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Biomedical subjects

N Nakajima

Publications and source records attributed to N Nakajima.

At least 109 records · Page 6Linked to original sources

Stereocontrolled reduction of alpha- and beta-keto esters with micro green algae, Chlorella strains.

The stereocontrolled reduction of alpha- and beta-keto esters using micro green algae was accomplished by a combination of the cultivation method and the introduction of an additive. The reduction of ethyl pyruvate and ethyl benzoylformate by the photoautotrophically cultivated Chlorella sorokiniana gave the corresponding alcohol in high e.e. (>99% e.e. (S) and >99% e.e. (R), respectively). In the presence of glucose as an additive, the reduction of ethyl 3-methyl-2-oxobutanoate by the heterotrophically cultivated C. sorokiniana afforded the corresponding (R)-alcohol. On the other hand, the reduction in the presence of ethyl propionate gave the (S)-alcohol. Ethyl 2-methyl-3-oxobutanoate was reduced in the presence of glycerol by the photoautotrophically cultivated C. sorokiniana or the heterotrophically cultivated C. sorokiniana to the corresponding syn-(2R,3S)-hydroxy ester with high diastereo- and enantiomeric excess (e.e.). Some additives altered the stereochemical course in the reduction of alpha- and beta-keto esters.

Chlorella↗

A phase III randomized study comparing oral doxifluridine and oral 5-fluorouracil after curative resection of gastric cancer.

To investigate the usefulness of oral doxifluridine (5'-DFUR), an active intermediate metabolite of capecitabine (XELODA), in gastric cancer patients after curative resection, we conducted a phase III randomized controlled study to compare oral 5'-DFUR and oral 5-fluorouracil (5-FU). 485 gastric cancer patients with Stage II or III operative findings at curative resection were registered and administered 5'-DFUR (460 mg/m2/day, daily, for two years) or 5-FU (115 mg/m2/day, daily, for the same period). Although no differences in overall survival or disease-free survival were detected, subset analysis showed 5'-DFUR was more effective in reducing peritoneal recurrence than 5-FU (p = 0.047), and in patients with Stage III or stage IIIb (histologic findings) in the 5'-DFUR group had more favorable disease-free survival curves and survival curves than the 5-FU group with similar stages.

Administration, Oral↗

[The relationship between the tumor uptake of gallium-67 and the effect of cisplatin-based preoperative chemotherapy or chemoradiotherapy for lung cancer].

Cisplatin has been usually used as the chemotherapy for lung cancer presurgically, though it is still difficult to predict downstaging of tumor from this drug. Four patients who underwent surgery achieved pathologic complete remissions in response to preoperative cisplatin-based chemotherapy with or without radiation. All of the Ga-67 citrate images in the four patients showed markedly increased uptake in tumors. According to the literatures, both Ga-67 and cisplatin binds to transferrin in the blood and transfers into the cells through transferrin-receptors expressed on the cell surface. The mechanism for Ga-67 and cisplatin uptake into tumor cells were alike. Marked tumor uptake on Ga-67 scintigraphy suggested that cisplatin-based chemotherapy or chemoradiotherapy was efficacious.

Aged↗

[Hepatectomy (parenchyma-preserving) for hilar cholangiocarcinoma].

The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy as surgical treatment for hilar cholangiocarcinoma. Ninety-three resected patients with hilar cholangiocarcinoma were included in this study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66); the parenchyma-preserving hepatectomy (PPH) group (n = 14); and the local resection (LR) group(n = 13). The EXH group underwent hepatectomy more extensive than hemihepatectomy, the PPH group underwent hepatectomy less extensive than hemihepatectomy; and the LR group underwent extrahepatic bile duct resection without hepatic resection. Surgical curability of the PPH and EXH groups was better than that of the LR group. Surgical morbidity was higher in the EXH group(48%) than in the LR group (8%) and the PPH group(14%) (p < 0.01 and p < 0.05, respectively). The survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR (29% vs 8% at 5 years, respectively, p < 0.05). However, no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analysis showed that significant prognostic factors for survival were resected margins, lymph node status, and vascular resection. In conclusion, PPH may be beneficial in highly selected patients based on cancer extent and high-risk patients with liver dysfunction and advanced age.

Analysis of Variance↗

[Autonomic nerve-sparing surgery combined with preoperative radio-chemotherapy in advanced lower rectal cancer patients].

Since 1985, we have studied autonomic nerve-sparing surgery combined with preoperative radiochemotherapy in patients with advanced rectal cancer to preserve genitourinary function without compromising radicality. The aim of this study was to evaluate postoperative genitourinary function and prognosis. A total of 84 patients with advanced rectal cancer underwent curative surgery combined with preoperative radio-chemotherapy. Of them, 76 underwent curative nerve-sparing surgery using radiation (42.6 Gy) and tegafur suppository. Postoperative genitourinary function, survival, and pelvic recurrence were investigated in these patients. The 5-year and 10-year disease-free survival rate was 80.7%, and the pelvic recurrence rate was 7.9% in patients receiving curative nerve-sparing surgery combined with radio-chemotherapy. All of these patients could micturate spontaneously, but preservation of sexual function was not as successful. Although this combined therapy is useful for curability and good postoperative quality of life, a new approach is needed to preserve sexual function.

