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Cardiotrophin-1 (CT-1) stimulates longitudinal myocardial cell hypertrophy. We examined the expression of CT-1, leukemia inhibitory factor (LIF), and gp130 by competitive RT-PCR and Western blotting in Dahl salt-sensitive (DS) rats with a high-salt diet, which showed a distinct transition from left ventricular hypertrophy (LVH) to congestive heart failure (CHF). The expression levels of CT-1 mRNA and protein were significantly increased at the CHF stage compared with the LVH stage and age-matched Dahl salt-resistant (DR) rats (n = 6 for each group). mRNA expression of LIF was not changed in the left ventricle at any stage by RT-PCR. gp130 mRNA and protein levels of DS rats at 11 and 17 wk were significantly increased compared with age-matched DR rats. The isolated myocyte length of DS rats at 17 wk was the longest among the four groups of rats. The LV end-diastolic dimension (LVDd) of DS rats, determined by echocardiography, was significantly increased at the CHF stage. There was a significant correlation between the CT-1 protein level and LVDd. CT-1 may play a role in ventricular remodeling during transition from LVH to CHF in the rat hypertensive model.

Background: We carried out a retrospective study comparing radical prostatectomy plus adjuvant hormone therapy with radical prostatectomy plus surveillance in patients with positive surgical margins to evaluate whether adjuvant hormone therapy is beneficial for disease free survival., Patients and Methods: Sixty-five patients with positive surgical margins after radical prostatectomy were included in this study. Twenty-six patients received adjuvant hormone therapy. Thirty-nine patients underwent surveillance with salvage hormone therapy at PSA failure. None of these 65 received androgen deprivation prior to surgery. Treatment outcomes were measured in terms of progression free survival., Results: Five year clinical progression free survival rates for the patients with positive surgical margins in the adjuvant therapy group and surveillance group were 85.9% and 80.0% respectively (p = 0.85). Clinical progression free survival between the groups was not statistically different in terms of seminal vesicle involvement and tumor grade. The difference of clinical progression free survival between the two groups approached statistical significance in poorly differentiated tumor (p = 0.08)., Conclusions: We conclude that adjuvant hormone therapy is not beneficial in terms of progression free survival in patients with positive surgical margins. Nevertheless, adjuvant hormone therapy could be beneficial in patients with poorly differentiated prostate cancer.

The residual amount of nonionized pesticides incorporated to foliage and stem (foliage) and seed (fruit) of crops via root hairs from the water phase was estimated using the uptake models newly including metabolic parameters by which the amount of intact pesticide remaining in crops was considered with its proportion in a transpiration stream. A new parameter was also introduced for the seed model that accounts for the pesticide loss by adsorption to the inner surface of xylem tissue. Validation of the model was conducted using six pesticides with soybean and spinach plants. The ratio of the predicted concentration of pesticide to the measured one was 0.44-1.49 and 0.57-2.93 with foliage and seed models, respectively, showing that these improved models would be effective as a prediction tool.

Background: Nitric oxide (NO) synthesized within sinoatrial cells recently has been shown to participate in the autonomic control of heart rate. We hypothesized that NO in the neuronal cells in the heart was increased and parasympathetically regulated heart rate after myocardial infarction (MI)., Methods and Results: We examined heart rate dynamics and neuronal NO synthase (nNOS) expression and activities in the atria of rats with MI 1, 3, 7, and 14 days after MI (n=7 to 22 for each group). Both the mRNA levels of nNOS in the atria determined by competitive reverse transcriptase-polymerase chain reaction and the protein levels determined by Western blotting were significantly increased compared with controls 1, 3, and 7 days after MI. nNOS activity in the atria 1 day after infarction was also increased in MI rats. nNOS immunoreactivity was observed in nerve fibers in the atria. After infusion of a specific inhibitor of nNOS and iNOS, 1-(2-trifluoromethylphenyl) imidazole (TRIM) (50 mg/kg IV), heart rate was significantly (P<0.01) increased in MI rats compared with controls 1, 3, and 7 days after MI. The iNOS-specific inhibitor, 1400W (10 mg/kg SC), did not significantly affect the heart rate in rats with MI. The effect of TRIM was abolished by pretreatment with L-arginine (25 mg/kg IV) or by parasympathetic blockade with atropine but not by propranolol. There was a strong correlation (r=0.837, P<0.0001) between the nNOS protein expression and heart rate change after TRIM infusion., Conclusions: These results indicate that increased nNOS parasympathetically decreased heart rate via the production of NO in rats with acute MI.

We evaluated the level of MCL1 gene expression using quantitative reverse transcription polymerase chain reaction in lymph nodes of patients with non-Hodgkin lymphoma (NHL). MCL1 expression in patients in complete remission (CR) was significantly lower than in patients with progressive disease (PD, P = 0.0043). The disease-free survival rate was significantly higher in patients with MCL1 levels below the median level (P = 0.007). We also found that the level of expression of MCL1 mRNA was related to that of vascular endothelial growth factor mRNA in NHL lymph nodes. Our data suggest that the MCL1 expression level could be considered a prognostic factor in NHL.

Two rearranged bands of the IgH gene were detected in a case with B cell chronic lymphocytic leukemia (B-CLL). The expressed VH gene was only VH1 with no somatic mutations in IgM and IgD. The expressions of C mu, C delta, and C gamma were detected by reverse transcription of RNA followed by the polymerase chain reaction (RT-PCR). Sequence analysis of the CDR3 regions of each PCR reaction product showed that the sequence of one rearranged allele was identical to those of the expressed VH1 gene, C mu and C delta, and the sequence of another rearranged allele was identical to that of C gamma. However, none of the expressed VH genes was detected in IgG. These findings suggest that this is a case of B-CLL lacking allelic exclusion and undergoing a class switch of one allele with the incomplete expression of the VH gene., (Copyright 2001 Wiley-Liss, Inc.)

