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Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 253 records · Page 14Linked to original sources

A new apparatus for studying feeding and drinking in the mouse.

The quantity of powder food consumed by individual mice was gauged with a newly developed apparatus that includes a specialized feeding station, an electric scale, and an interface to a computer that records the weight of the powder food jar. Using the measurements that exceeded the cutoff value, that is, the threshold between a mouse feeding or drinking event and scale noise, the reconstructed data were presented as the daily pattern of feeding and drinking in time resolution of 9 to 30 min. In this system, the ratio of noise to total consumption value was less than 4%. The fractal structure and fitting curve of this time series data were also analyzed by the nonlinear least-squares method, combined with the maximum entropy method. These analyses demonstrated that the mouse feeding event has circadian and ultradian periodicity. This apparatus and system are useful tools in studying the daily feeding pattern of mice.

Algorithms↗

Two-dimensional orientational response of smooth muscle cells to cyclic stretching.

It was hypothesized that an orientated cellular tissue for incorporation into vital, functioning hybrid artificial organs can be prepared by periodically applying mechanical stresses on a hybrid tissue. Therefore, the effect of cyclic stretching on the two-dimensional (2-D) orientation response of arterial smooth muscle cells (SMCs) was studied. Smooth muscle cells derived from bovine aortas were seeded onto transparent elastomeric membranes made of polyurethane, and subjected to periodical stretching with various amplitudes from 5-20% at frequencies of 15 to 120 RPM for up to 24 hours. Phase-contrast microscopic views of SMCs were time-lapse video recorded. The orientation angle to the direction of stretching (OA) and cellular longitudinal length (CLL) of individual cells were analyzed by a computerized image processor. After several hours, SMCs subjected to the stress exhibited orientation responses perpendicular to the direction of stretching, evidenced by a significant increase in OA. The responses were more rapid under operating conditions with higher amplitudes and frequencies of stretching. Meanwhile, little significant change in CLL was observed. These findings indicate that an applied mechanical stress induces a significant orientation response, without morphologic alteration of SMCs. The mechanically induced orientation response provides a fundamental basis for more structured hybrid organs and tissue engineering.

Animals↗

Development of a vascular prosthesis for a growing child. A graft expandable in vivo.

Specially designed vascular prostheses that can be dilated after implantation using a percutaneous transluminal angioplasty (PTA) balloon catheter have been developed. The grafts are made of woven polyester fiber fabrics, the circumferential yarns of which consist of two different types of polyester fiber bundles: One is a straight weak bundle, the other is a strong bundle wound around the former. The graft with an initial diameter of 6 mm could be dilated to 9 mm by luminal inflation of the balloon four to five times at 10 atmospheres (atm) in vitro. After disrupting the weak bundle by the dilatation procedure, the strong bundles were straightened, which maintained the enlarged diameter of the new caliber. Grafts of 6 mm in initial diameter implanted into the thoracic aortas of mongrel dogs for 3 months also could be dilated in vivo by inflating the PTA four to five times at 15 atm, as found in the vitro study. Macroscopic observation revealed that, around the dilated grafts, only a tiny hematoma was formed and nominal subsequent bleeding was observed, which indicated that the dilatation procedure was performed safely. The graft, which enables adaptation of the hydrodynamic property of the graft to the increased blood flow by PTA after implantation, is applicable in a growing child.

Angioplasty, Balloon↗

Highly oriented, tubular hybrid vascular tissue for a low pressure circulatory system.