Autonomic Nervous System↗

[A case of primary pulmonary artery myxosarcoma associated with severe pulmonary hypertension].

A 50-year-old man presented with progressive dyspnea on exertion, but with no history of chest pain or syncope. Chronic pulmonary thromboembolism was suspected and he was referred to our hospital. On ausculation, a grade 3 systolic murmur was heard, that was loudest in the fifth intercostal space lateral to the right sternal border. Chest radiography showed mild cardiomegaly and ventilation-perfusion scan revealed absence of perfusion in the left lung and the upper field of the right lung. Contrast-enhanced helical CT showed large mural defects in both main pulmonary arteries, clearly delineated by contrast medium. The left pulmonary artery was nearly completely occluded, and eccentric defects were observed projecting into the lumen of the pulmonary trunk. A tumor originating in the pulmonary artery was suspected, but a definitive diagnosis of the mass could not be made with pulmonary angiography and magnetic resonance imaging. The mean pulmonary arterial pressure was 50 mmHg. Further radiologic examinations failed to reveal the source of the embolus or tumor. It was decided to attempt surgical excision under total cardiopulmonary bypass. At operation, a gelatinous, lustrous, yellowish mass was found partially occluding the right main pulmonary artery and completely occluding the left. The tumor adhered tightly to the intima of the vessel and was inoperable. The patient could not be weaned from percutaneous cardiopulmonary support and died 3 days after surgery. Histologic examination of the excised specimen revealed myxosarcoma.

Chronic Disease↗

[Chorioretinal blood flow changes following acupuncture between thumb and forefinger].

PURPOSE: To evaluate the effects of acupuncture stimuli on general circulation and chorioretinal blood flow changes, and to determine the duration of effect and the learning effect. OBJECTS AND METHODS: Twelve healthy young volunteers were divided into two groups. One had no experience of acupuncture (Non-Experience group); the other had experience of acupuncture (Experience group). Hegu (LI 4) between thumb and forefinger was acupunctured. Chorioretinal blood flow was measured via Heidelberg retina flowmeter before, during, and after acupuncture stimuli. RESULTS: In both groups, chorioretinal blood flow increased significantly during stimuli, with continuous bradycardia. The Experience group showed greater changes than the Non-Experience group. CONCLUSIONS: Chorioretinal blood flow was increased through relative parasympathetic reaction by stimulating an acupuncture point. Acupuncture is a promising adjunctive therapy for ischemic ocular diseases.

Acupuncture Therapy↗

Stable earthworm serine proteases: application of the protease function and usefulness of the earthworm autolysate.

The fibrinolytic enzymes from Lumbricus rubellus [Nakajima, N. et al., Biosci. Biotechnol. Biochem., 57, 1726-1730 (1993), 60, 293-300 (1996), and 63, 2031-2033 (1999)] were further characterized to exploit their catalytic functions. These enzymes are stable in solution for long periods at room temperature and strongly resistant to organic solvents, even toluene and n-hexane. The serine proteases can act on various protein substrates such as elastin and hemoglobin as well as fibrin, and also catalyzed the hydrolysis of esters such as ethyl acetate and a bioplastic, poly[(R)-3-hydroxybutyrate] film. The enzymes, in the absence of microbial degradation, contributed to the production of the earthworm autolysate possessing antioxidant ability and protease activity, whose components were similar to those of soy sauce. The extract of the earthworm autolysate could be used as a peptone substitute in media for the cultivation of microorganisms.

Journal Article↗

Enhanced conformational diversity search of CDR-H3 in antibodies: role of the first CDR-H3 residue.

Through a conformation search by a simulation calculation, the relationships between the amino acid sequences and the conformations of the third complementarity-determining region of the antibody heavy chain (CDR-H3) were investigated to characterize the large conformational varieties of antibodies. Here, we focused on the structural role of the first CDR-H3 residue, and we selected two antibodies, 28B4 and PLG, whose CDR-H3 conformations are significantly different, having Trp and Gly at the first position, respectively. Multicanonical molecular dynamics simulations, with the advantage of enhanced sampling efficiency, were performed for the CDR-H3 fragments of 28B4 and PLG, and a modified CDR-H3 model of 28B4, where the first Trp residue was substituted with Gly. When the first CDR-H3 residue is Trp, almost all of the observed CDR-H3 loops were bent at the first residue. In contrast, when the first residue is Gly, large varieties of loop conformations were observed. The structural role of this Gly residue is discussed from the perspective of the other antibody structures in the database. When the surrounding residues were included in the calculations, CDR-H3 loop structures similar to those in the crystal structures were reproduced as the major conformations for both the 28B4 and PLG antibodies.

