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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 775 records · Page 43Linked to original sources

Evaluation of retinal microcirculatory alterations in the Goto-Kakizaki rat. A spontaneous model of non-insulin-dependent diabetes.

PURPOSE: To evaluate retinal microcirculation in the spontaneous diabetic GK (Goto-Kakizaki) rat over an extended time. METHODS: The dye-dilution technique with scanning laser ophthalmoscope-based fluorescein angiography was used to evaluate retinal circulation in GK rats with diabetes of 1, 3, and 5 months' duration and in age-matched controls. Scanning laser ophthalmoscope fluorescein angiograms were recorded after a 10-microliter bolus of 10% sodium fluorescein was injected into the tail vein, followed by a flush of 0.1 ml saline. Retinal mean circulation times (MCTs), vessel diameters, and retinal segmental blood flows (SBFs) were determined using computer-assisted image analysis on a frame-by-frame basis. RESULTS: The MCTs were significantly prolonged (P< 0.01) in the GK rat groups (2.60 +/- 0.31, 2.74 +/- 0.28, and 2.84 +/- 0.38 seconds at 1, 3, and 5 months' duration of diabetes, respectively) compared to the age-matched controls (1.94 +/- 0.20, 1.99 +/- 0.12, and 1.91 +/- 0.22 seconds, respectively). No significant differences were observed in the retinal arterial and venous diameters between groups at each time period. The SBFs were significantly reduced (P< 0.03) in the GK rat groups (12.0 +/- 1.5, 12.1 +/- 2.0, and 11.8 +/- 2.5 x 10(2) micrometer squared/second at 1, 3, and 5 months' duration of diabetes, respectively) compared to the controls (16.0 +/- 2.2, 16.7 +/- 1.8, and 17.2 +/- 2.5 x 10(2) micrometer squared/second, respectively). In either group, no significant changes with growth were observed in MCT, vessel diameters, or SBF, although the MCTs in the GK rat group tended to lengthen, and arterial and venous diameters in the GK rat group tended to increase with duration of diabetes. Goto-Kakizaki rats did not exhibit dense cataracts, the retinal circulation could be observed, and morphologic changes of diabetic retinopathy did not develop throughout the experimental period. CONCLUSIONS: A significant prolongation in MCT and a significant reduction in SBF appeared in GK rats at an early stage in diabetes. This tendency continued until 5 months' duration of diabetes. These results suggest that retinal circulatory abnormalities are found before observable retinopathy development in GK rats and that there may be some mechanism causing a reduction in SBF without changing major retinal vessel diameters at an early stage in non-insulin-dependent diabetes mellitus (NIDDM). In addition, this study demonstrates that the GK rat will be a useful model of non-insulin-dependent diabetes mellitus to evaluate retinal circulation over an extended time.

Animals↗

[Clinical evaluation of intra-operative radiotherapy combined with subtotal cystectomy for invasive bladder carcinoma].

From 1981 to 1994, intra-operative radiotherapy after subtotal cystectomy was performed on 22 patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition. All the patients received 25 to 30 Gy of radiotherapy focused on trigonum and internal urethral orifice after subtotal cystectomy with uretero-cutaneostomy. Of 22 patients, 15 patients died. Five patients died of bladder cancer, one died of gastric cancer, one died of rectal cancer and the others died of pneumonia, heart failure, sepsis and senility. The five-year survival rate was 41% and the cause-specific five-year survival rate was 75%. Local recurrence was seen only in one patients, who received second intra-operative radiotherapy and recovered well in complete remission. We believe that intra-operative radiotherapy after subtotal cystectomy is useful for patients with invasive bladder carcinoma on whom radical cystectomy could not be recommended because of old age or condition.

Aged↗

[Mitomycin C-DNA adduct detection in rat organs and human liver].

