Biomedical subjects

K Kanda

Publications and source records attributed to K Kanda.

At least 37 records · Page 2Linked to original sources

PubMed1994

A targeting model of boron neutron-capture therapy to hepatoma cells in vivo with a boronated anti-(alpha-fetoprotein) monoclonal antibody.

We described previously that 10B atoms delivered by monoclonal antibody (mAb) exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal neutron irradiation in vitro. In the present study, the delivering capacity of boronated anti-(alpha-fetoprotein) (AFP) mAb to carry 10B atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl-3-) (2-pyridyldithio) propionate. The number of 10B atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt gamma-ray spectrometry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of 3.0 mg 10B-conjugated anti-AFP mAb were 11.10 +/- 3.12 (SD, n = 6). 29.30 +/- 5.11, 33.02 +/- 11.8, and 12.91 +/- 5.62 ppm respectively. For control 10B-conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59 +/- 0.99, 10.37 +/- 2.86, 10.00 +/- 2.95, and 8.83 +/- 4.71 ppm respectively. The concentrations in blood were less than 0.40 +/- 0.10 ppm with anti-AFP mAb and less than 0.51 +/- 0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The number of 10B atoms delivered to the tumor cells was calculated to be 0.62 x 10(9), 1.63 x 10(9), 1.84 x 10(9) and 0.72 x 10(9) at each sampling time after injection of 10B-anti-AFP mAb. The amount of 10B atoms necessary for effective boron neutron-capture therapy was estimated to be 10(9)/tumor cell. We were able to carry 1.84 x 10(9) 10B atoms to AH66 tumor cells by using 10B-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the 10B-conjugated antitumor mAb could deliver a sufficient amount of 10B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.

Animals↗

PubMed1994

Glucocorticoids potentiate the action of atrial natriuretic polypeptide in adrenalectomized rats.

Adrenal insufficiency in human and rat is associated with an impairment of the diuretic response to water load, and only glucorticoids (GCs) restore this deficit. Our observation that GCs potentiate atrial natriuretic polypeptide (ANP)-stimulated cGMP production in cultured renal cells prompted us to examine the possibility that GCs may restore the diuretic response through the potentiation of ANP action. Initially, changes in urine volume and ANP levels were studied in adrenalectomized (Adx) and sham-operated intact rats after an oral water load of 5 ml/100 g BW. Urine volume after water load was 4.5 +/- 0.5 ml/30 min in the intact rats, whereas it was 0.8 +/- 0.2 ml/30 min in the Adx rats. In the intact rats, a significant increase in plasma ANP level was observed 30 min after the water load, whereas no increase was observed in Adx rats. This defective ANP response may be involved in the impairment of the diuretic response in Adx rats. Indeed, pretreatment of Adx rats with dexamethasone (Dex, 20 micrograms/100 g BW) increased plasma ANP levels even before water load and improved diuretic response. Subsequently, effect of iv administration of human or rat ANP at a pharmacological dose (2.5 micrograms/100 g BW) on urine volume, osmolarity, and urinary excretion of cGMP, and sodium was studied in Adx rats that received an oral water load 30 min before ANP. Dex treatment was achieved by per os administration 3 h before the ANP injection. In Adx rats, the urine volume after ANP administration was 1.2 +/- 0.1 ml/30 min, and pretreatment with Dex markedly increased the urine volume to 6.3 +/- 0.4 ml/30 min. Dex also increased ANP-induced osmolar and sodium excretion by 2.6- and 2.9-fold, respectively. Although urinary excretion of cGMP was increased in Adx rats by ANP administration, a further significant increase was observed by the pretreatment with Dex. Injection of (Bu)2cGMP to Adx rats pretreated with Dex resulted in a significant increase in urine volume and osmolar and sodium excretion. However, no significant increase in urine volume was observed in Adx rats not pretreated with Dex. The present study suggests that GCs restore the diuretic response to acute water load not only by increasing the secretion of ANP but also by potentiating ANP-stimulated cGMP production. Furthermore, GCs may augment ANP action at one or more steps other than cGMP formation because administration of (Bu)2cGMP to Adx rats did not correct the diuretic response to water load.

Adrenalectomy↗

PubMed1994

Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to the normal skin.

