Potential of (99m)Tc-MIBI for detecting bone marrow metastases.

In this study, we evaluated the potential of (99m)Tc-hexakis-2-methoxyisobutylisonitrile (MIBI) for detecting bone metastases in comparison with a conventional bone tracer. METHODS: (99m)Tc-MIBI and (99m)Tc-hydroxymethylene diphosphonate (HMDP) scans were obtained from 99 patients with proven malignant diseases and suspected bone metastases. We compared 373 lesions that showed abnormal uptake on (99m)Tc-MIBI scans or (99m)Tc-HMDP scans (or both). RESULTS: Bone metastases were confirmed in 334 of 373 lesions. Thirty-nine lesions on (99m)Tc-HMDP scans had false-positive findings, but only 2 of these lesions had false-positive findings on (99m)Tc-MIBI scans. (99m)Tc-MIBI and (99m)Tc-HMDP scans were equivalent in 168 of 334 lesions (50.3%). (99m)Tc-MIBI scans correctly detected more lesions than (99m)Tc-HMDP scans: 284 lesions (85.0%) versus 218 lesions (65.3%) (P < 0.005), respectively. (99m)Tc-MIBI scans showed a markedly higher sensitivity for detecting metastases in the femur and humerus compared with (99m)Tc-HMDP scans: 97 of 98 lesions (99.0%) versus 35 of 98 lesions (35.7%) (P < 0.005) and 21 of 22 lesions (95.5%) versus 11 of 22 lesions (50.0%) (P < 0.005), respectively. (99m)Tc-HMDP scans of 17 patients showed no abnormal images. However, (99m)Tc-MIBI scans correctly detected bone metastases, and subsequent development of multiple lesions was observed on follow-up (99m)Tc-HMDP scans of 15 patients. (99m)Tc-MIBI scans were superior to (99m)Tc-HMDP scans in the detection of metastases attributed to breast cancer, multiple myeloma, and hepatoma. On the contrary, (99m)Tc-MIBI scans were less sensitive than (99m)Tc-HMDP scans for detecting bone metastases attributed to prostate cancer in the other skeletal sites except for femur and humerus. CONCLUSION: (99m)Tc-MIBI scans have better sensitivity for detecting bone metastases and provide more specific complementary findings than conventional bone scans. (99m)Tc-MIBI accumulation attributed to bone marrow metastases may occur at an early stage, before the bone remodeling process in the surrounding bone can be detected on conventional bone scans.     

Angiotensin II receptor antagonist attenuates expression of aging markers in diabetic mouse heart.

BACKGROUND: Diabetes mellitus is an independent risk factor for heart failure. Diabetes mellitus causes other age-related cardiovascular diseases. We assessed the hypothesis that hearts from diabetic animals are associated with accelerated aging processes. We also examined the effect of an angiotensin II receptor blocker (ARB) on the expression of senescence-associated molecules. METHODS AND RESULTS: We administered an ARB (candesartan 10 mg/kg per day) or saline to diabetic db/db or control db/+ mice. The treatment was started when mice were 10-weeks-old, and continued for 15 weeks. Systolic function was impaired in db/db mice and candesartan improved cardiac function. The amount of phosphorylated Akt and S6 was decreased in saline-treated db/db mice, and candesartan treatment partially preserved phosphorylation. The amount of p21, p27, p53 or Rb was increased in the heart tissue of saline treated db/db mice. Candesartan treatment completely suppressed the increases of p21, p27, p53 and Rb. CONCLUSIONS: An ARB improved cardiac function of diabetic animals, and this was accompanied by decreases of senescence-associated molecules in the myocardium. ARB may be a modality for heart failure patients with diabetes mellitus.     

