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Biomedical subjects

S Matsuno

Publications and source records attributed to S Matsuno.

At least 91 records · Page 5Linked to original sources

Laparoscopic cholecystectomy, Calot's triangle, and variations in cystic arterial supply.

BACKGROUND: The extrahepatic biliary tree with the exact anatomic features of the arterial supply observed by laparoscopic means has not been described heretofore. Iatrogenic injuries of the extrahepatic biliary tree and neighboring blood vessels are not rare. Accidents involving vessels or the common bile duct during laparoscopic cholecystectomy, with or without choledocotomy, can be avoided by careful dissection of Calot's triangle and the hepatoduodenal ligament. METHODS: We performed 244 laparoscopic cholecystectomies over a 2-year period between January 1, 1995 and January 1, 1997. RESULTS: In 187 of 244 consecutive cases (76.6%), we found a typical arterial supply anteromedial to the cystic duct, near the sentinel cystic lymph node. In the other cases, there was an atypical arterial supply, and 27 of these cases (11.1%) had no cystic artery in Calot's triangle. A typical blood supply and accessory arteries were observed in 18 cases (7.4%). CONCLUSION: Young surgeons who are not yet familiar with the handling of an anatomically abnormal cystic blood supply need to be more aware of the precise anatomy of the extrahepatic biliary tree.

Bile Ducts, Extrahepatic↗

Nationwide epidemiological survey of chronic pancreatitis in Japan.

The aim of this study was to estimate the number of patients treated for chronic pancreatitis in 1994 in Japan and to explore the clinico-epidemiological features of chronic pancreatitis. Two surveys were conducted. Stratified random sampling was used to select departments in which patients with chronic pancreatitis were treated, and two different questionnaires were administered to obtain relevant information. From the first survey, the total number of patients treated for chronic pancreatitis in Japan in the year 1994 was estimated as 32,000 (95% confidence interval, 25,000-39,000). Clinico-epidemiological features, based on the 2,523 patients reported from the second survey, were subsequently clarified. The sex ratio (male/female) of the patients was 3.5. Alcoholic pancreatitis was the most common type in males (68.5%), and idiopathic pancreatitis in females (69.6%). Compared with the findings in the last survey in 1985, the proportion of patients with alcoholic pancreatitis has decreased slightly, from 58.7% to 55.5%, while that of idiopathic chronic pancreatitis has increased in both males and females. Patients diagnosed by advanced techniques such as computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) accounted for 68.1% of the total. The number of patients with chronic pancreatitis treated in 1994 in Japan, was estimated as 32,000, with an overall prevalence rate of 45.4 per 100,000 population in males and 12.4 per 100,000 population in females.

Adolescent↗

Splenic vein occlusion secondary to tuberculous lymphadenitis at the splenic hilum: report of a case.

We report a patient with splenic vein occlusion (SVO) secondary to tuberculosis. A 17-year-old male patient with mild epigastric pain and splenomegaly was found to have gastric varices by gastroscopy, and SVO by selective angiography. At operation, the splenic vein was occluded by hard fibrous tissue at the splenic hilum, and thus a splenectomy was performed. A microscopic examination of the tissue revealed caseous necrosis surrounded by epithelioid cells and Langhans-type giant cells. Although there were no other findings suggesting intestinal tuberculosis, it seemed that tuberculous lymphadenitis of the splenic hilum most likely caused the occlusion of the splenic vein. Because specific tests for tuberculosis were negative in both immunohistochemical staining for bacille Calmette-Guérin and polymerase chain reaction of DNA for Mycobacterium tuberculosis, the time of infection was assumed to have occurred a long time before. SVO can sometimes be seen in pancreatic diseases, but this patient with tuberculosis appears to be the first such reported case in the English literature.

Adolescent↗

Surgery today

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Journal Article↗

Rearrangement generated in double genes, NSP1 and NSP3, of viable progenies from a human rotavirus strain.

We generated rotavirus clones with rearrangement in vitro by serial passages of a human rotavirus strain (IGV-80-3) at high multiplicity of infection and determined nucleotide sequences of the rearranged genes from two distinct rotavirus clones, each of which possesses two rearranged genes: a common rearranged NSP1 gene and NSP3 gene with slightly different migration in polyacrylamide gel electrophoresis. Sequence analysis showed that the rearranged NSP1 and NSP3 genes had similar gene structures: concatemerization in a head to tail orientation and partial duplication of the open reading frame following the termination codon. The rearranged NSP1 gene had a direct repeat, whereas in the rearranged NSP3 gene, no such pattern was found.

Blotting, Northern↗

Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer.