A hierarchically structured hybrid vascular tissue was prepared from vascular cells and collagen. First a hybrid medial tissue was prepared by pouring a cold mixed solution of bovine aortic smooth muscle cells (SMCs) and Type I collagen into a tubular glass mold composed of a mandrel and a sheath (inner diameter, 1.5 mm; outer diameter, 7 mm; length, 7 cm). An SMC incorporating collagenous gel was formed with incubation at 37 degrees C. After the sheath of the mold was removed, the resulting fragile tissue cultured in the medium shrank in a time dependent manner to form an opaque, dense tissue. Seeding at a higher cell density and a lower concentration of collagen resulted in rapid and prominent shrinkage. Morphologic investigation showed that with time, bipolarly elongated SMCs and collagen fiber bundles became positioned around the mandrel. When the mandrel was removed, a tubular hybrid medial tissue was formed. A hybrid vascular tissue with a hierarchical structure was constructed by seeding endothelial cells onto the inner surface of the hybrid medial tissue. Prepared tissues tolerated luminal pressures as great as 100 mmHg and mechanical stress applied during the anastomotic procedure. This method allowed the authors to prepare hybrid medial tissues of predetermined size (specifically inner diameter, wall thickness, and length) and mechanical property, which all depend on the mold design, SMC seeding density, initial collagen concentration, and incubation period. Hybrid vascular tissues may provide physiologic functions such as antithrombogenicity and regulation of vasomotor tone when implanted into a venous system.

Animals↗

Applicability of the latissimus dorsi muscle in situ as a biomechanical energy source.

The purpose of this study was to assess the applicability of the latissimus dorsi muscle in situ as an energy source for a circulatory assist device. A pneumatic chamber, devised by the authors, was inserted beneath the muscle and compressed by contractions of the muscle so that muscle contractile power was converted into pneumatic pressure. The optimal insertion position of the chamber beneath the latissimus dorsi muscle, and the influence of chamber size on generated pneumatic pressure, were investigated. The pneumatic chamber functioned better when it was placed in a proximal position (third intercostal space) than in a middle or distal position. Using a mock circuit, the performance of the pneumatic chamber as an energy source for a circulatory assist device was evaluated. The pneumatic chamber was able to generate power sufficient to drive a right ventricular assist device as far as stroke work was involved. When the pneumatic chamber was operated with a high afterload, it could even be an energy source for aortic counterpulsation.

Animals↗

A compressive type skeletal muscle pump as a biomechanical energy source.

The purpose of this study was to assess the applicability of the conditioned latissimus dorsi muscle as an energy source for circulatory assist devices. The authors developed a pneumatic chamber as a muscle actuator. The pneumatic chamber placed between latissimus dorsi muscle and chest wall was compressed by the burst stimulated muscle and, thereby, converted muscle contractile power into pneumatic pressure. The authors report the performance of the implanted pneumatic chamber at a chronic phase, and the capability of the conditioned muscle in situ as an energy source for circulatory assist devices. Six adult mongrel dogs were used. At the first operation, a pacemaker for muscle conditioning and the pneumatic chamber were implanted. After 12 weeks of muscle conditioning, the performance of the pneumatic chamber with conditioned muscle was evaluated. The pressure generating capability of a chamber buried in fibrous adhesions was reduced to approximately 65% of that of a chamber without adhesions. The stroke volume and stroke work of the assist device driven by the developed pneumatic pressure were measured. The maximum stroke work of the circulatory assist was greater than the stroke work of the right ventricle, but less than that of the left ventricle. In respect to stroke volume, the pneumatic chamber could drive the circulatory assist device against not only a pulmonary range of afterload, but also a systemic range of afterload, when high pre load was available. These results indicate that the compressive skeletal muscle pump with conditioned latissimus dorsi muscle generates acceptable hemodynamic work for right ventricular bypass or aortic counterpulsation. In the long-term, the interface between tissue and actuator is the major obstacle to developing a muscle powered assist device.

Animals↗

Spontaneous occurrence of autoimmune cholangitis in senescent mice.