Algorithms↗

Mutational analysis of the p73 gene in human breast cancers.

In primary breast cancer, mutations of the p53 tumor suppressor gene lead to loss of growth-suppressive properties and poor outcome. Recently, a p53-related gene, termed p73, has been cloned and its gene product possesses a function similar to p53. p73 has been mapped at chromosome 1p36.3, a region frequently deleted in breast cancer, neuroblastoma and other malignancies. To elucidate the functional significance of p73 in the oncogenesis of breast cancer, we have studied genetic alterations of p73 in tissue specimens obtained from 87 patients with primary breast cancer. Thirteen percent of informative cases showed loss of heterozygosity (LOH) at the p73 gene. However, there was no correlation between the p73 LOH and clinical features such as histopathological types, metastatic behavior or expression of estrogen or progesterone receptor. The levels of p73 transcript in primary breast cancer were not significantly different from those in normal breast tissue. Moreover, PCR-SSCP analysis failed to detect any missense or frameshift mutations in the p73 gene. Our observations suggest that allelic loss, expression levels and mutations of the p73 gene may not contribute to oncogenesis of primary breast cancers.

Adult↗

Characterization of the transcriptional activator CBF1 from Arabidopsis thaliana. Evidence for cold denaturation in regions outside of the DNA binding domain.

A transcriptional activator, CBF1, from Arabidopsis thaliana, which has the AP2 domain for DNA binding and regulates the cold acclimation response, was overexpressed in Escherichia coli, purified, and characterized. Analyses of the interaction between CBF1 and the C-repeat/dehydration-responsive element by fluorescence measurement showed that CBF1 binds to C-repeat/dehydration-responsive element as a monomer irrespective of the temperature. CD spectra of the intact and truncated CBF1 proteins (1-213, 41-213, 41-157, and 41-146) were measured to examine the temperature-dependent changes of the secondary structure of CBF1. The results suggested that the CBF1 protein has regions exhibiting reversible cold denaturation in the range between 30 and -5 degrees C and also has a region exhibiting thermal denaturation between 40 and 60 degrees C. This cold denaturation occurred in both the N-terminal and acidic regions. The thermal denaturation occurred in the region encompassing the AP2 domain. The difference between the retention time of CBF1 at 4 degrees C and that at 25 degrees C in gel filtration, and the decrease of the sedimentation coefficient, s20,w, caused by the temperature change from 25 to 3 degrees C, strongly suggested that the cold denaturation was accompanied by the extension of the molecule. The possible cold denaturation observed here might be a physiologically important structural response of CBF1 to cold stress.

Arabidopsis↗

Molecular cloning of antisense transcripts of the mouse Xist gene.

Prior to X-inactivation, Xist is transcribed in unstable form. The initiation of X-inactivation is associated with the appearance of stable Xist transcripts which coat the X chromosome to be inactivated. Using strand specific RT-PCR analysis of the 5' region of Xist, we have detected antisense transcripts (Xist AS) in undifferentiated embryonic stem (ES) cells, but not in female somatic cells. Screening of a female ES cell cDNA library allowed us to isolate one poly(A)-tailed cDNA clone corresponding to this RNA. 5' RACE analysis showed that XistAS and the P1 sense product of Xist overlap by at least 707 bp. Expression of XistAS was also detected in early mouse embryos before random X-inactivation in the epiblast lineage. Although XistAS is low in abundance, it may be involved in destabilizing Xist mRNA in undifferentiated ES cells.

Animals↗

Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic T lymphocytes.

BACKGROUND AND OBJECTIVES: We evaluated the clinical efficacy of adoptive immunotherapy using in vitro activated cytotoxic T lymphocytes (CTL) in the treatment of patients with advanced cancer. METHODS: CTL were induced with the mixed lymphocyte and tumor cell culture method, in which lymphocytes isolated from patient peripheral blood mononuclear cells were mixed with inactivated autologous tumor cells. Activated lymphocytes were administered intravenously to 11 patients once every 2 weeks for 10 weeks (i.e., 5 doses). RESULTS: Tumor reduction and decreased tumor marker were observed in 4 patients. Notably, successful CTL induction was identified in all of these patients. In patients who did not show induction of CTL response, a decreased proportion of lymphocytes, especially CD8(+) cells, and increased levels of CD14(+) cells were frequently observed. Fluorescence-activated cell sorter analysis indicated that expression of HLA class I and costimulatory factor B7-1 molecules was diminished on tumor cells. This was partly recovered with interferon-gamma, which resulted in successful induction of a CTL response. CONCLUSIONS: It was suggested that in vitro CTL induction is difficult in patients with advanced cancer. However, once the cells were induced successfully, some favorable clinical effects were seen by the adoptive transfer of such cell populations.