BACKGROUND: The prognosis of patients with resected pancreatic cancer remains poor. This study evaluated the effect of adoptive immunotherapy (AIT) using intraportal infusion of lymphokine-activated killer (LAK) cells after curative resection and intraoperative radiation therapy (IORT) on advanced pancreatic cancer. METHODS: Twenty-nine consecutive patients with advanced pancreatic cancer (Japan Pancreas Society stage III or IV) were divided into two groups. The control group (n = 17) underwent tumour resection and IORT. The treatment group (n = 12) underwent resection, IORT and intraportal infusion of LAK cells combined with recombinant interleukin 2 (rIL-2). The incidence of liver metastasis and the survival rate of these two groups were compared. RESULTS: Although the overall survival between groups was not statistically different (P = 0.082), there were more patients (four) alive 3 years after operation in the test group (36 per cent versus zero), and the incidence of liver metastases in the treatment group was significantly lower (three of 12 versus ten of 15; P < 0.05). LAK therapy influenced survival positively in multivariate analysis. CONCLUSION: These preliminary observations suggest that AIT warrants further study as a possible adjuvant for patients undergoing curative resection and IORT for pancreatic cancer.

Combined Modality Therapy↗

DIGEST: digest

Professor Seiki Matsuno, Chief Editor oy Surgery Today (The Japanese Journal of Surgery), has selected from the January to March 2000 issues of the journal for this quarter's digest. A digest of BJS for the same period written by Professor Pierre Guillou, Associate Editor, appears in the Japanese journal.

Journal Article↗

Identification of cells responding to vasoactive intestinal peptide by measuring intracellular cyclic adenosine monophosphate in human colonic mucosa.

BACKGROUND: Although there is great deal of evidence suggesting that vasoactive intestinal peptide (VIP) has immunomodulating effects on human colonic lamina propria mononuclear cells (LPMC), it remains unclear which type of cell carries functional VIP receptors. In this study we investigated the presence of functional VIP receptors by measuring intracellular cyclic adenosine monophosphate (cAMP) in isolated epithelial cells, bulk LPMC, T cells, and macrophages in human colonic mucosa. METHODS: Epithelial cells and LPMC were isolated from non-pathologic segment of colonic mucosa of surgical specimens from five patients with colonic cancer. Mucosal T cells and macrophages were further isolated from LPMC. Each cell population was cultured with various concentration of VIP for 60 min at most. Then, intracellular cAMP was extracted and measured by enzyme-linked immunoassay. RESULTS: When isolated epithelial cells were examined, VIP increased intracellular cAMP in a dose-dependent fashion, as observed in HT-29 cells used as a positive control. In contrast, the concentration of cAMP was essentially stable in response to VIP when isolated LPMC were examined. This was the case even when separated T cells and macrophages were individually investigated. To evaluate the possible effects of enzyme digestion for LPMC isolation on the VIP response. HT-29 cells were precultured with collagenase and deoxyribonuclease (DNase 1), resulting in less enhancement of cAMP by VIP. CONCLUSIONS: In this study we failed to show VIP-responsive enhancement of cAMP in mucosal immune cells, suggesting that epithelial cells may be major effector cells of VIP in human colonic mucosa.

Aged↗

Functional construction of the anti-mucin core protein (MUC1) antibody MUSE11 variable regions in a bacterial expression system.

A bacterial expression system for the variable region fragments (Fvs) of the anti-MUC1 tumor antigen antibody MUSE11 has been constructed. The Fv fragment showed binding specificity toward TFK-1 cells, with slightly reduced affinity compared to its parent IgG. The single-chain Fv fragment was arranged in two orders, VH-linker-VL and VL-linker-VH. However, linking the regions with a flexible peptide linker (GGGGS)(3) or with a shorter linker (GGGGS) led to a dramatic decrease in the biological activity toward the target antigen in both arrangements, suggesting that the MUSE11 antibody loses its activity when the domains are linked with polypeptide linkers. These results indicate that the variable region domains of the anti-MUC1 antibody MUSE11 have specificity only in the Fv form, and that linking the domains strongly reduces the association with its target antigen. Gel filtration analysis indicates that the scFv has a dimeric structure, suggesting that the inactivation of MUSE11 scFv is due to unfavorable intermolecular associations of the scFv chains. To our knowledge, this is the first report of a significant reduction in affinity caused by linking the variable domains in both arrangements, i.e., VH-VL and VL-VH.

Animals↗

Construction of a diabody (small recombinant bispecific antibody) using a refolding system.