Mitomycin C-DNA adduct formation was detected in rat organs and also in human tissues by 32P-postlabeling assay. The adduct levels were 1-4 adduct/ 10(8) nucleotides in the human liver after 20 mg of mitomycin C by intra-artery administration and which level was higher comparing with the levels in the rat liver after 10 times more dosages of mitomycin C administration by intra-venous injection. The levels in the human liver were maintained at least 56 days after administration. Organ-specific differences of adduct levels were observed in rat experiments: the adduct levels of liver, lung and kidney were stable but rapidly decreased in stomach and colon. These results, which were obtained from the experiments using the normal parts of each organs may indicate that the drug effectivity for adduct formation was sufficient with smaller dose in the stomach and colon, but disappeared quickly, mean while, the drug effectivity was undergoing in relatively high levels for longer periods in the liver lung and kidney. The analysis of human liver samples may suggest that the selective intra-artery injection induced stronger drug effectivity for adduct formation in human organs.

Adult↗

[Pulmonary typical carcinoid with metastases to pulmonary hilar, and mediastinal lymph nodes].

A 50-year-old woman was admitted to our hospital complaining of recurrent bloody sputum and hemoptysis. Chest X-ray films showed an infiltrative shadow in the left lower lung field. Chest computed tomograms showed a nodular tumor shadow near the left B8 and this tumor shadow was found between A8 and A9 by pulmonary arteriography. Bronchoscopic examination revealed a red coagulum in the left B8 and cytologic examination of broncho alveolar lavage fluid revealed atypical squamous cells. With a clinical diagnosis of squamous cell carcinoma of the lung, a left lower lobectomy with hilar and mediastinal lymph node dissection was done. A milk-white tumor was found in the lower lobe of the resected lung. The pathological diagnosis of the resected tissue specimen was carcinoid, accompanied by pulmonary, hilar, and mediastinal lymph node metastases. Reduced immunofluorescence by Chromogranin A and serotonin staining were further evidence that the tumor was atypical. This case is very interesting in that the tumor metastasized to the lung and lymph nodes, even-though it was pathologically typical.

Carcinoid Tumor↗

Serum stimulation, cell-cell interactions, and extracellular matrix independently influence smooth muscle cell phenotype in vitro.

Vascular injury profoundly alters the vessel wall microenvironment, and smooth muscle cells respond with cell cycle re-entry, loss of contractile elements, extracellular matrix remodeling, and altered signaling by endogenous growth factors and their receptors. Environmental cues include stimulation by exogenous mitogens and both cell-cell and cell-matrix interactions. Modeling this process in smooth muscle cells in vitro, these environmental determinants were varied independently and the phenotypic consequences assessed. Mitogenic stimulation with serum promoted the synthesis of collagen and fibronectin and the expression of fibroblast growth factor receptor-1 and suppressed the content of smooth muscle alpha-actin, myosin heavy chain, and basic fibroblast growth factor. Low cell density (reduced cell-cell contact) was also associated with enhanced extracellular matrix protein production, increased fibroblast growth factor receptor-1 expression, and reduced contractile protein and basic fibroblast growth factor content. The influence of serum stimulation and reduced cell-cell contact were independent and additive. Provision of a type I collagen matrix blunted the influence of serum and cell-cell contact on collagen synthesis but had minor effects on other measures of phenotype. Environmental factors thus independently influence smooth muscle cell phenotype, including endogenous growth factor expression and responsiveness, which can in turn influence the microenvironment of the vessel wall after injury.

Actins↗

Changes in D-aspartic acid in human deciduous teeth with age from 1-20 years.

The racemization ration (D/L ratio) of aspartic acid in the dentin (collagen) of deciduous teeth was studied, using dentin of permanent teeth as a reference. D-aspartic acid in deciduous teeth was found to increase almost linearly with aging. The reaction velocity constant of racemization (kyr-1) in deciduous teeth (1.1915 x 10(-3)yr-1) was approximately double the value for permanent teeth (6.2550 x 10(-4)yr-1). The velocity of the racemization reaction was similar between deciduous teeth and permanent teeth in a dry state. The D/L ratio determined using transverse sections of deciduous teeth tended to be high in the crown and low in the root. The reaction velocity of racemization is considered to be affected to some extent by the tooth material, ambient temperature and salivary pH, but most importantly by physiologic resorption of deciduous teeth at the root associated with age.

Adolescent↗

Effects of the novel histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2-[[[5- (methylamino)methyl-2-furyl]methyl]thio]ethyl]-2-(methylsulfonyl) guanidine on gastric secretion and gastroduodenal ulcers in rats.

