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Biomedical subjects

S Nakano

Publications and source records attributed to S Nakano.

At least 343 records · Page 19Linked to original sources

A peptide-based human T cell leukemia virus type I vaccine containing T and B cell epitopes that induces high titers of neutralizing antibodies.

We have recently identified the principal linear neutralizing B cell epitopes of human T cell leukemia virus type I (HTLV-I) on the envelope protein gp46, amino acids (aa) 187-199, by using a number of human mAbs. We therefore propose that this region would be a good candidate for a peptide-based HTLV-I vaccine. To develop a peptide-based vaccine that can induce a high titer of neutralizing Abs against HTLV-I, we first synthesized peptides of various lengths containing aa187-199. Because the addition of gp46 aa181-186 or aa200-210 to either the N-terminus or C-terminus of SP187-199 did not alter the antigenicity of the principal neutralizing determinant, we prepared two peptide-based vaccines, MAP181-203 and MAP181-210, by conjugating SP181-203 and SP181-210 with a branched polylysine oligomer. In rabbits, X4 to X8 and X8 to X64 titers of the neutralizing Abs were induced by immunization with MAP181-203 and MAP181-210, respectively. Furthermore, high titers of neutralizing Abs (X40 to X320) were elicited in five different strains of rats by immunization with MAP181-210. We also identified the major T cell epitope on gp46 aa194-210 in various strains of rats immunized with MAP181-210. Furthermore, the peripheral T lymphocytes obtained from the majority of HTLV-I-infected patients including HTLV-I-associated myelopathy/tropical spastic paraparesis, adult T cell leukemia/lymphoma, and healthy carriers, proliferated in response to the peptides containing aa194-210. These results indicated that MAP181-210 contains a T cell helper epitope on aa194-210 not only in rats and rabbits, but also in humans with various HLA haplotypes. It is therefore possible that MAP181-210 could become one of the candidates for a peptide-based HTLV-I vaccine for human use.

Amino Acid Sequence↗

Concomitant coronary bypass grafting and curative surgery for cancer.

The surgical management of patients with concomitant critical coronary artery disease (CAD) and surgically resectable cancer is controversial. We evaluated 19 patients who underwent concomitant coronary artery bypass grafting (CABG) and curative operation for cancer of the stomach in 9 patients, the colon in 4, the lung in 4, and the breast in 2. Each cancer operation was performed under stable hemodynamics without any serious bleeding tendency, immediately after CABG with an average of 2.5 +/- 0.8 grafts. There were no operative deaths and no incidences of perioperative myocardial infarction. Postoperative complications developed in three of the patients with lung cancer: respiratory dysfunction caused by phrenic nerve paralysis in two and mediastinitis in one. During the mean follow-up period of 33 +/- 23 months, 5 patients died of recurrent cancer or non-cardiac disease; however, all 19 patients remained free from any postoperative cardiac events and their quality of life apparently improved. This experience suggests that such simultaneous correction would be safe and beneficial in carefully selected patients who have surgically correctable CAD and potentially curable cancer.

Adult↗

Percutaneous left ventricular assist system using a modification of the Dennis method: initial clinical evaluation and results.

A percutaneous left ventricular assist system (PLVAS) using a modification of the Dennis method was developed and implemented in 8 patients. Transseptal cannulation was performed under biplane fluoroscopy and/or transesophageal echocardiogram without encountering any problems. All the patients were in a state of severe cardiogenic shock, caused by acute myocardial infarction in 5, cardiomyopathy in 2, and postcardiotomy in 1, and were on intraaortic balloon pump support and/or percutaneous cardiopulmonary support (PCPS), in the form of partial cardiopulmonary bypass. Three patients who developed concomitant right heart failure required additional PCPS. All the patients were supported at 3.0 to 4.0 l/min for 76-284h for an average time of 159h. Three patients were successfully weaned from PLVAS and one of these patients, who had suffered an acute myocardial infarction, was discharged from hospital. The complications directly related to this system were minimal. Our observations led to the conclusion that PLVAS using our modification of the Dennis method is a simple, easy, and safe means of maintaining adequate systemic circulation in severely ill patients. As PLVAS is particularly effective for patients in cardiogenic shock following acute myocardial infarction, we believe that it will be applied routinely by many cardiac surgeons and cardiologists in the future.

