Pathologic features of spinal disorders in patients treated with long-term hemodialysis

STUDY DESIGN: Pathologic features of hemodialysis-associated spinal disorders were evaluated using preoperative radiographic images and histologic findings of the spinal lesions resected during surgery. OBJECTIVES: To investigate the pathology of hemodialysis-related spinal disorders and to determine the role of amyloidosis in the establishment of severe destruction of the spine. SUMMARY OF BACKGROUND DATA: The pathologic events leading to hemodialysis-associated spinal disorders are poorly understood. The distribution of amyloid deposits in the spine also has not been clarified. METHODS: Twenty patients with hemodialysis-associated spinal disorders were investigated regarding pathologic features of neural compression and spinal destruction. Preoperative radiographic images such as plain radiography, tomography, computed tomography, magnetic resonance imaging, and scintigraphy were assessed for the existence of an intracanal mass, hypertrophy of the ligamentum flavum, and destructive changes of the spinal components. Histologic examination also was conducted by light microscopy and scanning electron microscopy to determine the distribution pattern of amyloid deposits in the spinal components. RESULTS: Six patients with no destructive changes in the spine showed spinal canal stenosis. In the cervical spine, a main factor associated with spinal canal stenosis was the presence of intracanal amyloid deposits in three patients. In the lumbar spine, a main factor associated with spinal canal stenosis was hypertrophied ligamentum flavum in three patients. Destructive changes of the facet joints, intervertebral disc, and vertebral body were seen in the other 14 patients. Amyloid deposits were densely distributed at the enthesis of capsular fibers to the bone and in anular tears in the intervertebral discs. Vertebral end plates were destroyed by penetration of amyloid granulation into the vertebral body. Osteoclast activity in the destroyed vertebral bodies was enhanced, with no evidence of new bone formation. CONCLUSIONS: Amyloid deposits played an important role in the progression of spinal destruction and severe instability.     

Transforming growth factor-beta inhibits interferon-gamma secretion by lymphokine-activated killer cells stimulated with tumor cells

The effect of transforming growth factor-beta (TGF-beta) secreted by glioblastoma (T98G) cells on the secretion of interferon-gamma (IFN-gamma) by lymphokine-activated killer (LAK) cells stimulated with tumor cells was investigated in cocultures of LAK and Daudi cells supplemented with T98G culture supernatant, T98G culture supernatant preincubated with anti-TGF-beta 1 and anti-TGF-beta 2 neutralizing antibodies, anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, or natural human TGF-beta 1 or recombinant human TGF-beta 2. LAK cells were incubated with anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, and with T98G cells of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, with or without neutralizing antibodies. Addition of the supernatant from T98G cells to LAK/Daudi culture caused inhibition of IFN-gamma secretion by LAK cells. The inhibition was abolished by pretreatment of the supernatants with anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to the LAK/Daudi culture inhibited IFN-gamma secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to the LAK culture resulted in increased IFN-gamma secretion. T98G cells failed to stimulate LAK cells to secrete more IFN-gamma. Addition of anti-TGF-beta antibodies to the LAK-T98G culture resulted in increased IFN-gamma secretion by LAK cells. These results suggest that most malignant glioma cells which secrete high levels of TGF-beta can inhibit IFN-gamma secretion by LAK cells even after tumor cell stimulation.     

L-type calcium channels in the axon terminal of mouse bipolar cells

Two types of calcium current (I(Ca)) have been identified in the bipolar cell of the mouse retina: a transient (T-) type current and a long lasting (L-) type current. It has been suggested that the former is present in the soma and the latter in the axon terminal. To establish the cellular localization of the two types of I(Ca), bipolar cells of the mouse retina was studied electrophysiologically in a slice preparation, and immunocytochemically by staining specific calcium channels in isolated cells. The dihydropyridine-sensitive L-type I(Ca) was recorded in the axon terminal, and the T-type current was recorded in the somatic region. Strong immunoreactivity to a polyclonal antibody against the L-type calcium channel was found in the axon terminal. These observations suggest that the L-type I(Ca) is generated at the axon terminal and contributes to the transmission of sustained depolarization.     

Involvement of Ras in Bruton's tyrosine kinase-mediated JNK activation

Defects in Bruton's tyrosine kinase (Btk) result in B cell immunodeficiencies in humans and mice. Recent studies showed that Btk is required for maximal activation of JNK, a family of stress-activated protein kinases, induced by several extracellular stimuli including interleukin (IL)-3. On the other hand, IL-3-induced JNK activation is dependent on Ras. In the present study we have investigated whether Ras is involved in Btk-mediated JNK activation in BaF3 mouse pro-B cells. Overexpression of wild-type Btk protein in these cells enhanced JNK activation upon IL-3 stimulation, whereas expression of kinase-dead Btk partially suppressed JNK activation. Induced expression of the dominant negative Ras(N17) in the cells overexpressing wild-type Btk suppressed JNK activation. Importantly, overexpression of Btk enhanced the level of the GTP-bound, active form of Ras in response to IL-3 stimulation. Btk overexpression also increased the Shc-Grb2 association induced by IL-3 stimulation. Expression of either N17Ras or V12Ras did not impose any effects on Btk kinase activity. These data collectively indicate that Ras plays a role of an intermediary signaling protein in Btk-mediated JNK activation induced by the IL-3 signaling pathway.     

