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Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 631 records · Page 35Linked to original sources

An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging.

BACKGROUND: To determine the extent of dissection in curative resection for cancer of the pancreatic head, the mode of recurrence was determined at autopsy and by radiographic examinations. MATERIALS AND METHODS: Records of 45 patients who had undergone macroscopically curative resection of carcinoma of the head of pancreas were analyzed to determined the mode of recurrence. The mode of recurrence was divided into four types: hepatic metastasis, peritoneal dissemination, retroperitoneal recurrence, and distant metastasis. Retroperitoneal recurrence was subdivided into lymph node metastasis and local recurrence, primarily neural invasion and lymphatic invasion. RESULTS: Thirty patients experienced disease recurrence. Patients with Stage I or II disease experienced recurrence significantly less often than did patients with Stage III or IV disease (P < 0.05). Local retroperitoneal recurrence was discovered in 12 of 15 (80%) postmortem examinations, hepatic metastasis in 10 (66%), peritoneal dissemination in 8 (53%), and lymph node recurrence in 7 (47%). In 15 antemortem studies, retroperitoneal recurrence occurred most frequently (87%), followed by hepatic metastasis (53%). Almost all patients with liver metastasis also had local retroperitoneal recurrence. CONCLUSIONS: The frequency of retroperitoneal recurrence of carcinoma of the head of the pancreas suggests that retroperitoneal resection, including nerve plexi and lymph nodes, should be included in curative resections for patients with Stage I or II pancreatic cancer.

Adenocarcinoma↗

[Atherectomy with over-the-wire type catheter for femoro-popliteal artery stenosis: initial and eight month follow-up results].

Percutaneous atherectomy using Atherotrack was performed in 5 patients with symptomatic femoro-popliteal artery stenosis. All patients were men and ages ranged from 37 to 70. Four lesions were atherosclerotic and 1 lesion was post-operative anastomotic stenosis following traumatic popliteal artery injury. There was no technical failure and all lesions were successfully dilated with no or minimal residual stenosis. API returned within normal limit and patients were symptom-free immediately after the procedure. We experienced no major complication related to this procedure. Excised specimen included thickened fibrous intima, atherosclerotic materials, calcification, internal elastic lamina and fibrous media. Follow-up DSA 5 months after procedure showed good patency in 4 cases, and they remained free from symptoms in this follow-up period. In those patients, lesions were generally short and eccentric, run-off was good, and only thickened intimal tissue was obtained. Those factors seem to promise long-term patency and to be good indications of atherectomy. Restenosis as well as recurrence of claudication, however, developed in one patient with DM, who had long, tight, complex stenosis and poor run-off. Considerable amount of medial tissue was found in this specimen. We suspect that those factors were associated with reduced long-term patency rates.

Adult↗

[Blood flow measurement of renal artery branches, in special reference to interlobular artery by color Doppler].

Blood flow measurement was performed in 58 kidneys of healthy persons. Detection rate, maximum flow velocity (Vmax), pulsatility index (PI) and resistive index (RI) were measured at main renal artery, segmental artery, interlobar artery and interlobular artery with 2 D-Doppler ultrasound machines. Detection rate was highest at interlobar artery. Vmax and PI tended to fall down with arterial branching. Interlobular artery was usually not visualized by color flow mapping, but sometimes well visualized using Acuson machines. Additional measurement of interlobar and interlobular arteries were performed in such 15 cases, and the result was essentially equal to the above mentioned study.

Blood Flow Velocity↗

Purification and sequence determination of heat-stable enterotoxin elaborated by a cholera toxin-producing strain of Vibrio cholerae O1.

Four molecular species of heat-stable enterotoxins elaborated by a cholera toxin-producing strain of Vibrio cholerae O1 were isolated from its culture supernatant. The amino acid sequence of one of the enterotoxins was determined to be Phe-Ile-Lys-Gln-Val-Asp-Glu-Asn-Gly-Asn-Leu-Ile-Asp-Cys-Cys-Glu-Ile-Cys- Cys-Asn-Pro-Ala-Cys-Phe-Gly-Cys-Leu-Asn with three intramolecular disulfide linkages. The other enterotoxins had shorter amino acid sequences in the N-terminal regions, but possessed the same sequence in their C-terminal regions including the three disulfide linkages. The enterotoxins with the shorter N-terminal sequences showed more potent toxicities, and the minimum effective dose of the longest one with 28 amino acid residues was 10-folds of that of the shortest one.

