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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 505 records · Page 28Linked to original sources

Stimulatory effect of angiotensin II on calcium efflux from cultured bovine adrenal chromaffin cells.

The effect of angiotensin II on Ca2+ mobilization in cultured bovine adrenal chromaffin cells was examined. Angiotensin II (10(-7)M) increased the intracellular free Ca2+ level ([Ca2+]i) to a peak in the presence or absence of extracellular Ca2+, followed by decrease with time. Angiotensin II (10(-9)-10(-6)M) also stimulated 45Ca2+ efflux from cultured bovine adrenal chromaffin cells in a concentration-dependent manner. Its stimulatory effect on 45Ca2+ efflux was inhibited by the angiotensin II antagonist [Sar1, Ile8]-angiotensin II or [Sar1, Val5, Ala8]-angiotensin II. The increase in angiotensin II-stimulated 45Ca2+ efflux was dependent on the extracellular Na+ concentration. Angiotensin II also increased 22Na+ influx into the cells. These results indicate that stimulation of the angiotensin II receptor induces extracellular Na(+)-dependent Ca2+ efflux from cultured bovine adrenal chromaffin cells, probably by acceleration of Na+/Ca2+ exchange.

Adrenal Medulla↗

Calcium efflux from cultured bovine adrenal chromaffin cells induced by pituitary adenylate cyclase-activating polypeptide (PACAP): possible involvement of an Na+/Ca2+ exchange mechanism.

The effect of pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP1-38) on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. PACAP1-38 stimulated the efflux of 45Ca2+ from the cells in a concentration dependent manner (10(-9)-10(-7)M). This effect was inhibited by its potent receptor antagonist PACAP6-38. PACAP1-38 increased the formation of [3H]inositol phosphates and cyclic AMP in the cells. Forskolin, an activator of adenylate cyclase, also stimulated the efflux of 45Ca2+ from the cells. 3-Isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase, enhanced PACAP1-38-induced 45Ca2+ efflux from the cells. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, had no effect on the efflux of 45Ca2+ from the cells. The increases in 45Ca2+ efflux induced by PACAP1-38 and forskolin were reduced by deprivation of extracellular Na+ and the Na+/Ca2+ exchange inhibitor amiloride. In addition, PACAP1-38 stimulated 22Na+ influx into the cells, and this action was inhibited by amiloride. These results suggest that PACAP1-38 stimulates an Na+/Ca2+ exchange mechanism through activation of adenylate cyclase in cultured bovine adrenal chromaffin cells.

1-Methyl-3-isobutylxanthine↗

Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension.

Adrenomedullin is a strong vasorelaxing peptide discovered in pheochromocytoma tissue. Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to cause pulmonary hypertension. To test the hypothesis that adrenomedullin plays a role similar to that of atrial natriuretic peptide or brain natriuretic peptide in modulating right ventricular responses to pulmonary hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of monocrotaline treated rats with those of control rats. We also measured the effect of pulmonary hypertension on plasma level of the peptide. The concentrations of adrenomedullin immunoreactivity in right ventricle and plasma were significantly higher in monocrotaline treated rats than in control rats. The messenger RNA level of adrenomedullin in right ventricle was also higher in monocrotaline treated rats than in control rats. These results suggest that adrenomedullin participates in the mechanism to counteract the high blood pressure in pulmonary circulation.

Adrenomedullin↗

Plasma adrenomedullin in patients with primary aldosteronism.

Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from the pheochromocytoma tissue of humans. To examine the pathophysiological role of AM in primary aldosteronism (PA), the plasma concentration of AM in patients with PA was measured with a specific radioimmunoassay and compared to that in age- and sex-matched healthy normotensive subjects. In addition, the concentrations of AM as well as catecholamines in the plasma from both the adrenal vein and the inferior vena cava (IVC) were measured to determine whether or not the circulating AM in these PA patients is supplied from the adrenal medulla, which contains a much higher concentration of AM than any other human tissue does. The plasma concentration of AM in the PA patients (4.57 +/- 0.32 fmol/mL, n = 6) was significantly (P < .01) higher than that in the healthy subjects (3.06 +/- 0.20 fmol/mL, n = 12). A significant positive correlation (r = 0.62, P < .01) was observed between the mean blood pressure and the plasma AM level. The AM concentration in plasma from the adrenal vein was almost the same level as that from the IVC although the concentrations of both epinephrine and norepinephrine in the adrenal vein were much higher than those in the IVC. Therefore, it seems unlikely that the plasma AM in the PA patients is mainly supplied from the adrenal medulla. Judging from the potent hypotensive activity of AM, the present findings suggest that AM participates in defense mechanisms acting against the elevation of blood pressure in the patients with PA.

Adrenal Glands↗

The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan.

