PubMed Health⌕ Search

Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 595 records · Page 33Linked to original sources
PubMed1994

In vitro reactivity and in vivo biodistribution of the monoclonal antibody A7 using human gastric carcinoma cell lines.

The monoclonal antibody (MAb) A7 has been used to treat patients with colorectal or pancreatic carcinoma with encouraging results. We therefore determined if MAb A7 would also react with gastric carcinoma cell lines. MAb A7 reacted with seven of eight gastric carcinoma cell lines tested. The intensity of the reaction, measured by flow cytometry, was equal to that of WiDr (colon) and HPC-YS (pancreas) cell lines. In nude mice bearing xenografts of the MAb A7-reactive gastric cancer line MKN45, the percentage injected dose of MAb A7 per g of tumour tissue on day 7 was 9.79; this value was 77% of that on day 1. The in vivo tumour-to-blood ratio of MAb A7 was 2.77 on day 7. Therefore, MAb A7 has long-term retention at binding sites as well as a high probability, high intensity and high specificity of reactivity against gastric cancer, which make it an ideal drug carrier for immunotargeted chemotherapy and immunodiagnosis.

Adenocarcinoma↗
PubMed1994

Immunohistochemical study of graft-versus-host reaction (GVHR)-type drug eruptions.

Skin biopsies of graft-versus-host reaction (GVHR)-type drug eruptions in the acute phase were compared immunohistochemically with those in the chronic phase and also with non-GVHR type drug eruptions in the acute phase. Predominance of CD8+ T cells in the epidermal infiltrates, reduction in the number of epidermal OKT6+ dendritic cells (Langerhans cells), and increased expression of HLA-DR and ICAM-1 on keratinocytes were observed in the acute phase of GVHR-type, but not in either the chronic phase of GVHR-type or the acute non-GVHR type. These findings were similar to those of previous reports on skin lesions of acute GVH disease (GVHD) seen after bone marrow transplantation. Therefore, immunohistochemistry is not useful for differential diagnosis between acute GVHR-type drug eruptions and acute cutaneous GVHD. These findings also indicate that similar immunomechanisms may be involved in the pathogenesis of both GVHR-type drug eruptions and cutaneous GVHD.

Adult↗
PubMed1994

In vivo efficacy of neocarzinostatin coupled with Fab human/mouse chimeric monoclonal antibody A7 against human colorectal cancer.

The anticancer polypeptide neocarzinostatin (NCS) was covalently coupled to a human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo efficacy of this conjugate was examined. NCS concentration assay was carried out, and acute toxicity and tumoricidal effects were examined. The concentration assay, using anti-NCS monoclonal antibody, revealed that administration of the chA7Fab conjugate leads to a greater blood retention and a higher tumor accumulation of NCS, when compared to free NCS administration. The tumoricidal effect of chA7Fab-NCS was higher than that of either free NCS or the saline control, against antigen-positive tumors. In antigen-negative tumors there was no difference in toxic effect among the three preparations. Values of LD50, reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA7Fab-NCS and the free NCS, respectively. These results suggest that chFabA7-NCS may be a promising tool for targeting cancer chemotherapy.

Animals↗
PubMed1994

Biodistribution of neocarzinostatin conjugated to chimeric Fab fragments of the monoclonal antibody A7 in nude mice bearing human pancreatic cancer xenografts.

In this study, we conjugated chimeric Fab fragments of the monoclonal antibody (MAb) A7, which reacts with pancreatic cancers, to the antitumor drug neocarzinostatin (chA7Fab-NCS) and intravenously injected 125I-labeled chA7Fab-NCS into nude mice bearing a human pancreatic cancer xenograft. We compared the tumor localization of 125I-labeled chA7Fab-NCS with that of conventional 125I-labeled A7-NCS, which was produced by conjugation of MAb A7 and NCS. 125I-Labeled chA7Fab-NCS accumulated in the tumor earlier than 125I-labeled A7-NCS, and significantly larger amounts of 125I-labeled chA7Fab-NCS had accumulated in the tumor 1 hour after injection. The results suggest that chA7Fab may be a suitable carrier for NCS in immunotargeting therapy against pancreatic cancer.

Animals↗
PubMed1994

Cytotoxicity against varicella zoster virus infected targets in children with acute leukemia.