A treatment regimen for boron neutron capture therapy of malignant melanomas is described using 10B-paraboronophenylalanine as the tumor-targeting compound. As a therapeutic dose, we adopted the maximum tolerable dose for the skin regardless of tumor 10B concentration. In practice, the maximum neutron fluence should be decided prior to starting irradiation. For this purpose, the kinetics of the concentration of 10B in the blood and skin and the skin-to-blood ratios were analyzed in the six patients who received 170 mg/kg of the compound intravenously, and skin concentrations during irradiation were predicted using a standard skin factor curve. This yields a skin concentration at time T based on the blood concentration at time 0. We calculated the maximum tolerable fluence yielding but not exceeding 18 RBE-Gy by assuming that the RBE of 14N(n,p)14C and 10B(n, alpha)7Li reaction for skin damage is 2.5. Actual skin reactions in three of five patients treated with the therapy were, as predicted, within tolerable limits, and we were able to obtain complete tumor regression in four cases. The results indicate that application of our logical approach will be useful for subsequent cases and further development of this therapy.

Aged↗

PubMed1994

[Manometric study of the biliary sphincter zone: a comparison between the length of phasic activity and the narrow distal segment].

Motor activity of the sphincter of Oddi has been evaluated in 26 patients who underwent ERCP examination. Manometric recordings from the common bile duct and the sphincter of Oddi were performed with a single end-lumen perfused catheter. The number of successive 3 mm spaced black marks, observed during the pull-through from the first appearance of the proximal sphincter activity to that of duodenal pressure, was used to measure the length of the sphincter zone. In 14 of 26 patients, the length of phasic activity zone of the sphincter of Oddi was 9 mm. However, the narrow distal segment of the common bile duct was 15.1 +/- 3.6 mm in length. In same patients, the length of phasic activity zone was shorter than the anatomical one. The mean sphincter of Oddi pressure (SOP) at the distance of 6 mm from the papillary pore (77.8 +/- 22.1 mmHg) was greater than that of 9 mm (58.4 +/- 27.0 mmHg) and 12 mm (51.0 +/- 16.9 mmHg). These results suggest that the location of the orifice of catheter should be taken into consideration when comparing the SOP.

Adult↗

PubMed1993

Suppression of rabbit VX-2 subcutaneous tumor growth by gadolinium neutron capture therapy.

VX-2 tumors growing in hind legs of New Zealand White rabbits (n = 4) were exposed to thermal neutrons for 40 min (2.1 x 10(12) neutrons cm-2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5-6 fold higher than that in the contralateral tumor. Growth of gadolinium-infused tumors was significantly inhibited compared to that of control tumors (P < 0.05) between the 16th and 23rd days after treatment.

Animals↗

PubMed1993

Effects of isosorbide in patients with Menière's disease.

The effects of isosorbide on vertigo, disability, hearing loss and tinnitus in 32 patients with Menière's disease were evaluated after a 24-month observation period. Vestibular symptoms in 80% of patients were assessed as improved according to the 1985 AAO-HNS post-treatment reporting criteria. In contrast, the effect of this osmotic diuretic on cochlear symptoms was limited.

Administration, Oral↗

PubMed1993

Autonomic nervous system disturbance as etiological background of vertigo and dizziness.

In order to investigate whether dysautonomia lies behind vertigo and/or dizziness in the neurotological clinic, an electrocardiogram (ECG) R-peak to R-peak test (R-R test) along with the Schellong test were simultaneously performed in 136 subjects. ECG data were analyzed by a microcomputer, and R-R intervals were calculated. In a dynamic test performed during postural changes from the supine to the standing position, there were 23 of 55 (41.8%) positive test results in patients with peripheral vestibular disorders, 28 of 51 (54.9%) with central vestibular disorders, and 15 of 18 (83.3%) with spinocerebellar degeneration. In a static test with the patient in the standing position, there were 13 of 55 (29.1%) positive test results in patients with peripheral vestibular disorders, 16 of 51 with central vestibular disorders, and 8 of 18 (44.4%) with spinocerebellar degeneration. A significant difference in the positive rate between spinocerebellar degeneration and both other central and peripheral vestibular disorders in the dynamic test was observed. These results also demonstrated that dysautonomia upon postural changes might play an important role in the development of vertigo and dizziness and that it is provoked by disorders of the autoregulatory mechanisms of the cerebral blood flow. This test is presumed to be excellent for detecting dysautonomia by virtue of being non-invasive, having good reproducibility and being readily available to quantitative evaluation by using a microcomputer.