The effects of (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2- [[[5-(methylamino)methyl-2-furyl] methyl]thio]ethyl]-2-(methylsulfonyl)guanidine (CAS 140695-21-2, T-593), a new histamine H2-receptor antagonist, on gastric secretion and experimental gastric and duodenal lesion/ulcer models in rats were examined. The drug administered orally or intraduodenally significantly and dose-dependently inhibited both basal and histamine-stimulated acid secretion. Pepsin output was also inhibited by the drug nearly dose-dependently. The acid-inhibitory effect of T-593 persisted for 12 h after a single oral administration. T-593 potently protected the gastric mucosa against water-immersion stress-, indometacin- and HCl.acetylsalicylic acid-induced lesions, but it had no effect on HCl.ethanol-induced lesions. T-593 significantly prevented the development of mepirizole-induced duodenal ulcers. Spontaneous healing of kissing gastric ulcers was significantly enhanced when T-593 was administered for 14 days. The antisecretory and antilesion/antiulcer effects of T-593 were similar to those of ranitidine and omeprazole. It is concluded that T-593 is a potent antisecretory and antiulcer drug.

Animals↗

Enzyme triple staining for differentiation of lymphatics from venous and arterial capillaries.

5'-nucleotidase (5'-Nase)-dipeptidyl aminopeptidase IV (DAPase)-alkaline phosphatase (ALPase) triple staining was used to differentiate lymphatics from venous and arterial capillaries in a variety of mammalian tissue sections including human. This triple staining method facilitates specific identification under a light microscope of 5'-Nase activity in lymphatics, DAPase activity in venous capillaries and venules and ALPase activity in arterial capillaries and arterioles. This technique depicts initial lymphatics more clearly and extensively than other methods so far reported although some interspecies and tissue differences are obtained in each enzyme activity.

5'-Nucleotidase↗

Evaluation of biological responses to polymeric biomaterials by RT-PCR analysis. I. Study of IL-1 beta mRNA expression.

In this study, we introduce a novel research methodology, the evaluation of mRNA expression of cells contacting with polymeric materials using reverse transcription-polymerase chain reaction (RT-PCR) analysis HL-60 was used as a model of the macrophages. The expression of interleukin-1 beta (IL-1 beta) mRNA, a cytokine secreted by macrophages, was selected to estimate the extent of inflammation. The expression of IL-1 beta mRNA in the HL60 cells cultured on various substrates and in various conditions was studied. Expression of IL-1 beta could be successfully determined by RT-PCR analysis. A 48 h incubation period was necessary to clarify the expression of IL-1 beta mRNA. It became clear that lipopolysaccharide stimulation was not necessary in this analysis because of the high sensitivity of RT-PCR analysis. It is concluded that RT-PCR analysis is a powerful tool for studying cell-polymer interaction, and is a complementary method for ELISA.

Base Sequence↗

Successful engraftment of allogeneic CD34-enriched marrow cell transplantation from HLA-mismatched parental donors.

The CD34 antigen is expressed on pluripotent stem cells and the CD34+ cell has been shown to be capable of hematopoietic reconstitution in animal and human autologous grafts. We asked if CD34+ cells could reconstitute hematopoiesis in human allogeneic transplantation from a HLA-mismatched donor. Three pediatric patients with advanced leukemia received allogeneic CD34-enriched marrow cell graft from HLA two (two patients) or three (one patient) loci-mismatched parental donors. CD34+ cell selection was performed with mouse anti-CD34 antibody 9C5 and magnetic beads coated sheep anti-mouse IgG1. 1.53 to 2.48 x 10(9) marrow cells were processed and 2.53 to 7.89 x 10(7) positively selected cells were recovered. The selected population showed 93.7 to 99.0% CD34+ cells and total recovery of CD34+ cells from the starting population was 54.6 to 62.3%. CD34+ cell selection resulted in more than 99.9% depletion of CD5+ cells from the bone marrow. The patients received 2.53 to 7.25 x 10(6) CD34-enriched cells/kg after myeloablative therapy. All patients achieved trilineage engraftment that was confirmed by various genetic markers. Acute graft-versus-host disease (GVHD) was grade 0 (two patients) or grade I (one patient), and hematological recovery was successfully achieved as follows; the days to reach granulocytes over 0.5 x 10(9)/I were 11 to 13 days, reticulocytes over 2% was 18 to 28 days, platelets over 50 x 10(9)/I was 33 to 58 days. One patient is surviving without relapse of leukemia and two patients died after either mixed hematopoietic chimerism or leukemia relapse was observed. These studies suggest that CD34+ marrow cells are capable of hematopoietic reconstitution from HLA two or three loci-mismatched donors even with the lowest dose of mature T cells.