To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in pemphigus and bullous pemphigoid based upon 496 cases of pemphigus and 1113 cases of bullous pemphigoid in Japan. Results showed that (1) an association between internal malignancies and pemphigus was observed in 25 out of 496 cases (5.0%), while that with bullous pemphigoid was seen in 64 out of 1113 cases (5.8%). Such association ratios were significantly higher than that of the controls aged over 70 years old (0.61%); (2) The average ages of pemphigus/bullous pemphigoid with malignancy were 64.7 and 69.2 years, respectively. The association ratio of malignancy with pemphigus increased by age, while that with pemphigoid was not correlated with aging; (3) Lung cancer was most common in pemphigus and gastric cancer in bullous pemphigoid; (4) There were no significant differences in the titers of circulating antibody, the presence or extent of mucous involvement or annular erythema between bullous pemphigoid patients with malignancy and without malignancy. Our results indicated that detailed examination for internal malignancy is essential for those patients with pemphigus or bullous pemphigoid.

Aged↗

Detection of varicella-zoster virus (VZV) DNA in throat swabs and peripheral blood mononuclear cells of immunocompromised patients with herpes zoster by polymerase chain reaction.

BACKGROUND: Varicella-zoster virus (VZV) is rarely isolated from throat swabs and peripheral blood leukocytes from patients with herpes zoster by conventional virus isolation methods. The polymerase chain reaction (PCR) is a highly sensitive method to detect VZV genomes. It has been reported that VZV DNA was detected in the cerebrospinal fluid (Puchhammerstockl et al., 1991) and peripheral blood mononuclear cells (PBMC) of patients with VZV-associated neurological symptoms (Gilden et al., 1992) by PCR. OBJECTIVES: We used the nested double PCR to detect VZV DNA in patients with herpes zoster. STUDY DESIGN: Sixteen patients with herpes zoster, ten immunocompromised and six immunocompetent patients, were studied. Throat swabs and PBMC were collected weekly and examined for VZV DNA by the nested double PCR. RESULTS: VZV DNA was detected in 60% (6/10) of throat swabs and in 60% (6/10) of PBMC of immunocompromised patients, and in 16.7% (1/6) of throat swabs and in 33% (2/6) of PBMC of immunocompetent patients within two weeks after the onset of skin rash. VZV DNA was detected in throat swabs or PBMC of two patients 5 and 7 days after cessation of acyclovir. CONCLUSION: VZV DNA was detected in throat swabs and PBMC-associated viremia exist in patients with herpes zoster. It is suggested that VZV spread from sensory ganglia to the skin or pharyngeal area along the nerve fiber or hematogenously and local cutaneous replication of VZV can lead to viremia with subsequent hematogenous dissemination in patients with herpes zoster.

Journal Article↗

Markedly elevated levels of beta2-microglobulin in urine with measles viruria in patients with measles.

BACKGROUND: Measles is a highly contagious infectious disease in children. However, the pathogenesis has not yet been fully defined since susceptible cells to measles virus (MV) had not been developed. Recently, B95a cells, which are very susceptible to MV, have been reported. OBJECTIVES: To evaluate measles viruria in patients with measles, isolation of MV from urine was performed using B95a cells. STUDY DESIGN: Isolation of MV from supernates or sediments of urine in patients with measles was performed using B95a cells. The levels of beta2-microglobulin (MG) in urine and serum were also measured. RESULTS: MV was isolated from either supernates or sediments of urine. MV was isolated from 10 of 11 samples (91%) within 2 days of the appearance of a rash. MV was isolated from supernates of urine for up to 4 days after the appearance of a rash, and from sediments for up to 5 days. The levels of urinary beta2-MG were elevated within 2 days of the appearance of a rash. The levels of urinary beta2-MG with measles viruria were significantly higher compared to those without measles viruria. CONCLUSIONS: Measles viruria may occur early in all patients with measles and elevated levels of urinary beta2-MG in patients with measles may be the consequence of tubular injury.

Journal Article↗

The effect of intravenous and intra-tumoural chemotherapy using a monoclonal antibody-drug conjugate in a xenograft model of pancreatic cancer.

In order to investigate the efficacy of the intra-tumoural administration of an anticancer drug-monoclonal antibody conjugate in athymic nude mice bearing xenografts of a human pancreatic carcinoma, we examined the clearance of the murine monoclonal antibody A7 from the xenografts after intravenous or intra-tumoural administration and measured the antitumour effect of neocarzinostatin conjugated to MAb A7 following intravenous or intra-tumoural injection. Compared with 125I-labelled normal mouse IgG, a larger amount of 125I-labelled A7 remained in the tumour after both intravenous and intra-tumoural injection, and a significantly larger amount of 125I-labelled A7 remained in the tumour after intra-tumoural injection than that after intravenous injection. Moreover, a larger amount of 125I-labelled A7-NCS localized in the tumour after intra-tumoural injection than that after intravenous injection. Neocarzinostatin conjugated to MAb A7 showed greater activity against human pancreatic cancer than neocarzinostatin alone after both intravenous and intra-tumoural administration. Tumour growth was suppressed completely by the intra-tumoural administration of A7-NCS at a dose that did not suppress tumour growth via the intravenous route. These observations suggest that the intra-tumoural injection of neocarzinostatin conjugated to MAb A7 offers promise in treating pancreatic carcinoma.