Autonomic Nervous System↗

PubMed1993

[Factors effecting medication errors].

The purpose of this paper is to reveal factors that may occur or that may prevent medication errors, and to consider some measures of patients' safety. For this aim, we explored the characteristics of each ward and the characteristics of each nurse as well as their experiences about medication errors. The investigation was conducted at a approximately 650-bed university hospital located in a large urban center in Tokyo, and at a approximately 150-bed private hospital located in a suburb of Tokyo. Questionnaires were distributed in October 1991 and asked nurses to identify medication errors in which they had been personally committed within the past one-month. A response rate was approximately 70%. We were informed other information of each unit from head nurses--such as the unit size, case mix, nurse staffing and working schedule of nurses. Results indicate that on the questionnaires the nurses reported 10 times medication errors than they reported to head nurses. 56 percent of 155 nurses (except nurses who were working at an ICU and a mental ward) stated they had made medication errors or near misses during the 1-month reporting period. 30 percent of 155 stated they actually dealt with medication errors occurred by others. Several factors that effect medication errors have been identified by a stepwise discriminant analysis. The proportion of serious patient and the bed occupancy rate influenced the occurrence of medication errors. The educational career of a nurse, especially whether the nurse had been offered an assistant nursing program or not, related to dealing with and/or preventing medication errors.(ABSTRACT TRUNCATED AT 250 WORDS)

Discriminant Analysis↗

PubMed1993

Electron-equivalent dose for the effect of gadolinium neutron capture therapy on the growth of subcutaneously-inoculated Ehrlich tumor cells in mice.

The present in vivo study estimates the dose resulting from the gadolinium neutron capture reaction and the gadolinium enhancement extent of the thermal neutron effect. The assay is based on the time required from cell inoculation to the formation of tumors with an arbitrary size of 200 mm2. Mice were inoculated subcutaneously with Ehrlich tumor cells with or without meglumine gadopentetate (1.2 mg 157Gd/0.2 ml), and were exposed to 1.1 x 10(12) thermal neutrons cm-2(n 8), or 3 MeV electrons at three dose levels (each n 10). To reach 200 mm2 in size, it took 18.8 days for tumors treated with neutrons only and 34.7 days for those treated with gadolinium and neutrons. From the time-dose relation obtained with 3 MeV electrons, the equivalent doses corresponding to delays of 34.7 and 18.8 days were 15.0 and 7.4 Gy, respectively. Thus, gadolinium enhanced the thermal neutron effect two-fold (15.0/7.4) in the present study.

Animals↗

PubMed1993

[Renal autotransplantation and graft replacement for DeBakey IIIb dissecting aneurysm--a case report].

A successfully repaired case, a 53-years old man, who suffered DeBakey IIIb type dissecting aneurysm and renal dysfunction was reported. The right kidney, of which artery was originated from the false lumen, was autotransplanted to the right iliac system to improve the renal blood circulation. Then the descending aorta was segmentally replaced with the prosthesis under profound hypothermia, circulatory arrest and retrograde cerebral perfusion without cross-clamping the aortic arch. Three months later, aortography and catheterization study suggested that the reperfused left kidney resulted in renin-dependent hypertension. Kidney, therefore, was resected to improve blood pressure control. Patient recovered successfully, with no evidence of neurological complication.

Aortic Dissection↗

PubMed1992

Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules.

Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10(7) Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86 x 10(12) neutrons cm-2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P < 0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy.

Animals↗

PubMed1992

Factors causing difference in force output among motor units in the rat medial gastrocnemius muscle.