Adult↗

A 10-year survivor with unresectable hepatic metastases from sigmoid colon carcinoma treated with regional chemotherapy.

We treated a man with unresectable hepatic metastases from sigmoid colon carcinoma who has since survived for more than 10 years. A sigmoidectomy with lymph node dissection was performed and a continuous hepatic arterial infusion of 5-fluorouracil (5-FU) with intermittent infusion of mitomycin C (MMC) was administered for about 3 months after this operation. The total doses of 5-FU and MMC were 16 g and 84 mg, respectively. Tegafur also was administered orally at a dose of 600 mg/day for about 8 months. The carcinoembryonic antigen (CEA) level (which had reached 4,409 ng/ml preoperatively) normalized 4 months after surgery, and still remains normal. Very few patients with unresectable hepatic metastases survive for 5 or more years. However, regional chemotherapy can be effective in some patients.

Adenocarcinoma↗

Mantle cell lymphoma with the features of mucosa-associated lymphoid tissue (MALT) lymphoma in an HTLV-I-seropositive patient.

A case of small lymphocytic B-cell lymphoma with seropositivity for human T-cell leukemia virus type I (HTLV-I), whose clinical features were closely related to those of mucosa-associated lymphoid tissue (MALT) lymphoma, is presented. The neoplastic cells of the lymph node were immunologically positive for CD5, in addition to several B-cell markers, but negative for CD10, and cytogenetically carried a t(11;14)(q13;q32). These findings were fully consistent with so-called mantle cell lymphoma (MCL). In addition to the lymph nodes and bone marrow, multiple extranodal sites including lacrimal and salivary glands, lung and stomach (where MALT is present) were occupied by lymphoma cells. These extranodal lesions were immunologically identical to the lymph nodes (CD5(+), CD10(-)), but histologically showed lymphoepithelial lesions (LEL) characteristic of MALT lymphoma. These findings suggest a possible relationship between MCL and MALT lymphoma, and the neoplastic cells are thought to originate from the CD5-positive B cells, which are present near the areas across the mantle and marginal zones. Furthermore, HTLV-I-infection, which appears to create an immunodeficient state or modulate the B-cell response, is thought to play a role in B-cell lymphomagenesis.

Antigens, CD↗

Time-dependent thickening of the intima in aortocoronary saphenous vein grafts: clinicopathological analysis of 24 patients.

The present study was undertaken to investigate histological changes in aortocoronary saphenous vein grafts (SVGs) and the relationship between intimal thickening of the SVGs and the interval after grafting. The SVGs were divided into five groups according to the degree of intimal thickening and associated luminal narrowing: minimal thickening (0%-10% stenosis), slight thickening (11%-25% stenosis), slight-to-moderate thickening (26%-50% stenosis), moderate thickening (51%-75% stenosis), and severe thickening (76%-100% stenosis). SVGs showing minimal thickening had been implanted for 0-3 weeks, those with slight thickening for 2-13 weeks, those with slight-to-moderate thickening for 5-13 weeks, those with moderate thickening for 30-52 weeks, and those with severe thickening for 30-83 weeks. Thickening of the intima in SVGs (intimal hyperplasia) was time-dependent, and began as early as 2 weeks after the graft surgery. The change was diffuse and concentric, and observed from an aortic root to a coronary site. The major cell type involved in the intimal hyperplasia was the smooth muscle cell.

Aged↗

Effect of sleep stage on somatosensory evoked potentials by median nerve stimulation.

The effects of sleep stage on early cortical somatosensory evoked potentials (SEPs) and short-latency components elicited by median nerve stimulation were studied in 12 normal volunteers. The latency of P13 in the awake stage was not significantly different from that in any sleep stage. The latencies of N16, N20 and P20 were significantly prolonged while the amplitude of N20 was decreased during the non-rapid eye movement (NREM) sleep stage. P22, P23 and N24 components showed double peaks (P23a, P23b, N24a, N24b) during the NREM sleep stage in 6 subjects, while N24 showed a single peak and only P22 and P23 showed double peaks in 5 other subjects. The latencies and morphologies of SEPs during rapid eye movement sleep stage were almost the same as those during the awake stage. These findings suggest that NREM sleep affects the latency, amplitude and morphology of N16 and early cortical components.