Soft error susceptibility mapping of DRAMs using a high-energy nuclear microprobe

Soft errors in 16 Mbit dynamic random access memories (DRAMs) have been investigated using proton microprobes at 400 keV with a spot size of 1 × 1 μm². The newly developed susceptibility mapping can reveal the correlation between the particle hit-position position and the susceptibility to soft errors in a DRAM. The cell-mode soft-errors were found to take place by the incidence of ions within 6 μm around a monitored cell. These errors would be induced by minority carrier diffusion in a lateral direction. This result manifests the possibility of multiple-bit errors by the incidence of an energetic particle.     

EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum

Erythromycin and its derivatives are known to induce phase III-like contractions, which are similar to those induced by motilin, in the human gastrointestinal tract during the interdigestive state, but few detailed in vitro studies have been reported. We evaluated EM574, an erythromycin derivative, as a motilin receptor agonist in the human gastric antrum in vitro, using contraction studies of muscle strips and isolated myocytes, receptor binding assay and tissue section autoradiography. EM574 stimulated contractions of muscle strips in a concentration-dependent manner (10(-7)-10(-5) M), and this contractile effect was unaffected by pretreatment with atropine or tetrodotoxin. Isolated myocytes contracted in response to EM574 with a peak shortening at 10(-7) M, which was comparable to the response to motilin. EM574 displaced specifically 125I-motilin bound to smooth muscle homogenates with a Kd value of 7.8 x 10(-9) M, compared with 4.5 x 10(-9) M for motilin. Film autoradiograms showed that 125I-motilin-binding sites were localized in the muscle layers, and that the labeling disappeared in the presence of a 1000 times molar concentration of EM574. We conclude that EM574 directly stimulates smooth muscle cell contraction by acting on motilin receptors in the human gastric antrum in vitro.     

Elastic properties measurement of glass layers fabricated onsilicon wafers for microelectronics and micromachines

Elastic properties such as the Young's modulus, the Poisson's ratio and the density of Si-B-O glass layers fabricated on (100) silicon substrates by the flame hydrolysis deposition method were measured. Thicknesses of the layers were about 20 μm. It was found that the Young's modulus decreased with the boron dopant concentration. The Poisson's ratio was about 0.26 regardless of the boron dopant concentration. The measured elastic properties will be used in the design of micromachines fabricated with silicon substrates and glass layers     

Operation for chronic pulmonary thromboembolism accompanied by thrombophilia in 8 patients

BACKGROUND: Medical therapy for chronic pulmonary thromboembolism is limited, and surgical treatment has become more frequent recently. We have performed pulmonary thromboendarterectomy on 8 patients with chronic pulmonary thromboembolism accompanied by thrombophilia. METHODS: The patients were 6 men and 2 women aged 21 to 56 years (mean, 35 years). Five patients had antiphospholipid syndrome, 2 had protein C deficiency, and 1 had congenital antithrombin III deficiency. The preoperative condition was New York Heart Association functional class III in 5 and class IV in 3. Hypoxemia, marked pulmonary hypertension (mean pulmonary artery pressure, 47+/-6.7 mm Hg), and low cardiac output were observed in all patients. After a median sternotomy, deep hypothermia was induced using a cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral pulmonary arteries was performed under intermittent circulatory arrest. RESULTS: There were no operative deaths. Long-term respiratory management was needed postoperatively by 3 patients. In the remaining 5 patients, no reperfusion injury was observed. The arterial blood oxygen concentration improved, and the mean pulmonary pressure decreased to 16+/-5.5 mm Hg. The cardiac output also increased, and New York Heart Association functional class improved to I in 4 and II in 4 patients. CONCLUSION: Pulmonary thromboendarterectomy under deep hypothermic intermittent circulatory arrest was effective for chronic pulmonary thromboembolism accompanied by thrombophilia for which medical treatment is of limited value.     

A 14-ns 14-Mb CMOS DRAM with 300-mW active power

A 4-Mb high-speed DRAM (HSDRAM) has been developed and fabricated by using 0.7-μm L_eff CMOS technology with PMOS arrays inside n-type wells and p-type substrate plate trench cells. The 13.18-mm×6.38-mm chip, organized as either 512 K word×8 b or 1 M word×4 b, achieves a nominal random-access time of 14 ns and a nominal column-access time of 7 ns, with a 3.6-V V_cc and provision of address multiplexing. The high level of performance is achieved by using a short-signal-path architecture with center bonding pads and a pulsed sensing scheme with a limited bit-line swing. A fast word-line boosting scheme and a two-stage word-line delay monitor provide fast word-line transition and detection. A new data output circuit, which interfaces a 3.6-V V_cc to a 5-V bus with an NMOS-only driver, also contributes to the fast access speed by means of a preconditioning scheme and boosting scheme. Limiting the bit-line voltage swing for bit-line sensing results in a low power dissipation of 300 mW for a 60-ns cycle time