1. The isometric contractile properties and morphological characteristics of the muscle unit portion of motor units were investigated in the medial gastrocnemius (MG) muscle of Fischer 344 rats. Individual motor units were functionally isolated by stimulating single MG axons in finely dissected ventral root filaments. 2. To study the mechanical properties of the motor units in the rat MG muscle, ninety-six motor units in five animals were classified into three categories (type FF, FR and S units) using two physiological criteria: presence or absence of the 'sag' property and fatigability. The relative distribution of the different motor unit types in the sample was 35.4% for type FF, 47.9% for type FR, and 16.7% for type S units. 3. There was little overlap in the distribution of twitch contraction time between type F (including types FF and FR) and type S units. The mean value was 17.1 ms for type FF, 15.7 ms for type FR, and 28.0 ms for type S units. Type FF units produced the largest tetanic tension (mean +/- S.D.; 201 +/- 75 mN). Tension output of type S units was the smallest (15 +/- 6 mN), and that of type FR units was intermediate (100 +/- 45 mN). These values were significantly different. 4. A muscle unit portion of twenty-three motor units (8 FF, 6 FR, and 9 S units) was depleted of its glycogen through repetitive stimulation after characterization of its mechanical properties. Cross-sectional areas of units fibres and innervation ratio were directly measured in sections stained for glycogen using a periodic and acid-Schiff (PAS) reaction. Specific tension of unit fibres was calculated by dividing the maximum tetanic tension of a unit by its total fibre area. 5. The number of unit fibres ranged from 44 to 77 for type S, 116 to 198 for type FR, and 221 to 356 for type FF units, and differences among their means (66, 154 and 271, respectively) were significant. Tetanic tension was correlated with innervation ratio for all of the twenty-three units, or units within a particular type. 6. Mean fibre area for type S units (1983 microns2) was significantly smaller than that for type FF units (3489 microns2). Fibres belonging to type FR units had an intermediate size (2648 microns2). Correlation between tetanic tension and fibre area was significant for either all units or units within a particular type. 7. Total cross-sectional area was significantly different among the motor unit types, and was highly correlated to the maximum tetanic tension.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

The EBNA2-related resistance towards alpha interferon (IFN-alpha) in Burkitt's lymphoma cells effects induction of IFN-induced genes but not the activation of transcription factor ISGF-3.

Transfection of a plasmid encoding the Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene confers resistance to the antiproliferative effect of alpha interferon (IFN-alpha) in EBV-negative U968 cells (P. Aman and A. von Gabain, EMBO J. 9:147-152, 1990). We studied the expression of IFN-stimulated genes (ISGs) in two pairs of Burkitt's lymphoma cell lines, differing in the expression of the putative immortalizing gene of EBV, EBNA2. In EBNA2-expressing cells, the induction of four ISGs by IFN-alpha was strongly reduced or, in some cases, abolished. Chloramphenicol acetyltransferase reporter gene constructs containing different IFN-stimulated response elements were transfected into EBNA2-negative and EBNA2-positive cells. Induction of chloramphenicol acetyltransferase activity by IFN was impaired in EBNA2-positive cells. Also, a reporter gene construct driven by an IFN-gamma-sensitive promoter element was affected. However, as revealed by gel shift assays, EBNA2-positive and EBNA2-negative cells exhibited a nearly identical pattern of IFN-stimulated response element-binding proteins. Most important, activation of the factor ISGF-3, which previously has been shown to be required and sufficient for transcriptional activation of IFN-induced genes, was not inhibited in IFN-resistant cells expressing EBNA2. The mechanism of the EBNA2-related IFN resistance seems to be distinct both from the resistance mediated by hepatitis virus and adenovirus gene products and from the IFN resistance in Daudi cell variants. In these three cases, the transcriptional block of IFN-induced genes is due to inhibition of ISGF-3 activation and binding. Our data suggest that the EBNA2-related IFN resistance in Burkitt's lymphoma cells acts downstream of the activation of ISGF-3.

Antigens, Viral↗

PubMed1992

A 3',5'-cyclic adenosine monophosphate-dependent pathway is responsible for a rapid increase in c-fos messenger ribonucleic acid by adrenocorticotropin.

ACTH rapidly and transiently increases c-fos mRNA in the rat adrenals in vivo. The present investigation was undertaken in order to determine what kind(s) of second messenger systems is involved in this increase. Rat adrenal cells were grown in monolayers in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. After 2 days of culture, cells were treated with ACTH and various agents alone or in combination. The amount of c-fos mRNA was determined by dot blot hybridization and corticosterone levels in the media were measured by RIA. ACTH (300 pg/ml) increased c-fos mRNA transiently with a peak level after 60 min. A similar increase was observed when (Bu)2cAMP (1 mM) was substituted for ACTH. Pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H-89), a selective inhibitor of cAMP-dependent protein kinase, suppressed both basal and ACTH-increased c-fos mRNA. H-89 also suppressed corticosterone production. On the other hand, neither 12-O-tetradecanoyl-phorbol-13-acetate (100 ng/ml) nor elevated potassium ion (50 mM) affected the amount of c-fos mRNA and corticosterone production. Furthermore, pretreatment with cycloheximide (5 micrograms/ml) increased both basal and ACTH-increased c-fos mRNA. These results indicate that ACTH increases c-fos mRNA by phosphorylation of preexisting trans-acting factor(s) via cAMP-dependent protein kinase in common with steroidogenesis.

