Expression of cell-cycle modulators at the G 1 -S boundary, retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D 1 , and cyclin E was investigated with 104 hepatocellular carcinomas (HCC), as well as 90 of their adjacent noncancerous lesions and 9 normal liver control specimens. The labeling indices (LI) of pRb, p21, p16, and p27 were higher in HCC lesions than in the adjacent noncancerous lesions and normal controls. Especially, p27 LI in noncancerous lesions was significantly higher than that in normal livers (P ‫؍‬ .011). Aberrant p53 expression and cyclin D 1 and E overexpression were observed exclusively in HCC lesions. pRb was positive in 85.6% of the HCC cases and was not related to any clinicopathological parameters. The p21 LI was generally low (average, 5.5 ؎ 9.8). Although a negative regulator, p21 LI was higher in cases with intrahepatic metastasis (P ‫؍‬ .0359). The p16 LI was significantly decreased (P ‫؍‬ .0121) in cases with advanced stage. p27 LI was significantly decreased in cases with portal invasion (P ‫؍‬ .0409), poor differentiation (P F .0001), larger size (P ‫؍‬ .0421), and intrahepatic metastasis (P ‫؍‬ .0878, borderline significance). On the other hand, aberrant p53 expression showed positive relationships with poor differentiation (P ‫؍‬ .0004) and Ki-67 LI (P ‫؍‬ .0047). Cyclin D 1 overexpression was found in 32.6% of the cases and occurred more frequently in those with high Ki-67 LI (P ‫؍‬ .0032), pRb expression (P ‫؍‬ .0202), poor differentiation (P ‫؍‬ .0612, borderline significance), and intrahepatic metastasis (P ‫؍‬ .0675, borderline significance). Cyclin E was overexpressed in 35.5% and had positive relationships with Ki-67 LI (P ‫؍‬ .0269) and stage (P ‫؍‬ .0125). In univariate analysis, cases with p27 LI F 50 (P ‫؍‬ .0004), cyclin D 1 overexpression (P ‫؍‬ .0041), and cyclin E overexpression (P ‫؍‬ .0572, borderline significance) showed poorer outcomes for disease-free survival (DFS). In multivariate analysis, p27 expression could be recognized as an independent prognostic marker for DFS. These findings suggest that in HCC: 1) p27 is active against HCC progression in early phases and, possibly, hepatocarcinogenesis as a negative regulator and can be a novel prognostic marker for DFS; and 2) cyclin D 1 predominantly works for cell-cycle progression at the G 1 -S boundary. (HEPATOLOGY 1999;30:90-99.)

The bite force of 2594 school children (1248 males and 1346 females) living in northern Japan was investigated during oral health examinations in May and June 2001, using a new type of occlusal force gauge. The subjects were recruited from a variety of educational institutes and comprised: 73 nursery (3-5 years old), 1019 primary (6-11 years old), 902 junior high (12-14 years old) and 600 high (15-17 years old) school children. The measuring apparatus consisted of a hydraulic pressure gauge, with a bite element encased in a plastic tube. The bite force was measured at the first molar or second primary molar in the children presenting in the permanent and primary dentitions, respectively. The findings revealed significant variations in bite force between children of different ages. The average bite force was 186.2 N in males and 203.4 N in females of nursery school children; 374.4 N in males and 330.5 N in females of primary school children; 514.9 N in males and 448.7 N in females of junior high school children; and 545.3 N in males and 395.2 N in females of high school children. The prevalence of malocclusion in the nursery school children was found to be less than 30 per cent, which contrasted with almost 70 per cent in the high school children.

A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy group was substituted at the 8 position of the quinoline nucleus, was very stable under irradiation with long-wave UV light (UVA). Derivatives, a fluoroquinolone with no substitution (the 8-H analog) and one in which a fluorine was substituted (the 8-F analog), were degraded in their solutions by the UVA irradiation. The phototoxic inducibility by these derivatives was further studied in a murine model. When mice were dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body weight, the maximum dose given, and exposed to the UVA light, no inflammatory lesions were observed in their ears. Ear redness was marked in mice given more than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg. Histopathological changes, edema, and infiltration of neutrophils were also observed microscopically in groups receiving the 8-H or 8-F analog but not in groups receiving Q-35 (8-OCH3). Similar inflammatory reactions were observed to occur in a dose-dependent manner with other available fluoroquinolone antibacterial agents such as lomefloxacin, enoxacin, norfloxacin, ciprofloxacin and ofloxacin. These results suggest that the introduction of a methoxy group at the 8 position of the quinolone nucleus is important for the reduction of phototoxicity.

Q-35 [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methylaminopiperidine-1-yl)-4-oxoquinoline-3-carboxylic acid], a fluoroquinolone, has absorbance peaks at 333 and 286 nm. No spectral change was observed even when this aqueous solution was irradiated with 3 J of long-wavelength UV light (UVA) per cm2. On the other hand, its derivatives, which are unsubstituted (8-H analog) or which are substituted with fluorine at the 8 position (8-F analog), were found to have decreased antibacterial activities with a simultaneous increase in their cytotoxicities when they were degraded in a dose-dependent manner with respect to UVA irradiation. Similar results were observed with the other available fluoroquinolones. Enoxacin and lomefloxacin exposed to 0.3 J of irradiation per cm2 and norfloxacin, ofloxacin, and ciprofloxacin exposed to 1 J of irradiation per cm2 underwent absorption spectrum changes, an accompanying decrease in antibacterial activity, and an increase in cytotoxic activity. These results suggest that the introduction of a methoxy group into the 8 position of quinolones plays an important role in the stability of fluoroquinolones against irradiation by UV light.

Hospital-at-home (HaH) care is useful for patients with COVID-19 and an alternative strategy when hospital capacity is under pressure due to patient surges. However, the efficacy and safety of HaH in elderly patients with COVID-19 remain unknown. In Kyoto city, we conducted a retrospective medical record review of HaH care focused on elderly COVID-19 patients from 4 February to 25 June 2021. Eligible patients were (1) COVID-19 patients aged ≥70 years and those who lived with them or (2) COVID-19 patients aged <70 years with special circumstances and those who lived with them. During the study period, 100 patients received HaH care. Their median age was 76 years (interquartile range 56–83), and 65% were over 70 years. Among 100 patients, 36 (36%) had hypoxia (oxygen saturation ≤ 92%), 21 (21%) received steroid medication, and 34 (34%) received intravenous fluids. Although 22 patients were admitted to the hospital and 3 patients died there, no patients died during HaH care. HaH care may be safe and effective in elderly patients with COVID-19. Our study shows that HaH provides an alternative strategy for treating COVID-19 patients and can reduce the healthcare burden at hospitals.