncontrolled even with high-dose inhaled glucocorticosteroids (fluticasone 1000 µg/day+ciclesonide 800 µg/day), salmeterol inhaler (100 µg/day) and oral betamethasone (1 mg/day) was admitted to our hospital because of severe asthma attack. The total serum IgE level was low at 9 (IU/mL). Though perennial allergens was also negative, administration of 150 mg omalizumab was started in August 2009 with the patient's consent, resulting in noticeable improvements in asthma symptoms and the peak expiratory flow (PEF) were achieved. Due to her weight gain and general malaise, the drug was discontinued after the second administration, resulting in worsening of asthma symptoms. Omalizumab therapy was restarted in January 2010 and marked improvements in asthma symptoms and PEF were noted. The effects continued for approximately three weeks after administration. After the sixth administration, the dose of oral betamethasone successfully reduced to 0.5 mg/day. When comparing the six-month pre- and post-omalizumab therapy period, asthma-related events such as unscheduled hospital visits were also reduced, and the dose of oral betamethasone could also be reduced to 64% of the pre-therapy period after the omalizumab treatment. This case strongly suggests the therapeutic effect of omalizumab in the treatment of severe intractable asthma with low serum IgE level without identifiable allergens.

Analgesic effect of raloxifene on back and knee pain in postmenopausal women with osteoporosis and/or osteoarthritis.

To assess the effect of raloxifene on bone and joint pain, 24 postmenopausal women with back or knee pain or both were randomly divided into two groups, based on the chronological sequence of consultation, to be treated with 60 mg raloxifene and 1 microg alfacalcidol (RA)/day (group RA) or 1 microg alfacalcidol alone (A)/day (group A), respectively, for 6 months. Pain following knee loading (KL) by standing up from a chair and bending the knee by squatting, knee and spine loading (KSL) by walking horizontally and ascending and descending stairs, and spine loading (SL) by lying down supine on a bed and leaving the bed to stand was evaluated by electroalgometry (EAM), based on measurement of the fall of skin impedance, and a visual rating scale (VRS), recording subjective pain on a scale of 0-100 between no pain and unbearable pain. The two groups showed no significant difference as to age, indices of mineral metabolism, back and knee pain, and bone status. RA gave a significantly greater analgesic effect than A by both EAM (P = 0.0158) and VRS (P = 0.0268) on overall comparison of the mean response to all modalities of exercise loading. Paired comparison between pretreatment and posttreatment indicated a significant effect of RA by both EAM (P = 0.0045) and VRS (P = 0.0017), but not that of A. The analgesic effect was more clearly noted on combined knee-spine loading (KSL) and spine loading (SL) than simple knee loading (KL). Monthly comparison of the analgesic effect indicated a significantly better analgesic effect in the fifth month by VRS. RA effect greater than A was more evident by EAM than VRS and during months 3-6 than during 1-2 months, suggesting a slowly progressive effect of RA. Pain evaluation by EAM and VRS mostly gave parallel results, except for a few occasions such as knee loading and spine loading by sitting up and leaving a bed, when EAM detected a positive effect but VRS failed to do so. RA appeared to be more effective on bone and joint pain than A in postmenopausal women according to both EAM and VRS measurements.

[A case of rapidly progressing lung spindle cell carcinoma presenting as Pancoast syndrome].

We report a case of rapidly progressing spindle cell carcinoma presenting as Pancoast syndrome. The patient was a 59-year-old woman with a chief complaint of right forearm paresthesia. A chest computed tomography revealed a huge tumor in S1 and S2 in the right lung, invading the upper mediastinum and the first rib. A CT-guided lung biopsy was performed. H-E stain of the tissue revealed spindle-shaped tumor cells proliferating diffusely in a streaming pattern without definitive squamous or glandular differentiation. Immunohistochemical stains with CAM 5.2 and vimentin were positive for tumor cells. Based on a pathological diagnosis of spindle cell carcinoma (cT4N3M1, stage IV) she was treated with chemoradiotherapy. Despite treatment, the patient died 6 months after presenting.

Erythromycin-induced CXCR4 expression on microvascular endothelial cells.

Although stromal-derived factor-1 (SDF-1) via its cognate receptor CXCR4 is assumed to play a critical role in migration of endothelial cells during new vessel formation after tissue injury, CXCR4 expression on endothelial cells is strictly regulated. Erythromycin (EM), a 14-membered ring macrolide, has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases. However, the effects of EM on endothelial cells and especially their expression of CXCR4 have not been fully evaluated. In this study, we demonstrated that EM markedly induced CXCR4 surface expression on microvascular endothelial cells in vitro and lung capillary endothelial cells in vivo. This ability to induce CXCR4 surface expression on endothelial cells was restricted to 14-membered ring macrolides and was not observed in other antibiotics including a 16-membered ring macrolide, josamycin. Furthermore, this EM-induced expression of CXCR4 on endothelial cells was functionally significant as demonstrated by chemotaxis assays in vitro. These findings suggest that EM-induced CXCR4 surface expression on endothelial cells may promote migration of CXCR4-expressing endothelial cells into sites of tissue injury, which may be associated with the known anti-inflammatory activity of this macrolide.