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that the microtubule minus-end binding protein CAMSAP3 (calmodulin-regulated–spectrin-associated protein 3) plays a pivotal role in orienting the apical-to-basal polarity of microtubules in epithelial cells. In these cells, CAMSAP3 accumulated at the apical cortices, and tethered the longitudinal microtubules to these sites. Camsap3 mutation or depletion resulted in a random orientation of these microtubules; concomitantly, the stereotypic positioning of the nucleus and Golgi apparatus was perturbed. In contrast, the integrity of the plasma membrane was hardly affected, although its structural stability was decreased. Further analysis revealed that the CC1 domain of CAMSAP3 is crucial for its apical localization, and that forced mislocalization of CAMSAP3 disturbs the epithelial architecture. These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells.Microtubules play pivotal roles in fundamental cellular functions, including cell division, intracellular transport, and cell morphogenesis. They are dynamic structures with an intrinsic polarity of rapidly growing plus-ends and slowly growing minus-ends (1). In living cells, the microtubule minus-ends are stabilized by binding to specific molecules or structures, such as the γ-tubulin ring complex located at the centrosome (2). In epithelial cells, however, most microtubules do not emanate from the centrosome; instead, they are aligned along the apicobasal axis with their minus ends facing toward the apical domain (3–5). These observations suggest the presence of unidentified mechanisms that stabilize the minus ends of microtubules at apical regions. Such mechanisms have not yet been identified, although the potential involvement of microtubule-binding proteins, such as ninein, has been suggested (6).Although many proteins that modulate plus-end dynamics have been identified (7), how the minus-ends are controlled at noncentrosomal sites remains less well understood (2, 8–10). CAMSAP3 (also known as Nezha) is a member of the calmodulin-regulated–spectrin-associated proteins (CAMSAP)/Nezha/Patronin family proteins, which bind and stabilize the minus-ends of microtubules (11–18). In cultured mammalian cells, CAMSAP proteins have been shown to stabilize noncentrosomal microtubules in the cytoplasm or cell junctions (11, 14, 19, 20), suggesting their possible involvement in the spatial regulation of microtubule assembly in polarized cells, such as epithelial-specific longitudinal microtubule alignment.To date, no study has analyzed CAMSAP function in fully polarized epithelial cells, however. In the present study, we examined whether CAMSAP3 contributes to the epithelial-specific microtubule organization using intestinal epithelial cells. Our results demonstrate that CAMSAP3 plays a key role in tethering microtubules to the apical cortex in epithelial cells, and in turn regulates the positioning of organelles at their cytoplasm.     

Efficacy and safety of long-term oral falecalcitriol treatment in patients with renal osteodystrophy

We investigated, in a multicenter study, the efficacy and safety of long-term administration of falecalcitriol, a new active vitamin D₃, in patients with renal osteodystrophy of the osteitis fibrosa type associated with secondary hyperparathyroidism caused by chronic renal failure. Falecalcitriol was orally administered every day for 48 weeks. Administration was started at a dosage of 0.3 μg/day, and the dosage was changed whenever necessary according to serum calcium (Ca) level. As a result, significant inhibition of the bone resorption markers, i.e., intact parathyroid hormone (i-PTH), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), was observed from the 8th week, and the bone formation markers, i.e., total activity and bone fraction of alkaline phosphatase, were also significantly inhibited from the 12th week. The bone mineral density (BMD) change rate in the bones of the whole body determined by dual-energy X-ray absorptiometry remained almost constant. When subjects were stratified according to the inhibition rate of bone metabolic parameters, BMD tended to increase in the group with strong inhibition and to decrease in the group with weak inhibition. Mean serum Ca level significantly increased from 9.5 mg/dl, but mean level was subsequently maintained at about 10 mg/dl until the end of administration by adjustment of the doses. These findings suggested that falecalcitriol may inhibit and normalize accelerated bone metabolic turnover without inducing excessive increases in serum Ca level in secondary hyperparathyroidism. With respect to safety, no specific adverse reactions associated with the prolonged administration period were observed. Received: July 1, 1997 / Accepted: Aug. 29, 1997     

Spontaneous coronary artery dissection with left ventricular aneurysm--a case report of successful surgical repair

An aorto-coronary artery bypass operation combined with left ventricular aneurysmectomy was performed successfully in a 56-year-old man who had suffered spontaneous coronary artery dissection with left ventricular aneurysm. It is important to perform myocardial revascularization surgery even if the region for anastomosis is dissected.     