Adolescent↗

Pulmonary vascular resistance during exercise late after repair of large ventricular septal defects. Relation to age at the time of repair.

Postoperative pulmonary artery pressure and resistance were assessed during exercise in 32 patients late after repair of large ventricular septal defect with pulmonary hypertension. Nineteen patients had a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 (group 1) and 13 had a ratio between 0.50 and 0.96 (group 2). Age at the time of operation was 0.9 to 13.0 years (4.6 +/- 3.6) in group 1 and 0.8 to 15.8 years (4.3 +/- 4.2) in group 2. Age at the time of restudy was 9 to 21 years (14.5 +/- 3.0) in group 1 and 9 to 22 years (13.5 +/- 4.1) in group 2. Pulmonary artery pressure was measured in the supine position at rest and during exercise, as were the measurements underlying the calculations of pulmonary vascular resistance. Mean pulmonary artery pressure was 13 to 21 mm Hg (17 +/- 2) and 10 to 26 mm Hg (20 +/- 5) in groups 1 and 2, respectively, at rest, and this increased to 17 to 27 mm Hg (22 +/- 3) and 14 to 39 mm Hg (27 +/- 7) in groups 1 and 2, respectively, during exercise (p < 0.05). Pulmonary vascular resistance was 0.51 to 3.40 U.m2 (1.93 +/- 0.63) and 0.79 to 3.31 U.m2 (2.05 +/- 0.65) in groups 1 and 2 at rest. It was 0.58 to 2.24 U.m2 (1.36 +/- 0.57) and 0.81 to 3.85 U.m2 (2.18 +/- 0.97) in groups 1 and 2 during exercise (p < 0.01). Postoperative pulmonary vascular resistance during exercise correlated well with age at the time of repair in both groups (r = 0.65, p < 0.05 in group 1; r = 0.86, p < 0.001 in group 2). These data suggest that 85% of patients with a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 3.8 years old and 85% of those with a preoperative pulmonary-to-systemic resistance ratio of more than 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 1.1 years.

Adolescent↗

Transcatheter arterial embolization for massive bleeding from duodenal ulcers not controlled by endoscopic hemostasis.

BACKGROUND AND STUDY AIMS: We evaluated the efficacy of transcatheter arterial embolization (TAE) in patients in whom endoscopic hemostasis of a massively bleeding duodenal ulcer failed. PATIENTS AND METHODS: TAE was performed in 11 patients with endoscopically uncontrollable massively bleeding duodenal ulcers, and the results and long-time outcome were studied. Two additional cases of failed endoscopic hemostasis were treated surgically without TAE. The entire group of 13 patients represented 5% of endoscopically treated duodenal ulcers and 0.6% of all cases with upper gastrointestinal bleeding who underwent emergency endoscopy (n = 2073). All but one of these 13 patients had concomitant disease. RESULTS: Arteriograms performed before TAE revealed extravasation of contrast material around the gastroduodenal artery (GDA), the anterior superior pancreaticoduodenal artery (ASPD), or the posterior superior pancreaticoduodenal artery (PSPD) in six of 11 cases. We failed to stop the bleeding in one patient, in whom only the common hepatic artery side of the GDA bleeding site was embolized; this patient died. TAE was successful in the other ten patients, in whom the long stretch of the GDA, including the ASPD and PSPD, was embolized around the bleeding site. Two surgically treated patients died within a week. CONCLUSIONS: Our findings indicate that TAE may induce hemostasis in 90% of patients with serious concomitant diseases who have endoscopically uncontrollable massive bleeding from duodenal ulcers.

Aged↗

Effect of the cholecystokinin receptor antagonist loxiglumide on pancreatic exocrine function in rats after acute pancreatitis.

