Capability of Tissue Stem Cells to Organize into Salivary Rudiments

Branching morphogenesis (BrM), an essential step for salivary gland development, requires epithelial-mesenchymal interactions. BrM is impaired when the surrounding mesenchyme is detached from the salivary epithelium during the pseudoglandular stage. It is believed that the salivary mesenchyme is indispensable for BrM, however, an extracellular matrix gel with exogenous EGF can be used as a substitute for the mesenchyme during BrM in the developing salivary epithelium. Stem/progenitor cells isolated from salivary glands in humans and rodents can be classified as mesenchymal stem cell-like, bone-marrow-derived, duct cell-like, and embryonic epithelium-like cells. Salivary-gland-derived progenitor (SGP) cells isolated from duct-ligated rats, mice, and swine submandibular glands share similar characteristics, including intracellular laminin and α6β1-integrin expression, similar to the embryonic salivary epithelia during the pseudoglandular stage. Progenitor cells also isolated from human salivary glands (human SGP cells) having the same characteristics differentiate into hepatocyte-like cells when transplanted into the liver. Similar to the dissociated embryonic salivary epithelium, human SGP cells aggregate to self-organize into branching organ-like structures on Matrigel plus exogenous EGF. These results suggest the possibility that tissue stem cells organize rudiment-like structures, and the embryonic cells that organize into whole tissues during development are preserved even in adult tissues

Intrapulmonary metastasis of non–small cell lung cancer: A prognostic assessment

AbstractObjective: According to the revised TNM classification in 1997, intrapulmonary metastasis within the same lobe of the primary tumor is designated as T4 and intrapulmonary metastasis in a different lobe is M1. However, their prognostic implications remain unclear. To assess their prognoses, we retrospectively analyzed the postoperative survival of patients with and without intrapulmonary metastasis. Methods: From January 1982 to December 1996, 2340 patients with non–small cell lung cancer underwent surgical resection. The survival of patients having complete resection (n = 1534) was analyzed according to their intrapulmonary metastasis status: patients without intrapulmonary metastasis (n = 1393), those with metastasis in the same lobe (n = 105), and those with metastasis in a different lobe (n = 18). For comparison, patients with T4 disease without intrapulmonary metastasis in the same lobe (n = 54) and those with M1 disease without metastasis in a different lobe (distant M1, n = 18) were also analyzed. Results: The overall 5-year survivals were as follows: no intrapulmonary metastasis, 60%; stage T4 disease with no intrapulmonary metastasis, 34%; pulmonary metastasis in the same lobe, 34%; pulmonary metastasis in a different lobe, 11%; and distant M1, 6%. The differences in survival between patients with no pulmonary metastasis and those with metastasis in the same lobe (P <.001, log-rank test) and between patients with metastasis in the same lobe and those with distant M1 (P <.001) were significant. In contrast, there was no significant difference between patients with metastasis in the same lobe and those with T4 disease and no intrapulmonary metastasis or between patients with metastasis to a different lobe and those with distant M1. Conclusions: Prognostically, intrapulmonary metastasis within the same lobe of the primary tumor was comparable with T4 and that in a different lobe was comparable with M1. In terms of postoperative prognosis, the revised TNM classification for intrapulmonary metastasis seems to be appropriate.J Thorac Cardiovasc Surg 2001;122:24-

