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Biomedical subjects

K Komatsu

Publications and source records attributed to K Komatsu.

At least 361 records · Page 20Linked to original sources

Enterically transmitted non-A, non-B hepatitis in cynomolgus monkeys: morphology and probable mechanism of hepatocellular necrosis.

Two cynomolgus monkeys were inoculated with a stool extract originally derived from patients suffering from enterically transmitted non-A, non-B hepatitis. Subsequently, the primates developed self-limiting acute hepatitis and their liver tissues were obtained sequentially by needle biopsy or at sacrifice. Histologically, the liver tissues exhibited necroinflammation which appeared in parallel, both in time and magnitude, with elevation in serum aminotransferases. Necroinflammation was characterized by focal dropout of hepatocytes with accumulation of lymphocytes and macrophages. These lymphocytes were positive for a cytotoxic/suppressor immunophenotype. The hepatocytes surrounding these focal necroses showed depletion of glycogen granules and decrease in glucose-6-phosphatase and succinic dehydrogenase activities. Ultrastructurally, damaged hepatocytes around the focal necroses revealed marked dilatation of both rough and smooth endoplasmic reticula, swelling and disruption of the mitochondria and leakage of nuclear materials into the cytoplasm. Frequently, direct contact between the damaged hepatocytes and lymphocytes was noted. Virus-like particles measuring about 27 nm in diameter were observed singly or in small groups within the cytoplasm of damaged hepatocytes. Primary hepatocyte culture of a cynomolgus monkey, inoculated with a transmissible stool extract did not show any cytopathic change, although similar virus-like particles were recognized ultrastructurally in the cultured hepatocytes. Morphological analysis of in vitro and in vivo transmission studies in cynomolgus monkeys strongly supported the hypothesis of immune-mediated hepatocytolysis rather than a direct cytopathic effect of this hepatitis virus.

Animals↗

virG, a plasmid-coded virulence gene of Shigella flexneri: identification of the virG protein and determination of the complete coding sequence.

On the 230-kilobase-pair (kb) virulence plasmid of Shigella flexneri 2a strain YSH6000, at least seven separate genetic determinants have been identified. One of them, an approximately 4-kb region, virG, that is required for the Sereny reaction, was extensively studied to examine the role of the virG region. The phenotype of a VirG- mutant (M94) of YSH6000 in the cytoplasm of cultured MK cells was characterized by a kinetic study of the invading shigellae. The observed phenotype of M94 in the cytoplasm indicated that the virG locus is not required for multiplication of the invading shigellae, but is essential for their spread to adjacent cells. The DNA region necessary for the VirG function was localized to a 3.6-kb DNA sequence on the 230-kb plasmid. A 130-kilodalton polypeptide was confirmed to be the virG product. External labeling of bacteria with 125I indicated that the 130-kilodalton virG protein is exposed on the bacterial surface. The nucleotide sequence of 4,472 bp, which contains the functional virG gene and its own regulatory sequence, was determined, and a large open reading frame encoding 1,102 amino acid residues was identified.

Amino Acid Sequence↗

Whole-body hyperthermia-induced renal atrophy of mice as evinced by obstruction and degeneration of renal tubules caused by acute ischemia.

Effects of microwave-induced whole-body hyperthermia (WBH) on the mouse kidney were examined histologically for acute and late effects up to 150 days after WBH treatment at 43.5 degrees C (rectal temperature) for 20 min or 42 degrees C for 40 min. As a whole the damage could be divided into two types. One was the damage to distorted epithelial cells in the subcapsular region. This lesion was common in most animals, possibly caused by direct hyperthermic effect of microwave. The other was general renal atrophy accompanied with aqueous or protein-rich cysts due to a chain of physiological reactions of the whole body to WBH. The first reaction was characterized by general stasis of the blood stream in all parts of the kidney, which resulted in acute ischemia of some tissues. This was seen immediately by dilatation of the renal and interlobular veins as well as the bundles of capillaries in the medulla region. The subsequent event was rather specific cell necrosis of distal and collecting tubular epithelium as compared to proximal tubules. The cell destruction induced cell proliferation of the proximal tubular epithelia after two days. Later on, in accord with the recovery of the blood circulation, the proliferated cells were carried away into the lumen, these processes then resulting in obstruction of tubules through formation of protein casts in the lumen. The block incidentally led to the destruction of nephrons. The degenerated area sometimes consisted of aqueous or protein-rich cysts of various sizes after 7 to 30 days. Thereafter these cysts degenerated, decreasing in both number and size. Thus irreversible atrophy of the kidney developed after WBH.

Acute Disease↗

Prolylhydroxylase and collagenase activities in the healing of acetic acid-induced gastric ulcers in rats and the effects of cimetidine and elcatonin.

