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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 253 records · Page 14Linked to original sources

Antibody-dependent difference in biodistribution of monoclonal antibodies in animal models and humans.

The study was designed to clarify the difference in pharmacokinetics of monoclonal antibodies (mAb) in animal models and humans, and to elucidate the applicability of animal models. 99mTc-labeled murine mAb -- against carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule (NE150) -- and one chimeric mouse/human mAb against nonspecific cross-reacting antigen (chNCA) were administered i.v. to normal mice and athymic mice (370 kBq, 400 ng) xenografted with human cancer cells expressing antigens, and into patients with tumor (925 MBq, 1 mg). The biodistribution of two of the three mAb (not 99mTc-BW431/26) differed clearly in mice and patients. 99mTc-NE150 showed specific uptake in xenografted tumor and otherwise a normal biodistribution; however, clinical examination showed increased uptake in the liver with rapid blood clearance (mean alpha half-life = 31.1 min) compared with 99mTc-BW431/26 (28.4 h). 99mTc-chNCA demonstrated increased blood clearance and renal excretion in both normal and athymic mice, with accumulation in tumors. Clinical examination showed rapid blood clearance (mean alpha half-life = 6.4 min) and increased uptake in the liver. High-performance liquid chromatographic analysis of 99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the complex by the reticuloendothelial cells. The biodistribution of radiolabeled mAb in animal and human models was variable and specific for each of the three mAb. The results of animal studies with mAb should be evaluated carefully before being extrapolated to humans, on the basis of the nature of the mAb and interacting substances.

Animals↗

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗

Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma.

We examined the relationship between apoptosis and the progression of human gastric carcinoma. Studies were conducted on a total of 88 surgically removed stomachs, comprising 26 minute (less than 5 mm in diameter), 29 early (limited to the mucosal and submucosal layer) and 33 advanced carcinomas. Apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Serial sections were immunostained for p53 and Ki-67. The mean apoptotic indices (AI: percentage of TUNEL signal positive cells) of minute, early, and advanced carcinomas were 4.1 +/- 0.6, 3.8 +/- 1.2, and 4.0 +/- 1.2 in 46 well differentiated carcinomas, and 2.1 +/- 0.5, 2.7 +/- 0.9, and 2.2 +/- 1.1 in 42 poorly differentiated carcinomas, respectively. Similarly, the mean Ki-67 labelling indices (KI) were 39.2 +/- 7.8, 47.2 +/- 12.8, 52.6 +/- 13.1 in the former, and 35.0 +/- 9.3, 36.9 +/- 10.3, and 40.0 +/- 9.2 in the latter, respectively. Both mean AI and mean KI were significantly higher in well differentiated than in poorly differentiated carcinomas (P < 0.05). However, the value of mean AI did not differ among minute, early, and advanced carcinomas in either histological type, while KI increased gradually with tumour progression. The frequency of nuclear p53 expression did not differ among the three categories, implying that the gene mutation is an early event in gastric carcinogenesis. There was no statistical significance between nuclear p53 expression and mean AI. These results suggest that the progression of gastric cancer is defined by a gradual increase of proliferative activity and constant occurrence of apoptosis and that naturally occurring apoptosis is induced predominantly via a p53-gene-independent pathway.

Adenocarcinoma↗

Diagnosis of lumbar disc herniation by three-dimensional MRI.

The lumbo-sacral region has anatomical lordosis and two-dimensional magnetic resonance imaging (2D-MRI) cannot therefore show spinal roots including the dorsal root ganglions in one picture. This makes it difficult to present the lateral part of spinal root lesions. We have recently described a new three-dimensional magnetic resonance imaging (3D-MRI) method which allows a stereoscopic view of the spinal cord and spinal nerve roots. In the present study, we evaluated three 3D-MRI techniques, rapid imaging spin echo (RISE) small tip angle gradient echo (STAGE), and short TI inversion recovery (STIR), for detecting disc tissue degeneration, and spinal cord and nerve root compression for identification of nerve roots and detecting signal changes indicative of thickening of the nerve root, and for evaluation of the extent of herniation in 30 patients with lumbar disc herniation. The RISE method was superior for detecting signal changes in disc degeneration, (in 100% of patients) compared with the STAGE method (in 56.1% of patients). All methods poorly identified L4 roots compared with L5 or S1 roots. The STIR method was the best for identifying nerve roots (L4, 62.5%; L5, 87. 5%; S1, 91.7%). STAGE and STIR were useful for detecting injuries of the nerve roots. RISE showed disc extrusion better than the other techniques (in 64.7% of patients). The presurgical diagnosis on 3D-MRI agreed with the pathology findings at surgery in 71.4% of STIR, 55.6% of RISE, and 33.3% of STAGE MR images. Our results indicate that 3D-MRI is most useful for the diagnosis of lumbar disc herniation and spinal cord and nerve root compression. The STIR method is best for identifying abnormalities of the spinal cord, roots, and intervertebral discs.

