αVβ3 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, [Ca²⁺]_i, in rat osteocytes, and found that cells adherent to different matrices behave differently. Osteopontin and vitronectin, matrix molecules that bind the α_Vβ₃ integrin, induced larger responses to the hypotonic swelling than other matrix molecules that bind other integrins. Addition of echistatin, which is a soluble α_Vβ₃ ligand, significantly enhanced the hypotonic [Ca²⁺]_i increase in addition to inducing an immediate increase in [Ca²⁺]_i by itself. These results strongly support the contention that α_Vβ₃ integrin signaling in osteocytes interacts with that in mechanotransduction, which is downstream of SA-Cat.     

Effects of anti-parathyroid hormone-related protein monoclonal antibody and osteoprotegerin on PTHrP-producing tumor-induced cachexia in nude mice

We have previously demonstrated that parathyroid hormone-related protein (PTHrP) is a cachexia inducer, but it is still not known what PTHrP effects on target tissues induce the cachexia. Therefore, we examined the effects of anti-PTHrP antibody and osteoprotegerin (OPG) on PTHrP-producing tumor-induced cachexia. Nude mice bearing PTHrP-producing human lung cancer cells (HARA-B) exhibited cachexia with hypercalcemia 3–4 weeks after inoculation, accompanied by losses in body, adipose tissue, and muscle weight. OPG ameliorated hypercalcemia, as did neutralization of PTHrP with antibody; and it increased both body and adipose tissue weights. These increases in body and adipose tissue weight, however, were significantly less than those in mice treated with anti-PTHrP antibody. Simultaneous administration of OPG and anti-PTHrP antibody caused significant increases in body, adipose tissue, and muscle weight, along with an immediate decrease in blood ionized calcium levels. The increase in body weight was similar to that observed in mice treated with anti-PTHrP antibody alone, and the decrease in the blood ionized calcium levels was significantly greater than that in mice treated with OPG or anti-PTHrP antibody alone. These results suggest that an effect of PTHrP on target tissues other than hypercalcemia is involved in the development of cachexia. Expression of cachexia-inducing proinflammatory cytokines (interleukin-6 and leukemia inhibitory factor) is stimulated by PTHrP. This might be a mechanism by which PTHrP produces tumor-induced cachexia. It is also suggested that OPG and anti-PTHrP antibody synergistically act to ameliorate hypercalcemia, although the mechanism responsible for this is unclear.     

Surgical treatment for multiple colorectal metastases: efficacy of ablation therapy

Either hepatic resection, microwave coagulonecrotic therapy (MCN), or a combination of liver resection and MCN was performed in 166 patients with liver metastases from colorectal cancer. In 53 patients who underwent liver resection, the 1-, 3-, and 5-year actual survival rates were 85.0%, 51.2%, and 42.2%, respectively. In 77 who underwent MCN, the 1-, 3-, and 5-year actual survival rates were 82.8%, 46.7%, and 36.0%, respectively. In 34 who underwent both liver resection and MCN, the 1-, 3-, and 5-year actual survival rates were 84.2%, 41.6%, and 21.1%, respectively. The survival rates among the three groups did not differ significantly. Of 166 patients with liver metastases, 44 showed multiple liver metastases (H3). Of 44 patients with multiple liver metastases, 27 underwent MCN (mean tumor diameter 27.2 mm, mean number of tumors 11.2), and the 1-, 3-, and 5-year actual survival rates were 73.1%, 31.3%, and 25.1%, respectively. Of 44 patients with multiple liver metastases, 17 underwent both liver resection and MCN (mean tumor diameter 41.9mm, mean number of tumors 8.1), and the 1-, 3-, and 5-year actual survival rates were 66.3% and 14.7%, respectively. To perform MCN more effectively in the treatment of liver metastases, surgical margins around tumors should be from 10 mm to 15 mm, and both the feeding artery and drainage vein should be coagulated before MCN.     

The clinical course of microalbumiuria in 4 burn patients

BACKGROUND: In burn patients, microvascular permeability is increased. It is difficult to decide the time to administer albumin because it may induce pulmonary edema in the re-filling period. One report shows that microalbuminuria is correlated with endothelial injury and systemic microvascular permeability. METHODS: We measured urinary albumin/creatinine ratio (ACR) in 4 burn patients for 48 hours after injury. RESULTS: In all patients, ACR was elevated in the early period after injury. Moreover, ACR in 2 severe burn patients with burn total body area of over 30% was above the normal range. CONCLUSIONS: The present results show that ACR seems to be correlated with the level of microvascular permeability in 4 burn patients. We conclude that ACR may be a useful indicator to decide the time to administer albumin to a burn patient. However, further investigation is required to decide the threshold value of ACR in a severe burn patient whose ACR are kept above the normal range in the long-term.     