Amino Acid Sequence↗

Acorn barnacle Megabalanus rosa lectin (BRA-3): cDNA cloning, gene structure and seasonal changes of mRNA and protein levels.

We have isolated cDNA clones coding for a lectin (BRA-3) from the acorn barnacle, Megabalanus rosa. Sequence comparison of the cDNA clones has revealed polymorphism in the BRA-3 mRNA, which results from single-nucleotide (nt) differences at three positions. All three differences are within the coding region and cause conservative amino acid (aa) changes. The BRA-3 gene is composed of four exons, and the three single-nt differences are located on different exons. In addition, the BRA-3 mRNA and BRA-3 protein levels increased during early summer in a similar fashion, indicating that BRA-3 production is regulated mainly at the level of transcription.

Amino Acid Sequence↗

Syntheses of nephritogenoside and related compounds.

Nephritogenoside has been prepared by coupling of the acyl azide derivative of a N-triglycosyl dipeptide, derived from the corresponding hydrazide derivative of O-(2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl)-(1-->6)-O-(2,3,4-tri-O -acetyl - beta-D-glucopyranosyl)-(1-->6)-2,3-di-O-benzyl-1-N-[N-(tert-butoxycarbon yl)- L-aspart-1-oyl-(L-proline methyl ester)-4-oyl]-alpha-D-glucopyranosylamine, with a nonadecapeptide, followed by deprotection of the desired protected nephritogenoside. The N-triglycosyl pentapeptide also has been prepared as a model compound.

Amino Acid Sequence↗

Age-related deterioration in conditional avoidance task in the SAM-P/10 mouse, an animal model of spontaneous brain atrophy.

A novel inbred strain of mouse 'SAM-P/10' (Senescence Accelerated Mouse) is a model of age-related brain atrophy characterized by age-related loss and shrinkage of neurons in the cerebral neocortex. Age-related changes in learning and memory skills of SAM-P/10 mice were investigated using a newly developed conditional avoidance task in a T-maze. Comparisons were made with findings in the SAM-R/1 strain which shows a little loss and no shrinkage of neocortical neurons. Four-month-old SAM-R/1 and SAM-P/10 performed well during a 10-day training schedule of the conditional avoidance task. SAM-R/1 mice over 17 months of age were slower learners than younger SAM-R/1 mice but reached nearly the same high percentage avoidance as seen in the 4-month-old mice during the last 4 days of the schedule. Performance of the SAM-P/10 mice gradually worsened with aging and 10- to 12-month-old SAM-P/10 mice could not reach the percentage avoidance seen with the 4-month-old mice, even after the 10-day training. When the mean percentage of successful avoidance or escape behavior on every training day was plotted, the curves were much the same for both SAM-R/1 and SAM-P/10 mice, of any age. These results show that aged SAM-P/10 mice retained the left-right turning discrimination in the T-maze and lost the ability to predict the forthcoming aversive shock by associating conditioned stimulus and unconditioned stimulus.

Aging↗

Development of congenic strains of mice carrying amyloidogenic apolipoprotein A-II (Apoa2c). Apoa2c reduces the plasma level and the size of high density lipoprotein.

A congenic strain of mice with amyloidogenic apolipoprotein A-II (Apoa2c) on the genetic background of the amyloidosis-resistant SAM-R/1 strain was produced by 12 generations of backcrossing. Genome mapping using endogenous murine leukemia proviral markers was done in the congenic strain, termed R1.P1-Apoa2c. We confirmed that only a small region surrounding the apoA-II gene on chromosome 1 was transferred from the genome of the donor SAM-P/1 strain. The level and particle size of plasma high density lipoprotein were decreased in R1.P1-Apoa2c mice compared to those in the progenitor SAM-R/1 mice. The function of apoA-II can be studied using this strain of mice.

Amyloidosis↗

Heterogeneity in the molecular species of heat-stable enterotoxin of Vibrio cholerae non-O1 expressed by Escherichia coli carrying the cloned toxin gene.