Recent studies have demonstrated that cholecystokinin (CCK) receptor antagonists not only reduce the severity of pancreatitis but also inhibit pancreatic regeneration after pancreatitis. This study was undertaken, therefore, to examine the effects of the CCK receptor antagonist loxiglumide on the exocrine pancreas when given after an episode of acute pancreatitis that was induced in rats by a 4-h subcutaneous infusion of 20 micrograms/kg body weight/h cerulein. Biochemical changes and secretory function in response to 100 ng/kg body weight cerulein were determined after a 6-day treatment with saline, loxiglumide (50 mg/kg body weight), or CCK-8 (2.5 micrograms/kg body weight), which was given three times a day starting 24 h after the induction of acute pancreatitis. In the saline-treated rats, pancreatic enzyme contents and pancreatic juice and protein output were significantly low, whereas the pancreatic weight and protein and DNA contents were comparable to those of the controls without pancreatitis. Loxiglumide treatment, although significantly decreasing protein output, had no influence on pancreatic weight, protein and DNA contents, or pancreatic juice flow but increased the amylase and lipase contents compared to those of the saline-treated postpancreatitic rats. CCK-8 treatment also had no influence on pancreatic weight or protein and DNA contents but significantly increased the pancreatic enzyme contents and pancreatic juice and protein output compared to those of the saline-treated postpancreatitic rats. These results suggest that loxiglumide does not significantly inhibit the recovery of exocrine function but appears to accelerate the increase in pancreatic amylase and lipase contents even when given after an attack of acute pancreatitis.

Acute Disease↗

[Epidemiological studies on enteric adenovirus gastroenteritis in children].

Enteric adenoviruses (EAd), adenovirus (Ad) types 40 and 41, have been established as causative agents of gastroenteritis. By electron microscopic (EM) survey of acute gastroenteritis in children in the Matsuyama area, Ad were detected in 275 of 6476 fecal samples obtained from 1980 to 1993. Two-hundred-thirteen Ad-positive samples were tested for serotyping by the enzyme-linked immunosorbent assay (ELISA) using three monoclonal antibodies, Ad group-specific, Ad 40 type-specific and Ad41 type-specific antibody. Of 199 samples serotyped by ELISA, 65 were identified as Ad40, 73 as Ad41, 1 as double infection with Ad40 and Ad41, and 60 as Non-EAd. About 70% of Adenovirus detected by EM were suggested to be EAd. Other epidemiological feature was as follows: EAd were detected throughout the year. The predominant serotype was Ad40 during 1980-1985, while Ad41 were observed after 1986. EAd were detected most frequently from the children aged 0-3 years. The incidence of fever in EAd positive group was lower (30%) than that (67%) in the Non-EAd positive group. The incidence of vomiting, nausea and respiratory symptoms was higher in Ad41 associated infections than Ad40.

Adenoviridae↗

Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats.

Pancreatic exocrine function of a new inbred strain Otsuka Long-Evans Tokushima Fatty (OLETF) rat that develops spontaneous persistent hyperglycemia was evaluated in in vitro isolated pancreatic acini and compared with that in the control Long-Evans Tokushima Otsuka (LETO) rat. Serum glucose and insulin concentrations in the OLETF rats were significantly high (glucose: 270 +/- 12 vs. 208 +/- 10 mg/100 ml, P < 0.01; insulin: 12.4 +/- 1.7 vs. 4.9 +/- 0.6 ng/ml, P) < 0.01), whereas pancreatic wet weight was significantly low (803 +/- 20 vs. 1,138 +/- 17 mg, P < 0.01) compared with those in the LETO rat. Pancreatic acini isolated from the OLETF rat were totally insensitive to cholecystokinin (CCK)-8 stimulation at concentrations of up to 100 nM. However, neither the responsiveness nor the sensitivity to carbamylcholine, bombesin, and secretin of the acini from the OLETF rat was altered or even increased, probably due to the larger amylase content in the OLETF rat acini compared with those of the LETO rat acini (31.5 +/- 2.0 vs. 13.0 +/- 1.1 Somogyi units/micrograms DNA, P < 0.01). The responsiveness to fluoride, a direct activator of guanine nucleotide-binding protein, in the OLETF rat acini was similar to that in the LETO rat, suggesting that the transmembrane signaling and effectors and subsequent intracellular signal transduction molecules in the OLETF rat acini are normal. Moreover, 125I-CCK binding to the acini prepared from the OLETF rat was totally absent. These present results indicate that the OLETF rat has a selective defect in the binding of CCK to its receptors on the acinar cell surface.