We performed electron microscopic studies of eight nonfunctioning adrenocortical adenomas (NFA) and nine aldosterone-producing adenomas (APA) obtained from surgical specimens. A comparison of these two types of adenomas was conducted by morphometric analysis of random electron micrographs. The organelles measured included mitochondria (M), smooth-surfaced endoplasmic reticulum (SER), rough-surfaced endoplasmic reticulum (RER), lipid vacuoles (LV), and lysosomes (Ly). The content of steroid hormones, including 17-alpha hydroxyprogesterone (17-OHP), aldosterone (Ald), and other steroid hormones, was measured in adenoma tissue from six NFA and eight APA. The percentages of the areas of the organelles M, SER, and RER per total cell area in the NFA were significantly lower than those in the APA. The average content of Ald in adenoma tissues in APA was markedly higher than that in the NFA, while the mean content of 17-OHP in the NFA was significantly higher than that in APA. In conclusion, NFA are morphometrically characterized by a reduction in organelles such as M, SER, and RER, compared with findings in APA. From the quantitative analysis of steroid hormones, it was suggested that NFA produce more precursor substances with less hormone activity than APA and that steroidgenesis in NFA is shifted to a glucocorticoid pathway, as indicated by the elevated 17-OHP concentration.

Objectives: This study investigates the influence of erectile dysfunction (ED) on daily life and the attitude of citizens toward ED treatments., Materials and Methods: A mail survey targeting married males and females, aged 30-79, was conducted throughout the nation. The effective responses were 2,034 males and 1,820 females., Results: The ED prevalence rate of male respondents was 29.9% and that of females (indicating the recognition of husband's ED) was 30.1%. For both males and females, the frequency of sexual intercourse and satisfaction about their sexual lives were significantly lower in respondents with ED. 23.6% of males with ED and 16.0% of females whose husbands have ED experienced a negative influence of their married lives. Among male ED sufferers, however, only 4.8% of them had consulted a physician. The reasons cited most often for not consulting a physician were: "no influence on daily life", "not annoyed by ED", and "no interest in sex", Moreover, the barriers to visiting physicians were frequently cited, such as "shyness", "don't know which hospital to go to", and "expensive". With regard to insurance coverage of ED treatment, 80% or more of both men and women say that "it should be reimbursed for all ED patients" or "it should be conditionally reimbursed"., Conclusions: It becomes clear that ED is found at considerable frequency. However, only 4.8% of ED patients had received appropriate treatment at medical facilities. With regard to insurance coverage for ED treatment, it turned out that 80% or more of both men and women supported reimbursement for ED treatment.

A 45-year-old man was diagnosed as having acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy, and allogeneic BMT from his HLA-identical sister was performed on November 13, 1997. He developed acute GVHD (grade II), but quickly recovered after methyl-PSL pulse therapy. On June 5, 1998--day 202 after BMT--abdominal pain developed. X-ray and CT examinations showed pneumatosis intestinalis, pneumoperitoneum, pneumomediastinum and abdominal free air. We performed oxygen administration and methyl-PSL pulse therapy, and this quickly improved the symptoms. Corticosteroid and chronic GVHD were thought to be the causative factors of pneumatosis intestinalis in this case. Although pneumatosis intestinalis is relatively rare, it is one of the important potential complications that can occur after allogeneic BMT.

Background: This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied., Method: Of the 71 patients who underwent surgery, 54 patients had no neoadjuvant therapy (group 1), 10 patients were preoperatively administered IFN-gamma (group 2), and the remaining seven patients preoperatively received IFN-gamma and transarterial embolization (group 3). Both TP and Factor VIII immunostaining were performed on formalin-fixed, paraffin-embedded archival tissue from 71 renal cell carcinoma specimens, while TIL immunostaining was performed on frozen sections. Positive immunostaining was quantitatively scored by a computer-assisted digital image analysis. For TIL, positive results were semiquantitatively scored., Results: A significant difference in the recurrence-free rate was recognized for Groups 1, 2 and 3 (P < 0.05). Therefore, the median TP-positive rate (PR), VIII-PR, number of microvessels and positive mean vascular area levels were investigated, between the recurrence cases (n = 6) and the recurrence-free cases (n = 11). Only the TP-PR levels showed a significant difference among them (P = 0.044). In regards to the neoadjuvant cases, a significant correlation was observed between both VIII-PR and CD4 (r = 0.815) as well as between VIII-PR and CD11b (r = 0.756)., Conclusion: There was no clear evidence that the neoadjuvant treatment would increase the recurrence-free survival in patients with localized renal cell carcinoma. TP-PR might be a predictor of postoperative recurrence in patients with localized renal cell carcinoma.

We have developed a new adhesive for surgical use. The new adhesive is made of three components: porcine collagen, poly(L-glutamic acid) and water-soluble carbodiimides (WSC). The optimum concentration of each component was determined by measuring the time required for gel formation in experiments in vitro. Using these optimum concentrations, we applied the adhesive to wounds made on rats. A conventional fibrin glue was used as a control. Measurement of tensile strength and histological examination were performed 5, 7, 10, and 14 days after the operation. The tensile strength of wounds treated with 2.5 mg/mL collagen glue was not significantly different from that of wounds treated with fibrin glue except at 7 days after the operation (p < 0.05 by Student's t-test). Histological examination revealed that the speed of cell infiltration into, and absorption of 2.5 mg/mL collagen glue was slower than for fibrin glue, but faster than for 5.0 mg/mL collagen glue. One of the important advantages of our collagen glue is that the absorption rate of it can be controlled by the collagen concentration. Therefore, it seems to be adequate for sealing air leakage from the lung, which takes a relatively long period for recovery. Moreover it does not contain human serum, and, hence, it requires no blood donation and can be obtained with low cost., (Copyright 2000 John Wiley & Sons, Inc.)