The biological activity of the heat-stable enterotoxin of Vibrio cholerae non-O1 (NAG-ST) was found to be predominantly associated with the periplasmic extract (about four-fold higher than the culture supernatant) of a recombinant E. coli (JM109) strain carrying the NAG-ST toxin gene. Four molecular species of NAG-ST, two each from the periplasmic extract and culture supernatant of JM109, were purified. Amino acid sequence analysis of the four NAG-ST peptides isolated by HPLC revealed that they all differed from that of the mature 17-amino acid residue NAG-ST released by V. cholerae non-O1. The M(r)-values of the peptides obtained from the periplasmic extract were 4331 and 2785, while those recovered from the culture supernatant were 3154 and 2785. It thus appears that V. cholerae NAG-ST is synthesized as larger molecules in the recombinant E. coli strain. The differences in sizes of the exported NAG-ST molecule could relate to differences in the enzyme cleavage system between E. coli and V. cholerae.

Amino Acid Sequence↗

Histological evaluation of the intrahepatic biliary tree in intrahepatic cholesterol stones, including immunohistochemical staining against apolipoprotein A-1.

Apolipoprotein A-1 is known to be one of inhibiting factors of cholesterol nucleation in bile, and decreased activity of apolipoprotein A-1 is considered to predispose cholesterol-supersaturated bile to formation of cholesterol crystals. To study the pathogenesis of the intrahepatic formation of cholesterol stones, we examined surgically resected liver specimens from six patients with intrahepatic cholesterol stones and compared the characteristic histopathological features with those of intrahepatic calcium bilirubinate stones, using morphological examination and immunohistochemical staining against apolipoprotein A-1. Morphologically, in all six patients with cholesterol stones the severity of chronic proliferative cholangitis with proliferation of the mucus-producing glandular elements in the walls of the large bile duct or periductal tissues was less extensive than that seen with calcium bilirubinate stones, and cholesterol crystals had formed in the septal and interlobular bile ducts. Immunohistochemically, unlike the normal liver and calcium bilirubinate stone-containing lobes, the hepatocytes and the epithelial lining of the bile ducts and peribiliary glands of the cholesterol stone-containing lobes did not react completely (some of the epithelial cells reacted only faintly) with apolipoprotein A-1 antibody. These findings suggest that an abundance of mucous substance and bacterial infection of the biliary tree may not be necessary for the formation of cholesterol stones, compared with findings in cases of calcium bilirubinate stones. We suggest that cholesterol crystals may be produced in the septal and interlobular bile ducts in the microenvironment of cholesterol-supersaturated bile and decreased activity of apolipoprotein A-1.

Adult↗

Persistent hyaloid vascular system in age-related cataract in a SAM strain of mouse.

The cataractogenesis of age-related cataract in a strain of Senescence-Accelerated Mouse; SAM-P/9 was investigated. In the mature cataract, funnel-shaped tissue of the persistent hyaloid vascular system extended from the retinal papilla and covered the extremely protruding posterior pole of the cataractous lens, as seen using a stereomicroscope. Longitudinal examination of the eyes with transparent lenses using an ophthalmoscope revealed that the hyaloid vascular system persisted in about 90% of the 5-week-old mice, at least unilaterally. The eyes with transparent lenses in some old mice retained this tissue and a retrospective study revealed that cataract never occurred in eyes without this tissue. Microphthalmos was not observed. Histologically, in the eyes with transparent lenses, the posterior lens capsule covered with a hyaloid vascular system became very thin but only a few lens fibre cells just inside the capsule had swelled. In the lens of the mature cataract or even with initial changes, the lens capsules ruptured. Electron microscopic examination showed that the persistent hyaloid vascular system was tissue consisting of capillary and mesenchymal cells. These observations suggest that the persistent hyaloid vascular system is a necessary but not sole factor for age-related cataract formation in SAM-P/9, and that other age-related factors probably have a role.

Aging↗

Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats.