Effect of interferon α on calcium and bone metabolism in patients with chronic hepatitis

We investigated the changes of natural type of interferon-α (IFNα) on calcium and bone metabolism in patients with chronic hepatitis C. Natural IFNα was injected intramuscularly at daily doses of 6 million units for 2 weeks to 10 patients with chronic hepatitis caused by hepatitis C virus, and followed by 3-times-a-week administration for another 10 weeks. The markers for bone metabolism including serum bone-Gla protein (BGP) concentration and urinary excretion of pyridinolines (pyridinoline and deoxypyridinoline) were measured before and during the treatment. The twelve-week administration of IFNα reduced pyridinoline excretion from 39.7±13.3 (SD) pmol/μ mol · creatinine to 28.3±8.1 pmol/μ mol · creatinine (p<0.06), and that of deoxypyridinoline from 6.51±3.38 pmol/μ mol · creatinine to 3.91±2.07 pmol/μ mol · creatinine (p<0.01), although serum levels of BGP and parathyroid hormone (PTH) did not show any significant changes. The ratio of BGP/urinary pyridinoline increased from 0.098±0.074 to 0.198±0.093 at the end of 12th week (p<0.03), and that of BGP/deoxypyridinoline increased from 0.630±0.502 to 1.550±0.788 at 12th week (p<0.02). Serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) did not change significantly during the study. IFNα reduces bone resorption in contrast with insignificant effects on bone formation in patients with mild to moderate hepatitis. The effects on calcium and bone metabolism may give beneficial effects for patients with high turnover osteoporosis.     

A case of advanced esophageal cancer with suspected tracheoesophageal fistula that responded to chemoradiotherapy

Chemoradiotherapy combined cisplatin, 5-FU and radiation was carried out in an advanced esophageal cancer with suspected tracheoesophageal fistula after insertion of an expandable metallic stent. Regression of the primary tumor was observed, and oral intake could be started. Chemoradiotherapy after insertion of the expandable metallic stent was useful in this case of advanced esophageal cancer with suspected tracheoesophageal fistula.     

Undifferentiated spindle-cell carcinoma of the gallbladder: an immunohistochemical study

A case of undifferentiated spindle-cell carcinoma of the gallbladder is described. A 72-year-old man presented with right hypochondralgia and fever. Imaging studies revealed a well-demarcated solid tumor (with a necrotic center) in the gallbladder that invaded the liver and transverse colon. On gross examination of the surgical specimen, the cut surface of the polypoid tumor showed nodular invasive growth. Microscopically, the tumor was composed of atypical spindle-shaped tumor cells that proliferated in a whirling or interlacing pattern. The tumor also showed foci with a malignant epithelial component that simulated a carcinosarcoma. Immunohistochemically, the biphasic differentiation of the tumor was highlighted by the different immunoreactivity to antibodies against cytokeratins, epithelial membrane antigen (EMA), and vimentin shown by the malignant epithelial components and the spindle-cell components. However the latter showed faint positivity for cytokeratin antibody. These results suggested that the spindle-cell carcinoma of the gallbladder originated from cholecystic mucosa and showed sarcomatous reaction or dedifferentiation, as indicated by the presence of vimentin-positive cells. The proliferation index, as detected by ki-67, in the spindle-cell component was higher than that in the epithelial component, which may account for the more aggressive biological behavior of the spindle-cell component.     

Adult case of an omphalomesenteric cyst resected by laparoscopic-assisted surgery

This report describes an extremely rare adult case of an omphalomesenteric cyst resected by laparoscopic-assisted surgery. A 29-years-old Japanese man was referred and admitted to Kyushu University Hospital because of an abdominal mass and an elevated serum CEA (carcinoembryonic antigen) level (21.3 ng/mL) in August 2001. Abdominal CT and US demonstrated a cystic mass with septum and calcification. Laparoscopy showed a large mass to be attached to his abdominal wall, measuring 110 mm x 70 mm x 50 mm and filled with mucus. The mass was resected by laparoscopic-assisted surgery. The histological findings of its wall showed fibromuscular tissue, adipose tissue, calcification, and an intestinal structure. It was finally diagnosed to be an omphalomesenteric cyst.