Diabodies are the recombinant bispecific antibodies (BsAbs), constructed from heterogeneous single-chain antibodies. Usually, diabodies have been prepared from bacterial periplasmic fraction using a co-expression vector (i.e. genes encoding two chains were tandemly located under the same promoter). Some diabodies, however, cannot be expressed as a soluble material owing to inclusion body formation, which limits the utilization of diabodies in various fields. Here we report an improved method for the construction of diabodies using a refolding system. As a model, a bispecific diabody binding to adenocarcinoma-associated antigen MUC1 and to CD3 on T cells was studied. One chain consisted of a VH specific for MUC1 linked to a VL specific for CD3 with a short polypeptide linker (GGGGS). The second was composed of a VL specific for MUC1 linked to a VH specific for CD3. The two hetero scFvs were independently obtained from intracellular insoluble fractions of Escherichia coli, purified, mixed stoichiometrically (at an equivalent molar ratio of 1:1) and refolded. The refolded two hetero scFv has a hetero-dimeric structure, with complete specificity for both target cells [i.e. MUC1 positive cells and CD3 positive lymphokine-activated killer cells with a T cell phenotype (T-LAK)]. Evaluation of the in vitro efficacy of T-LAK with the diabody by growth inhibition assay of cancer cells demonstrated maximum growth inhibition of cancer cells to reach approximately 98% at an effector:target ratio (E:T ratio) of 10, almost identical with that with anti-MUC1xanti-CD3 chemically synthesized BsAbs (c-BsAbs). This is the first report of the construction of a diabody using a refolding system.

Antibodies, Bispecific↗

The antiangiogenesis effect of interleukin 12 during early growth of human pancreatic cancer in SCID mice.

Interleukin 12 (IL-12) is a heterodimeric cytokine that exerts a potent antitumor effect through its pleiotropic actions. It was recently reported that IL-12 has also a potent antiangiogenic effect through the induction of IFN-gamma, which triggers the production of chemokines such as IP-10 that has been shown to have antiangiogenesis properties. In this study we transfected the IL-12 gene into a human pancreatic adenocarcinoma cell line (PK-1). PK-1 cells transfected with the green fluorescence protein (gfp) gene were used as positive controls. The in vitro growth curve and in vivo tumor growth of transfectants (IL-12/PK-1 and gfp/PK-1) were compared with those of parental cells. The SCID mice used in this study were administered antiasialo GM-1 Ab (100 microg, i.p., twice weekly) to deplete the remaining immunoeffector cells, NK cells. Using a skinfold chamber model, we observed and recorded tumor angiogenesis by intravital microscopy. In vitro growth of IL-12/PK-1 and gfp/PK-1 cells was not different from that of wild-type PK-1 cells (wt/PK-1). However, IL-12 transfected PK-1 cells did not develop into tumors as did the wt/PK-1 cells after subcutaneous inoculation in antiasialo GM-1 Ab administered SCID mice. The growth of IL-12/PK-1 tumors was restored in mice treated with anti-IL-12 antibody. We found that IL-12/PK-1, in contrast to gfp/PK-1 and wt/PK-1, failed to initiate an angiogenic response, as observed in the skinfold chamber model. These results indicate that the antiangiogenesis effect of IL-12 alone, without immune system involvement, is sufficient to block the growth of human pancreatic cancer.

Adenocarcinoma↗

Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic cancer is one of the diseases with the poorest prognosis, but the associated genetic alterations are not yet well understood. The genetic alterations reported to date in pancreatic cancer include frequent mutations of the KRAS, TP53, p16, and SMAD4 genes. Mutation of the TP53 gene was reported to be associated with a poor prognosis. In this study, we analyzed the association of loss of heterozygosity (LOH) with clinicopathological features to attempt to devise effective methods in the future for clinically applying our results to diagnosis and treatment. METHODS: A total of 55 tumors from patients with primary pancreatic ductal carcinomas (34 men and 21 women, mean average age 63.9 yr) in which all the relevant clinical and pathological data were available were analyzed. A total of 46 cases were surgically resected, and nine cases were not. Tumor cells as well as corresponding normal cells were collected by microdissection under a microscope, and DNAs were purified. Allelotype analysis was performed by the PCR-based method, and the results were statistically analyzed. RESULTS: LOH of > or =30% were observed on chromosome arms 17p (47%, 17/36), 9p (45%, 14/31), 18q (43%, 15/35), 12q (34%, 10/29), and 6q (30%, 10/33). LOH of 12q, 17p, and 18q were significantly associated with a poor prognosis. Concordant losses of 6q with 17p and 18q were significantly associated with a poor prognosis. Concordant losses of 6q with 17p and of 12q with 18q were also found. CONCLUSIONS: Because LOH of 12q, 17p, and 18q are significantly associated with a poor prognosis, mutation of the putative tumor suppressor genes on these chromosome arms may play significant roles in the disease progression. Concordant losses of 6q with 17p and of 12q with 18q suggest that protein products of putative tumor suppressor genes on 6q and 12q may function in association with TP53 and SMAD4, respectively.

Alleles↗

Identification of genes involved in mucosal defense and inflammation associated with normal enteric bacteria.