To investigate the contribution of the cardiac renin-angiotensin system to ventricular dilatation after myocardial infarction, we examined the effects of 3-week treatments with an angiotensin converting enzyme inhibitor, delapril, and a selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on haemodynamics and ventricular angiotensin II contents in myocardial-infarcted rats. TCV-116 reduced mean aortic pressure, and prevented the increase of right and left ventricular weight, left ventricular end-diastolic pressure and volume of myocardial-infarcted rats, to a similar extent to delapril. Thus, AT1 receptor-mediated action of angiotensin II plays a central role in the development of ventricular dilatation. Angiotensin II contents in the right and non-infarcted left ventricles (6.0 +/- 1.0 and 5.9 +/- 0.7 pg/g tissue, respectively, mean +/- S.E.M.) of myocardial-infarcted rats were not different from those of sham-operated rats. However, angiotensin II contents in the infarcted scar (21.7 +/- 3.5 pg/g) of myocardial-infarcted rats were 4.2-fold higher than those in the left ventricle of sham-operated rats. Delapril reduced angiotensin II contents in the right and non-infarcted left ventricles, and the scar by 48, 81 and 60%, respectively, but did not reduce plasma angiotensin II in myocardial-infarcted rats. TCV-116 also decreased angiotensin II in the right and non-infarcted left ventricles by 57 and 56%, respectively, while increased plasma angiotensin II by 4.3-fold. Thus, the prevention of ventricular dilatation by these two agents was associated with the decrease in ventricular angiotensin II contents. These observations suggest that the cardiac renin-angiotensin system rather than the circulating system may play an important role in ventricular dilatation after myocardial infarction.

Analysis of Variance↗

Effects of coenzyme Q10 administration on pulmonary function and exercise performance in patients with chronic lung diseases.

Serum coenzyme Q10 (CoQ10) levels were measured at rest and during incremental exercise in 21 patients with chronic obstructive pulmonary disease (COPD) and 9 patients with idiopathic pulmonary fibrosis (IPF). The mean serum CoQ10 levels at rest in patients with COPD and IPF were 0.56 +/- 0.20 and 0.45 +/- 0.16 microgram/ml, respectively. In both groups these levels were decreased compared with those of healthy subjects. In the patients with COPD, CoQ10 levels were significantly correlated with body weight, however, there was no correlation between CoQ10 levels and ventilatory function, PaO2, VO2/kg at rest, or maximal VO2. In eight of nine patients whose PaO2 at rest was lower than 75 torr, serum CoQ10 levels were lower than 0.5 microgram/ml. We studied the effects of the oral administration of CoQ10 at 90 mg/day for 8 weeks on pulmonary function and exercise performance in eight patients with COPD. Serum CoQ10 levels were significantly elevated in association with an improvement in hypoxemia at rest, whereas pulmonary function was unaltered. Oxygen consumption during exercise was not changed, whereas PaO2 was significantly improved, and heart rate was significantly decreased compared with the results obtained at an identical workload at baseline. Furthermore, lactate production was suppressed during the anaerobic exercise stage after CoQ10 administration, and exercise performance tended to increase. These data suggested that CoQ10 has favorable effects on muscular energy metabolism in patients with chronic lung diseases who have hypoxemia at rest and/or during exercise.

Aged↗

Dose study of the immunosuppression of FK 506 in canine lung allo-transplantation.

The immunosuppressive effect of FK506 (FK) in comparison to cyclosporine A (CsA) on lung graft rejection was demonstrated using 24 mongrel dogs with left lung allotransplantation. The cytotoxic activity of peripheral blood mononuclear cells was evaluated using donor skin fibroblasts. In eight dogs not given immunosuppression, the grafted lungs lost aeration 5-10 days postoperatively, and histologic findings revealed grade II rejection and cytotoxic activity elevated to between 10.7 and 60.5%, being an average of 31.2% at an effector/target (E/T) ratio of 50. Of 12 dogs treated with FK, none demonstrated a cytotoxic activity of 10% or more at an E/T ratio of 50. Moreover, histologic examinations of the specimens obtained by open chest biopsy revealed no signs of rejection during the first 10 postoperative days of FK administration, except in one dog showing grade I rejection from the FK 0.05 mg/kg group. A dose study of the duration until the onset of graft rejection and the elevation of cytotoxic activity after the termination of FK administration revealed approximately 1-2 weeks in the FK 0.05 mg/kg group, 3-4 weeks in the 0.1 mg/kg group, and later in the 0.4 mg/kg and 2.0 mg/kg groups. However, severe body weight loss was seen in the 0.4 mg/kg and 2.0 mg/kg groups postoperatively, without recovery even after the termination of FK. In fact, two dogs died of pneumonia possibly derived from general emaciation. These results suggest the optimal concentration of FK in canine lung allo-transplantation to be 0.1 mg/kg intramuscularly.

