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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 577 records · Page 32Linked to original sources

Effect of intravenously administered fat emulsion on liver function in totally depancreatized dogs.

Total Pancreatectomy was performed under nembutal anesthesia in 16 adult mongrel dogs after a 24-hour fast, and the depancreatized dogs were given parenteral nutrition containing fat emulsion. Serum lipids, intravenous fat tolerance and post-heparin lipolytic activity were determined and liver biopsy was done to demonstrate the presence or absence of fatty liver. The animals were divided into three groups: group A (n = 6) received fat emulsion 1 g/kg/day; group B (n = 5), fat emulsion 2 g/kg/day; and group C (n = 5), no fat emulsion. Blood levels of cholesterol and phospholipid were increased in group B, while only a mild elevation of the blood triglyceride (TG) level was noted in group A. In group C, cholesterol and phospholipid levels were decreased, and hypoglycemia was liable to occur. The rate of disappearance of blood fat (K2) was decreased two weeks after surgery in group B, but there were no significant change in the other two groups. These findings suggest that if insulin is present, the administration of fat emulsion will not cause fatty liver.

Animals↗

[The role of gallium-67 citrate scintigraphy in gastro-intestinal malignant lymphoma].

To evaluate the clinical usefulness of gallium-67 scintigraphy in the detection of the gastrointestinal (GI) non-Hodgkin's lymphoma (NHL) and in the assessment of the therapeutic effects, gallium-67 scintigraphy was reviewed on 24 cases (25 lesions; stomach in 20, ileum in 2, and terminal ileum and/or cecum in 3). Twenty-three out of the 25 lesions (92.0%) were detected by gallium-67 scintigraphy, while barium study could detect all of the 25 lesions. The sizes of the gallium-67 negative 2 lesions were the smallest of all (2.5 and 3.0 cm). The tumor size was considered to the most important factor in the detection by gallium-67 scintigraphy, while the histological classification and the location of the tumor were not related to its detectability. Findings in follow-up gallium-67 scintigraphy after therapy on 10 cases were correlated well with the therapeutic effects. These data suggest that gallium-67 scintigraphy is useful for the detection of GI involvement of NHL and for the assessment of therapeutic effects.

Adult↗

Site-directed mutagenesis of Asp-376, the catalytic phosphorylation site, and Lys-507, the putative ATP-binding site, of the alpha-subunit of Torpedo californica Na+/K(+)-ATPase.

Point mutations of Asp-376 of the alpha-subunit of Torpedo californica Na+/K(+)-ATPase (the site of phosphorylation during the catalytic cycle) to Asn, Glu or Thr led to virtual abolishment of Na+/K(+)-ATPase activity and ouabain-binding capacity. Replacement of Lys-507 of the same subunit (the putative ATP-binding site) by Met resulted in decreases in Na+/K(+)-ATPase activity and ouabain-binding capacity. These results are in agreement with those reported for rabbit sarcoplasmic reticulum Ca2(+)-ATPase (Maruyama, K. and MacLennan, D.H. (1988) Proc. Natl. Acad. Sci. USA 85, 3314-3318).

Adenosine Triphosphate↗

Mechanisms of intracellular pH regulation in the hamster inner medullary collecting duct perfused in vitro.

To examine the mechanisms of H+ transport in the mid-inner medullary collecting duct of hamsters, we measured the intracellular pH (pHi) in the in vitro perfused tubules by microscopic fluorometry using 2',7'-bis(carboxyethyl)-carboxyfluorescein (BCECF) as a fluorescent probe. In the basal condition, pHi was 6.74 +/- 0.04 (n = 45) in HCO3(-)-free modified Ringer solution. Either elimination of Na+ from the bath or addition of amiloride (1 mM) to the bath produced a reversible fall in pHi. After acid loading with 25 mM NH4Cl, pHi spontaneously recovered with an initial recovery rate of 0.096 +/- 0.012 (n = 23) pH unit/min. In the absence of ambient Na+, after removal of NH+4, the pHi remained low (5.95 +/- 0.10, n = 8) and showed no signs of recovery. Subsequent restoration of Na+ only in the lumen had no effect on pHi. However, when Na+ in the bath was returned to the control level, pHi recovered completely Amiloride (1 mM) in the bath completely inhibited the Na(-)-dependent pHi recovery. Furthermore, elimination of Na+ from the bath, but not from the lumen, decreased pHi from 6.97 +/- 0.07 to 6.44 +/- 0.05 (n = 12) in the HCO3-/Ringer solution or 6.70 +/- 0.03 to 6.02 +/- 0.5 pH unit/min in the presence of CO2/HCO3-, whereas it did not recover in the absence of CO2/HCO3-.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

The role of gallium 67 imaging in non-Hodgkin's lymphoma of the gastrointestinal tract.