The biliary lesions that developed spontaneously in senescent female C57BL/6NCrj mice were investigated. Degeneration of the bile duct epithelium was observed in 12 of 13 mice (92%), destruction of bile duct epithelial cells was seen in six of 13 mice (46%) and chronic non-suppurative destructive cholangitis was found in three of 13 mice (23%). The biliary lesions were characterized by prominent round cell infiltrates in the portal areas. Extra-hepatic lesions such as sialoadenitis were observed in six mice (46%) and pancreatis in seven (53%). IgM class antipyruvate dehydrogenase antibody was positive in one of three C57BL/6NCrj mice not given anti-Lyt 2 antibody and in three of six C57BL/6NCrj mice injected with anti-Lyt 2 antibody. These lesions were not observed in male C57BL/6NCrj mice, young female C57BL/6NCrj mice, or ICR mice. However, by transferring the splenic cells of senescent female C57BL/6NCrj mice to 6 week old females, the biliary lesions could be transferred at the rate of 6/9. The lymphocytes infiltrating in the bile ducts were CD8 positive lymphocytes. Moreover, in the ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia, CD8 positive lymphocytes often formed broad contacts with the epithelial cells. The biliary lesions developing spontaneously in these mice are similar to those found in human primary biliary cirrhosis.

Aging↗

Significance of sublobular hepatic necrosis in the progression of chronic hepatitis C.

The clinical characteristics of hepatitis C virus associated chronic liver diseases (C-LD) in 17 patients were compared with hepatitis B virus associated diseases (B-LD) in 47 patients, by analysing the histological findings of the liver and the change in serum alanine aminotransferase (ALT) level. The persistence of the moderate abnormality in ALT (> 100 IU/L) for longer than 1 year was more frequently seen in the C-LD group (P < 0.01), although the severe exacerbation of the disease with ALT higher than 500 IU/L was more frequent in the B-LD group (P < 0.01). The patients with the histological finding of sublobular hepatic necrosis (SN) in the C-LD group progressed to advanced stages more frequently than those with SN in the B-LD group (P < 0.05). Furthermore, nine of 10 patients with SN in C-LD finally progressed to hepatocellular carcinoma (HCC) in 52 +/- 23 months, whereas three of 16 with SN in B-LD developed HCC in 81 +/- 34 months. Although the morphological features of SN in C-LD and B-LD were almost the same, SN in C-LD seemed to be a more significant diagnostic condition for the progression to liver cirrhosis or HCC. The patients with SN in the C-LD group should be closely followed for the early detection of HCC, although further study with a greater number of patients is necessary.

Adult↗

Fas gene promoter -670 polymorphism in gynecological cancer.

Single-nucleotide polymorphism at -670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas -670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08-6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05-2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter -670 may be associated with the risk of cervical cancer in a Japanese population.

Adult↗

Review: biological effectiveness of thermal neutrons and 10B(n,alpha)7Li reaction on cultured cells.

There are only a few reports on the relative biological effectiveness (RBE) of thermal neutrons and 10B(n,alpha)7Li reactions either in vitro or in vivo. The data in this paper summarize almost all previously published in vitro data. Because only a few reactors are available for biomedical purposes, it is difficult to make a comparison of data from experiments using the same kind of radiation, and also to make a comparison of data from experiments using the different kinds of radiations. However, it is indispensable for boron neutron capture therapy to make a radiobiological analysis. More intensive study, including repair process and oxygen effect, is necessary for establishing the fundamental basis of the clinical application of boron neutron capture therapy.

Animals↗

Estimation of absorbed dose in the covering skin of human melanoma treated by neutron capture therapy.

A patient with malignant melanoma was treated by thermal neutron capture therapy using 10B-paraboronophenylalanine. The compound was injected subcutaneously into ten locations in the tumor-surrounding skin, and the patient was then irradiated with thermal neutrons from the Musashi Reactor at reactor power of 100 KW and neutron flux of 1.2 X 10(9) n/cm2/s. Total absorbed dose to the skin was 11.7-12.5 Gy in the radiation field. The dose equivalents of these doses were estimated as 21.5 and 24.4 Sv, respectively. Early skin reaction after irradiation was checked from day 1 to day 60. The maximum and mean skin scores were 2.0 and 1.5, respectively, and the therapy was safely completed as far as skin reaction was concerned. Some factors influencing the absorbed dose and dose equivalent to the skin are discussed.