Background: In human prostate carcinogenesis, many genetic analyses including conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, and 18q., Methods: Using the laser-captured microdissection method, the authors extracted genomic DNA from 23 cases of prostate carcinomas including 59 different lesions and 8 biopsy specimens. Using (32)P-labeled primers, the authors analyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported., Results: Of 10 cases in which the authors found LOH at any of the loci, 8 cases showed a heterogeneous LOH pattern. In four cases, the authors also found replication error (RER) at some of the loci examined. There was no significant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in foci at classification pT2 (1 of 28 foci, 3%) compared with those at classification pT3 (13 of 44 foci, 30%). In pT3 samples, LOH events in extraglandular foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in biopsy specimens correlated well with those in foci from surgical material showing the same histologic characteristics., Conclusions: Prostate carcinoma is a genetically multicentric carcinoma, and the genetic heterogeneity is well correlated with histologic differentiation. The frequency of LOH events increased according to the degree of tumor progression.

Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumor suppressor gene occur frequently in both endometrial carcinoma and ovarian endometrioid carcinoma. To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometrial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometriosis, 3 cases displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displayed no LOH events in either lesion. In no cases were there LOH events in the endometriosis only. Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.

In the present report we investigated the differential expression of three types of nitric oxide synthase (NOS) in the left ventricle after myocardial infarction in rats. One, 3, 7, 14, 28 and 56 days (n=6-12 for each group) after ligation of a coronary artery, tissue samples were obtained from infarcted and non-infarcted tissues. The mRNA and protein levels of neuronal (n) NOS, endothelial (e) NOS and inducible (i) NOS were sequentially determined by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting. Progressive left ventricular dilatation and gradual reduction in fractional shortening were confirmed by echocardiography. The expression levels of nNOS were significantly increased 1, 3 and 7 days post-infarct compared to those of sham-operated rats in both the infarcted (P<0.01) and non-infarcted regions (P<0.01). Immunohistochemical analysis showed that nNOS was localized in nerve fibers in the left ventricle and that the number of positive fibers after myocardial infarction had increased compared to that in sham-operated rats. With regard to eNOS, no significant changes in expression levels were detected between infarcted hearts and sham-operated controls. The level of iNOS expression peaked three days post-infarct and then decreased in the infarcted tissue, whereas it increased one day post-infarct, peaked at 14 and 28 days post-infarct and was still elevated in the chronic stage in the ventricular septum. iNOS immunoreactivity was detected in spared cardiomyocytes and macrophages in the infarcted region, and in cardiomyocytes in the ventricular septum. The expressions of three types of NOS were differentially regulated and iNOS produced in the non-infarcted region may contribute to the progression of heart failure after myocardial infarction in rats.

In this paper, the stereochemical resolution of racemic cyclohexane-1,2-diamine platinum(II) dimyristates on chiral stationary phases (CSP) is described. These CSP are Pirkle phases chiral column (Sumichiral OA-2500, 3100, 3200, 3300, 4000, 4100). Among them, the Sumichiral OA-2500 column gave the best results. The effects of the temperature and mobile phase composition as well as the hydrophobicity of the analytes on the chromatographic separation are described.

In a previous study, we replaced a 5 cm gap created in the canine intrathoracic esophagus with an artificial esophagus. However, although newly formed esophageal tissue subsequently bridged the gap, mild stenosis occurred, and this seemed to be caused by inadequate regeneration of the skeletal muscle. In the present study, we evaluated whether omental pedicle wrapping (OMPx) of the prosthesis could promote tissue regeneration and whether prolonged retention of the silicone tube within the prosthesis could prevent stenosis. A gap was created in 14 dogs, and the defect was repaired by our prosthesis. OMPx was performed in 5 of the 14 dogs (OMPx group) but not in the rest (control group). The silicone tube was retained for 4 weeks in the control group and for 8 weeks in the OMPx group. All of the dogs in the control group survived for more than 3 months, except for those that were killed. Four dogs in the OMPx group died within 3 months, one caused by perforation at 7 months. Only the thin epithelial and submucosal layer regenerated in the OMPx group. OMPx is not effective for promoting tissue regeneration, and prolonged retention of the silicone tube interrupts epithelial regeneration.

The purpose of this study was to demonstrate the benefits of cytoreductive surgery for renal cell carcinomas that also involve the liver. Between 1994 and 1997, four patients with renal cell carcinoma with liver involvement were surgically treated with nephrectomy and hepatectomy. Two of them underwent a simultaneous hepatectomy and nephrectomy (group 1), and the remaining two patients underwent a hepatectomy after a nephrectomy and had a diagnosis of postoperative recurrence (group 2). Two patients, one from each group, died of multiple bone metastasis and lung metastasis 30 months and 12 months after the hepatectomy; the second patient from group 1 died 40 months after the first operation due to gastrointestinal hemorrhaging. The second patient from group 2 displayed no evidence of recurrence 18 months after the second surgical procedure. The survival rates for these patients were 66% and 33% at 1 and 3 years, respectively. Autopsy studies revealed that one patient from group 2 had a local recurrence in the liver while the other two patients from group 1 did not. Our results suggested that a progressive approach may therefore be useful for patients demonstrating renal cell carcinoma where there is liver involvement.

Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting in myocardial cell hypertrophy. To clarify the role of CT-1 and the gp130-signaling pathway during ventricular remodeling after myocardial infarction, we examined the expression of CT-1 and gp130 in a rat model of myocardial infarction. At 1, 3, 7, 14, 28 and 56 days (n=12 for each group) after ligation of a coronary artery, tissue samples were obtained from infarct tissue, the ventricular septum and the right ventricle. All animals developed large myocardial infarctions, with infarct sizes ranging from 39.8% to 50.3%. Progressive left ventricular dilatation and inadequate hypertrophy of the surviving myocardium were confirmed by echocardiography. CT-1 and gp130 mRNA levels were determined by semiquantitative reverse transcription-polymerase chain reaction using 1 or 5 microg of total RNA followed by Southern blotting. The densitometric analysis of the Southern blots revealed a significant increase in CT-1 and gp130 mRNA levels (P<0.01) compared with those of the sham-operated rats at 1, 3, 7, 14, 28 and 56 days post-infarct in the infarct area, the ventricular septum (non-infarcted area) and right ventricle. The protein levels of CT-1 and gp130, determined by Western blot analysis, were significantly increased (P<0.05) compared with those of sham-operated rats, peaked during the acute stage and declined thereafter in the three regions described above. Immunohistochemical staining showed that CT-1 and gp130-immunoreactivities were detected in cardiomyocytes and fibroblast-like cells and that the intensity of staining was increased at 7 days post-infarct compared with that in sham-operated rats. An augmented CT-1 and gp130 system thus appears to play an important role during ventricular remodeling after myocardial infarction., (Copyright 2000 Academic Press.)

