Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 415 records · Page 23Linked to original sources

PubMed1996

Serological and immunochemical analysis of Lewis y (Ley) blood group antigen expression in epithelial ovarian cancer.

The expression of Ley blood group antigen in epithelial ovarian cancer tissues and cell lines has been studied using a Ley-specific monoclonal antibody (MAb 3S193). In ovarian cancer specimens, Ley was expressed in 75% of the 140 tumor specimens examined, with strong or moderate expression being observed in 56% of the samples. Seven of the 11 ovarian cancer cell lines studied were Ley-positive. Using immunochemical approaches, Ley epitopes were found to be expressed on 4 types of carrier molecules: CA125 ovarian cancer antigen, MUC-1 mucins, lower m.w. glycoproteins and glycolipids. In cell lines, Ley was more commonly expressed on MUC-1 mucin than on CA125, whereas in tumor specimens Ley was commonly found on both CA125 and MUC-1. The biochemical nature of the smaller Ley glycoproteins was not determined, but it was shown that they were not CEA and LAMP-1, known Ley carriers in some other tumor types. Glycolipids carrying Ley epitopes were detected in both ovarian cancer cell lines and tumor specimens. The presence of Ley epitopes on a number of different molecular carriers, including 2 major ovarian cancer antigens (CA125 and MUC-1), explains the high incidence of Ley in ovarian cancer. The high expression of Ley in ovarian cancer and the availability of specific murine and humanized MAbs make Ley an attractive candidate target for clinical studies.

Antibodies, Monoclonal↗

PubMed1996

Recombinant human interferon alpha-2b (rh IFN alpha-2b) therapy for steroid resistant idiopathic thrombocytopenic purpura (ITP).

The efficacy of recombinant human interferon alpha-2b (rh IFN alpha-2b) in the treatment of steroid resistant idiopathic thrombocytopenic purpura (ITP) was studied in 50 cases. Forty-one patients treated with rh IFN alpha-2b three times a week, six of 18 (33.3%) in the low dose group (150 x 10(4)IU: 3 MIU) and four of 20 (20.0%) in the high dose group (300 x 10(4)IU: 3 MIU) responded with platelet counts increasing to above 50 x 10(9)/L. Because of the exacerbation of thrombocytopenia and nasal bleeding, treatment was discontinued within 2 weeks in three patients out of 41 cases. On the other hand, six of nine patients (66.7%) treated with 3 MIU of IFN alpha-2b once a week for 8 weeks showed satisfactory response. Treatment with either administration schedule did not result in sustaining platelet counts above 50 x 10(9)/L for a long time after treatment. The results indicate that once a week administration schedule of rh IFN alpha-2b is more efficacious for platelet counts increasing for short period in patients who failed to respond to steroid and other medications than other schedules. The maintenance of this treatment schedule will allow sustained increased platelet levels, resulting in relief of bleeding tendency, while also being cost effective in comparison with other IFN treatment schedules and achieving better patient compliance without flu-like symptoms.

Adolescent↗

PubMed1996

Applicability of monoclonal antibody Fab fragments as a carrier of neocarzinostatin in targeting chemotherapy.

Two types of fragments of MAb A7 were produced to improve the efficacy and safety in targeting chemotherapy with neocarzinostatin. In this study, 125I-labeled F(ab')2 and Fab fragments of MAb A7 and 125I-labeled MAb A7 were injected intravenously into mice with pancreatic carcinoma xenografts, and the accumulation of each antibody in the tumors was compared. A greater amount of the 125I-labeled Fab fragments of MAb A7 localized in the tumor 2 h following the injection than was observed with the other probes. Relatively less 125I-labeled MAb A7 localized in the tumor 2 h following the injection than was observed with the other two probes. Moreover, reaction of rabbit antimouse IgC with the Fc portion, which is the most immunopotent region of the Fab and F(ab')2 fragments of MAb A7 and MAb A7, was determined by ELISA; the weakest reaction was observed with the Fab fragments of MAb A7. These results suggest that the Fab fragments of MAb A7 may be more suitable carriers of an anticancer drug that is inactivated rapidly in the blood, such as NCS, in targeting chemotherapy than either intact MAb A7 or the F(ab')2 fragments of MAb A7.