Adult↗

[Immediate surgical treatment for the traumatic pulmonary pseudocyst: a case report].

Nonpenetrating blunt trauma causing pulmonary pseudocyst is very rare. A 25-year-old young male suffered from motor vehicle accident. He was transferred to our hospital with severe hemoptysis. Immediately he was intubated and kept under mechanical ventilation. A chest X-ray film and CT-scan revealed a marked cavity lesion surrounded by an extensive infiltrate and alveolar air consolidation. Ordinary, it has benign clinical courses by conservative management. However, he was suffered massive and continuous bleeding from endobronchial tube. Therefore, one lung ventilation using a uni-vent tube blocker was performed. After twelve hours blockade, the cavity lesion was enlarged and trans-bronchial bleeding was continued severely. Emergency right lower lobectomy was carried out successfully.

Accidents, Traffic↗

[Role of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

Examinations of peritoneal lavage smears (LC) and gastric wall brushing smear cytology (BC) appear to be important for determining accurately the stage of gastric cancer. We have been carrying out such examinations during gastric cancer surgery for 7 years. In the present study, we evaluated the results obtained from 287 patients with gastric cancer. Tumor invasion and peritoneal dissemination were correlated with a positive incidence of cancer cells in LC and/or BC. Gastric cancer showing serosal invasion was classified into positive for LC and/or BC and negative for LC and/or BC. Patients positive for LC and/or BC had a poorer prognosis. For future gastric cancer treatment, patients positive for peritoneal cytology are expected to be targeted for intensive treatment during or before surgery.

Adenocarcinoma↗

[Direct detection of human cytomegalovirus in urine specimens from bone marrow transplant patients by polymerase chain reaction].

Human cytomegalovirus (HCMV) infection is a major causative life-threatening agent that results in opportunistic infections in bone marrow transplant patients. Since antiviral therapy is available for severe HCMV infections, methods to rapidly identify infected patients are needed so that therapy can be promptly instituted. In this study, we used direct method to detect HCMV in urine specimens by nested polymerase chain reaction (nested-PCR) to monitor urinary excretion of HCMV in patients undergoing bone marrow transplantation. The viral DNA was amplified directly from preheated urine without further treatment prior to amplification. Five microliter of urine proved to give the most efficient amplification. The detection limit of the PCR assay for detection of HCMV was 10 copies/microl. The positive rate of the PCR assay and the tissue culture method for detection of HCMV were 15 of 61 (24.6%) and 4 of 61 (6.6%), respectively. Sensitivity and specificity of the PCR assay were 100% and 81% respectively. Based on these data, urinary excretion of HCMV in 21 patients undergoing bone marrow transplantation were monitored weekly by the PCR assay. As a result, in addition to a higher sensitivity, the PCR assay allowed to identify HCMV infection 3.1 (1 approximately 5) weeks earlier than culture method or antibody elevation. Repeated monitoring of virus excretion by this rapid and simple method was useful to promptly detect HCMV infection, allowing proper institution of antiviral drug therapy in patients undergoing bone marrow transplantation.

Adolescent↗

Familial amyotrophic lateral sclerosis with a two base pair deletion in superoxide dismutase 1: gene multisystem degeneration with intracytoplasmic hyaline inclusions in astrocytes.

We performed a comparative neuropathological study on two siblings with familial amyotrophic lateral sclerosis (FALS). The clinical course of the sister who died at age 46 was 18 months, and that of the brother who died at age 65, 11 years. The neuropathological findings of the female were compatible with FALS with posterior column involvement. Her brother had multisystem degeneration in addition to the motor neuron disturbance; Lewy body-like hyaline inclusions (LBHIs) were present in the affected neurons of the degenerative lesions. Eosinophilic inclusions were seen in many astrocytes of the affected areas of the male FALS patient. Immunohistochemical assays revealed that most astrocytic inclusions reacted with the antibodies against Cu/Zn-superoxide dismutase 1 (SOD1) and ubiquitin; immunoreactivity was essentially the same as that of the neuronal LBHIs. Ultrastructurally the astrocytic inclusions were composed mainly of 15- to 25-nm granule-coated fibrils and granular material, resembling LBHIs of the neurons. Despite the dissimilar neuropathological features, both patients had the same two base pair deletion in exon 5 of the SOD1 gene. These findings suggest that FALS due to an SOD1 gene mutation is potentially a multisystem degenerative disorder, affecting not only neurons, but also astrocytes.