Adrenal Glands↗

PubMed1992

[A case of erythropoietin-producing renal cell carcinoma with a skin metastasis].

An 83-year-old man came to our hospital complaining of asymptomatic gross hematuria. We found a subcutaneous tumor in his chest and an abdominal mass in his left upper quadrant. Laboratory data showed red blood cell count of 737 x 10(4)/mm3 and hemoglobin level of 17.9 g/dl. The serum erythropoietin level measured by radioimmunoassay was considerably high. He underwent left nephrectomy and tumor resection in the chest wall. Serum erythropoietin level became normal following surgery and erythrocytosis disappeared. Histological findings revealed renal cell carcinoma, alveolar type, clear cell subtype, grade 2. The erythropoietin levels of the extracts of the cancer tissue and the normal kidney tissue were 2430 mU/g and 59.5 mU/g, respectively. Lung, liver and bone metastases appeared four months after the operation and serum erythropoietin level increased again.

Aged↗

PubMed1992

[Development of a method to prevent degenerative changes of the vein graft for arterial reconstruction].

Autologous vein graft is frequently used for arterial reconstruction in vascular surgery. Its' long-term patency rate, however, is low because of the degenerative changes of the vein wall. Of the basis of our hypothesis that the degenerative changes are mainly caused by an over-distension of vein wall in arterial system, in this study, autologous vein grafts of rabbit (N = 56) were implanted in the carotid arteries. To prevent overdistension, some of the grafts were covered with prosthesis which was made of microporous, compliant biodegradable polyurethane and were compared with those without prosthesis. The integrity of the architecture of the vein wall covered with prosthesis was well preserved at 6 weeks after implantation, where the biodegradation of prosthesis induced an optimal arterialization of the vein grafts. The results indicate that this method may prevent the degenerative changes of vein wall such as fibrosis and intimal hyperplasia, which would cause poor long-term patency of vein graft used for arterial reconstruction.

Animals↗

PubMed1991

Diuretics modify [Arg8]vasopressin-stimulated cAMP but not atrial natriuretic peptide-stimulated cGMP formation in renal cells.

The present study was undertaken to examine whether sulfonamide-derived diuretics affect [Arg8]vasopressin (AVP)-stimulated or atrial natriuretic peptide (ANP)-stimulated cyclic nucleotide formation in cells cultured from rat or dog kidney. In rat renal cells, all four sulfonamide-derived diuretics examined significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations of 10(-4) and 10(-3) M, while basal cAMP formation was unchanged by the diuretics. When cells were stimulated with 10(-7) M AVP, low ceiling diuretics (indapamide and trichlormethiazide) did not suppress cAMP formation, while high ceiling diuretics (furosemide and azosemide) significantly suppressed cAMP formation at concentrations of 10(-4) and 10(-3) M. The suppressive effect of the diuretics on AVP-stimulated cAMP formation in vitro paralleled the reported diuretic potency of the agents in vivo. In dog renal cells, all four diuretics significantly suppressed 10(-9) M AVP-stimulated cAMP formation at concentrations from 10(-6) to 10(-5) M, while these diuretics did not change basal cAMP levels. High ceiling diuretics suppressed 10(-7) M AVP-stimulated cAMP formation, whereas low ceiling diuretics did not. The difference in effective doses between rats and dogs seems to be consistent with the species difference observed in vivo. None of the diuretics affected basal levels of intracellular cGMP or ANP-stimulated cGMP formation in cultured rat renal cells. In addition to the inhibition of the Na/K/Cl co-transporter, it is suggested that most sulfonamide-derived diuretics act, at least in part, by inhibiting the actions of AVP.

Animals↗

PubMed1991

Otoneurological manifestations of the Shy-Drager syndrome.

Three patients with the chief complaints of dizziness while standing up or blackouts were diagnosed correctly as having the Shy-Drager syndrome at the Department of Otolaryngology. Both the electrocardiogram R-peak to R-peak interval and the Schellong test revealed disorders of the autonomic nervous system in each of these cases. Electronystagmography also demonstrated pathology of the oculomotor system and/or central vestibular system. Postural balance was also abnormal in one of the cases. Auditory brain-stem responses were normal in all three cases.

Electrocardiography↗