うつ症状が室温低値と血圧高値の関連に及ぼす影響

Objectives: Cold exposure accounts for more than 7% of all-cause mortality worldwide, and cold-induced blood pressure (BP) elevation and consequent cardiovascular events are partially responsible. For prevention, it is important to identify risk factors for exaggerated temperature-sensitivity of BP but this is not fully understood. This study investigated whether depressive symptoms affect the relationship between indoor temperature and BP. Methods: We conducted a cross-sectional analysis of 1076 community-based individuals who were at least 60 years of age. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale at a cutoff point of 4/5. We performed ambulatory BP monitoring and indoor temperature measurement on two consecutive days during the cold season in Nara, Japan. Results: When using daytime SBP as a dependent variable, multilevel linear regression analyses showed that lower daytime indoor temperature was significantly associated with higher daytime SBP in the depressive group (n = 216, β = -0.804, P < 0.001) but not in the nondepressive group (n = 860, β = -0.173, P = 0.120); moreover, a significant interaction between depression and daytime indoor temperature was observed (P = 0.014). These relationships were independent of potential confounders including age, gender, BMI, medications, and physical activity. Similar results were obtained for morning SBP, nocturnal SBP dipping, and morning BP surge. Conclusion: The results suggest that depressive participants are more likely to have cold-induced BP elevation than nondepressive participants. Further longitudinal studies are warranted to determine whether people with depressive symptoms are at a high risk for cold-related cardiovascular events.博士（医学）・甲第859号・令和5年3月15

Effect of acetylcholine on the highly stenotic coronary artery: Difference between the constrictor response of the infarct-related coronary artery and that of the noninfarct-related artery

AbstractTo examine the constrictor response of the infarct-related stenotic coronary artery in comparison with that of noninfarct-related stenotic arteries, acetylcholine in maximal doses of 100 μg for the left and 50 μg for the right coronary artery was injected into the 16 infarct-related coronary arteries of 16 patients with previous myocardial infarction (group 1) and into 19 stenotic coronary arteries of 16 patients with stable angina without myocardial infarction (group 2). Acetylcholine's effects on lumen diameter and area were quantitatively analyzed at the stenotic segment and its proximal segment without significant stenosis.Acetylcholine decreased lumen diameter and area at the stenotic segments from 0.72 ± 0.18 to 0.18 ± 0.33 mm and from 0.45 ± 0.22 to 0.10 ± 0.22 mm2, respectively, in group 1 (both p < 0.01) and from 0.75 ± 0.22 to 0.49 ± 0.30 mm and 0.48 ± 0.29 to 0.26 ± 0.23 mm2, respectively, in group 2 (both p < 0.01). Acetylcholine decreased the diameter and area at the proximal segment from 2.71 ± 0.75 to 2.38 ± 0.6 mm and from 6.18 ± 3.4 to 4.71 ± 2.23 mm2, respectively, in group 1 (both p < 0.01) and from 2.31 ± 0.67 to 1.95 ± 0.59 mm and from 4.5 ± 2.97 to 3.22 ± 1.96 mm2, respectively, in group 2 (both p < 0.01). The changes in diameter and area at the stenotic segment in group 1 were significantly greater than those in group 2 (both p < 0.01); there were no significant differences between groups in the changes at the proximal segment. Total or subtotal occlusion of the stenotic artery was induced in 11 (69%) patients in group 1 compared with 4 (21%) patients in group 2 (p < 0.01 group 1 vs. group 2).It is concluded that the constrictor response to acetylcholine of the stenotic segment of the infarct-related coronary artery is enhanced as compared with that of noninfarct-related arteries

The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Background: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear. Methods: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model. Results: We obtained the following results: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. Conclusion: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis

A single-chip 20-channel speech spectrum analyaer using a multiplexed switched-capacitor filter bank

金沢大学理工研究域　電子情報学系A single-chip speech spectrum analyzer which contains a 20-channel filter bank, a 9-bit-resolution analog-to-digital converter, and a 396-bit buffer memory is described. Several efficient design techniques were used to realize the equivalent 308th-order transfer functions on a single chip monolithic MOS circuit. A new time-division-multiplexed switched-capacitor filter technique is introduced which can easily cancel DC offsets which appear in the multiplexed channel outputs. The LSI was fabricated in 3.5-μm CMOS technology, with a 7.0×6.5 mm/SUP 2/ die size, a power consumption of 150 mW, with a single power supply of +5 V. Experimental results show that designed performance was realized