Animals↗

Augmentation of antitumor immunity in regional lymph nodes by local immunotherapy.

We have previously reported that the antitumor effect of OK-432, a streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (OK-432/fbg) [1]. In order to elucidate the effects of this immunotherapy on regional lymph nodes (RLN), we carried out both morphological and functional analyses of the RLN from colonic cancer patients treated with OK-432/fbg. Computer-aided morphometry revealed that the maximal cross-sectional areas and the broadest diameters of the RLN were significantly greater (p < 0.01) in patients who had undergone local immunotherapy than in patients who had not. The component structures of RLN, such as sinus, follicle and paracortex, were all enlarged in the OK-432/fbg-treated patients, and necrosis of metastatic tumors was observed. RLN lymphocytes recovered from OK-432/fbg treated patients showed elevated reactivity to phytohemagglutinin (PHA) and the stimulation index was clearly higher than that of control patients. Flow cytometric analysis revealed a predominance of T-cells, especially CD4 subsets, and higher positivity for both CD25 and HLA-DR. Furthermore, RLN lymphocytes killed more effectively K562 and Daudi cells in the patients who had had immunotherapy. These results suggest that the effect of local immunotherapy with OK-432/fbg is not restricted to the site of injection but extends to the lymph nodes, and contributes to tumor regression through the augmentation of cellular immunity.

Aged↗

The effect of local immunotherapy for breast cancer using a mixture of OK-432 and fibrinogen supplemented with activated macrophages.

OK-432 is an immunomodulatory agent prepared from a strain of Streptococcus pyogenes. We have previously reported that intratumoral injection of a mixture of OK-432 and fibrinogen (hereinafter referred to as OK/fbg) is very effective in the local immunotherapy for colorectal cancer. However, we found that the intratumoral injection of OK/fbg into tumor tissues of breast cancers did not always induce a strong antitumor effect. With conventional OK/fbg treatment, tumor necrosis observed in breast cancer tumors was significantly less than that in colorectal cancer tumors; the formation of fibrin meshwork and macrophage infiltration, in particular, were poor. In this study, the OK/fbg mixture was supplemented with activated macrophages for local immunotherapy of breast cancers. Macrophages were prepared from peripheral blood of breast cancer patients and activated with 0.05 mg/ml of OK-432. Between 2-7 days before operation, a single intratumoral injection of the above mixtures was done. The addition of activated macrophages to the OK/fbg mixture resulted in marked degrees of fibrin meshwork formation, macrophage infiltration and cancer cell necrosis. These findings suggest that the recruitment of macrophages in tumor stroma and their activation are necessary for sufficient induction of antitumor immunity, and supplementation of activated macrophages at the site of immune reaction may be an alternative method for reinforcement of the antitumor effect of local immunotherapy.

Breast Neoplasms↗

The pattern of lymph node involvement in carcinoma of the head of the pancreas. A histologic study of the surgical findings in patients undergoing extensive nodal dissections.

To clarify the pattern of lymph node metastasis in carcinoma of the pancreas, lymph node involvement was examined in forty-two patients who underwent extensive nodal dissections, including the paraaortic lymph nodes. The correlation between the spread of the tumor and lymph node involvement was evaluated: The most common site of involved lymph nodes was the retropancreatic region. The prevalence of nodal metastases was 78.6%. Metastases to the paraaortic region were present in seven patients, among whom metastases in the paraaortic region were most common in the median region from the celiac artery to the inferior mesenteric artery and in the space between the aorta and the vena cava. The risk of lymph node metastases tended to increase with tumor size, except in the paraaortic region, where the correlation between the frequency of metastasis and tumor size was poor. The probability of lymph node metastases increased with the degree of lymphatic invasion (ly) and the growth pattern of the tumor (INF) and was high in patients with invasion into the retropancreatic tissue and in tumors with scirrhous histology. These results indicate that even in small cancers, lymph nodes of the paraaortic region frequently harbor metastases and should be dissected en block during radical resections of pancreatic cancer.

Humans↗