We examined the changes in prolylhydroxylase (PH) and interstitial collagenase (CA) activities in the healing of acetic acid-induced gastric ulcers in rats. Gastric ulcers were induced by subserosal injection of acetic acid, and confirmed by endoscopy on the third day. At the acute stage of ulceration, PH activity was not high but CA activity was increased. At the healing stage, PH activity was increased but CA activity gradually decreased to a normal level. Cimetidine did not effect PH activity but tended to increase CA activity in the healing. On the contrary, elcatonin increased PH activity but had little effect on CA activity. The above enzymes seems to be indispensable in the healing of gastric ulcers and effects of antiulcer agents on these enzymes must be considered.

Acetates↗

[Accumulation of liquids in the small intestine in mice after hyperthermia].

Female adult mice were subjected to 1) sublethal, 2) midlethal and 3) supralethal doses of systemic hyperthermia. In these mice, death occurred soon or several hours after the heat treatment depending on the severity of heating. In every cases, however, progression of the disseminated intravascular coagulation (DIC) syndrome such as decrease in thrombocyte count, condensation of circulating blood and liquid accumulation in the lumen of small intestines was with nearly the same speed indicating that the DIC was not the main cause of the death.

Animals↗

[Quantitative assessment of myocardial viability following coronary artery bypass grafting using exercise thallium-201 myocardial single photon emission computed tomography and left ventricular regional wall motion].

Using exercise thallium-201 myocardial single photon emission computed tomography (SPECT) and % radial shortening (%RS), 58 patients were evaluated before and after coronary artery bypass grafting (CABG) to quantitatively assess myocardial viability and the effect of CABG. The patient was classified, according to redistribution pattern, as group I with only complete redistribution (20 cases) and group II with including incomplete redistribution (22 cases) and group III with no redistribution (16 cases). 1. Group I was expected complete improvement of ischemic myocardium after CABG but regional left ventricular wall motion was unchanged (sigma i%RS: 142.5 +/- 54.7----138.4 +/- 39.6, sigma a%RS: 201.2 +/- 51.1----238.2 +/- 68.2). 2. Group II was expected to diminish ischemic size after CABG and left ventricular regional wall motion was significantly improved (sigma i%RS: 68.8 +/- 25.9----154.9 +/- 42.6 p less than 0.01, sigma a%RS: 108.4 +/- 62.3----178.9 +/- 77.6, p less than 0.05). 3. Group III was no significant change of ischemic size and left ventricular wall motion after CABG (sigma i%RS: 67.8 +/- 24.1----83.9 +/- 19.2, sigma a%RS: 86.0 +/- 29.0----94.0 +/- 33.9). The present study suggests that quantitative assessment of myocardial viability using exercise thallium-201 myocardial SPECT and %radial shortening was useful method to determine the indication and to assess the effect of CABG.

Adult↗

Potentiation and inhibition of tumor cell invasion by host cells and mediators.

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, the preculture with macrophages (0.1 less than macrophage/tumor cell less than 1.0) was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta or with activated platelets. A factor with anti-invasive potential (IIF) was extracted from rat liver. It inhibited the directed migration but not the growth of the tumor cells and was effective on their in vivo invasion and metastasis, as well.

Animals↗

Neutron-energy-dependent oncogenic transformation of C3H 10T1/2 mouse cells.

The relative biological effectiveness (RBE) of a range of neutron energies relative to 250-kVp X rays has been determined for oncogenic transformation and cell survival in the mouse C3H 10T 1/2 cell line. Monoenergetic neutrons at 0.23, 0.35, 0.45, 0.70, 0.96, 1.96, 5.90, and 13.7 MeV were generated at the Radiological Research Accelerator Facility of the Radiological Research Laboratories, Columbia University, and were used to irradiate asynchronous cells at low absorbed doses from 0.05 to 1.47 Gy. X irradiations covered the range 0.5 to 8 Gy. Over the more than 2-year period of this study, the 31 experiments provided comprehensive information, indicating minimal variability in control material, assuring the validity of comparisons over time. For both survival and transformation, a curvilinear dose response for X rays was contrasted with linear or nearly linear dose responses for the various neutron energies. RBE increased as dose decreased for both end points. Maximal RBE values for transformation ranged from 13 for cells exposed to 5.9-MeV neutrons to 35 for 0.35-MeV neutrons. This study clearly shows that over the range of neutron energies typically seen by nuclear power plant workers and individuals exposed to the atomic bombs in Japan, a wide range of RBE values needs to be considered when evaluating the neutron component of the effective dose. These results are in concordance with the recent proposals in ICRU 40 both to change upward and to vary the quality factor for neutron irradiations.

Animals↗

Factor from rat liver with antiinvasive potential on rat ascites hepatoma cells.