Amylases↗

A comparative evaluation of pressure-triggering and flow-triggering in pressure support ventilation (PSV) for neonates using an animal model.

The triggering system in pressure support ventilation needs to respond rapidly, especially in neonates. The aim of this study was to compare the effects of flow-triggered and pressure-triggered pressure support ventilation on neonatal mechanical ventilation using an animal model. Respiratory flow, airway pressure, oesophageal pressure, and diaphragmatic electromyogram were measured during pressure support ventilation in five anaesthetized rabbits. The animals were connected to a VIPBIRD (Bird, U.S.A.) (CPAP mode, pressure support ventilation, 5 cm H2O and PEEP 0 cm H2O). Flow-triggering sensitivity was set at 0.2l/min, 0.5l/min, 1.01l/min, or 1.5l/min. Pressure-triggering sensitivity was set at -1.0 cm H2O. Shorter trigger delay and longer pressure support time were observed in flow-triggering. There was also less diaphragmatic activity in flow-triggering as evidenced by the amplitude of integrated diaphragmatic electromyogram and negative deflection of oesophageal pressure. The findings suggest that flow-triggering will prove superior to pressure-triggering in pressure support ventilation for neonates.

Animals↗

Inhibition of doxorubicin-induced cell death in vitro and in vivo by cycloheximide.

We studied the effects of the protein synthesis inhibitor, cycloheximide (CH), on cell killing by doxorubicin (DOX) in vitro and in vivo. At the concentration of CH used (1 microgram/ml) the cytotoxicity of DOX was reduced in cultured P388 leukemia cells. An analysis of the DNA histogram obtained by flow cytometry showed that DOX exerts its growth-inhibitory effect by blocking the cell cycle at the G2/M phase in P388 cells. Treatment with CH diminished this blocking effect. When CH was added to the growth medium before DOX exposure, no change in intracellular DOX accumulation was observed. Treatment with CH (15 mg/kg) significantly diminished the lethality of DOX (20 mg/kg) in mice and it also reduced the antitumor activity of mice with P388 leukemia. Thus, CH inhibited cell death induced by DOX in vitro and in vivo. These results suggest that CH has an antagonistic effect on the pharmacological actions of DOX in cells and mice. The cytoprotective effect of CH may be due to protein synthesis inhibition.

Animals↗

Non-obese Cushing's syndrome in an aged woman with non-insulin-dependent diabetes mellitus.

A 76-year-old diabetic woman with non-obese Cushing's syndrome developed poor glycemic control with glibenclamide. She presented with a slight weight loss while bedridden due to a fall. Cushing's syndrome in this patient was suspected because of hypercortisolemia with eosinopenia, and adrenal Cushing's syndrome was diagnosed by endocrine and radiological examinations. A right adrenal adenoma was confirmed by autopsy. In this patient, progressive obesity and other common features of Cushing's syndrome may have been concealed by aging itself and coexisting diabetes mellitus.

Age Factors↗

Phlegmonous colitis in a patient with liver cirrhosis, hepatocellular carcinoma and acute promyelocytic leukemia.

We describe a case of phlegmonous colitis occurring in a 70-year-old man with liver cirrhosis, hepatocellular carcinoma and acute promyelocytic leukemia. He developed an acute abdominal emergency and died during the first day of admission. Autopsy revealed a colon lesion characterized by suppurative inflammation associated with marked edema and hemorrhage in the submucosa. These findings were identical both macroscopically and microscopically to those of phlegmonous colitis.

Aged↗

Granular cell tumor in the ascending colon.

We describe a case of multiple polypoid lesions that occurred in the colon of a 62-year-old man. Eight of the lesions were demonstrated by barium enema, and five were examined histologically. A small nodule in the submucosa of the ascending colon was histologically identical to granular cell tumor, characterized by nested growth of large tumor cells with ample granular cytoplasm and small round nuclei. Immunohistochemically, the cells were positive for S-100, neuron-specific enolase and vimentin, and negative for alpha-smooth muscle actin and desmin.

Colonic Neoplasms↗