A 72-year-old woman, who has been administered prednisolone and azathioprine with diagnoses of idiopathic thrombocytopenic purpura (ITP) and autoimmune hepatitis (AIH), underwent a complete medical examination because of monoclonal gammopathy (IgG-kappa). Tumors were found in the ileum and descending colon. Pathological examination of biopsy specimens suggested a diagnosis of marginal zone B-cell lymphoma of the MALT type with a high-grade component. Flow cytometric analysis by two-color staining revealed that the neoplastic B cells expressed CD38, CD19, IgG and kappa, but not CD5 or CD10. There were no abnormal plasma cells in bone marrow smears. The patient achieved complete remission after receiving three cycles of THP-COP chemotherapy, which resulted in a decrease of the IgG level to within the normal range. These findings indicated that monoclonal IgG-kappa might be produced by lymphoma cells. However, the relationship of the immunosuppressive agents to the pathogenesis of the MALT lymphoma remains to be clarified.

Background: We evaluated the changes in the response of detrusor muscle to 5-hydroxytryptamine (5-HT; serotonin) and its receptor mechanisms in pathologic bladder of diabetes mellitus rats., Methods: Eight-week-old male Wistar rats were given an intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in order to induce diabetes mellitus (4 weeks' duration). The bladder strips (10 x 2 mm) were subjected to a tension of 1.0 g in organ baths for the measurements of isotonic contractile responses to 5-HT or relaxation responses to 5-HT antagonists., Results: Bladder strips from STZ-diabetic rats responded to 5-HT with greater contractions than did those of control rats, given vehicle alone. However, bladder strip weights gradually increased in the STZ-diabetic rats as compared with control rats and when the contractile response to 5-HT was expressed as a percentage of the response to 10(-1) mol/L KCl there was no statistically significant difference between the groups. In both control and diabetic rats, the 5-HT3 selective antagonist did not markedly inhibit the contractile response to 5-HT. In contrast, the 5-HT2A selective antagonist inhibited the contractile response to 5-HT in a dose-dependent manner., Conclusions: These results suggest that the increased contractile response to 5-HT in diabetic rats' bladder is related to smooth muscle hypertrophy and/or hyperplasia and indicate that this effect is mediated by activation of 5-HT2A receptors.

We developed hard biscuit containing 30% wheat bran (WB biscuit) and administered it to 12 volunteers at 7.5 g/day (7.5 g group) or 15 g/day (15 g group) as wheat bran for 12 weeks. After 12 weeks, the dietary fiber intake from foods other than wheat bran decreased slightly in the both groups, in the 15 g group was the decrease notable especially, after the beginning of WB biscuit administration. We suggest that a closest attention to changes in dietary habit associated with intervention is needed in intervention studies using patients leading a normal life.

Type 2B von Willebrand disease (vWD) is a von Willebrand factor (vWF) subtype with increased binding affinity for platelet glycoprotein (GP) Ib and is characterized by increased ristocetin-induced platelet agglutination at low concentrations of ristocetin. Usually there are no high molecular weight multimers of vWF, and platelet counts are within normal ranges in patients with type 2B vWD. We identified a variant of type 2B vWD showing the full range of vWF multimers in plasma accompanied by thrombocytopenia, which seemed to be caused by circulating platelet aggregation. Since the A1 domain and surrounding region of vWF alleles, in which mutation sites are known to be clustered in type 2B vWD, appeared normal on nucleotide sequencing, this increased binding affinity of vWF for GPIb may be due to a novel mechanism differing from that which usually underlies type 2B vWD.

Objectives: Intrathoracic esophageal replacement with an artificial esophagus is considered difficult. We attempted to replace the intrathoracic esophagus with an artificial esophagus composed of a collagen sponge with a double-layered silicone tube and examined the state of host tissue regeneration., Methods: A 5-cm long gap was created in the intrathoracic esophagus in 9 dogs and repaired by interposition of our prosthesis. The dogs were fed only by intravenous hyperalimentation for 28 days. The silicone tube was removed at 29 days after the operation, and oral feeding was reintroduced., Results: One dog was put to death at each of the following times: 1, 2, 3, 3, 6, 12, and 24 months after the operation. One dog is still surviving without problems after more than 26 months. One dog died of malnutrition at 10 months. In all dogs, the host regenerated tissue had replaced the resulting gap at the time of silicone tube removal. The mucosa had fully regenerated within 3 months and the glands within 12 months. The process of stenosis and shrinkage was complete within 3 months and did not advance thereafter. The lamina muscularis mucosae were observed as islets of smooth muscle within 12 months. Although the skeletal muscle regenerated close to the anastomoses, it did not extend to the middle of the regenerated esophagus even after 24 months., Conclusions: Use of a collagen sponge with a double-layered silicone tube was shown to be feasible even in the thorax and to allow the regenerated host tissue, consisting of the mucosa, glands, and lamina muscularis mucosae, to replace the esophageal gap.

17 cases of patients with diabetes mellitus who had urinary frequency symptom for which anti-cholinergic agents proved ineffective were given Sarpogrelate Hydrochloride (Anplag), a selective 5-HT 2 receptor antagonist. Efficacy was judged using IPSS and QOL scores after 2 weeks medications, these showed that all cases had improved their urinary frequency during the days as well as the night. This was especially true for the QOL score. One time urinary volume markedly increased, but there was no statistical significance after medication in maximum flow rate and residual urine. At the same time, a separate group of 14 mainly BPH cases did not improve entirely. It is believed that reaction in the detrusor muscle with hyperreflexia of diabetes mellitus patients can reach 5-HT, and its reaction is believed to reach via the 5-HT 2 receptor. This paper is a first clinical report of making use of 5-HT 2 antagonist as hyperactive detrusor on diabetes mellitus patients.