Aged↗

Behavior of arterial wall cells cultured on periodically stretched substrates.

Cells in vital tissues align to form the most efficient configuration for functioning. Vascular cells of arterial walls are constantly exposed to fluid shear stress and pressure-induced periodic strain component, both of which are induced by pulsatile flow. In the present study, the effect of cyclic strain on the cellular orientation response and morphological changes of bovine arterial wall cells such as endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts (FCs) was studied. Cells seeded onto transparent elastomeric films were subjected to periodic stretch-relaxation under various amplitudes ranging from 5 to 20% and at frequencies ranging from 15 to 120 RPM for up to 24 h. Time-lapse video-recorded images of stress-loaded cells were analyzed by a computer-aided morphometric system to quantitatively evaluate the cellular orientation responses and morphological changes. The stress-loaded cells tended to align perpendicularly to the direction of stretch with time, regardless of cellular species. More pronounced orientation was attained under operating conditions with higher amplitude and frequency of stretching. The response of SMCs and FCs advanced more rapidly than that of ECs. Meanwhile, little morphological change was observed, irrespective of stress-loading or nonloading. Understanding of mechanically induced orientation response provides a fundamental basis on tissue engineering and biomechanics.

Animals↗

Mechanical stress-induced orientation and ultrastructural change of smooth muscle cells cultured in three-dimensional collagen lattices.

The effect of tensile stress on the orientation and phenotype of arterial smooth muscle cells (SMCs) cultured in three-dimensional (3D) type I collagen gels was morphologically investigated. Ring-shaped hybrid tissues were prepared by thermal gelation of a cold mixed solution of type I collagen and SMCs derived from bovine aorta. The tissues were subjected to three different modes of tensile stress. They were floated (isotonic control), stretched isometrically (static stress) and periodically stretched and recoiled by 5% above and below the resting tissue length at 60 RPM frequency (dynamic stress). After incubation for up to four wk, the tissues were investigated under a light microscope (LM) and a transmission electron microscope (TEM). Hematoxylin and eosin-stained LM samples revealed that, irrespective of static or dynamic stress loading, SMCs in stress-loaded tissues exhibited elongated bipolar spindle shape and were regularly oriented parallel to the direction of the strain, whereas those in isotonic control tissues were polygonal or spherical and had no preferential orientation. In Azan-stained samples, collagen fiber bundles in isotonic control tissues were somewhat retracted around the polygonal SMCs to form a random network. On the other hand, those in statically and dynamically stressed tissues were accumulated and prominently oriented parallel to the stretch direction. Ultrastructural investigation using a TEM showed that SMCs in control and statically stressed tissues were almost totally filled with synthetic organelles such as rough endoplasmic reticulums, free ribosomes, Golgi complexes and mitochondria, indicating that the cells remained in the synthetic phenotype. On the other hand, SMCs in dynamically stressed tissues had increased fractions of contractile apparatus, such as myofilaments, dense bodies and extracellular filamentous materials equivalent to basement membranes, that progressed with incubation time. These results indicate that periodic stretch, in concert with 3-D extracellular collagen matrices, play a significant role in the phenotypic modulation of SMCs from the synthetic to the contractile state, as well as cellular and biomolecular orientation.

Animals↗

In vitro reconstruction of hybrid arterial media with molecular and cellular orientations.