An acid/ethanol extract of normal rat liver, both in vitro and in vivo, inhibited the invasion by a highly invasive subpopulation of rat ascites hepatoma cells, AH 130 (LC-AH cells). The addition of 10-80 micrograms/ml extract inhibited the formation of penetrated colonies of LC-AH cells underneath the cultured mesothelial cell (M-cell) monolayer. The tumor cells pretreated with the extract showed the diminished colony formation. Preincubation of the extract with plasma membranes prepared from LC-AH cells abolished the effect of the extract, suggesting a binding of the inhibitory entity [tentatively termed as "invasion-inhibiting factor" (IIF)] to the tumor cell surface. The extract did not inhibit the growth of LC-AH cells, but suppressed their directed migration underneath the M-cell monolayer. A concomitant i.p. injection of the extract with LC-AH cells into rats prevented the invasion by tumor cells of the peritoneum and formation of tumor nodules in the peritoneum and mediastinum, indicating that IIF inhibited the tumor cell invasion and metastasis in vivo, as well. Upon ultrafiltration and gel fractionation, about 60% of IIF activity was recovered in the fraction corresponding to the molecular weight in the range of Mr 3000-4000. This activity was heat-stable at 100 degrees C at neutral pH but labile at acidic pH and was inactivated by the treatment with pronase. The rest of the activity of IIF was found in the fraction of more than Mr 25,000.

Animals↗

In vitro mechanics of the periodontal ligament in impeded and unimpeded rat mandibular incisors.

Load-deformation curves and/or the stress-strain curves were obtained by the mechanical testing of transverse sections of impeded and unimpeded rat incisors in vitro to evaluate more precisely the mechanical properties of the periodontal ligament. Perimeters of the lingual dentine and socket wall and the sectional area of the periodontal ligament were measured radiographically. An extension rate of 5 mm/min in an extrusive direction was used. The average maximum shear load, the elastic stiffness (tan beta) and the failure energy in shear in the impeded group were respectively 6.4, 6.0 and 5.7 times those in the unimpeded group. The average maximum deformation was similar. The average maximum shear stress, the elastic stiffness (tan alpha) and the failure strain energy density in the impeded group were respectively 7.2, 8.1 and 6.5 times those in the unimpeded group. The average maximum strain in the unimpeded group was significantly greater (1.4 times) than that in the impeded group. Mechanical responses of the periodontal ligament seem to be very sensitive to internal and external disturbance of the tooth: changes in such properties may be detectable even when other techniques fail to reveal differences. Our method provides a useful tool for such mechanical analysis.

Alveolar Process↗

The oncogenic potential of a combination of hyperthermia and chemotherapy agents.

The modulating effect of 43 degrees C hyperthermia on the induction of oncogenic transformation by the antineoplastic agents, actinomycin D, mitomycin C, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined using the C3H 10T1/2 cell line. For any given level of cytotoxicity, cells exposed to the three chemotherapy agents at 37 degrees C showed similar frequencies of transformation. Transformation frequencies induced by all three drugs were reduced by hyperthermia. The reduction was most pronounced for cells exposed to BCNU, and to a lesser extent, by cells exposed to actinomycin D and mitomycin C. The modulating effects of heat on drug-induced transformation incidence appeared to be independent of whether application of heat and drug was concurrent or sequential.

Animals↗

Oncogenic transformation by charged particles of defined LET.

Neoplastic transformation incidence and cytotoxicity were scored in the C3H/10T1/2 cell system following irradiation with charged particles of defined linear energy transfer (LET) produced at the Radiological Research Accelerator Facility of Columbia University. Cells cultured in monolayers, attached to thin Mylar sheets, were irradiated with accelerated protons, deuterons or helium-3 ions, and the results compared with X-rays. Defined LET values obtained by using the track segment mode, ranged from 10 to 120 keV/microns. For X-rays, and for the charged particles of lower LET, the dose-response curves for cell survival have a marked initial shoulder. With increasing LET, there is a progressive decrease in the size of the shoulder and for the highest LETs, survival curves approximate an exponential function of dose. The transformation incidence, likewise, showed a direct correlation to LET over the dose range examined. The efficiencies of transformation, however, appeared to approach a plateau between 80 and 120 keV/micron. Transformation data were analyzed using a linear-quadratic function of dose for the transformation probability. This latter quantity, when analyzed using microdosimetric consideration, suggests that the target volume for this end point is of the order of micrometer.

Animals↗

Diminished sympathetic excitation of locus coeruleus noradrenergic neurons in the conscious mature spontaneously hypertensive rat.

We undertook a study to determine whether the activation of the nucleus locus coeruleus might be responsible for the sympathetic hyperactivity in the spontaneously hypertensive rat (SHR). Conscious mature SHR showed increased arterial pressure and plasma catecholamines with electrical stimulation of the locus coeruleus. However, SHR showed smaller increases in arterial pressure and plasma noradrenaline than Wistar-Kyoto rats (WKY). The spontaneous unit discharge in locus coeruleus neurons responded reciprocally to peripherally induced changes in arterial pressure and blood volume. However, the unit discharge in the SHR locus coeruleus is less responsive than that in WKY. Therefore, the locus coeruleus in mature SHR does not seem to be involved in the hyperactivity of the sympathetic nervous system. However, this may not be the case in young SHR.

Animals↗