Genetic structure and diversity of Japanese kokanee Oncorhynchus nerka stocks as revealed by microsatellite and mitochondrial DNA markers.

Genetic structure and diversity of nine Japanese kokanee (landlocked) Oncorhynchus nerka stocks and anadromous O. nerka from the North Pacific and the Canadian Lake Cultus population were examined using microsatellite and mitochondrial DNA. Sequence analyses of the cytochrome b region of mtDNA for Japanese kokanee O. nerka stocks on Honshu and Hokkaido islands revealed that most Japanese stocks were monomorphic of one major haplotype, which was also dominant in the Lake Cultus population and anadromous O. nerka in the North Pacific. Assignment tests using microsatellite DNA revealed that there was no clear-cut population structure in Japanese kokanee O. nerka stocks.

[Thymic cancer with superior vena cava invasion reconstructed by ready-made Y-graft].

A 57-year-old woman was admitted to our hospital with a complaint of left supraclavicular lymph node's swelling in January 2007. Computed tomography (CT) showed the lobulated tumor suspected of superior vena cava (SVC) invasion, located in the anterior mediastinum, 5 x 3 cm in size. The patient underwent thymectomy, resection of SVC, and partial resection of the right upper lobe. SVC was reconstructed by ready-made Y-graft (Hemashied phi 18 x 9 mm). Histopathological diagnosis was thymic cancer, poorly differentiated squamous cell carcinoma. The patient was discharged on 21st postoperative day. Postoperative radiotherapy (RT : 12.6 Gy) was canceled for the side effect. Alternatively, adjuvant chemotherapy [carboplatin (CBDCA) +paclitaxel (PTX)] was administered. Additional RT (50 Gy) was given to the lesion of local recurrence 1 and half year after the operation. The patient was alive without any signs of recurrence after RT. Left side bypass graft was patent at 8 months postoperatively, but was obliterated thereafter. Right side bypass is patent at more than 2 years postoperatively. Ready-made Y-graft can be one of the choices of SVC reconstruction.

[Video-assisted thoracic surgery (VATS) for clinical stage I lung cancer in consideration of the diameters and characteristcs of each tumor and the technical limitations of VATS].

UNLABELLED: We planned an intervention study to investigate the late outcome of limited surgery for cStage IA lung cancer by several video-assisted thoracic surgery (VATS) procedures. METHODS: VATS partial resection was done for non-solid tumors less than 1.5 cm in maximum diameter with non-solid component on high resolution computed tomography (HRCT) [group A]. VATS segmentectomy with minor thoracotomy with ND1 + alpha lymph node dissection was done for tumors less than 2.0 cm in maximum diameter that was not included in the group A (group B). Tumors of less than 3.0 cm in diameter that did not fit into the other 2 groups were treated by VATS lobectomy with minor thoracotomy plus ND2 lymph node dissection (group C). RESULTS: A total of 159 patients were enrolled during the 5-year enrollment period (group A: 21 patients, group B: 43 patients, group C: 95 patients). The recurrence-free 5-year survival rate was 100% in the group A, 82.8% in the group B, and 78.4% in the group C, showing no significant differences between the groups. Twenty-eight % of patients was switched to surgical techniques involving more extensive resection in the group A and B. while 6% of the patients was switched to thoracotomy overall. The overall recurrence rate was 10.7% (n=17), while the locoregional and distant recurrence rate was 5.7% (n=9) and 5.0% (n=8), respectively. CONCLUSIONS: This controlled intervention study suggested that limited surgery by VATS approaches for cStage IA lung cancer are acceptable as cancer operation.

Odorant receptor gene choice and axonal projection in the mouse olfactory system.

In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses a single type of odorant receptor (OR) out of approximately 1,000 in a monoallelic manner. Furthermore, OSNs expressing the same OR converge their axons to a specific set of glomeruli on the olfactory bulb. These two basic principles are fundamental to the peripheral olfactory system, and are regulated by the expressed OR protein itself. Singular OR gene choice is ensured by the combination of stochastic enhancer-promoter interaction and negative-feedback regulation by OR proteins. In the axonal projection, OR-derived cyclic AMP signals and neuronal activity determine the expression levels of axon guidance/sorting molecules, and thereby direct glomerular positioning and axon sorting.

[Surgical treatment of lung cancer in octagenarian patient].

Because average life span of Japanese is getting longer, we sometimes meet elder lung cancer patients of over 80. They often have many complications, so we are worried about how to treat them. Recently we met 8 elder patients with lung cancer, and we performed surgical operation for them. Six patients performed partial lung resection or lobectomy had no complications after operation. But 2 patients with respiratory disorder who performed lobectomy and chest wall resection had some complications after operation. In such patients, careful postoperative management is needed, and continuous positive airway pressure (CPAP) ventilation with pressure support (PS) may be useful to prevent respiratory complications.