We have developed a novel collagen membrane with excellent mechanical properties using a new method and examined its breaking strength, microstructure, and absorption behavior in vivo. Types I and III atelopeptide collagen extracted from porcine skin by treatment with pepsin were used. One volume percent collagen hydrochloride solution, pH 3.0, was frozen in a cast, then freeze-dried and pressed. Both surfaces of the resulting membrane were coated with 2% w/v collagen hydrochloride solution, pH 3.0, and dried. This procedure was then repeated 10 times, and the membrane was finally heated in vacuo. Microstructural observation showed that the inner part of the membrane consisted of piles of thin collagen nonwoven fabric layers, whereas the coated surface consisted of an amorphous collagen layer. The breaking strength of this membrane with a thickness of 0.5 mm was 73.5 N/cm in dry conditions. The mechanical strength of the membrane was 3.4 to 10.8 times greater than that of control membranes that had not been subjected to coating procedures. The absorption of this membrane was investigated by an implantation test in rabbits. The absorption rate of the membrane in vivo was similar to that of the noncoated control material, and only minimal tissue reaction was evident. Because the mechanical properties of this membrane, made from only collagen, are adequate for suturing without reinforcement by other materials, and its absorption in vivo has so far been equal to that of collagen membranes, the membrane is potentially applicable for various surgical uses such as replacement of tissue defects.

We examined the relationship between the expression of mutant p53 and Ki-67 antigens in urinary bladder transitional cell carcinoma and the pathological and clinical findings. Tissues were obtained from 28 patients with bladder carcinoma who underwent total or partial cystectomy. An ABC immunostaining method and two primary antibodies (DO-7 and MIB-1 antibodies) were used. The percentages of p53 and Ki-67 antigen-positive cells to the total number of cells were regarded as the p53 and Ki-67 labeling indices (LI) respectively. There were no statistically significant correlations between p53 LI and the histological grade or stage, although p53 LI increased slightly in the high grade and high stage group. There was a statistically significant correlation between Ki-67 LI and the histological grade and stage (p < 0.05). The correlation between p53 LI and Ki-67 LI was linear. Some cases had a p53 LI below the mean even though the Ki-67 LI was higher. The clinical course was characteristic of superficial bladder carcinoma initially, but progressed to invasive bladder carcinoma over the next several years. These results suggest that even cases initially diagnosed as superficial bladder carcinoma with a low p53 LI may progress to invasive bladder carcinoma in subsequent years. Therefore, it is important that the patient be followed-up.

We manufactured an esophageal prosthesis made of a collagen sponge supported by an inner silicone tube. The collagen was derived from porcine skin and was crosslinked by dehydrothermal treatment. We implanted our prosthesis in nine dogs after resecting a 5 cm length of the thoracic esophagus. Intravenous hyperalimentation was performed for 4 weeks after the surgery. After 29 days, the inner silicone tube was removed endoscopically and oral feeding was restarted immediately. All nine dogs survived more than 1 month, and three of the nine dogs survived for more than 1 year. Endoscopically, the luminal surface of the regenerated esophagus was covered with a lustrous, smooth mucosa, but stenosis was observed in the midregion of the regenerated esophagus. Microscopically, no foreign material remained at the reconstructed site 1 month after surgery; the collagen sponge was absorbed and replaced by host tissue. Complete epithelization was observed within 3 months. Regeneration of the lamina muscularis mucosae, esophageal glands, and skeletal muscle were observed near the anastomoses. Our artificial esophagus holds promise for esophageal reconstruction in a clinical setting, even in the thorax.

We evaluated facial nerve regeneration using a collagen tube as a nerve conduit in five cats. In three 5 mm of the facial nerve were resected, a collagen tube was implanted, and a 5 mm segment of the opposite facial nerve was resected, reversed 180 degrees, and sutured back as an autologous nerve graft. In one a collagen tube was implanted on one side, and in the remaining one a 5 mm nerve segment was reversed. Histological, electrophysiological, and horseradish peroxidase labelling examinations were carried out 4-24 weeks postoperatively. Histological study showed that the nerve was well vascularised and regenerated. Electrophysiological examination confirmed the recovery of evoked electromyograms through to the regenerated axons. Horseradish peroxidase examination also confirmed restoration of the whole facial nerve. The collagen tube is an efficient nerve conduit.

We have previously reported on a straight artificial trachea developed by our group that can be applied to the cervical and thoracic trachea. In this study, a new Y-shaped artificial trachea was designed and adapted for experimental replacement of defective tracheal bifurcations in 20 dogs. The Y-shaped Marlex mesh tube was reinforced with a polypropylene spiral and coated with collagen made from porcine skin. This coating process makes the prosthesis biocompatible and airtight. Replacement of the tracheobronchial bifurcation was performed through a right thorachotomy, and omentopexy was added in all 20 dogs. Six of the 20 dogs have survived. The causes of death of the other 14 dogs were obstruction of the main bronchus (one dog), omental necrosis (three dogs), and air leakage from the prostheses and suture points (10 dogs). In all six surviving dogs, the artificial tracheas are covered with regenerated tissue and there is no evidence of stenosis or dehiscence. These results indicate that the prosthesis can be effective and safe in the long-term; however, air leakage from the prosthesis is a serious complication. Therefore, a better method is needed to make the prosthesis airtight to improve the postoperative result.

Background: Xiao zhi ling (XZL), which consists of Chinese nutgalls and aluminium potassium sulphate, is used as a local injection for the treatment of internal haemorrhoids in China. It is also used for endoscopic sclerotherapy of oesophageal varices. To date, however, it has not been compared with other sclerosants with regard to its safety and efficacy., Methods: In the present study, the effect on the endothelium and the haemolytic and thrombosing effects of XZL were compared with those of 5% ethanolamine oleate and 1% polidocanol, using an endothelial cell line and red blood cells taken from rats and the dorsal marginal ear vein of rabbits. In addition, XZL was injected into the area surrounding varices in rats and its efficacy was studied endoscopically and histologically., Results: Xiao zhi ling reduced the size of varices in rats after causing severe damage in the injected region. Compared with the other two sclerosants, however, XZL had little effect on the endothelium and was the least haemolytic compound. Furthermore, XZL did not cause thrombosis in the injected vein of a rabbit., Conclusions: These results suggest that XZL is another type of sclerosant with astringent rather than detergent properties. This compound should be used to treat oesophageal varices by paravariceal injection in smaller doses than 5% ethanolamine oleate and 1% polidocanol.