Adult↗

Bilateral tactile agnosia: a case report.

This study reports a 64-year-old right-handed male who manifested bilateral tactile recognition deficits. They were diagnosed as bilateral tactile agnosia, since the patient showed difficulty in semantic association of objects despite preserved hylognosis and morphognosis. The patient had a bilateral lesion in the subcortical region of the angular gyrus. The case reported by Endo et al. (1992) had a right hand tactile agnosia due to a subcortical lesion in the left angular gyrus. Our findings support Endo's hypothesis that tactile agnosia occurs when the somatosensory association cortex is disconnected from the semantic memory store located in the inferior temporal lobe by a subcortical lesion of the angular gyrus. We suggest that the extent of the lesion in the tactual-semantic pathway is related to the severity of tactile agnosia and the types of the tactile naming errors.

Agnosia↗

Novel physiological functions of cathepsins B and L on antigen processing and osteoclastic bone resorption.

Lysosomal cathepsin B plays an essential role in the processing of ovalbumin as an exogenous antigen to produce the complex between antigenic-peptide and major histocompatibility-complex class II. Administration of cathepsin B inhibitors, E-64, CA-074 and vitamin B6, caused the strong suppression of the Th-2 type immune responses. We found that pyridoxal phosphate (PAP), a coenzyme form of vitamin B6, inhibits the activities of cathepsin B and L in vitro and vitamin B6 administration induces the inhibition of the lysosomal cathepsin activities in vivo. The production of an antigenic epitope (I323-R339) of ovalbumin by antigen presenting cells was suppressed by cathepsin B specific inhibitors. The ovalbumin dependent production of immunoglobulins (IgE and IgG1) and of the corresponding interleukin (IL-4) was suppressed by cathepsin B inhibitors, while the production of IgG2a and interferon (INF-gamma) was increased. The switch of helper T lymphocyte functions from the type-2 to the type-1 may be induced by the cathepsin B inhibition. The experimental bone pit formation, i.e., osteoclastic bone collagen degradation test, induced by parathyroid hormone was markedly suppressed by the administration of pyridoxal, because of the inhibition of cathepsin L type cysteine proteases in bone.

Animals↗

Increasing incidence of streptococcal impetigo in atopic dermatitis.

Streptococcal impetigo associated with atopic dermatitis has dramatically increased from 1989 to 1994 in outpatients visiting our hospital, totalling 174 cases. The most frequent causative agents were group A streptococci (Streptococcus pyogenes, 70.7%) followed by group G (19.5%) and group B (9.8%). Streptococcus was isolated singly in 28.2% of cases and in concomitant with Staphylococcus aureus (S. aureus) in 71.8%. Major clinical features of streptococcal impetigo, especially caused by group A streptococci, were non-bullous pustules with thick crusted ceiling. Impetigo caused by group G or B streptococci generally formed smaller sized pustules of fewer numbers. Impetigo was usually present, associated with severe eczematous lesions. Various degrees of fever were noticed in 32.8% (group A, 39.8%; group G, 17.6%; group B, 11.8%) during active stages. The lesions on the face often resembled Kaposi's varicelliform eruption in any group. Systemic antimicrobial agents were administered in 71.3% of cases and the remainder were treated with topical antibiotics (oxytetracycline hydrochloride) or disinfectants (povidone-iodine). Recurrence occurred within a month in 38.0% of cases treated with topical agents only and in 17.7% treated with systemic antimicrobial agents. Antimicrobial susceptibility tests and the results of treatment seem to indicate that cephems, as well as penicillins, are the first choice of treatment for streptococcal impetigo.

Adolescent↗

Therapy-related AML after successful chemotherapy with low dose etoposide for virus-associated hemophagocytic syndrome.

A 19-year-old male patient with virus associated hemophagocytic syndrome (VAHS) began receiving chemotherapy including etoposide (cumulative dose of 900 mg/m2 intravenously) and Ara-C (cumulative dose of 360 mg/m2 intravenously) in July 1994. He achieved complete remission, but developed acute myelomonocytic leukemia (AML, FAB M4) with t(9;11)(p22;q23) in March 1997 and a rearrangement of the MLL gene was also recognized. The MLL gene rearrangement is closely associated with secondary leukemia with an 11q23 translocation. It is highly likely that this case of AML was caused by the cytostatic treatment the patient received, including etoposide for VAHS.

Adult↗

c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma.