Animals↗

PubMed1996

p53 gene mutation is not directly related to tumoricidal effects of preoperative radiochemohyperthermia therapy for rectal cancers.

BACKGROUND: Several studies have recently demonstrated that apoptosis of cancer cells is triggered by diverse adjuvant cancer therapies and the induction of apoptosis correlates with the sensitivity of the primary tumor to such therapies. METHODS: We investigated the factors modulating adjuvant cancer therapies by examining p53 gene mutations and chromosome 17p allelic losses in 15 rectal cancers treated by a preoperative combined therapy consisting of radiation, intraluminal hyperthermia and 5-fluorouracil suppositories. RESULTS: The point mutations were detected in 7 of 15 (46.7%) tumors by single-stranded conformational polymorphism and direct sequencing. Allelic losses at chromosome 17p were also detected in 7 of 15 (46.7%) tumors by dinucleotide-repeat polymorphisms. There was no correlation between p53 gene abnormalities and the preoperative tumoricidal effect of the therapy. CONCLUSIONS: We conclude that p53 gene abnormalities do not directly increase resistance to the combined adjuvant therapy.

Alleles↗

PubMed1996

CD43 expression in a B cell lymphoma, WEHI 231, reduces susceptibility to G1 arrest and extends survival in culture upon serum depletion.

CD43 is a major surface sialoprotein on hemopoietic cells, whose extracellular domain is heavily O-glycosylated. The functional role of CD43 in the hemopoietic system is not fully understood; however, it has been suggested that CD43 may have a role in cell-cell repulsion and in modifying T cell proliferation and activation. CD43 is expressed in immature B cells in the bone marrow, but not by peripheral B cells, except for B-1 B cells and plasma cells. To analyze the biological effect of CD43 in B-lineage cells, we transfected mouse CD43 cDNA into a CD43- B cell lymphoma, WEHI 231, and the growth and survival in culture were compared to those of a parental cell line, human CD8 transfectants, and CD43- revertants established from CD43+ clones. We observed that CD43 expression supported cell growth in culture upon serum reduction, whereas growth of CD43- cell lines was barely detected under this condition. CD43- cell lines accumulated in G1 phase of the cell cycle, and the numbers of viable cells were greatly reduced during culture upon serum depletion, whereas expression of CD43 reduced the susceptibility to G1 arrest and temporarily retarded the apoptotic process, which, in turn, resulted in an increase and maintenance of the number of viable cells in culture. The results suggest that CD43 may have some role in the survival and expansion of B-lineage cells. The biological effect of CD43 was initiated without stimulation by cross-linking and was significantly impaired by replacement of the extracellular domain by the human CD8 extracellular domain. The basis of these regulatory processes is discussed.

Animals↗

PubMed1996

TPN-induced fulminant beriberi: a report on our experience and a review of the literature.

Fulminant beriberi, once considered a rare disease, is now being encountered more frequently, yet little is known about its clinical features. This study was undertaken to determine the clinical features of total parenteral nutrition (TPN)-induced fulminant beriberi by reviewing the clinical data on 10 of our own patients who developed this complication, and 33 cases documented in the literature. TPN-induced fulminant beriberi became evident 4-40 days after the initiation of TPN, and was more likely to develop in patients with malignancies, ulcerative colitis, and short bowel syndrome, as well as in those receiving chemotherapy. Although the patients manifested various symptoms, very few developed the classical signs of beriberi or the constant findings seen in alcoholic patients. The severity of metabolic acidosis was extremely high and refractory to bicarbonate administration, but it responded quickly to intravenous (i.v.) thiamine. Thus, rapid i.v. administration of at least 100 mg of thiamine is imperative, and the patient must be transferred to the intensive care unit when TPN-induced fulminant beriberi develops.