Amyotrophic Lateral Sclerosis↗

[A basic study on gastric emptying test using barium grains and effect of drugs on gastric emptying in rats].

We reported an experimental study on a new non-invasive method for evaluation of gastric emptying by abdominal X-ray after administration of radiopaque barium grains. Adult male Wistar rats weighing around 200 g were used. After they were fasted for 24 hours, 1 ml of gruel mixed with 10 barium grains (1 mm diameter) was introduced into the rat stomach with a catheter. The rats were sacrificed at 30, 60, 90, 120 and 150 minutes after the introduction of the gruel. X-rays were taken at each time point and grains in the stomach were counted in the X-ray photographs. All barium grains were emptied from the stomach in 150 minutes. After incision of the abdomen, the residual gastric contents were weighed. A positive correlation was found between the grains in the stomach and the weight of the contents. We studied the effects of cisapride, scopolamine buthylbromide and enprostil on the gastric emptying time by this method. Cisapride accelerated gastric emptying, whereas scopolamine buthylbromide delayed it. A prostaglandin E2 analog, enprostil delayed the gastric emptying. This method was found to be a simple procedure which is outstanding for quantitative determination and useful in evaluating gastric emptying functions.

Animals↗

Ca(2+)-dependent activation of the 33-kDa protein kinase transmits thrombin receptor signals in human platelets.

Thrombin stimulation induces a dramatic increase in the activity of the 33-kDa serine/threonine kinase (PK33) in human platelets (10). The Arg-Gly-Asp (RGD) peptide, an inhibitor of the thrombin-mediated aggregation of platelets, did not affect the PK33 activation induced by thrombin suggesting that the activation of this kinase occurs independently from platelet aggregation. To identify a potential role of Ca2+ and calmodulin in the regulation of PK33, the effect of several Ca2+/calmodulin inhibitors on the thrombin-induced activation of PK33 was assessed using denaturation/renaturation method. Pretreatment of platelets with EGTA decreased the maximum PK33 activity induced by thrombin. The chelation of both the extra- and the intracellular Ca2+ by EGTA and by acetoxymethyl ester of 5,5'-dimethyl-bis-(0-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) decreased further the PK33 activation by thrombin. Preincubation of platelets with the anticalmodulin agent, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide (W13), inhibited markedly the activation of PK33 by thrombin, whereas the inactive structural analog N-(4-aminobutyl)-2-naphthalenesulfonamide (W12) and the myosin light chain kinase inhibitor 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML9) showed very weak inhibitory effects. Treatment of resting platelets with the calcium ionophore, A23187, activated PK33 in a dose-dependent manner; phorbol 12-myristate 13-acetate enhanced this effect. However, the two foregoing agents did not induce similar degree of PK33 activities as thrombin. These results indicate that the activation of PK33 is independent of the formation of the GPIIb/IIIa-fibrinogen complex and that it might be regulated by a Ca(2+)-dependent pathway.

Blood Platelets↗

[Successful second stage operations for bilateral giant bullae with cardiovascular disease by thoracotomy and thoracoscopic surgery: a case report].

A 65-year-old male was admitted to our hospital because of bilateral giant bullae and right side pneumothorax. He had had a myocardial infarction and had been receiving medications. Considering his age, ischemic heart disease and hypertension, we excised the bullae in two operations. The first operation was open chest bullectomy of a giant bulla and small bulla on the right side. After this procedure, his clinical course was uneventful. In the second operation, thoracoscopic excision of the left side giant bulla was performed using only one endoscopic stapler by rotating each side of the bulla and making a clear excision line between the bulla and normal lung. His post operative course was excellent and he was discharged from our hospital on the 15th day after the second operation.

Aged↗