Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Organization of the trigeminal and facial motor nuclei in the hagfish, Eptatretus burgeri: a retrograde HRP study

We studied the trigeminal and facial motor nuclei of the hagfish by the retrograde HRP method. We distinguished 4 components in a single column of the motor nuclei of the trigeminal nerve and the facial nerve, viz., the pars magnocellularis of the trigeminal motor nucleus (mVm), the anterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp1), the posterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp2) and the facial motor nucleus (mVII). Although in Nissl preparations only the mVm could be distinguished from the rest of the nucleus, the boundaries of the other 3 components were clearly demarcated in HRP preparations. Intramuscular injections into two representative antagonistic jaw muscles revealed that there was no apparent topological organization of the neurons pertaining to the opening and closing muscles in the mVm and mVp1, but both antagonistic muscles were innervated bilaterally. Although the hagfish does possess a cartilaginous jaw, the organization pattern of the motor nuclei of the jaw muscles seems to be the most primitive of all living vertebrates.     

Ontogeny of behavioral sensitization to cocaine

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56–60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21–25 or 28–32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.     

HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals.

BACKGROUND: The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. METHODS: In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. RESULTS: Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%). CONCLUSIONS: The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation.     

Techniques for difficult cases of laparoscopic cholecystectomy

Our basic techniques for the management of difficult cases of laparoscopic cholecystectomy (LC) are presented in this article. If access to Calot's triangle cannot be gained safely, dissection should be started at the fundus or body of the gallbladder (GB), rather than the neck (fundus-first method). In cases with a short and wide cystic duct, a transfixing suture should be applied for ligation instead of clipping. EndoGIA is useful for ligating and transecting this case to avoid a subsequent stricture caused by normal method of ligation. Intraoperative cholangiography should be performed near the neck of the GB in cases in which orientation is lost during dissection. More dissection should be performed in the direction of the junction of the bile ducts after orientation is regained. In cases with GB filled with stones accompanied by severe fibrosis, part of the GB is incised to remove the stones and expose the lumen of the GB. Confluence stones can be removed by placing an incision on the GB side of the junction of the duct. The incised part is closed with suture. A cystic tube (C-tube) is placed in the common bile duct through the cystic duct for decompression. In more difficult cases in which dissection cannot be started safely at any location, the body and the fundus of the GB are excised, and a drain is placed at the neck of the GB. Dissection can be carried out from the main surgeon's or the assistant's side depending on the situation, and cooperation between the two surgeons is mandatory to achieve safe LC in difficult cases. When performing the LC, one must have a low threshold for converting to open surgery if injuries cannot be managed safely.     

Transcranial magnetic stimulation of the facial nerve]

It was the object of the present study to determine whether transcranial facial nerve stimulation using a magnetic coil can be clinically applicable, and to find the site where the facial nerve is best stimulated. A magnetic coil was placed over the parieto-occipital skull of the subjects for stimulation, and the facial nerve was electrically stimulated in its intracranial and peripheral courses. Then an electromyogram was recorded from the nasalis muscle of the face on the stimulated side. In 9 healthy volunteers, 18 facial nerves received magnetic and electric stimuli in the peripheral region, and the actual site of stimulation was estimated from the conduction velocity of the nerve. The conduction velocity was 56.6 +/- 4.8 m/s, and the latency between CMAPs for electric at the magnetic stimuli to the posterior tragus was 1.23 +/- 0.21 ms. Therefore, the position stimulated by magnetic coil was estimated to be 70.0 +/- 11.4 mm central to the posterior tragus, i.e., near the root exit zone. In two patients undergoing surgery in the cerebellopontine angle, transcranial magnetic stimulation and electrical stimulation of the intracranial facial nerve were compared intraoperatively. The CMAP produced by transcranial magnetic stimulation coincided closely with that produced by direct electrical stimulation of the root exit zone. Thus, the facial nerve was stimulated at the root exit zone, and this method could be expected to be useful for evaluation of disorders of the intracranial facial nerve.     

Surgical technique of experimental lung transplantation in rabbits.