Adenocarcinoma↗

Induction of bone resorbing-activity by mouse stromal cell line, MC3T3-G2/PA6.

Unfractionated mouse long-bone cells prestimulated with rat parathyroid hormone (PTH) for 7 days (PTH-prestimulated long-bone cells; PTH-psLB cells) contained about 20% tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells and about 0.2% TRAP-positive multinucleate cells. When PTH-psLB cells (1.0 x 10(5)/slice) were cultured on dentine slices, about 100 resorption lacunae (pits) per slice were formed by 6 h after the start of culture, while the number of TRAP-positive multinucleate cells on the dentine slices did not increase. When the number of inoculated cells was plotted versus the number of pits formed during the 6-h cultivation, a sigmoid curve was generated. When PTH-psLB cells (1.0 x 10(3)/slice) were cocultured with various mouse stromal cell lines, the MC3T3-G2/PA6 line was found to increase the number of pits. Since this activity was manifested within a short period of time (4 h), and as there was no change in the number of TRAP-positive multinucleate cells, we postulate that the activity of MC3T3-G2/PA6 is exerted on mature osteoclastic cells capable of resorbing bone rather than on some differentiation step of the osteoclast cell lineage. With respect to the mechanism of expression of this activity, it is unlikely that MC3T3-G2/PA6 produces a soluble factor, because no activity was seen when MC3T3-G2/PA6 and PTH-psLB cells were cultured separately across a membrane in a Transwell. These results suggest that cell-to-cell contact and communication between PTH-psLB cells and MC3T3-G2/PA6 may be a crucial event for the stimulation of osteoclastic bone resorption by MC3T3-G2/PA6.

Animals↗

Branchial cyst of the nasopharynx: resection via the endonasal approach.

We present a rare branchial cyst of the nasopharynx in a 57-year-old man. The cyst was located at the higher level between the roof and the left lateral band of the nasopharynx, and was removed by the endonasal approach following a preparatory septoplasty. While several cases of nasopharyngeal cysts have previously been reported, this appears to be the first case of the resection of such a cyst via the endonasal approach, and is a useful, and potentially less injurious, alternative to the transpalatal approach.

Branchioma↗

Proadrenomedullin N-terminal 20 peptide (PAMP), an endogenous anticholinergic peptide: its exocytotic secretion and inhibition of catecholamine secretion in adrenal medulla.

In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca(2+)-dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC50 = 50.1 microM) and catecholamines (EC50 = 63.0 microM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP [1-20]NH2 inhibited carbachol-induced 22Na+ influx via nicotinic receptors (IC50 = 2.5 microM in a noncompetitive manner and thereby reduced carbachol-induced 45Ca2+ influx via voltage-dependent Ca2+ channels (IC50 = 1.0 microM) and catecholamine secretion (IC50 = 1.6 microM). It did not alter high K(+)-induced 45Ca2+ influx via voltage-dependent Ca2+ channels or veratridine-induced 22Na+ influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca(2+)-dependent exocytosis in response to nicotinic receptor stimulation.

Adrenal Medulla↗

Distribution and characterization of immunoreactive adrenomedullin in porcine tissue, and isolation of adrenomedullin [26-52] and adrenomedullin [34-52] from porcine duodenum.

Using a sensitive radioimmunoassay which recognizes the carboxy-terminal region of porcine adrenomedullin, the distribution of immunoreactive adrenomedullin was widely distributed in porcine tissue, and its concentration was highest in adrenal medulla (126 +/- 32 fmol/mg wet tissue; mean +/- SD). Relatively high concentrations of immunoreactive adrenomedullin were found in the right atrium, lung, duodenum, and pituitary gland. The molecular form of immunoreactive adrenomedullin in all porcine tissues was found to be almost wholly porcine adrenomedullin itself by analysis with reverse-phase high-performance liquid chromatography coupled with radioimmunoassay. Minor molecular forms of immunoreactive adrenomedullin were found in the porcine duodenum. These were isolated and identified as adrenomedullin [26-52] and adrenomedullin [34-52].

Adrenomedullin↗

Haemodynamic responses to rat adrenomedullin in anaesthetized spontaneously hypertensive rats.