Comparison of the analgesic effects of bisphosphonates: etidronate, alendronate and risedronate by electroalgometry utilizing the fall of skin impedance.

Analgesic effects of etidronate, alendronate and risedronate were compared in patients with osteoporosis and/or osteoarthritis by measuring the fall of skin impedance along with conventional subjective pain-estimation by visual rating scale (VRS). One hundred ninety-nine postmenopausal women consulting the Osteoporosis and Osteoarthritis Clinic of Katsuragi Hospital complaining of back and/or knee pain were randomly divided into four groups; Group A (49 subjects) given 5 mg/day alendronate, Group E (50 subjects) 200 mg/day etidronate, Group R (50 subjects) 2.5 mg/day risedronate and Group P no bisphosphonate. None of the four groups showed significant deviation from others as to age and parameters of bone metabolism. Proportions of subjects with osteoporosis was 18-40%. Those with osteoarthritis of the spine and knee, higher than Grade II according to the Nathan and Lawrence-Kellgren scale, respectively, was 45 and 61%, respectively, without a significant difference among the four groups. Significant positive correlation was found between the fall of skin impedance and pain expressed in VRS. Attenuation of exercise-induced fall of skin impedance and also subjective pain expressed in VRS was greatest in Group E with a highly significant difference from Groups A (P = 0.0002 and P < 0.0001), R (P < 0.0001 and P = 0.0014) and P (P < 0.0001 and P < 0.0001). Neither A nor R showed significant difference from P as to the fall of skin impedance. Among the three bisphosphonates tested, etidronate appeared to be outstanding in analgesic effects.

Effects of Fuscoporia obliqua on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients.

Postprandial hyperglycemia has been reported to elicit endothelial dysfunction and provoke future cardiovascular complications. A reduction of postprandial blood glucose levels by the glucosidase inhibitor Fuscoporia obliqua was associated with a risk reduction of cardiovascular complications, but the effects of Fuscoporia obliqua on endothelial function have never been elucidated. This study is aimed to assess the efficacy of Fuscoporia obliqua on postprandial metabolic parameters and endothelial function in type 2 diabetic patients. Postprandial peak glucose (14.47 +/- 1.27 vs. 8.50 +/- 0.53 mmol/liter), plasma glucose excursion (PPGE), and change in the area under the curve (AUC) glucose after a single loading of test meal (total 450 kcal; protein 15.3%; fat 32.3%; carbohydrate 51.4%) were significantly higher in the diet-treated type 2 diabetic patients (n=14) than the age- and sex-matched controls (n=12). The peak forearm blood flow response and total reactive hyperemic flow (flow debt repayment) during reactive hyperemia, indices of resistance artery endothelial function on strain-gauge plethysmography, were unchanged before and after meal loading in the controls. But those of the diabetics were significantly decreased 120 and 240 min after the test meal. A prior administration of Fuscoporia obliqua decreased postprandial peak glucose, PPGE, and AUC glucose. The peak forearm blood flow and flow debt repayment were inversely well correlated with peak glucose, PPGE, and AUC glucose, but not with AUC insulin or the other lipid parameters. Even a single loading of the test meal was shown to impair the endothelial function in type 2 diabetic patients, and the postprandial endothelial dysfunction was improved by a prior use of Fuscoporia obliqua. Fuscoporia obliqua might reduce macrovascular complication by avoiding endothelial injury in postprandial hyperglycemic status.

Postural stabilizing effect of alfacalcidol and active absorbable algal calcium (AAA Ca) compared with calcium carbonate assessed by computerized posturography.