AIMS: The c-erbB-2 proto-oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c-erbB-2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of the expression of c-erbB-2 in cholangiocarcinoma and hepatolithiasis, a condition occasionally associated with cholangiocarcinoma. METHODS AND RESULTS: In this study, we evaluated immunoreactivity for the c-erbB-2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis (n = 20), fetal livers (n = 36) and normal adult livers (n = 6). In normal adult livers and fetal livers, expression of c-erbB-2 protein could not be detected in hepatocytes or intrahepatic biliary cells. In hepatolithiasis, there was overexpression of c-erbB-2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated intrahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative for c-erbB-2 protein. Moreover, the biliary cell expression of the c-erbB-2 protein correlated significantly with Ki67 labelling index. On the other hand, aberrant expression of c-erbB-2 was found in 33/47 (70%) cholangiocarcinomas. The c-erbB-2 expression in cholangiocarcinomas did not correlate with Ki67 labelling index or p53 expression. CONCLUSIONS: These results indicate that aberrant expression of c-erbB-2 protein is found in cholangiocarcinoma and also in noncancerous biliary proliferative lesions such as hepatolithiasis. These findings also suggest that c-erbB-2 oncogene participates not only in cholangiocarcinogenesis but also in biliary cell proliferation in non-neoplastic conditions.

Adult↗

In vitro effect of contrast agents during immunoradiometric assay for tumour-associated antigens.

The aim of this study was to investigate if contrast agents interfere with the performance of an immunoradiometric assay (IRMA) in vitro for serum tumour-associated antigen. Each of five carcinoembryonic antigen (CEA)-positive sera, CA-130-positive sera and tissue polypeptide antigen (TPA)-positive sera was mixed with six contrast agents: Ioversol 350, Iopamidol 370, Iomeprol 300, Iomeprol 400, Iohexol 300 and Gadopenteic acid in 50:50, 50:20, 50:5.0, 50:1.0, 50:0.5 and 50:0.1 microl proportions. Following IRMA, the interference of binding rates in each mixture was calculated, and the serum concentrations of CEA, CA-130 and TPA were estimated and compared with the originals. All contrast agents used were able to inhibit the binding rate with IRMA and the inhibition rates were in proportion to the amount of contrast agent. The detection of serum concentrations of CEA, CA-130 and TPA was significantly inhibited in the mixtures with more than 5.0 microl of contrast agent in all cases. Apart from Iomeprol 400, there was no significant inhibition of detection at the lowest concentrations of contrast agents. Iomeprol 400 was the strongest inhibitor and Gadopenteic acid the weakest inhibitor for each IRMA of the contrast agents employed. In conclusion, our results demonstrate that contrast agents may reduce the immunoreaction of antibody and antigen and lead to in vitro inhibition during immunoassays. It would be unwise to perform any plasma/serum immunoassay on a sample collected within 24 h of the administration of contrast agent considering the pharmacokinetics.

Aged↗

99Tcm-labelled chimeric human/mouse anti-granulocyte antibody bone marrow scintigraphy: a preliminary clinical study.

Bone marrow scintigraphy using 99Tcm-labelled chimeric anti-granulocyte antibody (anti-NCA-95) was performed in 17 patients with haematological disorders and skeletal metastases. Chimeric anti-NCA-95 antibody (chNCA95 Ab, 0.2 mg) labelled with 444 MBq 99Tcm was administered to obtain bone marrow images 4 h post-injection. One week later, an 111In-chloride bone marrow scan was performed on nine patients with haematological disorders. Lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B) uptake ratios were calculated for each scan. In six patients with suspected skeletal metastases, 99Tcm-HMDP bone scans were performed. No patient had any adverse reaction or any immune reaction over 20 weeks. In the patients with haematological disorders, the L/B and I/B ratios of the 99Tcm-chNCA95 Ab scan were 3.41 +/- 0.90 and 1.23 +/- 0.31, whereas those of the 111In-chloride scan were 1.58 +/- 0.32 and 1.00 +/- 0.32, respectively. In assessing findings of irregular central bone marrow uptake and peripheral expansion of the bone marrow, the 99Tcm-chNCA95 Ab scan was much better than the 111In-chloride scan. In the six patients with suspected skeletal bone metastases, three true-positive and two true-negative results were observed. This preliminary study has revealed that 99Tcm-chNCA95 Ab scanning is safe and useful in the diagnosis of haematological disorders and skeletal metastases.

Adult↗

Expression of pancreatic alpha-amylase protein and messenger RNA in hilar primitive bile ducts and hepatocytes during human fetal liver organogenesis: an immunohistochemical and in situ hybridization study.