Anesthetic management of a patient with mitochondrial encephalomyopathy under total intravenous anesthesia

This report describes a patient with mitochondrial encephalomyopathy who underwent tracheostomy under total intravenous anesthesia. This 15-year-old girl had been suffering from aspiration pneumonia repeatedly. Anesthesia was induced with propofol (30 mg) and fentanyl (50 microg), and the trachea was intubated without a muscle relaxant. The patient was mechanically ventilated also without a relaxant, and anesthesia was maintained with a continuous infusion of propofol 4-10 mg x kg(-1) x hr(-1) and a bolus injection of fentanyl 25 microg. Bispectral index (BIS) was monitored and maintained at 15-65. The patient showed smooth recovery from anesthesia, and the BIS value returned to the pre-anesthetic level 15 minutes after completion of the anesthesia. Her postoperative course was uneventful. We conclude that total intravenous anesthesia by propofol and fentanyl is a preferable method for the management of the patient with mitochondrial encephalomyopathy.     

Low adjusted serum ionized calcium concentration shortly after birth predicts poor outcome in neonatal hypoxic-ischemic encephalopathy

AIM: Hypoxic-ischemic reperfusion injury causes either necrosis or apoptosis, and the influx of ionized calcium into cells is the major cause of both types of cell death. The aim of this study was to investigate whether or not the serum ionized calcium concentration in neonates with hypoxic-ischemic encephalopathy (HIE) could be used to predict their outcome. METHODS: Serum samples were obtained shortly after birth from 20 HIE neonates who had not urinated or received treatment with calcium. Serum ionized calcium concentrations were adjusted for pH using a correction formula. Twelve neonates without any disease were selected as a control. The results were compared between nine HIE neonates who made a full recovery, 11 who died or had neurologic deficits, and 12 normal neonates. RESULTS: Considered together, the two HIE groups had lower serum ionized calcium concentrations (1.05 +/- 0.10 mmol/L) than the control group (1.22 +/- 0.07 mmol/L; P < 0.0001). Moreover, serum ionized calcium concentrations in the group with the poor outcome (0.99 +/- 0.07 mmol/L) were lower than those in the group that made a full recovery (1.13 +/- 0.06 mmol/L; P=0.0016). CONCLUSIONS: The serum ionized calcium concentrations shortly after birth were significantly lower in neonates with HIE who had a poor outcome. Low concentrations may reflect multiple organ damage, particularly involving the brain.     

Case of a giant mucinous ovarian carcinoma with bone metastasis

We report the case of a 51-year-old Japanese woman with a giant (50.75-kg) ovarian tumor. The histopathologic diagnosis was mucinous cystadenocarcinoma. After surgery, the patient was intubated and connected to a respirator for 8 days. Thereafter, she was diagnosed with bone metastasis to the hip bone and the femur.     

Nuclear and Cytoplasmic Inclusion Bodies in Pinealocytes of the Cotton Rat, Sigmodon hispidus: An Electron Microscopic Study

Electron microscopic observations on pinealocytes of cotton rats (Sigmodon bispidus) killed in October revealed the presence of cytoplasmic inclusion bodies (CIBs) and two kinds of nuclear inclusions--coiled bodies and granular inclusion bodies. These inclusions were usually not bounded by a membrane. CIBs showed round or irregular profiles and consisted of granular and filamentous materials of moderate electron opacity intermingled with electron-lucent areas. Nuclear granular inclusions appeared as homogeneous or heterogeneous granules of variable electron opacity, which usually exhibited round profiles of variable diameters and consisted of granular and filamentous elements. Electron-opaque granules were observed in perinuclear spaces, dilated cisternae of rough endoplasmic reticulum, as well as in the central portion of CIBs. In CIBs containing granules, the peripheral region was composed of the moderately electron-opaque substance seen in usual CIBs, while the central core was occupied by a granular and filamentous substance and an intervening electron-lucent matrix. Since an electron-opaque granular substance in nuclei, perinuclear spaces, cisternae of rough endoplasmic reticulum, and the central portion of CIBs may occur concomitantly, the granules seen in these sites may be related. Coiled bodies were round in profile and were composed of electron-opaque strands consisting of granular and filamentous elements and intervening material of low electron opacity. This structure, frequently located in close proximity to the nuclear granular inclusions, may play a role in the formation of the intranuclear granules in cotton rat pinealocytes.