[Simultaneous resection of pulmomary metastasis of colon cancer and primary lung cancer].

A 70-year-old woman was admitted with a complaint of weight loss and an abnormal shadow on the chest X-ray. On palpation, the unmobilized mass, measuring 5 cm, was located in the left lower abdomen. The barium-enema examination showed the filling defect of the sigmoid colon. Chest computed tomography (CT) showed a tumor, measuring 20 x 20 mm, located in the right upper lobe (S3) and a nodule, measuring 3 mm, located in the right lower lobe (S8). At first, we performed sigmoidectomy (D 3) for the colon cancer. Next, performed right upper lobectomy and a partial resection of the right lower lobe. Histopathologically, the one is a primary lung cancer, the other is a metastatic lung cancer. With an increase in colorectal and lung cancer, similar cases as ours seem to increase in number. When we treat multiple lung nodules with malignancy of other organs, we should consider 3 types of cases, 1) only primary, 2) primary and metastatic, 3) only metastatic.

[Negative pleural cytology after intrapleural perfusion hyperthermo-chemotherapy for malignant pleural effusion].

We gave intrapleural perfusion hyperthermo-chemotherapy to a 72-year-old woman in whom malignant pleural effusion developed after surgery for primary cancer. This procedure involved irrigating the pleural space for 2 hours with a water solution at 42-43 degrees containing 240 mg cisplatin using specially devised extracorporeal circuits. Thoracoscopy was used to examine the intrapleural cavity and to place the catheters for perfusion. The patient had an uneventful postoperative course and was discharged for hospital on the second postoperative day. Thereafter, she experienced good quality of life with negative pleural cytology. Unfortunately, the patient died 3 months after the therapy, but the cause of death was unknown and there was no cancer recurrence. This technique may be safe and feasible for controlling malignant effusion to preserve quality of life, although the survival benefit has not yet been clarified.

[Subjective criteria of chest CT findings for predicting pathological features and postoperative outcomes of small peripheral lung cancer (< or = 2 cm)].

One hundred fifty five patients with completely resected peripheral non-small cell lung cancer, clinically diagnosed 2 cm or less in diameter, are retrospectively reviewed on their preoperative chest CT films, clinico-pathological features, and postoperative outcomes. Pathologic type was classified according to Noguchi's classification. 7% and 8% of all the patients had pathologic N 1 and N 2 diseases, respectively. 19% of all the patients undergone limited resection (segmentectomy or partial resection). Maximum area of the tumor/soft tissue density area of the tumor (M/S ratio) was manually measured by chest CT film. According to the logistic regression analysis, M/S ratio was the only predicting factor of regional lymph node metastasis among factors including pleural indentation, spiculation, and maximum area of the tumor. Univariate analysis showed that maximum area of the tumor, pleural indentation, and M/S ratio were the significant factor for postoperative disease free survival. According to multivariate analysis of postoperative disease free survival with adjustment for operative modality, the result was same as that of univariate analysis. In conclusion, our determined criteria of the chest CT accurately predicted pathological status and postoperative outcome of patients with small peripheral lung cancer. These factors would be useful for stratification factor of prospective clinical study.

Surgically treated primary lung cancer associated with Brugada syndrome: report of a case.

A 71-year-old man with primary lung cancer associated with Brugada syndrome was safely operated on following the placement of an implantable cardioverter defibrillator (ICD). During examinations for Brugada syndrome, a tumor in the apicoposterior segment of the left lung was incidentally detected by chest computed tomography. Following the implantation of an ICD, surgical treatment of the left lung tumor was scheduled. A lung biopsy was thoracoscopically performed and adenocarcinoma was diagnosed based on a frozen section analysis. A left upper lobectomy with lymph node dissection was performed through a standard posterolateral thoracotomy. Ventricular fibrillation, which occurred during the night of the first day following surgery, was successfully managed by the ICD.

The PU.1 and NF-EM5 binding motifs in the Igkappa 3' enhancer are responsible for directing somatic hypermutations to the intrinsic hotspots in the transgenic Vkappa gene.

Somatic hypermutation is a key mechanism in generating Ig with higher affinities to antigen, a process known as affinity maturation. Using Igkappa transgenes, the 3' enhancer (kappaE3') has been shown to play an important role in introducing hypermutations. In order to identify the cis-acting elements that regulate hypermutagenesis, we have generated transgenic substrates containing mutations/deletions in the kappaE3' region. Here, we report that base substitutions in the kappaE3', either in the PU.1 or in the NF-EM5 binding motif, not only reduce the mutation rate but also disrupt the directed mutagenesis in the intrinsic hotspots of the Igkappa transgene.