Acidosis↗

PubMed1996

Liposarcoma developing in the paratesticular region: report of a case.

A 74-tear-old man presented to our hospital with a 2-year history of a painless and slow-growing fixed mass in the left paratesticular region. There were no specific abnormalities in the laboratory data, and the tumor markers were within normal limits. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US) revealed findings suggestive of either inguinal hernia or lipoma. However, intraoperatively, the tumor was observed to roll up the isolateral spermatic cord and testicular vessels, which led to the differential diagnosis of liposarcoma. The tumor was then widely resected along with the left testis, spermatic cord, and testicular vessels. Histopathologic study confirmed the diagnosis of well-differentiated liposarcoma, but no malignant cells were found in any of the surgical margins. A periodical follow-up has been performed by US every 3 months, and no evidence of recurrence or metastasis has been seen in the 6 months since his operation, without any postoperative adjuvant therapy.

Aged↗

PubMed1996

Pseudomyxoma peritonei concomitant with early gastric cancer: report of a case.

The preoperative diagnosis of both appendiceal carcinoma and pseudomyxoma peritonei is difficult because of the nonspecific nature of the associated symptoms. More than 50% of all patients with carcinoma of the appendix are diagnosed with and treated for acute appendicitis. In addition, there have been few reports on patients with an appendiceal carcinoma or pseudomyxoma peritonei in association with other synchronous or metachronous malignancies of the alimentary tract. We herein report the first known patient with synchronous early gastric cancer and pseudomyxoma peritonei, in which the origin was correctly identified preoperatively.

Adenocarcinoma↗

PubMed1996

Effects of calciseptine on unitary barium channel currents in guinea-pig portal vein.

Effects of synthesized calciseptine (CaS), found naturally in the venom of the black mamba, on voltage-dependent Ca2+ channels in smooth muscle cells of the guinea-pig portal vein were investigated. In the whole-cell voltage-clamp configuration, extracellular application of CaS (>/= 10 nM) inhibited the inward current in a concentration- and voltage-dependent manner at a holding potential of -90 mV. The Ca2+ current recorded at a high holding potential (-50 mV) was approximately 8 times more sensitive to CaS than that at a more negative holding potential (-90 mV). CaS (50 nM) shifted to the left the steady-state inactivation curve obtained by using single 8-s conditioning pulses of various amplitudes. When CaS (>/= 200 nM) was present in the pipette, the Ca2+ current remained for the duration of the experiments (more than 60 min) in the whole-cell configuration. Two different Ca2+ channel conductances are present in this tissue (25-pS and 12-pS channels). Both channels are blocked by dihydropyridine (DHP) derivatives, but have different sensitivities. In the cell-attached condition, CaS hardly changed the activity of either unitary Ca2+ channel current. To prevent the "run down" of the Ca2+ channels in cell-free conditions, we added cardiac cytosol, a supernatant from homogenized cardiac cells and an endogenous Ca2+ channel activating factor, in the pipette. The unitary Ca2+ channel currents were then recorded using the outside-out membrane patch configuration. Application of CaS (1 microM) in the bath completely blocked the open events of the 25-pS Ca2+ channel. CaS (10 nM) in the bath reduced the mean open time and channel availability, resulting in a decrease in the open probability of the 25-pS channel currents without affecting the amplitude of the single-channel conductance. CaS also reduced the open probability (though less potently) and channel availability of the 12-pS Ca2+ channel without a change in its amplitude. From these results, we conclude that CaS has inhibitory effects on the voltage-dependent Ca2+ current that are similar to those of DHP derivatives and that it acts from the outside of the membrane.

Animals↗

PubMed1996

Monoclonal antibodies specific to the integral membrane protein P0 of bovine peripheral nerve myelin.