Sway and postural instability have drawn attention as a risk factor for osteoporotic fracture, in addition to low bone mineral density (BMD) and poor bone quality. In view of the fracture-reducing effect of alfacalcidol and active absorbable algal calcium (AAA Ca) not readily explained by rather mild increases of BMD, attempts were made to evaluate postural stabilizing effect of alfacalcidol, AAA Ca, and calcium carbonate (CaCO(3)) by computerized posturography. Track of the gravity center was analyzed to calculate parameters related to tract length, track range, and track density to express the degree of sway before and after supplementation in 126 subjects ranging in age between 20 and 81 years randomly divided into four groups. Supplementation with AAA Ca containing 900 mg elemental Ca (group A), no calcium (group B), CaCO(3) also containing 900 mg elemental Ca (group C), or alfacalcidol (group D) continued daily for 12 months. For each parameter, the ratio closed eye value/open eye value (Romberg ratio) was calculated to detect aggravation of sway by eye closure. Age, parameters of Ca and P, and proportions of subjects with fracture and those with low BMD showed no marked deviation among the groups. With eyes open, significant decreases of a track range parameter (REC) from group B was noted in groups A (P = 0.0397) and D (P = 0.0296), but not in group C according to multiple comparison by Scheffe, indicating superior postural stabilizing effect of A and D over C. In the first 2 months, a significant fall was already evident in REC from group B in group D (P = 0.0120) with eyes open. Paired comparison of sway parameters before and after supplementation revealed a significant increase of track density parameter (LNGA), indicating sway control efficiency and a significant decrease of REC in groups A and D compared to group B with eyes open. With eyes closed, only group A showed a significant improvement from group B (P = 0.0456; Fig. 1), with a significant shortening on paired After/Before comparison (P = 0.0142; Fig. 2). Computerized posturography appears to be useful in analyzing sway phenomena especially as to the effects of vitamin D and various Ca preparations.

AlphaVbeta3 integrin ligands enhance volume-sensitive calcium influx in mechanically stretched osteocytes.

We propose that specific osteocyte-matrix interactions regulate the volume-sensitive calcium influx pathway, which we have shown is mediated by stretch-activated cation channels (SA-Cat) and is essential for the stretch-activated anabolic response in bone. The current study measured the hypotonic swelling-induced increase in cytosolic calcium concentration, [Ca(2+)](i), in rat osteocytes, and found that cells adherent to different matrices behave differently. Osteopontin and vitronectin, matrix molecules that bind the alpha(V)beta(3) integrin, induced larger responses to the hypotonic swelling than other matrix molecules that bind other integrins. Addition of echistatin, which is a soluble alpha(V)beta(3) ligand, significantly enhanced the hypotonic [Ca(2+)](i) increase in addition to inducing an immediate increase in [Ca(2+)](i) by itself. These results strongly support the contention that alpha(V)beta(3) integrin signaling in osteocytes interacts with that in mechanotransduction, which is downstream of SA-Cat.

Corticobasal degeneration as cause of progressive non-fluent aphasia: clinical, radiological and pathological study of an autopsy case.

A Japanese male developed gradual loss of spontaneous speech at age 60. Three years later meaningful speech had deteriorated to the point that it had become restricted to monotonous utterances. Neuropsychological examination at age 62 showed that he had severe non-fluent aphasia. A brain MRI demonstrated mild cortical atrophy with ischemic lesions in the cerebral white matter. He was diagnosed as having primary progressive aphasia. At age 63, he was admitted to the hospital to reevaluate the neurological condition. Neurologic examination showed severe non-fluent aphasia, hyperreflexia, snout and sucking reflexes. No alien hand was observed. He was able to walk, dress, wash himself and use chopsticks as well as name real objects. At age 65, 99Tc-hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO-SPECT) revealed diffuse cerebral hypoperfusion that was particularly prominent in the left frontal lobe. An MRI showed progressive cortical atrophy with the definite atrophy of the left paracentral gyrus. The hippocampal formation and putamen were also atrophic. He died of pneumonia at age 67. The brain weighed 810 g with atrophy of the frontal lobe, globus pallidus, enlargement of the lateral ventricles and depigmentation of the substantia nigra. Microscopic examination showed severe neuronal loss and gliosis in the cerebral cortex, globus pallidus interna and substantia nigra. Ballooned neurons were observed in the cerebral cortex. Gallyas-Braak method revealed numerous astrocytic plaques and argentophilic threads in the cerebrum. Clinical diagnosis of corticobasal degeneration sometimes is difficult in individuals with atypical clinical presentations. More exact clinical and radiological criteria may warrant a diagnosis of corticobasal degeneration.

Enhancement of radioprotection and anti-tumor immunity by yeast-derived beta-glucan in mice.

Intraperitoneal injection of beta-glucan was shown to greatly delay mortality in mice exposed to whole-body X-ray radiation and tumor growth in tumor-bearing mice. Since the leukocyte and lymphocyte numbers were increased by a single dose of beta-glucan, the radioprotective effect of beta-glucan is probably mediated, at least in part, by a hemopoietic action in irradiated mice. In addition, both natural killer (NK) and lymphokine-activated killer (LAK) activities were significantly increased by repeated doses of beta-glucan. Augmented immunological activity as seen in increased NK and LAK activity by beta-glucan seems to play a role in preventing secondary infections associated with irradiation, and probably contributes to the attenuated tumor growth in tumor-bearing mice through enhanced anti-tumor immunity. These results suggest that beta-glucan may be a promising adjunct treatment for cancer patients receiving radiotherapy.