Treatment of the unstable distal radius fracture with external fixation and a hydroxyapatite spacer.

A prospective study was performed on 25 patients (15 women, 10 men) with unstable fractures of the distal radius selectively treated with a dynamic type of external fixation combined with a hydroxyapatite spacer. The fractures ranged from type VI to type VIII according to Frykman's classification. The patients' mean age at surgery was 49 years (range, 19-75 years). The mean follow-up period was 2.5 years, and overall outcome was assessed using Gartland and Werley's demerit point system as modified by Sarmiento. Radial inclination was 26 degrees +/- 4 degrees at the time of reduction and 26 degrees +/- 5 degrees at follow-up, palmar tilt was 9 degrees +/- 2 degrees at reduction and 8 degrees +/- 3 degrees at follow-up, and ulnar variance was 1.4 +/- 0.6 mm at reduction and 2.1 +/- 0.9 mm at follow-up. The mean range of motion at follow-up was 80 degrees +/- 10 degrees in flexion, 80 degrees +/- 10 degrees in extension, 85 degrees +/- 10 degrees in supination, and 80 degrees +/- 5 degrees in pronation. The outcome in 24 of 25 patients was evaluated as excellent. In the surgical treatment of unstable fractures of the distal radius using external fixator, the fracture reduction should be supported with bone graft or a bone substitute, and a hydroxyapatite spacer was considered to be a useful substitute for a bone graft.

[On line display of the reconstructed pressure waves of the radial artery from the monitored output pressure waves at the same site].

The input-output relationship of transducer and catheter system is described by linear, second-order differential equation with three coefficients: inductance (L), resistance (R), and capacitance (C). Once the natural frequency (fo) and the damping ratio (beta) of the monitoring system have been measured, three coefficients of the differential equation are uniquely obtained. We measured the frequency response of the monitoring system, which we usually use in our hospital, to obtain fo and beta, and reconstructed the original input arterial pressure wave from output signal on the display using the simple time-domain approach. The analysis of this linear, second-order differential equation, is applicable in on-line bedside monitoring, because the calculation of this equation is simpler than that using Fourier's translation. The pressure waves of the radial artery both monitored (output) and restored (input) were depicted on the same display at the same time. We can evaluate the changes in systemic circulation from the changes in the wave shapes of arterial blood pressure.

Characterization of the influence of polyol fatty acid esters on the permeation of diclofenac through rat skin.

In this study, we investigated the effect of sefsols on the skin to clarify the mechanism of the sefsol enhancement effect. In vitro percutaneous absorption experiments were performed using Franz diffusion cells. Removal of the stratum corneum and delipidization of the skin increased the permeation of diclofenac from aqueous suspension, with the enhancement effects being similar for both treatments. Further enhancement effects of diclofenac permeation by sefsol through the stripped and delipidized skin were not observed. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to investigate the biophysical changes in the stratum corneum lipids by sefsols. One of the sefsols, propylene glycol mono caprylate (S-218), induced higher and broader absorbance shifts in both asymmetric and symmetric C-H bond stretching regions. However, no significant differences were observed among the sefsols with respect to peak heights and areas for both absorbances when compared with H2O treatment. These results suggest that sefsol may change the lipid-chain fluidity of the stratum corneum without lipid extraction. The accumulated amounts of diclofenac in the skin significantly increased in the presence of sefsol. Also, the amounts of diclofenac in the skin increased with the amount of sefsol in the skin. This sefsol enhancement effect was reversed at 12 h after treatment. Thus, enhancement of the diclofenac flux by sefsols is reversible and may be due to a change in the lipid-chain fluidity of the stratum corneum and improvement in drug partitioning to the stratum corneum.

[Assessment of stage IIB lung cancer from the pathological factors].

In our experience, the prognosis of patients with pathological T3N0M0 lung cancer is generally poor, the 5-year survival rate being almost the same as that of patients with stage IIIA disease. Thus, we assessed patients with stage IIB disease by examining the pathological factors, lymphatic invasion, vessel invasion, histological type, differentiation, tumor size, and node dissection. Lymphatic invasion was found to be positive in 20 of 21 cases, patients with T3N0M0 lung cancer, and all of those with positive vessel invasion had a significantly poor prognosis. This indicates that positive lymphatic and vessel invasion could be a prognostic factor predicting a poor outcome. Patients with T3N0M0 lung cancer that are found to have this poor prognostic factor may not be diagnosed as having stage IIB disease.