Two monoclonal antibodies (mAbs), 58A and 46E, were generated against the major protein P0 of bovine peripheral nervous system myelin (PNSM). The reactivities of the mAbs were assessed by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry. Both mAbs, 58A and 46E, reacted to PNSM of bovine, human, rat and rabbit, but not to chicken PNSM or the brains of rat and rabbit. In the Western blot, these mAbs showed specific binding to bovine P0 as well as deglycosylated P0, but not to myelin-associated glycoprotein (MAG) of bovine spinal cord. The analyses of the lysylendopeptidase-digested peptides of bovine P0 revealed that the epitopes for the mAbs 58A and 46E were located on the amino acid residues 68-79 and 210-216, respectively. Since the mAbs 58A and 46E recognize the extracellular domain and the cytoplasmic domain of P0, respectively, they could be useful for studies on P0's role in myelin formation, its adhesive properties, and functions of the N-terminal extracellular and C-terminal cytoplasmic domains of the protein.

Amino Acid Sequence↗

PubMed1996

Increased plasma adrenomedullin levels in chronic congestive heart failure.

Adrenomedullin is a potent vasodilator peptide and occurs in circulating blood of human beings and experimental animals. Because it is produced in intact aorta of rats and in cultured vascular endothelial cells, adrenomedullin seems to participate in regulation of local vascular tone. To determine the pathophysiological roles of adrenomedullin, we investigated its plasma concentrations in 49 patients with heart failure. Plasma adrenomedullin levels increased significantly with advancing severity of the disease (New York Heart Association functional class I, 4.1 +/- 1.0; II, 5.6 +/- 1.6; III, 6.4 +/- 0.8; IV, 13.2 +/- 6.8 (fmol/l). Plasma adrenomedullin was correlated with pulmonary artery pressure (r = 0.44, p = 0.0114) and pulmonary capillary wedge pressure (r = 0.53, p = 0.0002). These findings indicate that adrenomedullin may play some important role in the pathophysiologic makeup of heart failure by its vasodilating effects against the concomitant exaggeration of humor pressor agents such as catecholamine and the renin-angiotensin system. Hemodynamic changes in pulmonary circulation may have some influence on the increased synthesis and secretion of plasma adrenomedullin in chronic congestive heart failure.

Adrenomedullin↗

PubMed1996

Increased plasma adrenomedullin in acute myocardial infarction.

Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.

Adrenomedullin↗

PubMed1996

Hypoglossal neurinoma extending intra- and extracranially: case report.

BACKGROUND: Hypoglossal neurinoma is very rare; our case is the 46th case. CASE DESCRIPTION: We report a 59-year-old woman with hypoglossal neurinoma. Her equilibrium state was disturbed due to vestibular dysfunction and she exhibited right hypoglossal palsy with glossal hemiatrophy. Computed tomography (CT) revealed a large bony erosion of the right hypoglossal canal. Magnetic resonance imaging (MRI) revealed intra- and extracranial tumor extension. There was an intracranial mass attached to the enlarged hypoglossal vertebral and posterior inferior cerebellar artery medially. The extracranial part of the mass extended along the course of the hypoglossal nerve through the enlarged hypoglossal canal. The intracranial part of the tumor was totally removed via the transcondylar approach. The diameter of the origin of the posterior interior cerebellar artery was narrow before tumor removal; it increased after surgery due to decompression. A histological diagnosis of neurilemoma was made. Her symptoms due to vestibular dysfunction disappeared postoperatively. CONCLUSIONS: Our patient's difficulty with balance was thought to be an ischemic symptom due to circulation disturbance of the posterior inferior cerebellar artery. It disappeared after tumor removal. Surgery may be necessary later if further growth of the extracranial part of the neurinoma becomes evident.

Brain Neoplasms↗

PubMed1996

Adrenomedullin: a new modulator of vascular tone.

We have discovered a novel hypotensive peptide, designated "adrenomedullin", in human pheochromocytoma extracts. It has potent and long-lasting vasodilatory effects in several vascular systems. In addition to adrenomedullin, another hypotensive peptide, termed PAMP, is also produced from the adrenomedullin precursor. Although initially isolated from human pheochromocytoma and porcine adrenal medullary tissue, adrenomedullin mRNA is highly expressed in several peripheral organs including cardiovascular tissues. Taken together with the presence of adrenomedullin-specific receptors on VSMCs and the significant increase in plasma immunoreactive adrenomedullin levels in patients with hypertension, renal failure and congestive heart failure, adrenomedullin may participate in the pathogenesis of these diseases as a factor regulating blood pressure and circulation.