A mitogen for growth-arrested cultured bovine aortic smooth muscle cells was purified to homogeneity from the supernatant of cultured human umbilical vein endothelial cells by heparin affinity chromatography and reverse-phase high performance liquid chromatography. This mitogen was revealed to be tissue factor pathway inhibitor-2 (TFPI-2), which is a Kunitz-type serine protease inhibitor. TFPI-2 was expressed in baby hamster kidney cells using a mammalian expression vector. Recombinant TFPI-2 (rTFPI-2) stimulated DNA synthesis and cell proliferation in a dose-dependent manner (1-500 nM). rTFPI-2 activated mitogen-activated protein kinase (MAPK) activity and stimulated early proto-oncogene c-fos mRNA expression in smooth muscle cells. MAPK, c-fos expression and the mitogenic activity were inhibited by a specific inhibitor of MAPK kinase, PD098059. Thus, the mitogenic function of rTFPI-2 is considered to be mediated through MAPK pathway. TFPI has been reported to exhibit antiproliferative action after vascular smooth muscle injury in addition to the ability to inhibit activation of the extrinsic coagulation cascade. However, structurally similar TFPI-2 was found to have a mitogenic activity for the smooth muscle cell.

Flat plates made from a copolymer of epsilon-caprolactone and L-lactide (P-CL-LA) [50:50 (w/w), molecular weight 1.62 x 10(5); 20 x 10 x 1 mm size] were subcutaneously implanted into 50 young, male Wistar rats (P-CL-LA group). After 24 months the plates had become a mass of small pieces, which were concentrated in an area of 3 x 2 x 1 mm. For comparison, 50 rats were implanted with medical-grade polyethylene plates (PE group) while another set of 50 rats was subjected to the same operation but without an implant (Sham Op group). Tumors arose in 25 rats from the P-CL-LA group: 24 were malignant mesenchymal tumors at the implant sites. In the PE group, tumors appeared in 16 rats (14 at the implant sites and two ectopically). The average tumor latency was 578+/-84 days in the P-CL-LA group and 452+/-102 days in the PE group. There was no difference in tumor incidence between the P-CL-LA and PE groups (p < 0.05). In the Sham Op group, two malignant tumors appeared over 2 years. Pathologically, these induced tumors arose from the inflammatory cells surrounding the degrading fragments of P-CL-LA within the tissue capsule. This indicates that relatively slowly degrading material can induce malignant tumors at a similarly high rate to nonabsorbable medical grade PE, at least in this animal model.

Laparoscopic operation has been an alternative method in not only adults but children. We presented two children with true hermaphroditism who were performed by open gonadectomy and laparoscopic gonadectomy respectively. Both patients at the age of 4, and 2 years showed karyotypes of 46, XX, and were raised as girls. In the first case left ovary and right ovotestis were revealed by open gonadal biopsy and right ovotestis was removed by open surgery. In another case bilateral ovotestes were revealed by laparoscopic gonadal biopsy and resected by laparoscopic procedure. Laparoscopy was very useful for detecting the gonadal structures to confirm the diagnosis in intersex patients. True hermaphrodite is one of uncommon intersex anomalies, therefore the diagnosis should be made to demonstrate the coexistence of both ovarian and testicular tissues definitely. We estimated laparoscopic gonadectomy in pediatric true hermaphrodite and concluded that laparoscopic gonadectomy was as profitable as open gonadectomy.

A 42-year-old woman had been given a diagnosis of malignant lymphoma, follicular, small cleaved cell. She had undergone chemotherapy including etoposide (1,500 mg/total) and was in her second complete remission. Four years and 4 months later, refractory anemia with excess of blasts (RAEB) with dup(11) (q21q23) x 2 developed in the patient and progressed to acute myeloid leukemia (AML-M5b). Despite regression of the AML to RAEB, a clone with the additional abnormality of del(20) (q11q13.1) appeared and transformed the RAEB into AML-M6. Rearrangement of the MLL gene was observed, and FISH analysis demonstrated that the signal sequences from the gene's 5' and 3'-terminal regions had detached. RT-PCR techniques detected a tandem duplication of MLL gene exons 2 through 8. This was considered to be one of the mechanisms behind the formation of the 11q23 abnormality observed in this patient.

Peripheral T cell neoplasms originating from gamma/delta T cells are rarely reported, despite the development of hepatosplenic lymphoma from gamma/delta T cells. We report a case of multiple generated gamma/delta T cell lymphomas presenting in the subcutaneous tissue and small intestine in a patient with accompanying capillary leak syndrome. The patient, a 43-year-old male presented with remarkable systemic edema, pleural effusion, and ascites. Widespread tumors were evident in the subcutaneous tissue and in the small intestine. A biopsy revealed anaplastic large cell lymphoma in these lesions. Phenotypic examination showed that the neoplastic cells were positive for the surface markers CD3 and TCR delta, but negative for CD4, CD8 and TCR beta. Genomic analysis revealed a clonal rearrangement of the TCR genes encoding the gamma, delta, and beta chains. A polymerase chain reaction analysis of the gene encoding the TCR delta chain showed that the rearrangement occurred between V delta 3 and J delta 1, suggesting that neoplastic cells were generated in the early stages of T cell differentiation.