BACKGROUND: Although rabbits have often been used as an experimental model for the analysis of lung preservation, there are no reports of long-term survival after rabbit lung allotransplantation. The purpose of this study was to establish a lung allotransplantation model for the evaluation of acute lung rejection in the rabbit and to investigate the transplantation techniques in the rabbit. METHODS: Left unilateral lung allotransplantations were performed in 10 pairs of Japanese white male rabbits, weighing from 2.8 to 3.7 kg. Rabbits were divided into two groups. Group A rabbits (n=5) received Cyclosporine A (CsA) (20 mg/kg/day) orally for 5 days postoperatively, while Group B rabbits (n=5) received no CsA. All rabbits were sacrificed at the fifth postoperative day for histological examinations. RESULTS: Anastomoses of the pulmonary vein were achieved by using the atrial cuff technique. Satisfied blood flow was obtained in all arterial and venous anastomosis sites. Bronchial anastomosis was also well healed and all rabbits could maintain adequate spontaneous ventilation. In Group A, histopathology revealed that three cases were grade A0, one was grade A1 and the other was A2. In Group B, three cases lived for five days, and histopathology showed two cases were grade A2 and one case was grade A3. CONCLUSION: We established a left unilateral lung allotransplantation model in the rabbit and observed suppression of acute rejection of the transplanted lung by CsA. This study suggests that the rabbit is also an experimental model suited for the analysis of lung preservation as well as lung allotransplant rejection.     

Inhibition of IgE formation in mice by glycoproteins from corn silk

The inhibitory effects of glycoproteins separated from a hot water extract of corn silk (U-CSE) on the formation of IgE antibodies after primarily and secondarily challenged responses with dinitrophenyl (DNP)-ovalbumin (OVA) antigen in mice were investigated using the passive cutaneous anaphylaxis (PCA) test. When U-CSE was given intranasally or intraperitoneally the day before primary immunization, IgE antibody production was strongly inhibited. Furthermore, it was found that new formation of IgE antibodies was readily inhibited by U-CSE administration in mice with high levels of IgE after primary immunization. It was also found that U-CSE markedly suppressed IgE antibody formation in secondarily challenged responses with the antigen. U-CSE may be clinically applicable to type I allergic diseases.     

A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia

Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.     

Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation

Human luteal cells have been reported to express human leukocyteantigen-DR and lymphocyte functional antigen-3 on the cell surface,suggesting physiological interaction between luteal cells andT-lymphocytes through the menstrual cycle into early pregnancy.To elucidate the role of peripheral lymphocytes on corpus luteumdifferentiation, the effect of peripheral blood mononuclearcells (PBMC) on steroidogenesis by luteal cells was investigated.The production of Th-2 cytokines such as interleukin (IL)-4and IL-10 by the co-cultured cells was also examined, and theeffects of these cytokines on progesterone production by lutealcells were investigated. Corpora lutea were obtained from eightnon-pregnant women in the luteal phase and five women in earlypregnancy for luteal cell culture. PBMC were isolated from unrelatedwomen in the follicular phase, secretory phase, and early pregnancy.After co-culture with allogenic PBMC for 48 h, progesteroneproduction was significantly enhanced by PBMC from the secretoryphase and early pregnancy in the non-pregnant luteal cell culture.In the pregnant luteal cell culture, a significant increasein progesterone production was also observed by the co-culturewith PBMC from women in early pregnancy, showing that PBMC havea luteotrophic effect. The stimulatory effects of PBMC werealso observed in co-culture conditions which prevented directcell-to-cell interaction with luteal cells, showing the minorinfluence of mixed lymphocyte reaction. By co-culture with PBMC,the production of IL-10, but not IL-4, was significantly augmentedin luteal cell culture derived from non-pregnant women, whereasthe production of both IL-4 and IL-10 was significantly enhancedin the luteal cell culture derived from pregnant women. Moreover,IL-4 and IL-10 promoted progesterone production by culturedluteal cells, especially in the luteal cell culture derivedfrom corpora lutea of early pregnancy. These findings indicatethat PBMC stimulate progesterone production by luteal cellsand suggest the involvement of PBMC in corpus luteum functionand differentiation probably via the Th-2-type lymphocytes.