Adrenomedullin↗

PubMed1996

Vestibular neurectomy: a histological and clinical study of results.

Posterior fossa vestibular neurectomy has become one of the most effective surgical procedures for control of vertigo symptoms in Menière's disease. A small group of patients continue to have vertigo and demonstrable vestibular function by electronystagmography (ENG) post-operatively. Another group of patients may have no vertigo, despite residual vestibular function on caloric testing. In an effort to correlate histological findings with clinical outcome, nerve biopsies were taken from seven patients undergoing vestibular neurectomy. Fibre counts of nerve biopsies were compared with clinical, audiometric and ENG results. Results of this study demonstrate that complete reduction of vestibular response (on caloric testing) and clinical cure of vertigo can be obtained despite a variable number of nerve fibres at vestibular neurectomy.

Adult↗

PubMed1996

Clinicopathological characteristics of gastric cancer in the elderly.

The clinicopathological features of 380 elderly patients 70 years of age or older with gastric cancer were reviewed retrospectively from hospital records between 1969 and 1993. They were then compared with 1134 middle-aged patients between 40 and 69 years. The elderly constituted 18.4% of all gastric cancer patients 20 years ago but now comprise 24.4% of all patients in the most recent decade, despite the overall decrease in the rate of gastric cancer. The distinguishing histological features of gastric cancer in the elderly were an intestinal type of cancer, expansive tumour growth and synchronous multiplicity of the lesions. Elderly patients had a similar rate of tumour extension but had poorer survival as compared with the middle-aged patients. Post-operative death within 30 days after surgery was also higher in the elderly than in the middle-aged patients.

Adolescent↗

PubMed1996

Effects of neocarzinostatin-chimeric Fab conjugates on the growth of human pancreatic carcinoma xenografts.

Neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of MAb A7 (chA7Fab) directed against human pancreatic carcinoma. The anti-tumour effect of chA7Fab-NCS was tested in a nude mouse model on pancreatic carcinoma and compared with A7-NCS or NCS alone. The anti-tumour effect of chA7Fab-NCS increased in a dose-dependent manner and was significantly greater than either A7-NCS or NCS. Tumour growth was completely suppressed after the administration of chA7Fab-NCS. An enzyme-linked immunosorbent assay with rabbit anti-mouse immunoglobulin was performed to examine the antigenicity of chA7Fab. ChA7Fab had less reactivity with rabbit anti-mouse immunoglobulin than either whole antibody A7 or murine Fab fragments of A7. Thus, chA7Fab-NCS can inhibit human pancreatic cancer growth in an animal and may be useful for targeting chemotherapy to pancreatic cancer in humans.

Animals↗

PubMed1996

Distribution of neocarzinostatin conjugated to biotinylated chimeric monoclonal antibody Fab fragments after administration of avidin.

We have developed chimeric Fab fragments of MAb A7 (chA7Fab) and have reported on their potential usefulness as a carrier of neocarzinostatin (NCS). However, a large amount of chA7Fab accumulates in the kidneys which might cause renal failure. This was one of the major side-effects of the chA7Fab-NCS immunoconjugate administered to humans. To decrease the kidney accumulation of chA7Fab, chA7Fab was biotinylated and administered with a subsequent injection of avidin to nude mice with pancreatic cancer. The accumulation of biotinylated chA7Fab in the blood and the kidneys decreased significantly after the injection of avidin. In a separate experiment with biotinylated chA7Fab-NCS, the blood and kidney accumulation decreased significantly after the injection of avidin. These findings suggest that the injection of biotinylated chA7Fab complexed with NCS followed by avidin may be safer and may permit the administration of larger doses of NCS without the subsequent development of renal failure.

Animals↗