To eliminate the role of natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), and polymorphonuclear leukocyte (PMN)-mediated cytotoxicity in Varicella zoster virus (VZV) infections, peripheral blood mononuclear cell (PBMC)-mediated NK and ADCC, and phorbol myristate acetate-stimulated PMN-mediated cytotoxicity against VZV-infected targets were studied in children with leukemia. Natural killer and PMN-mediated cytotoxic activity was depressed for 6 months after complete remission and ADCC activity was depressed for 1 year after complete remission. The magnitude of three cytotoxic mechanisms in leukemic children gradually increased while they continued in complete remission. These results suggested that decreased cytotoxic activities of PBMC and PMN might contribute to serious VZV infections and susceptibility to herpes zoster in leukemic children.

Adolescent↗
PubMed1994

A flow cytometric method for measurement of hydrogen peroxide generation by pediatric polymorphonuclear leukocytes stimulated by Staphylococcus aureus and Escherichia coli.

The generation of hydrogen peroxide (H2O2), one of the reactive oxygen species, by polymorphonuclear leukocytes (PMN) stimulated by Staphylococcus aureus and Escherichia coli was studied in infants by cytofluorography. After heparinized whole blood was incubated with bacteria for 60 min, generated H2O2 was measured. The positive rate of H2O2 generation of PMN and mean fluorescent intensity of positive PMN stimulated by S. aureus and E. coli were significantly reduced in infants aged < 1 year and H2O2 generation increased with advancing age. In 10-15 year old children, the level of generated H2O2 reached adult levels. When sera from 1 year old children were added to separated PMN from healthy adults, H2O2 generation was reduced. In contrast, H2O2 generation by PMN from 1 year old children was increased by the addition of adult sera. These results suggest that the ability to generate H2O2 in response to S. aureus and E. coli is lower in infants and that such reduced activity may be related to the susceptibility of such infants to S. aureus and E. coli infections.

Adolescent↗
PubMed1994

Allergenicity and tolerogenicity of amlexanox in the guinea pig.

Amlexanox (AMLX), an anti-allergic agent, is available in Japan as Elics opthalmic solution, Solfa nasal douche and Solfa tablets. Cases of allergic contact dermatitis induced by Elics ophthalmic solution, which contains 0.25% AMLX, were reported within a year of its introduction. We therefore examined the contact sensitizing potency of AMLX. Guinea pigs sensitized to 0.25% AMLX exhibited a strong positive patch test reaction. Further, AMLX-sensitized animals developed rashes following oral and systemic challenge with AMLX. This animal model reflected the clinical experience of systemic contact dermatitis due to AMLX. The non-responsiveness induced by oral administration of AMLX to AMLX-induced animals was transient, and clinical prophylaxis by desensitization with oral AMLX may only increase the risk of systemic contact dermatitis. On the other hand, there have been few reports of drug eruption from oral Solfa tablets in spite of their wide use. Therefore, we also examined the induction of tolerance by oral administration of AMLX. Oral administration of AMLX before sensitization resulted in complete non-responsiveness. It seems likely that a substantial reduction in the risk of AMLX sensitization by Elics may be achieved by prior oral administration of Solfa tablets containing AMLX.

Administration, Oral↗
PubMed1994

Gold dermatitis due to ear piercing: correlations between gold and mercury hypersensitivities.

A case of allergic contact dermatitis due to gold pierced earrings is reported. The patient developed recurring redness and swelling on her earlobes a month after the wearing of pierced-type gold earrings, which was followed by the appearance of reddish nodules around the puncture marks. Patch tests revealed positive reactions to 0.1% mercuric chloride, 1% gold sodium thiomalate and 0.2% chloroauric acid. We also demonstrated that guinea pigs contact-sensitized with a mercuric compound developed positive patch test reactions to both mercuric and gold compounds. These results suggest that there may be correlations between gold and mercury hypersensitivities.

Adult↗
PubMed1994

Eruptive clear cell hamartoma of sweat duct.

A histologically unique condition of the sweat duct was found in a miliaria-like papular eruption on the extensor surfaces of extremities of a 41-year-old female patient. The hypertrophic epithelium of the sweat duct wall consisted of extensively vacuolated clear cells. There was mild hyperkeratosis around the sweat duct orifice. The eccrine gland cells showed only partial vacuolization. Since this condition is not related to any of the other known benign changes of the eccrine duct, we report it with a presumptive descriptive diagnosis of eruptive clear cell hamartoma of sweat duct.