1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive peptide, were examined in anesthetized 16-18 week old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). 2. An intravenous injection of rat AM dose-dependently reduced the mean blood pressure (MBP) with a concomitant fall in total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in both strains of rats. Percent changes in MBP, TPRI and CI were not different between SHR and WKY. 3. The plasma half-life of rat AM in SHR was similar to that in WKY when it was administered at the dose of 1.0 nmol/kg. 4. These findings indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The haemodynamic responsiveness to exogenous AM and its pharmacokinetics in SHR were comparable with those in WKY.

Adrenomedullin↗

Changes in nerve fibers adjacent to transplanted VX2 carcinoma in rabbit tongue.

This study was undertaken to examine the relationship between malignant tumor tissue and nerve fibers using a transplantation model and nerve fiber strains. Most of the neural tissue, as well as the other host tissues, showed severe degenerative changes as the transplanted tumor grew. Furthermore, the degenerative changes were chiefly confined to the area anterior to the tumor. These changes were probably provoked chiefly by the compressive effects of the rapidly enlarging transplant. The results could possibly explain clinical symptoms such as paralysis or disturbances in the movement of the tongue observed occasionally in some patients with lingual carcinomas.

Animals↗

[Four cases of hemolytic uremic syndrome (HUS) associated with serotype O165 verotoxin producing Escherichia coli (VTEC) identified by LPS-solid phase enzyme-linked immunosorbent assay (ELISA)].

Enzyme-linked immunosorbent assay using LPS derived from newly recognized serotype O165 verotoxin producing Escherichia coli (VTEC) could identify 4 cases of hemolytic uremic syndrome (HUS) associated with O165 VTEC. All 4 cases showed a typical clinical course seen in VTEC-associated HUS. We screened 33 cases of HUS whose pathogen was not identified by culture of serodiagnosis. The O165 serotype was not thought to be important not only as a VTEC but also as an enteropathogenic E. coli. However, the prevalence, 4 cases, was as high as of O111 serotype, which is the second major serotype of VTEC in Japan. We have to be careful for this serotype when we look for the pathogen of the patients with hemorrhagic colitis or with HUS.

Bacterial Toxins↗

[Therapeutic evaluation of combination therapy using human native immunoglobulin preparation for i.v. administration, with antibiotics and G-CSF in severe infections in the field of internal medicine].

A human native immunoglobulin liquid preparation for intravenous injection, was used in combination with antibiotics and G-CSF to study its efficacy and safety in 49 patients with severe infections (Granulocyte counts were or= 38 degrees C) which had not responded to antibiotic and G-CSF therapy of a 3-day or more duration. As a result of the Committee judgment, 49 patients were included in this study; 30 (61.7%) were included in efficacy and safety analysis. The analysis of 30 patients consisted of 9 patients (30.0%) with suspected septicemia, 5 (16.7%) with pneumonia, and 4 (13.3%) with septicemia. All patients had severe underlying diseases such as leukemia and malignant lymphoma. Clinical efficacy of Immunoglobulin preparation was judged by the doctors in charge to be "excellent" and "good" in 70.0% of the total cases. The rate of effectiveness was calculated from the results of the Committee judgment was 83.3% when "excellent" and "good" cases were included. No side effects were observed in all cases. Our results suggest that the immunoglobulin in combination with G-CSF is very effective on patients with severe infections.

Adult↗

G alpha q and G alpha 13 regulate NHE-1 and intracellular calcium in epithelial cells.

To understand the mechanisms by which G protein-coupled signaling systems regulate NHE-1 in epithelial cells, we expressed G alpha q and G alpha 13 in a renal epithelial cell line. We studied two signaling systems that have been implicated in NHE-1 regulation [intracellular Ca (Cai) and phospholipase C activity] and measured NHE-1 activity, mRNA, and antigen. Expression of alpha qWT and alpha qQ209L (a GTPase-deficient mutant) increased basal Cai and altered the kinetics of the bradykinin-induced Cai signal. The initial bradykinin-induced spike in Cai was prolonged and the plateau was higher in cells expressing alpha qWT and alpha qQ209L than in control cells. Cells expressing alpha 13WT also had a higher basal Cai and plateau after stimulation by bradykinin, but Ca release from intracellular stores was similar to that in control cells. Expression of all three alpha-chains increased NHE-1 activity, antigen, and mRNA. The alpha qQ209L had the greatest effect increasing activity by approximately twofold. The alpha 13WT increased NHE-1 activity by approximately 1.5-fold, and alpha qWT increased activity 1.2-fold. These studies demonstrate that alpha q and alpha 13 alter regulation of Cai but by different mechanisms. The Ca signal or another signal generated by alpha q and alpha 13 regulate(s) NHE-1 at the levels of activity, antigen, and mRNA.

Animals↗