Telomere length in human liver diseases

Abstract: To determine the role of telomere-mediated gene stability in hepatocarcinogenesis, we examined the telomere length of human liver with or without chronic liver diseases and hepatocellular carcinomas (HCC). The mean telomere restriction fragment (TRF) length of normal liver (n=13), chronic hepatitis (n=11), liver cirrhosis (n=24) and HCC (n=24) was 7.8±0.2, 7.1±0.3, 6.4±0.2 and 5.2±0.2 kb, respectively (mean±standard error). TRF length decreased with a progression of chronic liver diseases and that in HCC was significantly shorter than that in other chronic liver diseases (p<0.05). The ratios of TRF length of HCC to that of corresponding surrounding liver of well differentiated (n=7), moderately differentiated (n=10) and poorly differentiated (n=4) HCCs were 0.83±0.06, 0.75±0.05 and 0.98±0.09, respectively. The ratio of poorly differentiated HCC was significantly higher than that of moderately differentiated HCC (p<0.05). A comparison between the size and telomere length ratio of moderately differentiated HCCs revealed a decrease of the ratio with size until it reached 50 mm in diameter. In contrast, the ratio increased as the size enlarged over 50 mm. These findings suggest that the gene stability of the liver cells mediated by the telomere is reduced as chronic liver disease progresses and that telomerase is activated in poorly differentiated HCC and moderately differentiated HCC over 50 mm in diameter.     

Laparoscopy-assisted distal gastrectomy with 3-cm laparotomy, left hepatic lobe compression technique, and selection of automatic anastomosis device

In this study, we performed laparoscopy-assisted distal gastrectomy (LADG) and lymph node dissection with an incision of 3 cm aiming at radical cure and low invasiveness. We introduce and discuss this technique of minilaparotomy and recommend a device for anastomosis. In LADG, a skin incision of 5cm or greater is made in order to pull out the stomach in other institutes. Whether function is distinctly better after laparoscopy-assisted surgery than after abdominal section has not been elucidated so far, so we should seek an aesthetic advantage. We have used a 3-cm abdominal wound to date. If the wound is smaller than this, the body of the SDH25 cannot be inserted, and currently a wound less than 3cm may thus not be possible. The shaft of the SDH is straight, making it easy to confirm the direction even through a laparoscope. The shaft of the anvil head of the PPCEEA is too long, so that when it is connected with the body through the 3-cm incision, it is necessary to draw it through the remnant stomach to a great extent.     

Procedural implications of intravascular ultrasound morphologic features of chronic total coronary occlusions

Although the success rates of percutaneous coronary intervention of chronic total occlusions (CTOs) have improved, morphologic features are not well known. We analyzed experience at 4 centers where intravascular ultrasound (IVUS) was performed in 67 native artery CTO lesions (mean CTO duration 6.3 months) just after the lesion was crossed with a guidewire (n = 7) or after dilatation with a 1.5-mm (n = 46) or 2.0-mm (n = 14) balloon. IVUS detected calcium somewhere in the CTO in 96%; however, only 68% had mild calcium. IVUS identified a proximal end of the CTO in all lesions, but a distal end of the CTO in only 50%. An intramural hematoma was observed in 34% of CTOs, suggesting that the guidewire frequently entered the medial space during successful recanalization. CTOs were longer, vessel area was smaller, and total calcium index was greater in lesions with hematomas (p = 0.003, 0.05, and 0.03, respectively). Inadequate reflow after the procedure was observed in 9% and was associated with longer lesions and intralesional calcium. CTO length as measured with angiography was shorter than the length as measured with IVUS (p = 0.02). Calcium was detected on the angiogram in 61% (p = 0.054 vs IVUS). Most typical angiographic findings associated with a low rate of procedural success were not associated with different IVUS morphologies. In conclusion, CTO lesions had multiple small calcium deposits, intramural hematomas were common and were indicative of guidewire penetration into the medial space during the CTO procedure, especially in long calcified lesions in smaller vessels, and inadequate reflow after the procedure was correlated with more complex CTO morphology.     

Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative

OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.     

The effect of reminiscence music therapy sessions on changes in depressive symptoms in elderly persons with dementia

This study examined the effectiveness of reminiscence focused music therapy treatment on depressive symptoms in elderly people with dementia. Twenty elderly (3 male & 17 female) who were diagnosed as having dementia and residing at 2 different residential care facilities in Florida were assigned to 1 of 4 small groups. Each of the participants served as his or her own control in an O1 O2 X O3 design. The depressive symptoms were measured using Cornell Scale for Depression in Dementia. The differences between the scores of pretest, posttest 1 after a week of 5-day no treatment, and posttest 2 after a week of 5-day reminiscence focused music therapy treatment were compared. A one-way analysis of variance (ANOVA) and Newman-Keuls Multiple Comparison Procedure indicated statistically significant differences between pretest and posttest 2 as well as posttest 1 and posttest 2, while no significant differences were found between pretest and posttest 1. Results indicated that participation in small group reminiscence focused music therapy groups might help to reduce depressive symptoms in elderly people with dementia. Results of behavioral observations and future implications are also discussed.     

Chondrosarcoma of the ethmoidal and sphenoidal sinuses. A case of chondrosarcoma arising from postparanasal sinuses

A case of chondrosarcoma originating within the postethmoidal and sphenoidal sinuses with intracranial invasion will be reported. The patient, a 54-year-old female, presented severe headaches and diminished visual acuity of the right eye. Angiographic findings showed both the left carotid artery to be completely occluded and the right inner carotid artery to be narrowed at the site of the carotid bifurcation. Computerized tomography scan findings showed a tumor, located mainly in the frontal base and temporal fossa, that had invaded the cranium through the skull base. Several tumor excisions were performed using a combined extranasal and transmaxillary approach. The diagnosis 'chondroma' was changed to 'chondrosarcoma' during autopsy.     

A survey of utilization of and problems with the MSDS in chemical substances management at workplaces in Kanagawa Prefecture]

Kanagawa Occupational Health Promotion Center conducted a survey on how the MSDS is utilized at workplaces with more than 50 employees handling chemical substances, and what measures are taken to help employees to thoroughly understand information in the Material Safety Data Sheet (MSDS). Questionnaires were sent out to 265 enterprises in Kanagawa prefecture, putting questions to industrial physicians and industrial hygiene supervisors. The objective of the survey was to find out how MSDS is adopted in the system to manage occupational health, what improvements the survey respondents want in MSDS and what expectations the respondents have of our center. 193 enterprises (72.8%) returned answers to the questionnaire. The major findings are as follows. (1) In many companies, information on hazardous/toxic materials is "controlled by a division using such materials", and roughly half of the companies have compiled a common list shared throughout the company. (2) For the most part suppliers submit to the MSDS. Larger companies have a higher rate of posting up or filing the MSDS at their workplaces. Only 25.8% of the companies "rewrite the MSDS so that workers can understand it." (3) Companies that carry out a hazard/toxicity assessment before introducing a new chemical substance account for 72.1%, which is higher than we expected. It indicates that even though the companies don't manage the MSDS adequately, they are highly concerned about hazard control of chemical substances. (4) The rate of answering that "the current MSDS is not easy to understand" is higher among large-sized enterprises and lower among enterprises with fewer than 300 employees. (5) Asked what improvement needs to be made on the MSDS, the industrial physicians and industrial hygiene supervisors gave same answers such as "Workers find the terminology difficult to understand." and "Levels of toxicity can't be clearly identified." (6) The respondents expect our center to provide information for the MSDS. In conclusion, it is considered that in order to prepare understandable MSDSs to workers in enterprises, the role of our center to provide information and education on the MSDS to respondents was important.     