Adult↗
PubMed1994

Regulation of ATP-sensitive K+ channels by ATP and nucleotide diphosphate in rabbit portal vein.

The modulation of ATP-sensitive K+ (KATP)-channel activity was investigated by recording single-channel currents in isolated smooth muscle cells from rabbit portal vein. K(+)-channel openers (KCOs; pinacidil, lemakalim, and nicorandil) induced burstlike openings of single KATP channels in the cell-attached configuration. After patch excision, KATP channels showed "run-down" phenomenon in the presence of KCOs, but subsequent application of Mg-ATP (1 mM) restored KATP-channel activity. Removal of Mg-ATP resulted in transient augmentation of KATP currents, which eventually decayed out. Nucleotide diphosphates (NDPs; GDP, ADP, UDP, IDP, and CDP) also induced channel reopening in the presence of KCOs, which was markedly enhanced by addition of Mg2+ in millimolar concentrations at the internal side of the membrane. The dose-response relation between ATP and the UDP-induced KATP-channel activity was shifted to the right in the presence of Mg2+ (2 mM). These results suggest that intracellular ATP, NDPs, and Mg2+ regulate the channel state of KATP channels (operative and inoperative states) and that KCOs open KATP channels only in the operative state.

Adenosine Diphosphate↗
PubMed1994

Neonatal lupus erythematosus: dissolution of atrioventricular block after administration of corticosteroid to the pregnant mother.

Histopathologic and immunofluorescence findings of facial annular erythema on a 3-month-old female child, as well as serological detection of anti-SS-A (Ro) and anti-SS-B (La) antibodies, led to the diagnosis of neonatal lupus erythematosus (LE), while no sign of abnormality in the conducting system of the heart was found. During the pregnancy of the present child her mother, with positive anti-SS-A and anti-SS-B antibodies, had a history of Sweet's syndrome. She was treated with corticosteroid, resulting in a gradual diminution of the existing complete atrioventricular block of the fetus. This history may implicate a potential therapeutic effect for the congenital heart block associated with neonatal LE of corticosteroid given to the pregnant mother.

Female↗
PubMed1994

Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects.

Adrenomedullin is a novel hypotensive peptide, newly discovered in pheochromocytoma. Because immunoreactive adrenomedullin is present in human plasma, adrenomedullin may play a role in regulating blood pressure. A recent report showed that human adrenomedullin mRNA is expressed not only in pheochromocytoma but also in the normal adrenal medulla, kidney, lung, and ventricle. However, whether or not these organs actually release adrenomedullin into the circulation remains unknown. To investigate the sites of production and degradation of adrenomedullin in human subjects, we obtained blood samples from various sites and measured immunoreactive adrenomedullin concentrations. In study 1, blood samples were obtained from the infrarenal inferior vena cava, suprarenal inferior vena cava, superior vena cava, right atrium, right ventricle, pulmonary artery, pulmonary capillary, left ventricle, and aorta during cardiac catheterization in 15 patients with ischemic heart disease (67 +/- 10 years). In study 2, blood samples were taken from the infrarenal inferior vena cava, suprarenal inferior vena cava, right and left renal veins, and left adrenal vein in 5 hypertensive patients (42 +/- 14 years) suspected of having renovascular hypertension. In study 3, peripheral venous blood samples were obtained in 2 patients (males, 45 and 36 years old) with pheochromocytoma at rest and during hypertensive attacks. Plasma adrenomedullin concentrations were measured by a newly developed radioimmunoassay. In study 1, there were no significant differences in plasma adrenomedullin concentrations in various sites of the right-side circulation. There was no step-up of plasma adrenomedullin levels in the coronary sinus. However, the plasma concentration of adrenomedullin in aorta was slightly but significantly lower than in pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1994

Regulation of hormone-sensitive calcium influx by the adenylyl cyclase system in renal epithelial cells.