To evaluate the clinical usefulness of gallium 67 imaging in the detection of gastrointestinal (GI) non-Hodgkin's lymphoma (NHL) and in the assessment of the therapeutic effects, images were reviewed in 24 cases (25 lesions: stomach, 20; ileum, 2; and terminal ileum and or cecum, 3) and were compared using barium studies and, in 16 cases, computerized tomography (CT). In all, 23 (92.0%) of the 25 lesions were detected by 67Ga citrate imaging, the barium studies detected all 25, and CT detected 15 of 16 lesions (93.8%). The two lesions not identified by imaging and the one not found by CT were the smallest of all. In 2 (8.7%) of the 23 lesions positively identified by 67Ga-citrate imaging, both CT and imaging revealed the extent of the tumor more accurately than did the barium studies. In all but one of the patients, a close correlation existed between the imaging results and the therapeutic effects. These data suggest that 67Ga imaging is useful in conjunction with CT and barium studies for the detection of GI NHL and for the assessment of both the spatial extent of disease and the therapeutic effects, although a lack of 67Ga uptake after therapy does not always indicate a good therapeutic effect.

Barium Sulfate↗

Single photon emission computed tomography (SPECT) using N-isopropyl-p-(123I) iodoamphetamine (IMP) in the evaluation of patients with epileptic seizures.

To evaluate the clinical usefulness of IMP SPECT in the diagnosis of epilepsy, 6 normals and 52 patients in the interictal phase were studied. Thirty min after an intravenous injection of 111 MBq IMP, SPECT was performed using a rotating gamma camera. Of 21 patients with simple partial seizures, a localized decrease of uptake was shown in 16, and an increase in 3. Topologically, these findings corresponded well to the ictal symptoms. Nine of 13 patients with localized epileptic EEG had a good correspondence between the findings on EEG and IMP SPECT. In 20 of 23 with complex partial seizures, the coronal images showed laterality of uptake in the temporal lobes, whereas the CT was normal in 14. However, these findings on IMP SPECT agreed with the EEG in the temporal leads in only 5 cases. Of 8 patients with primary generalized seizures, a diffuse cerebral decrease was shown in 3 of 4 patients with convulsive seizures (grand mal), and a normal uptake in 3 of 4 patients with non-convulsive seizures (petit mal). However, 2 patients showed a localized decrease, therefore, we determined that they suffered from partial seizures evolving to secondarily generalization. From these data, we concluded that IMP SPECT could be a useful method in the diagnosis of epilepsy.

Adolescent↗

Tracheal reconstruction by esophageal interposition: an experimental study.

The purpose of this study was to assess the possibility of reconstructing a circumferential tracheal defect with autogenous esophagus. In 6 mongrel dogs, a circumferential defect involving seven rings of the cervical trachea was reconstructed by interposing pedicled esophagus. A silicone T tube was used as a stent. The vertical limb of the T tube (usually referred to as the horizontal limb when used in humans) was cut shorter after the cervical wound had healed well, and it eventually was buried subcutaneously. Two dogs died 36 days after operation, and 1 died 28 weeks after operation. In no dog was the cause of death related to the operation or to a respiratory tract complication. Two dogs were put to death 4 weeks and 32 weeks after operation. They were well until then, and all the anastomoses between the trachea and the esophagus had healed fully without formation of granulation tissue. One dog is alive and well 14 months after operation. The vertical limb of the T tube retracted into the subcutaneous space, and there is no open cervical wound. Esophageal interposition might be a feasible technique for tracheal replacement in select groups of patients.

Anastomosis, Surgical↗

Possible role of renal prostaglandin E2 in natriuresis associated with supraventricular tachycardia.