Objective: Attempts have been made to replace esophageal defects with a variety of artificial materials. However, because of the artificial nature of the materials, problems such as infection, leakage, stricture, or dislocation could not be avoided. Therefore we have designed a new type of artificial esophagus that is gradually replaced by host tissue., Methods: Our artificial esophagus was a two-layered tube consisting of a collagen sponge matrix and an inner silicone stent. We used it to replace 5 cm esophageal segmental defects in 43 dogs, and the inner silicone stent was removed endoscopically at weekly intervals from 2 to 4 weeks., Results: In the 27 dogs from which the silicone stent was removed at 2 or 3 weeks, constriction of the regenerated esophagus progressed and the dogs became unable to swallow within 6 months. In the 16 dogs from which the silicone stent was removed at 4 weeks, highly regenerated esophageal tissue successfully replaced the defect, leaving no foreign body in the host. Moreover, the regenerated esophagi had stratified flattened epithelia, striated muscle tissue composed of an inner circular and an outer longitudinal muscle layer, and esophageal glands., Conclusions: Even in mature adult higher mammals, esophageal high-order structures can be regenerated provided that an adequate three-dimensional extracellular structure is put in place for a sufficient period.

Animal models resembling the human situation are very useful to investigate human disease. However, there has been no evidence of esophageal varices in rats with liver cirrhosis. In the present study, to determine whether intrahepatic portal hypertension produced by liver cirrhosis induces esophageal varices in rats, the esophagus was examined endoscopically in rat models of liver cirrhosis. All rats given carbon tetrachloride or thioacetamide and six of seven rats given a choline-deficient diet had esophageal varices or venous dilatation after 16 weeks of treatment, although the varices in one rat given carbon tetrachloride and in two rats given a choline-deficient diet were reduced from weeks 16 to 18. These findings suggest that timing is important when studying esophageal varices in rat models of liver cirrhosis. It is concluded that certain models of liver cirrhosis in rats could be used as models of esophageal varices due to intrahepatic portal hypertension.

To clarify the indoor behavior of insecticides in space spraying, an aerosol canister (containing a mixture of 0.45 g d-tetramethrin and 0.06 g d-resmethrin in a 300-mL product) was applied to a typical Japanese room under various conditions and temporal concentrations in air; floor, walls, and ceiling were monitored. Air concentrations were chiefly dependent on ventilation rates but not on air circulation by an air conditioner. During a periodic spraying, the airborne insecticides did not accumulate in the room, but the floor residues gradually increased with the number of sprayings. After cessation of spraying, however, dislodgeable residues on the floor decreased with time. The time-dependent behavior of d-tetramethrin was simulated by a mathematical model (InPest) developed by the authors, and it was found that the estimated values agreed fully with actually measured values. The simulation model also clarified the amount of insecticide evaporated from the room material, the amount vented to the outdoors, and so on. Indoor exposure levels of d-tetramethrin and d-resmethrin to the room's occupants were estimated with the monitored concentrations when a 10-sec spraying was done twice a day for 30 days. The margins of safety, which were obtained by dividing the no observed effect levels by the exposure levels, were over 100 for unclothed occupants, even in the room with the windows closed.

To clarify the indoor behavior of insecticides in residual spraying equivalent to a crack and crevice treatment, an aerosol canister (containing a mixture of 0.9 g d-phenothrin and 1.1 g d-tetramethrin in a 300-mL product) was applied to a typical Japanese room under various conditions, and temporal concentrations in air and on the floor, walls, and ceiling were monitored. Air concentrations were chiefly dependent on ventilation rates but not on air circulation. During a periodic spraying, the airborne insecticides did not accumulate in the room, but the floor residues gradually increased with the number of sprayings. After cessation of spraying, however, dislodgeable residues on the floor decreased with time. The time-dependent behavior of d-phenothrin was simulated by a developed simulation model (InPest), which helped a more comprehensive understanding of the insecticide behavior. Indoor exposure levels of d-phenothrin and d-tetramethrin to room occupants were estimated with the monitored concentrations when a 2.5-min spraying was done four times over an 8-week period. The margins of safety, which were obtained by dividing the no observed effect levels by the exposure levels, were over 100 for unclothed occupants, even in a room with the windows closed.

Background: Reconstruction of a long section of the trachea is clinically problematic. Tracheal reconstructions using prostheses have met with limited success due to local infection, hemorrhage, luminal stenosis and prosthesis dislocation., Methods: We have designed a porous type of tracheal prosthesis in which the mesh is sealed with collagen sponge. We used this prosthesis (50 mm in length) to reconstruct the cervical trachea in 10 mongrel dogs and evaluated its efficacy., Results: One dog died due to an accident with anesthesia at 6 weeks and 1 of suffocation at 10 weeks. The other 8 dogs had an uneventful postoperative course until they were killed between 6 and 24 months after implantation. At sacrifice, all the prostheses had become completely incorporated into the host. Microscopic examination revealed advanced formation of a new epithelial lining in 1 dog at 6 months, and a confluent epithelial lining was observed in another dog at 12 months. Central stenosis was not significant in any of the animals., Conclusions: This tracheal prosthesis gives good results in canine tracheal reconstruction, and appears very promising for the clinical repair of tracheal defects.

The sensitivities of oligosaccharide derivatives in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) were compared using two matrixes, 2,5-dihydroxybenzoic acid (DHBA) and alpha-cyano-4-hydroxycinnamic acid (CHCA). For this purpose, maltopentaose was tagged with 2-aminopyridine (PA), 4-aminobenzoic acid ethyl ester (ABEE), and trimethyl-(p-aminophenyl)ammonium chloride (TMAPA). DHBA was more advantageous for enhancement than CHCA. Among the derivatives, the sensitivity with the PA-tagged maltopentaose showed a 100-fold improvement over the native one with DHBA as a matrix, while the oligesaccharide derivatized with ABEE and TMAPA gave 30- and 10-fold increases in sensitivity over the underivatized one. To obtain structural information from these derivatized oligosaccharides, postsource decay (PSD) during flight in the field-free drift in MALDI-TOFMS was measured. Predictable and reproducible fragmentation patterns could be obtained in all cases. Furthermore, we found matrix-dependence fragmentation with the PA-labeled oligosaccharide. With CHCA, a simple spectrum ascribable to Y series ions was obtained. On the other hand, both B and Y series ions were clearly observed in the DHBA case. The results demonstrate the usefulness of derivatives for sensitive analysis of oligosaccharides with MALDI.