AIMS/BACKGROUND: This study was conducted to evaluate the expression of pancreatic digestive enzymes in hilar bile ducts and hepatocytes during human fetal liver organogenesis. METHODS: We investigated the expression of pancreatic alpha-amylase protein and messenger RNA (mRNA) in hilar primitive bile ducts and hepatocytes by immunohistochemistry and in situ hybridization techniques, using 11 human fetal livers of various gestational ages. The specificity of the immunohistochemistry and in situ hybridization procedures was confirmed by Western blot analysis and in situ hybridization using sense probes, respectively. RESULTS: Immunoreactivity of pancreatic alpha-amylase protein and expression of pancreatic alpha-amylase mRNA were present not only in the primitive ductal cells of the hilar region including the ductal plate, remodelling bile ducts and remodeled bile ducts but also in primitive hepatocytes of the hilar region, though the immunoreactivity and mRNA signals in the primitive hepatocytes disappeared in the third trimester. There was perfect correlation between immunohistochemistry and in situ hybridization. CONCLUSIONS: These results suggest that primitive biliary cells and hepatocytes of the hilar region in the human fetus do express pancreatic alpha-amylase protein and mRNA, and that the primitive biliary epithelial cells and hepatocytes in the hilar region share a common cell lineage with exocrine pancreatic cells.

Bile Ducts, Intrahepatic↗

[Two cases of hematological malignancies diagnosed before death as aspergillosis with skin lesion].

We report two cases of aspergillosis with skin lesions. The first involved a 63-year-old female with acute lymphocytic leukemia. In 1992, she received chemotherapy for acute leukemia. Subsequently, she noted swelling of her leg, a skin biopsy was performed and Aspergillus flavus was isolated. The second patient was a 71-year-old male with myelodysplastic syndrome. In 1996, he developed a massive inguinal abscess from which Aspergillus fumigatus was isolated. The prognosis of aspergillosis was poorer in the case with skin swelling than in the one with a massive abscess.

Aged↗

Gefarnate increases PAS positive cell density in rabbit conjunctiva.

AIMS: The effects of three drugs for the treatment of gastritis and gastric ulcer--gefarnate, ecabet sodium, and troxipide--on periodic acid Schiff (PAS) positive cell density in rabbit conjunctiva in vivo were investigated. METHODS: Eye drops containing gefarnate (0.1%, 1%), ecabet sodium (0.1%, 1%), or troxipide (0.1%, 1%) were instilled in both eyes of rabbits, six times a day for 7 days. On the eighth day, filter paper was gently pressed on the bulbar and palpebral conjunctiva, and impression cytology was performed with PAS staining. Three points in each specimen were selected randomly, and PAS stained cells were counted. RESULTS: The instillation of gefarnate increased PAS positive cell density significantly at the concentration of 1% (p < 0.05). In contrast, instillation of ecabet sodium or troxipide failed to change PAS positive cell density. CONCLUSIONS: These results demonstrated that gefarnate stimulates PAS positive cell density in rabbit conjunctiva.

Abietanes↗

Neuronal activity in GP and Vim of parkinsonian patients and clinical changes of tremor through surgical interventions.

Microrecordings were performed during pallidotomy and thalamotomy for Parkinson's disease (PD). Neuronal activity in globus pallidus (GP) was in general agreement with previous studies of human and primate models of PD. Neuronal activity, where frequency of tremor appeared to oscillate independently from peripheral input, was encountered in GPi. In contrast, neuronal activity in Vim regarding frequency of firing also correlated with tremor and was passively driven by kinesthetic stimuli with a somatotopic arrangement. Pallidal lesions based on microrecording induced relative reductions of tremor, while small Vim lesions immediately alleviated tremor. Basal ganglia pathology due to dopamine depletion could generate oscillatory neuronal activity in GPi, which may cause tremor. However, peripheral feedback to the motor cortex via Vim is also significant for tremorgenesis, because Vim may be an excitatory driving source for motor cortical neurons. Thus, a Vim lesion could reduce excitability of the motor cortical neurons and abolish tremor.

Electromyography↗

Dissociation of letter and picture naming resulting from callosal disconnection.

BACKGROUND: Detailed mapping of the corpus callosum for functional fractionation in humans remains incomplete. OBJECTIVE: To examine separable interhemispheric transfer of visual information by callosal fibers, especially in the splenium. METHODS: We examined callosal disconnection signs in a 14-year-old boy with a lesion confined to the posterior part of the splenium and reviewed reported cases with callosal lesions. RESULTS AND CONCLUSION: The patient presented with left hemialexia as the only manifestation of callosal disconnection syndrome. The only difficulty demonstrated was in reading aloud or copying letters, which were presented tachistoscopically to the left visual field, with his right hand. He could copy letters presented to his left visual field with his left hand, however. Therefore, left hemialexia was not due to hemiamblyopia or hemineglect. There was no anomia for pictures and colors in the left visual field. MRI revealed that the lesion was limited to the ventroposterior end of the splenium. Review of 40 reported patients with callosal lesions suggests that the anterior to middle part of the splenium is involved in transferring picture information from the language-nondominant hemisphere to the language-dominant hemisphere and that the ventroposterior part is involved in transferring letter information.

Adolescent↗