Aged↗

Hepatic resection for colorectal metastases: analysis of prognostic factors.

PURPOSE: Hepatic resection affords the best hope of survival for patients with colorectal carcinoma metastatic to the liver. However, recurrences are observed in about 60 percent of patients after curative hepatic resection. The purpose of this study was to examine the prognostic factors of patients undergoing curative hepatic resection for colorectal metastases. METHODS: Between April 1984 and September 1997, 168 patients underwent curative hepatic resection for colorectal metastases. The clinicopathologic factors studied for prognostic value were gender, age, primary site, nodal status of primary tumor, time of metastases, preoperative serum level of carcinoembryonic antigen, hepatic tumor size and distribution, number of metastases, type of hepatic resection, resection margin, presence of micrometastases in resected specimen and microscopic fibrous pseudocapsule between the hepatic tumor and surrounding hepatic parenchyma, nodal status of hepatoduodenal ligament, adjuvant regional chemotherapy, and perioperative transfusion. RESULTS: The overall survival was 42 percent at three years and 26 percent at five years, including a 3.5 percent 60-day surgical mortality rate. Thirty-one percent of patients had micrometastases located at a median distance of 3 mm from the metastatic tumor edge. Presence of microscopic fibrous pseudocapsule was observed in 28 percent of patients. Univariate and multivariate analyses showed that significant prognostic factors for survival were nodal status of primary tumor, number of metastases, resection margin, microscopic fibrous pseudocapsule, and adjuvant regional chemotherapy. CONCLUSIONS: We conclude that 1) hepatic resection is effective in select patients with colorectal metastases; 2) adequate resection margin and adjuvant regional chemotherapy can improve outcome; and 3) microscopic fibrous pseudocapsule may offer additional postoperative information as an independent prognostic factor.

Adult↗

Sutured wound in myxomatous mitral valve one month after repair surgery: report of two cases.

There have been no reports concerning wound healing at the site of the suture line in myxomatous leaflets. We microscopically studied the sutured wounds in two myxomatous posterior mitral leaflets which underwent quadrangular resection of the frail middle segment followed by primary suture. The sutured wounds had a thick scar which was abundant in collagen fibers about 1 month after the repair surgery. This suggests that severe myxomatous degeneration itself would not be a cause of wound dehiscence, and that a sutured wound could be a cause of rigidity and deformity of leaflets.

Humans↗

A successful case of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension with a thrombus in the right ventricle.

Chronic thromboembolism is a frequent cause of progressive hypertension and carries a poor prognosis. Medical treatment is not effective and surgery provides the only potential for a cure at present. We herein report a successful case of thromboendarterectomy treated via a median sternotomy with intermittent circulatory arrest. A 43-year-old man was admitted to our hospital complaining of progressive dyspnea, edema of the lower extremities, and a fever with an unknown origin. A subsequent definitive evaluation showed him to be suffering from surgically accessible chronic thromboembolic pulmonary hypertension with a thrombus in the right ventricle. He underwent a pulmonary thromboendarterectomy and thrombectomy via a median sternotomy with intermittent circulatory arrest on November 24, 1994. Postoperatively he showed a marked improvement in his hemodynamic status and blood gas analysis. He has also returned to work with no trouble. Deep vein thrombosis appeared to be the pathogenesis of this case, but we could not find the origin of his unknown fever. He is currently being controlled by treatment with methylprednisolone as before.

Adult↗

Nerve-sparing surgery for advanced rectal cancer patients: special reference to Dukes C patients.

Several nerve-sparing operations for advanced rectal cancer that aim to preserve genitourinary function without compromising tumor clearance have been developed in Japan. The aim of this study was to evaluate the survival and local recurrence of these procedures in Dukes B and C patients. A total of 177 patients with advanced rectal cancer underwent curative nerve-sparing surgery (NSS) over the last 11 years; 52 were Dukes B patients and 54 were Dukes C. Altogether 36 had Dukes C1 and 18 had Dukes C2 tumors, 13 with lateral lymph node metastases, designated lateral LN(+). The 5-year survival rate was 92% for Dukes B, 67% for Dukes C1, and 39% for Dukes C2 patients: 11% for Dukes C2 patients with lateral LN(+). The local recurrence rate was 6% for Dukes B, 11% for Dukes C1, and 33% for Dukes C2 patients: 20% for the lateral LN(-) group and 39% for the lateral LN(+) group. Almost all of the patients undergoing NSS could micturate spontaneously, but preservation of sexual function was not as successful. Although there is no guarantee of preserving satisfactory sexual function, our NSS is an acceptable procedure for Dukes B, C1, and C2 patients without lateral lymph node metastases.

Adult↗