Background: We conducted ultrastructural studies to clarify the fine structure of penile plaques and adjacent corpora cavernosa, and the causative basis for the process, in Peyronie's disease., Methods: Penile plaques and adjacent corpora cavernosa were obtained during surgical extirpation from 5 patients with Peyronie's disease. Control tissues from the tunica albuginea and adjacent corpora cavernosa were obtained at penile amputation from 2 patients with penile cancer. Prepared tissues were examined by using electron microscopy., Results: Penile plaques were composed of collagen fibrils, amorphous particulate material, and fibroblasts in all patients. In 1 of 5 patients, myofibroblasts were found in the border area between the lesion and underlying structures. Smooth-muscle cells and endothelial cells resembling myofibroblasts were noted in adjacent corpora cavernosa. In this patient, the plaque progressively enlarged, and was removed within 1 year of onset of the induration., Conclusions: Fibromatosis in Peyronie's disease involves both fibroblasts and myofibroblasts, which undergo sclerosis in some phase. In addition, smooth-muscle cells and endothelial cells in the adjacent corpora cavernosa may be incorporated in the fibromatosis.

Reconstructions of the intrathoracic trachea in 24 dogs were done with the use of 50 mm long collagen-conjugated tracheal prostheses. Omental wrapping was also done in 14 of the dogs (omentopexy group) to evaluate the efficacy of this option in comparison with results in the other 10 dogs (control group). All 24 dogs had uneventful postoperative courses and were killed at 4 weeks or 3, 6, or 12 months after the operation. Better epithelialization and fewer complications, such as mesh exposure and luminal stenosis, were observed in the omentopexy group than in the control group. Angiography and analysis of regenerated blood vessels revealed that vessel ingrowth had started within 4 weeks and that vessel formation reached its maximal point within 6 to 12 months in the omentopexy group. In contrast, revascularization of the subepithelial region in the control group was poor even after 3 months, and vessel formation continued for as long as 12 months. The differences between the two groups were considered to be mainly a result of the speed of blood vessel ingrowth into the regenerated mucosa. We conclude that our prosthesis can be used safely for intrathoracic tracheal reconstruction and that omental wrapping is a useful supplementary method that reduces the occurrence of complications.

A cis-acting regulatory region within the first intron of the human platelet-derived growth factor (PDGF) A-chain gene has been identified that functions to negatively regulate transcription of PDGF A-chain promoter/CAT reporter constructs in both A172 and HeLa cells and that functions independent of position, orientation, and promoter context. Further dissection of this region revealed several independently acting negative regulatory elements that exhibited cell-type specificity. These results suggest that the first intron of the PDGF A-chain gene contains negative regulatory elements that may cooperate to regulate the cell-type specific expression of the PDGF A-chain gene.

We encountered a male patient with marked basophilia and eosinophilia complicated by anemia, thrombocytopenia, myelofibrosis, and hyperhistaminemia. Since morphological abnormalities were unclear and since chromosome analysis showed 45,XY,-7, a diagnosis of basophilic-eosinophilic myeloproliferative disorder was made. After administration of prednisolone and cytarabine ocfosfate, basophil and eosinophil levels decreased, but blasts transiently appeared in the peripheral blood. Chromosome analysis performed at the time of appearance of blasts showed a clone with 45,XY,-7,del(16)(q22). Subsequently, pancytopenia developed, after which white blood cell count and its classification were normal, as were chromosome findings. In this patient, monosomy 7 seemed to have induced myeloproliferative disorder with basophilia and eosinophilia, and del(16)(q22) may have enhanced the eosinophilia.

A 68-year-old female diagnosed as having Sézary syndrome because of generalized erythroderma and increased lymphocytes with convoluted nuclei in 1988 was treated with steroids. However she did not respond to therapy and died due to pneumonia and aggravation of Sézary syndrome in September, 1994. Dyspeptic diarrhea was observed for two months before she died. Autopsy revealed local deposition of amyloid A protein in the mucosa of the small intestine, which might have been the cause of dyspeptic diarrhea. This was a rare case which Sézary syndrome accompanied by localized amyloidosis.

A 69-year-old woman was admitted with generalized lymph node swelling and huge splenomegaly. CD5(+), Sm-IgM (+) and SmIgD (+) lymphocytes were increased in lymph nodes, spleen and bone marrow, and she was diagnosed as having mantle cell lymphoma. A diagnosis of hyper-IgE syndrome was also made, because IgE was markedly increased (174,780 u/ml) and chronic dermatitis, which was often complicated with infection, occurred repeatedly on her extremities. In this case, interleukin-4 was considered to be one of the factors involved in the hyper-IgE syndrome, because increased IgG1 and reduced IgG2 were observed. Immunological abnormality associated with the hyper-IgE syndrome seemed to contribute to the development malignant lymphoma in this case.

In the study reported here we have examined the nerve regeneration that occurs over a 25-mm gap using a novel biodegradable nerve guide tube. The tube was a composite of polyglycolic acid (PGA) mesh coated with collagen which was filled with neurotrophic factors. The left sciatic nerve of ten adult cats was dissected. The stumps were connected by the tube, and fixed gap. Histological examinations carried out 4-16 months after implantation of the tube revealed regeneration of well vascularized nerve tissue. Regeneration of both myelinated, unmyelinated axons and Schwann cells was confirmed by electron microscopy 5 months after surgery. Following injection of horseradish peroxidase (HRP) into a site peripheral to the regenerated segment of the sciatic nerves, motoneurons in the ventral horn of the spinal cord, afferent terminals in the medial portion of the dorsal column of the medulla oblongata, and sensory afferent nerve terminals in the dorsal horn of the spinal cord were labelled. Electrophysiological examinations revealed restoration of evoked electromyograms and sensory evoked potentials (SEPs) recorded from the cerebral cortex as well as the spinal cord. We also found that some of the regenerated motor axons exhibited branching in the regenerated segments. In two cases, a single motoneuronal axon from the regenerated side projected to both flexors and extensors, simultaneously. Our results indicate that the PGA-collagen composite tube is a promising tool for use as a nerve guide tube in peripheral nerve regeneration.