We investigated the possible role of renal prostaglandin (PG) E2 in natriuresis associated with supraventricular tachycardia (SVT). In five female patients with paroxysmal tachycardia, SVT was artificially induced and then stopped 60 min later. Before, during, and after SVT, plasma levels of arginine vasopressin and atrial natriuretic peptide (ANP) and the urinary excretion of sodium and PGE2 were measured. Polyuria was observed during SVT. However, natriuresis did not occur until immediately after the termination of SVT. During SVT, the plasma levels of arginine vasopressin tended to decrease. When SVT was terminated, the vasopressin levels increased significantly (p less than 0.01). Urinary excretion of PGE2 tended to decrease during SVT and then increased significantly (p less than 0.01) after SVT ended. Urinary excretion of sodium was correlated (r = 0.699, p less than 0.001) with the urinary excretion of PGE2. Plasma ANP increased during SVT, but there was no correlation with urinary sodium excretion. These results suggest that renal PGE2, the biosynthesis of which may be stimulated by a increase in plasma vasopressin, is an important factor contributing to the natriuresis observed after the end of SVT.

Adult↗

Somatostatin is increased in the dorsal root ganglia of adjuvant-inflamed rat.

To determine whether biosynthesis of somatostatin is enhanced in the primary sensory neurons by inflammatory pain, we examined the effects of adjuvant inoculation on the content of immunoreactive somatostatin, mainly composed of somatostatin-14 and somatostatin-28, in the dorsal root ganglia and the spinal cord of the rat. The adjuvant inoculation, which produced long-lasting inflammation and hyperalgesia, increased the content of immunoreactive somatostatin, especially somatostatin-14, in the dorsal root ganglia at L4-L6 levels with no change in the dorsal and ventral horns of lumbar enlargement. Such an increase was enhanced by an intrathecal injection of colchicine (0.2 mg) that inhibits axonal flow of somatostatin. Chronic administration of the anti-inflammatory analgesic, sodium diclofenac (3 mg.kg-1.d-1), abolished an adjuvant-induced increase in the content of immunoreactive somatostatin in the dorsal root ganglia. These results suggest that the turnover (biosynthesis and axonal flow) of somatostatin in the primary sensory neurons is enhanced in the presence of persisting inflammatory pain, and support the idea that somatostatin-containing primary afferents are involved in the transmission of pain in the spinal dorsal horn.

Animals↗

Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells.

Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-E alpha molecules and have aspartic acid at residue 57 of the I-A beta chain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-cell functions, was injected intraperitoneally into [NOD----C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1 mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation. Transplantation of a stem-cell-enriched population from (NZW x BXSB)F1 mice into normal mice also induced autoimmune disease in the recipients. These results indicate that both systemic autoimmune disease and organ-specific autoimmune disease originate from defects that reside within the stem cells; the thymus and environmental factors such as sex hormones appear to act only as accelerating factors.

Animals↗

Multiple antigenic epitopes expressed on gag proteins, p26 and p15, of a human immunodeficiency virus (HIV) type 2 as defined with a library of monoclonal antibodies.

Thirty-two hybridoma clones producing monoclonal antibody (MAb) against HIV-2[GH-1] were established from mice immunized with NP-40-disrupted purified whole virus of a Ghanaian isolate of human immunodeficiency virus type 2 (HIV-2), strain HIV-2[GH-1]. Of these 32 MAbs, 20 reacted with p26 and the other MAbs recognized p15 of the HIV-2[GH-1] isolate. From the results of serological characterization by these MAbs, p26 and p15 were identified as capsid proteins and matrix protein, respectively, of HIV-2[GH-1] gag products. In addition to two gag proteins, a 55-kD protein corresponding to the primary translational product of gag gene and 39-kD protein corresponding to an intermediate product of cleavage of p55 were recognized by these MAbs in the lysate of HIV-2[GH-1]-infected cells. Moreover, these MAbs were used to analyze the number of antigenic epitopes on p26 and p15 of HIV-2[GH-1] isolate. The results of cross-reactivity with different HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates and competitive binding assay suggest that there are at least four and five antigenic epitopes in p26 and p15, respectively, of the HIV-2[GH-1] isolate. The biological activity of MAbs was studied by performing syncytium inhibition assay and infection inhibition assays. However, our MAbs could not inhibit syncytium formation and infection by cell-free virus.