Normal luminal bacteria and their products play a role in experimental colitis and inflammatory bowel disease. However, what molecules from what cells are responsible for mounting and maintaining the mucosal defense against luminal flora is still uncertain. The aim of this study was to identify epithelial gene products involved in mucosal defense and inflammation associated with ubiquitous enteric bacteria. Germ-free ICR mice were given an oral bacterial suspension prepared from conventional components (bacterial reconstitution). Small intestinal and colonic epithelial cells were isolated from bacteria-reconstituted, germ-free, and specific pathogen-free mice. Differential gene expression was investigated by differential display, Northern blot, and sequence analysis. Bacterial reconstitution resulted in acute but self-limited colitis. In epithelial cells, we observed the induction of small intestine-specific genes of the cryptdin family and colon-specific expression of serum amyloid A1 gene. This novel approach allows the identification of known and novel gene products involved in mucosal defense against luminal microorganisms and the associated inflammatory response.

Animals↗

[The role of preoperative staging for pancreatic cancer].

Despite the poor prognosis of pancreatic carcinoma patients, surgical resection remains the only potentially curative treatment. As it has been demonstrated that extended radical surgery does not lead to a better prognosis, accurate staging to select those patients who may benefit from resection is essential. According to the report of a national survey of pancreatic cancer in 1997, patients with S0 or S1, RP0 or RP1, and N0 or N1 disease have longer survival periods compared with patients with S2, RP2, and N2 disease. Therefore patients classified as Stage I, Stage II, or Stage III are recognized as candidates for surgical resection. Patients classified as Stage IVb because of positive P factor or positive H factor are selected for conservative treatment such as chemotherapy and irradiation. It remains to be clarified whether patients classified as Stage IVa should undergo surgical resection or not. Future prospective randomized studies of patients with Stage IVa disease will reveal whether surgical resection or chemoradiation is effective. Helical CT is useful to evaluate S and RP factors for definitive preoperative staging. CT-AP can reveal occult metastases to the liver. These preoperative evaluations should be evaluated along with histological findings.

Humans↗

The effect of modified ultrafiltration in pediatric open heart surgery.

Since 1997 we have performed modified ultrafiltration (MUF) in pediatric open heart operations. To elucidate the clinical effects of MUF, patients under 20 kg in weight who underwent corrective open heart operation since 1997 are divided into 2 cohorts according to the enforcement of MUF (control group versus MUF group) retrospectively. Procedures, age, bodyweight, cardiopulmonary bypass (CPB) time, operation time, amount of donor blood use, postoperative inotrope dose, postoperative intubation time, and postoperative gas exchange capacity of lung expressed with respiratory index (RI) were compared between groups. Furthermore, a multiple linear regression analysis was performed to find independent correlates with postoperative RI. Finally scattergrams of intubation time and RI were drawn against several factors. In univariate analyses, the MUF group had significantly shorter intubation time and better RI. Multivariate analysis revealed that the enforcement of MUF was an independent correlate of postoperative RI. Analyses on the scattergrams revealed that the above mentioned favorable effects of MUF were prominent in the patients younger than 3 years or weighing less than 10 kg. We concluded that MUF had significant effects on pulmonary function preservation in pediatric open heart operations, especially for smaller children.

Body Weight↗

[A study of liver metastasis from colorectal cancer in which hepatic resection was performed after hepatic arterial infusion chemotherapy].

We experienced 5 cases of liver metastases from colorectal cancer, in which hepatic resection was carried out after down sizing by hepatic arterial infusion chemotherapy. In addition, a histological study about the effect of chemotherapy on the liver tumor was performed. Primary lesions were located at the sigmoid colon (2), cecum (1), descending colon (1) and rectum (1). We carried out hepatic arterial infusion chemotherapy using mainly 5-FU. The total amount of 5-FU was 10-81 g. Tumor volumes were reduced by 12.5-24%, and they were judged PR. However, surgery was indicated due to obstruction of the proper hepatic artery or other side effects. Postoperative courses were uneventful and the hospital stays were from 17-61 days, and all patients were still alive in tumor-free condition at writing. By the histological study of the excised specimen, we recognized not only remarkable fibrous changes or calcifications but also overt viable cancerous cells. We conclude that the option of hepatic resection after controlling the development of the cancer by hepatic arterial infusion chemotherapy is a rational strategy of treatment for liver metastasis from colorectal cancer.

Aged↗

[A case of lateral origin of the left internal mammary artery].

A 66 years old men, with left anterior descending coronary artery (LAD) stenosis and aortic valve stenosis, underwent coronary artery bypass grafting (CABG) to LAD with left internal mammary artery (LIMA) and aortic valve replacement. His postoperative course was uneventful. But, postoperative angiogram showed that his patent LIMA graft was originated from much lateral side of the left subclavian artery. Internal mammary artery is considered the most ideal graft for CABG, but its' anomality is not well known. We present this rare case with the anomalous origin of LIMA.

Aged↗