To study signaling pathways regulated by alpha s and alpha i1 in renal epithelial cells, we expressed mutant, activated forms of alpha s and alpha i1 in a continuous proximal tubule cell line (MCT cells). alpha sQ227L increased cAMP production, and alpha ilQ204L reduced forskolin-sensitive cAMP production. alpha ilQ204L increased and alpha sQ227L decreased bradykinin-induced Ca influx across the cell membrane, but neither mutant affected bradykinin-stimulated intracellular Ca release or basal Ca influx. Bradykinin-stimulated Ca influx was reduced by dibutyryl cAMP, isoproterenol, and forskolin. Expression of a mutant regulatory type I subunit for cAMP-dependent protein kinase with reduced affinity for cAMP and treatment with KT-5720, a specific cAMP-dependent protein kinase inhibitor, enhanced Ca influx to a degree similar to that in cells expressing alpha ilQ204L. Bradykinin-stimulated c-fos mRNA expression is partially dependent on extracellular Ca. alpha sQ227L reduced and alpha ilQ204L enhanced bradykinin-stimulated c-fos expression. Consequently, in bradykinin-stimulated cells, the adenylyl cyclase system regulates Ca influx through cAMP-dependent protein kinase, but not intracellular Ca release. Furthermore, the Ca influx mechanism acts as an integrator of two signaling pathways such that Ca-dependent signals are damped by activators of adenylyl cyclase and enhanced by inhibitors of adenylyl cyclase.

Adenylyl Cyclases↗
PubMed1994

Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure.

Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet cAMP. We measured plasma concentration of adrenomedullin in patients with essential hypertension and chronic renal failure. As compared with normal subjects, plasma adrenomedullin was increased by 26% (P < 0.05) in hypertensives without organ damage and by 45% (P < 0.005) in those with organ damage. The increase in plasma adrenomedullin was more prominent in renal failure than in hypertension. Renal failure patients with plasma creatinine of 1.5-3, 3-6, and > 6 mg/dl had higher plasma adrenomedullin levels than healthy subjects by 78% (P < 0.05), 131% (P < 0.001), and 214% (P < 0.001), respectively. Moreover, adrenomedullin showed intimate correlations with norepinephrine, atrial natriuretic peptide, and cAMP in plasma (r = 0.625, P < 0.001; r = 0.656, P < 0.001; and r = 0.462, P < 0.001; respectively). Thus, plasma adrenomedullin is supposed to increase in association with changes in sympathetic nervous activity and body fluid volume in hypertension and renal failure. Considering its potent vasodilator effect, adrenomedullin may be involved in the defense mechanism preserving the integrity of the cardiovascular system in these disorders.

Adrenomedullin↗
PubMed1994

Strial dysfunction in a melanocyte deficient mutant rat (Ws/Ws rat).

A homozygous mutant rat at the white spotting (Ws) locus showing a deficiency of melanocytes has recently been found (4, 5). The function and morphology of the inner ear of the Ws/Ws rat were examined by auditory brainstem response (ABR), endocochlear DC potential (EP), and electron microscopy. The mean ABR threshold of the Ws/Ws rat was significantly higher than that of the control +/+ rat. Most Ws/Ws rats showed no or very little EP. In electron microscopy, the stria vascularis of the Ws/Ws rat proved to be very thin and flat with poor interdigitation of marginal cells, and absence of intermediate cells. The organ of Corti appeared to be intact in both the +/+ rat and the Ws/Ws rat. These electrophysiological and morphological findings suggest that the Ws/Ws rat suffered from severe hearing loss caused by strial dysfunction.

Acoustic Stimulation↗
PubMed1994

[Tympanoplasty in cholesteatoma otitis media with normal hearing].

Thirteen cholesteatomas, with hearing within 20dB, were operated on from 1985 to 1992. Their mean age was 22.1 years, and the mean follow-up period 1.8 years. Eleven cases were pars flaccid type, and 2 cases pars tensa type. Tympanoplasties were performed by the canal down method (4 cases), the canal up method (3 cases), both transmeatal atticotomy and scutumplasty (4 cases) and both the canal down method and mastoid obliteration (2 cases). Postoperative hearing results of three averaged speech frequencies were within 20dB in 11 cases and between 20 and 30dB in 2 cases. No recurrent cholesteatoma or extrusion of columella occurred during the follow-up period. One of the cases operated on by the canal down method showed postoperative mastoid cavity problems, and one of the cases operated on by the canal up method showed retraction of the pars flaccida. These findings prompted us to operate on cholesteatoma cases with normal hearing and to recommend tympanoplasty with transmeatal atticotomy and scutumplasty.

Adolescent↗