Congenital cystic adenomatoid malformation of the lung with an esophageal cyst: report of a case.

The authors report the case of a 7-month-old girl found to have both congenital cystic adenomatoid malformation of the lung (CCAM) and esophageal cyst. She suffered repeated episodes of pneumonia and exhibited signs of respiratory distress on admission to our hospital. Chest radiography and magnetic resonance imaging (MRI) showed 2 different kinds of cystic lesions. Resection of the lower lobe of the right lung and excision of the posterior mediastinal cyst were performed. Histologic examination showed Stocker type I CCAM and esophageal cyst. Coexistence of both CCAM and esophageal cyst is extremely rare. The authors speculate that the pathologies of this case originated from a regional disturbance of common embryologic origin during 2 different phases of lung-bud foregut malformations.

Fatal diffuse atheromatous embolization following endovascular grafting for an abdominal aortic aneurysm: report of a case.

A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was admitted to our hospital for endovascular grafting. Preoperative computed tomography and angiography showed friable mural thrombus in the suprarenal and infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the patient suffered cerebral infarction, and disseminated intravascular coagulopathy with multiple organ failure developed, resulting in early death on the third day after surgery. An autopsy revealed diffuse atheromatous embolization into the celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash buttock), and peripheral arteries. This case report serves to demonstrate that an abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a contraindication to endovascular grafting, and that predicting the possibility of diffuse atheromatous embolization by detecting a shaggy aorta is the best way to prevent this catastrophic complication.

Axonal projection of olfactory sensory neurons during the developmental and regeneration processes.

We have studied the projection of olfactory sensory neurons (OSNs), during the developmental and regeneration processes, using the transgenic mouse carrying the differently tagged odorant receptor genes, MOR28. We have found that the axon terminals of the two sets of MOR28-positive OSNs, one expressing the lacZ tag and the other expressing the green fluorescent protein gene, are dispersed and intermingled at early developmental or regeneration stages. Projection areas become more distinct and separated at later stages, however, two sets of axon fibers are not typically bundled or segregated during pathfinding. It appears that segregation of axons mainly occurs when they target at the olfactory bulb to form the glomerular structure.

Influence of pH on the permeability of p-toluidine and aminopyrine through shed snake skin as a model membrane.

The influence of pH on the permeability of p-toluidine (pKa, 5.3) and aminopyrine (pKa, 5.0) through shed snake skin as a model membrane was studied. The pH was adjusted to several values, and the solubility of the drugs in each donor was measured. Flux rates and permeability coefficients were calculated from the steady-state penetration portions. The flux rates of p-toluidine decreased as the pH value in the donor solution increased. On the other hand, the flux rates of aminopyrine were constant at any pH value. The permeability coefficients of each drug increased as the pH value in the donor solution increased. The partition coefficients (octanol/buffer) of each drug were dependent on the molecular fraction of un-ionized species. From these results, it is suggested that ionized species of p-toluidine transports through shed snake skin, but the ionized species of aminopyrine does not.

Monoallelic expression of the odourant receptor gene and axonal projection of olfactory sensory neurones.

BACKGROUND: We have previously generated transgenic mice carrying the murine odourant receptor gene, MOR28, tagged with lacZ. In this animal, the endogenous MOR28 is differently tagged with GFP. It was found that the transgenic and endogenous MOR28 genes are expressed in a mutually exclusive manner and that the two sets of olfactory sensory neurones (OSNs), each expressing either the transgenic or the endogenous MOR28, project their axons to separate glomeruli. RESULTS: Our fluorescent in situ hybridization (FISH) revealed that the two endogenous alleles of MOR28 are also mutually excluded for their transcriptional activation. Therefore, we studied whether there would be any segregation in the projection of the two subsets of OSNs: one set expressing the paternal and the other expressing the maternal allele. It was found that the OSNs for both alleles shared the same glomerulus for their projection, but the projection targets were segregated within the glomerular structure. CONCLUSION: Two subsets of neurones expressing either the transgenic or the endogenous MOR28 target their axons to two separate glomeruli based on the differences in the genetic backgrounds, nature of tagging, and chromosomal locations. In contrast, neurones expressing a maternal or paternal allele share the same glomeruli, but tend to target to segregated areas within the glomerular structure. The segregation was more prominent with increased differences in the genetic background between the two alleles.

Ras mediates effector pathways responsible for pre-B cell survival, which is essential for the developmental progression to the late pre-B cell stage.

Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21(ras) in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21(Asn-17) (Ha-ras) was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21(ras) activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21(ras) activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21(ras) mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.