Myocardium tissue ablation with high-peak-power nanosecond 1,064- and 532-nm pulsed lasers: influence of laser-induced plasma

BACKGROUND AND OBJECTIVES: We investigated the mechanism and characteristics of porcine myocardium tissue ablation in vitro with nanosecond 1,064- and 532-nm pulsed lasers at laser intensities up to approximately 5.0 GW/cm(2). Particular attention was paid to study the influence of the laser-induced plasma on the ablation characteristics. The applicability of these two lasers to transmyocardial laser revascularization (TMLR) was discussed. STUDY DESIGN/MATERIALS AND METHODS: Porcine myocardium tissue samples were irradiated with 1,064- and 532-nm, Q-switched Nd:YAG laser pulses, and the ablation depths were measured. The temporal profiles of the laser-induced optical emissions were measured with a biplanar phototube. For the ablated tissue samples, histological analysis was performed with an optical microscope and a polarization microscope. RESULTS: The ablation efficiency at 1,064 nm was higher than that at 532 nm. The ablation threshold at 1,064 nm (approximately 0.8 GW/cm(2)) was lower than that at 532 nm (approximately 1.6 GW/cm(2)), in spite of the lower absorption coefficient being expected at 1,064 nm. For the 1,064-nm laser-ablated tissues, thermal damage was very limited, while damage presumably caused by the mechanical effect was observed in most of the cases. For the 1,064-nm laser ablation, the ablation threshold was equal to the threshold of the laser-induced optical emission (approximately 0.8 GW/cm(2)), while for the 532-nm laser ablation, the optical emission threshold ( approximately 2.4 GW/cm(2)) was higher than the ablation threshold. CONCLUSIONS: We considered that for the 1,064-nm laser ablation, the tissue removal was achieved through a photodisruption process at laser intensities of > approximately 0.8 GW/cm(2). At laser intensities of > 3.0 GW/cm(2), however, the ablation efficiency decreased; this can be attributed to the absorption of incoming laser pulses by the plasma. For the 532-nm laser ablation, the tissue removal was achieved through a photothermal process at laser intensities of > approximately 1.6 GW/cm(2). At laser intensities of > 2.4 GW/cm(2), a photodisruption process may also contribute to the tissue removal, in addition to a photothermal process. With regard to the ablation rates, the 1,064-nm laser was more suitable for TMLR than the 532-nm laser. We concluded that the 1,064-nm Q-switched Nd:YAG laser would be a potential candidate for a laser source for TMLR because of possible fiber-based beam delivery, its compact structure, cost effectiveness, and easy maintenance. Animal trials, however, have to be carried out to evaluate the influence of the tissue damage.     

Development of human renal cell carcinoma (RCC)--the responsible genes for the development of hereditary and sporadic human RCCs

Renal Cell Carcinoma (RCC) is classified into six cell pathological types by the Thoenes classification (5). Deletion of DNA (loss of heterozeigosity: LOH) is seen with a high frequency in human RCC of all 6 types at chromosome 3p 14-25. The presence of at least three tumor suppressor genes at this domain has been pointed out. The VHL gene, one of the tumor suppressor genes (TSG), was identified in 1993 at chromosome 3p25-26 as the gene responsible for VHL disease. As a consequence, it was demonstrated that inactivation of the von Hippel-Lindau (VHL) gene is responsible for sporadic clear cell RCC. Activating mutations of c-Met receptor type tyrosine kinase has been demonstrated in papillary renal cell carcinoma families. Possible involvement of the FHIT tumor suppressor gene, located at the fragile site (FRA3B) of chromosome 3p14, has been detected in sporadic RCC. Recently, methylation of RASSF1A at chromosome 3p21.3 was pointed out in sporadic RCC. Thus, it has become apparent that chromosome 3p14-25 3 has possible TSGs for RCC. Furthermore, it was pointed out in April that germline mutation of fumarate hydratase, a Krebs cycle enzyme (FH), is present in multiple cutaneous and uterine leiomyomatosis families that develop papillary RCC. The functional significance in these genes for the development of RCC is still not apparent, except for the VHL gene. Thus, there is still a long way to go before we find all responsible TSGs in all pathological subtypes in sporadic RCC.