Animals↗

Sodium sensitive and sodium retaining hypertension.

The differences between sodium sensitive and sodium retaining hypertension were theoretically considered using a water tank model of body fluid volume-blood pressure regulation. If an outlet valve is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume and output from the outlet, which represent mean arterial pressure (MAP), cardiac output (CO) and urinary Na+ excretion. The height of the outlet from the tank bottom and the size cross-sectional area, of the outlet correspond to the x-intercept and slope of the renal function (pressure-natriuresis) curve, respectively. In both nonsodium sensitive hypertension, due to the shift of the curve toward a higher blood pressure level (elevated height of the outlet) without change in the slope (size of the outlet), and sodium sensitive hypertension, due to the depressed slope of the curve (reduced outlet size), not only MAP (water level) but also CO (water volume) are increased, resulting in sodium retaining hypertension, if TPR (reciprocal of base area) remained unchanged, while CO is relatively unchanged, resulting in nonsodium retaining hypertension, if TPR is elevated. Thus, the MAP and its sensitivity to sodium intake is determined by the renal function curve. Since body fluid volume is determined by both the renal function curve and TPR, however, changes in TPR during the development of hypertension is a major factor in determining whether or not the body fluid volume has to change only a small amount or a large amount. Therefore, the sodium sensitivity of blood pressure and sodium retention must be considered separately.

Blood Pressure↗

Aortic regurgitation secondary to Behçet's disease. A case report and review of the literature.

Cardiac complications, especially aortic regurgitation, are very rare in Behçet's disease. This report describes a patient with a complicated abnormality of the aortic valve apparatus and severe aortic regurgitation secondary to Behçet's disease. In the literature, flail prolapsed valve, perforated valves and ruptured pseudoaneurysms of the sinus of Valsalva have been reported. Echocardiography may be most useful to detect these anatomically complex abnormalities and therefore to elucidate the cause of aortic regurgitation in Behçet's disease.

Aortic Valve Insufficiency↗

Conversion of cholesterol to pregnenolone mobilizes cytochrome P-450 in the inner membrane of adrenocortical mitochondria: protein rotation study.

Rotation of cytochrome P-450 was examined in bovine adrenocortical mitochondria before and after an enzymatic transformation of cholesterol into pregnenolone by cytochrome P-450scc in the presence of malate. Rotational diffusion was measured by observing the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane normal" model. The measurements were used to investigate substrate-dependent intermolecular interactions of cytochrome P-450 with other redox components. Rotational mobility of cytochrome P-450 was significantly dependent on the decrease in cholesterol content by side chain cleavage reaction catalyzed by cytochrome P-450scc. In a typical experiment, the observed value for the normalized time-independent anisotropy r(infinity)/r(0) was decreased from 0.78 in control mitochondria to 0.60 after conversion of 21% of cholesterol to pregnenolone, while no significant change was observed for the average rotational relaxation time phi of about 700 microseconds. Significantly high values of r(infinity)/r(0) = 0.78 and 0.60 imply co-existence of mobile and immobile populations of cytochrome P-450. Since we observed that the heme angle tilted 55 degrees from membrane plane, 22% (control mitochondria) and 40% (after conversion of cholesterol to pregnenolone) of cytochrome P-450 in mitochondria are calculated to be mobile in the preparation. The significant mobilization of cytochrome P-450scc molecules caused by the conversion of cholesterol to pregnenolone is likely due to changes in protein-protein interactions with its redox partners, since the lipid fluidity was kept unchanged by the cholesterol depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Establishment of a phylogenetic survey system for AIDS-related lentiviruses and demonstration of a new HIV-2 subgroup.

We designed a universal primer (UNIPOL) for DNA amplification of AIDS-related viruses. The phylogenetic tree constructed from the presumed sequences amplified with UNIPOL was representative of the tree calculated from whole pol gene sequences so far reported. UNIPOL was able to amplify the sequences of all four major groups of primate lentiviruses and also that of a distinct virus from a Ghanaian patient with an AIDS-related complex, designated GH-2. This strain scarcely hybridizes with known HIV/simian immunodeficiency virus (SIV) DNA probes. Sequence analysis of the only amplified fragment revealed rapidly that GH-2 was quite similar to the recently reported HIV-2ALT(D205) and that these two viruses form a new subgroup distint from known HIV-2 and SIVmac/SIVsm in the large HIV-2 group. This system will be useful for further phylogenetic study of various primate lentiviruses.