A hybrid medial tissue composed of a type I collagen gel, into which smooth muscle cells (SMCs) derived from bovine aortic media were 3-dimensionally (3D) embedded, was constructed around an elastomeric silicone tube (outer diameter: 8 mm). Subsequently, hybrid tissues thus prepared were subjected to three modes of mechanical stimulation in the medium: one was subjected to flotation with no disturbance (isotonic control), the second was kept isometrically (static stress) and the third was subjected to continuous periodic stretch by inflation of the embedded silicone tube which stimulated arterial pulsation (dynamic stress, amplitude: 5% in inner diameter; frequency: 60 RPM). After a 5-day culture period, hybrid tissues were morphologically investigated. In control gels, polygonal SMCs and extracellular collagen fiber bundles were randomly oriented. On the other hand, upon static or dynamic stress loading, bipolar spindle-shaped SMCs and dense collagen fiber bundles were aligned circumferentially around the silicone tube, which proceeded with time. The orientations of SMCs and collagen fibers were more prominent in dynamically stressed hybrid tissues than those in statistically stressed ones. The pulsatile stress-loaded hybrid medial tissue mimicked the media of native muscular arteries in terms of cellular and molecular orientations.

Aorta↗

Phenotypic reversion of smooth muscle cells in hybrid vascular prostheses.

Our purpose was to evaluate whether or not and when phenotypic modulation of smooth muscle cells (SMCs) in hybrid vascular prostheses preincorporated with SMCs occurs upon implantation. Two types of hybrid vascular grafts incorporated with vascular cells derived from canine jugular veins were prepared: grafts containing a collagen gel layer covered with an endothelial monolayer at the luminal surface (Model I graft) and those containing an endothelial monolayer and SMC multilayer (Model II graft). They were bilaterally implanted into carotid arteries of the same dogs from which the cells had been harvested for 2 wk (n = 3) and 12 wk (n = 3). The time-dependent changes in populations of three SMC phenotypes (synthetic, intermediate, and contractile) in the neoarterial layers were quantified by morphometric evaluation using a transmission electron microscope in hybrid vascular grafts. Before implantation, all the SMCs were of the synthetic phenotype. In Model II grafts at 2 wk, synthetic and intermediate SMCs were dominant especially in the luminal layer. On the other hand, neoarterial layers at 12 wk were dominated by contractile SMCs, which were evenly distributed throughout the entire neoarterial tissues. A markedly delayed phenotypic reversion was noted for the Model I grafts at 12 wk. In the hybrid grafts, during about 3 mo of implantation, neoarterial SMCs transformed from the synthetic to the contractile phenotypes, which was promoted by SMC incorporation.

Animals↗

The seroepidemiology of hepatitis A and B in a Japanese town.

Sera collected from 1,118 healthy children and adults aged between four years and 90 years during the period 1989 to 1990, were tested for serological markers of hepatitis A virus (HAV) [antibody to HAV (anti-HAV)] and hepatitis B virus (HBV) [hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBsAb)]. The overall prevalence rates of anti-HAV, HBsAg, and anti-HBV were 20.2%, 0.36%, and 5.1%, respectively. No body was found to be positive for anti-HAV below 30 years of age but more than 70% of the adults aged 50 years or over were positive for anti-HAV. The level of exposure of HAV infection is declining in Japan and paradoxically at the same time a vast majority of people are becoming susceptible to more severe illness. The fall in prevalence of HBsAg possibly represents the positive impact of ongoing vaccination programs and other preventive measures against HBV.

Adolescent↗

Temperature influences induction of a J7W-1-related phage in Bacillus thuringiensis serovar indiana.

Induction of a plasmid-integrative J7W-1-related phage in Bacillus thuringiensis serovar indiana by ethidium bromide was influenced by the temperature at which the host cells were cultured. Under optimal growth conditions, the maximum titer of the phage produced by the serovar indiana reached 1.2 x 10(6) PFU/ml at 37 degrees C while at 27 degrees C it was lower by an order of magnitude (1.3 x 10(5) PFU/ml). The temperature-sensitive period was estimated to occur early during the phage induction. However, the temperature effect observed with the serovar indiana did not occur with the serovar israelensis. In the latter case, the phage induction was the same at 37 degrees C or 27 degrees C. Thus we assume that the temperaturesensitive phage induction observed with the serovar indiana as host was not a phenomenon caused by the phage genome but rather by product(s) encoded by certain host gene(s).

Bacillus Phages↗