Acquired Immunodeficiency Syndrome↗

The effect of pravastatin in relation to low density lipoprotein receptor activity.

Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, suppresses new synthesis of cholesterol via HMG-CoA in hepatocytes. As a result, low density lipoprotein (LDL) receptor activity in the liver is enhanced, which leads to lowering of plasma cholesterol. Inhibitors are shown to be effective in heterozygous familial hypercholesterolaemia (FH). Although FH heterozygotes are defined genetically as possessing half the normal LDL receptor activity, some heterogeneity of LDL receptor activity is observed in these patients. To see whether the effect of an inhibitor is related to LDL receptor activity in each patient, pravastatin was administered to 7 FH heterozygotes for 3 months at a daily dose of 10 mg; their mean LDL receptor activities measured before the therapy were 45.0 +/- 9.9% of the normal control. After medication, mean serum total cholesterol decreased from 349.0 to 279.7 mg/dl (p less than 0.05), and LDL-cholesterol decreased from 272.6 to 207.7 mg/dl (p less than 0.05). A significant correlation between the initial LDL receptor activity and the effect of pravastatin was not proved. However, the pre-treatment level of LDL-cholesterol was positively correlated (r = 0.795) with the absolute decrement of LDL-cholesterol after 3 months (p less than 0.05). This implies that the more LDL-cholesterol was elevated, the more pravastatin was effective.

Adult↗

Voltage-dependent Ca2+ channels are involved in regulation of steroid synthesis by bovine but not rat fasciculata cells.

Bovine but not rat fasciculata cells show a concentration-dependent stimulation of the production of corticosteroids by addition of external Ca2+ to the incubation medium. Both cell types respond to ACTH in a concentration-dependent manner. Increasing concentrations of K+ (0-20 mM) cause increased production of corticosteroids and accelerated influx of Ca2+ in bovine fasciculata cells but no change in either of these two parameters in rat fasciculata cells. Two inhibitors of Ca2+ channels (nifedipine and PY108-068) inhibit both the production of steroids by unstimulated bovine cells and the stimulation produced by three agents (ACTH, (Bu)2 cAMP, and K+). Half-maximal inhibition of these responses was produced in each case by submicromolar or low micromolar concentrations of the inhibitors. These inhibitors are without effect in rat fasciculata cells. One Ca2(+)-channel agonist (BAY K8644) stimulated synthesis of steroids by bovine cells and potentiated the response to ACTH. The agonist acts in the low micromolar range but was without effect on rat cells or on the responses of steroid synthesis by these cells to either ACTH or dibutyryl cAMP. Moreover, bovine fasciculata cells show specific binding sites for [+]PN 200-110, a specific ligand for 1,4-dihydropyridine receptors associated with voltage-dependent Ca2+ channels [dissociation constant (Kd), 14.3 nM; maximum number of binding sites (Bmax), 0.52 pmol/10(6) cells]. Rat cells show no specific binding of PN 200-110. We conclude that bovine fasciculata cells possess voltage-dependent Ca2+ channels which are involved in the regulation of steroid synthesis in these cells and that rat fasciculata cells are without such channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Procaine inhibits cyclic AMP-induced steroidogenesis in isolated bovine adrenocortical cells.

Effects of procaine on dibutyryl adenosine 3',5'-cyclic monophosphate ((Bu)2cAMP)-, Ca2(+)- or forskolin-induced steroidogenesis were examined in isolated bovine adrenocortical cells. Procaine (less than 1.0 mM) caused a marked suppression of (Bu)2cAMP- or forskolin-induced steroidogenesis in the absence of extracellular Ca2+, but did not affect on Ca2(+)-induced steroidogenesis in the cells. (Bu)2cAMP decreased the cell associated 45Ca2+. However, procaine (300 microM) inhibited this effect of (Bu)2cAMP. These results suggest that procaine may abolish (Bu)2cAMP-induced Ca2+ release from intracellular calcium store(s) and inhibits steroidogenesis.

Adrenal Cortex↗