Biomedical subjects

Y Uzuka

Publications and source records attributed to Y Uzuka.

At least 37 records · Page 2Linked to original sources

PubMed1999

Molecular cloning of the canine nicotinic acetylcholine receptor alpha-subunit gene and development of the ELISA method to diagnose myasthenia gravis.

We investigated the molecular structure of canine nicotinic acetylcholine receptor (AChR) alpha-subunit gene and developed an enzyme-linked immunosorbent assay (ELISA) as an immunological method to diagnose myasthenia gravis (MG). Canine AChR alpha-subunit cDNA was constructed from mRNA isolated from skeletal muscle of five dogs using the reverse transcriptase-polymerase chain reaction and its molecular structure was determined. The canine AChR alpha-subunit gene had 1371 base pairs encoding 457 amino acids and had a 96.1% homology to the human AChR alpha-subunit gene at the amino acid level. From the results of sequencing the DNA, specific antibodies to the acetylcholine binding domain of the canine AChR alpha-subunit were produced by immunizing rabbits with synthetic oligopeptides (alpha-subunit 183-200 amino acids). The specificity of the rabbit anti-oligopeptide serum was examined by Western blot analysis using an E. coli-expressed AChR alpha-subunit protein and an AChR alpha-subunit protein fraction prepared from canine skeletal muscle as an antigen. An ELISA assay was developed using oligopeptides corresponding to the binding domain to diagnose canine MG; specific antibodies were detected from two dogs with MG, one diabetic dog and two healthy dogs among 25 dogs examined. Further examinations of the ELISA using a large number of samples of clinically MG-positive and MG-negative dogs are needed to establish its usefulness in MG diagnosis.

Acetylcholine↗

PubMed1999

Chemical control of Haematobia irritans with 0.5% topical ivermectin solution in cattle.

A field trial was conducted to evaluate the efficacy of a topical formulation of ivermectin administered at the dose of 500 micrograms/kg against horn flies (Haematobia irritans) in cattle. Eighty-eight cattle in four herds naturally exposed to horn flies were used in the trial. Replicates were formed of two herds. Within replicates, one herd was randomly allocated to the untreated control and the other to the ivermectin treatment group. Horn fly counts were taken on the treatment day (Day 0) and on Days 7, 14, 21, 28, and 35 post-treatment. There were no horn flies on any cattle in the treatment group, whereas all the control cattle were continuously infested by horn flies on each examination day.

Administration, Topical↗

PubMed1997

Effect of simultaneous bilateral tibial nerve stimulation on somatosensory evoked potentials (SEP) in dogs.

Since somatosensory evoked potentials (SEP) by hindlimb nerve stimulation are known to ascend bilaterally in the spinal cord, it was investigated whether or not simultaneous bilateral stimulation causes facilitation or inhibition of the stimuli. In an experiment using 36 adult Beagle dogs, the difference between simultaneous bilateral stimulation and unilateral stimulation was studied as to latencies and amplitudes. No significant difference was noted. However, the detection of far-field potentials by bilateral stimulation was not effective in which case far-field potentials did not recorded by unilateral stimulation. It was therefore confirmed that simultaneous bilateral stimulation does not cause facilitation or inhibition in the relay pathways, and does not affect the latency.

Animals↗

PubMed1996

Threshold changes in auditory brainstem response (ABR) due to the administration of kanamycin in dogs.

Auditory brainstem response (ABR) is a useful method in evaluating auditory function in human. To investigate the ABR threshold is more effective than to pursue the trends in each component of ABR. In this study, tone burst sound stimuli were employed and the ABR threshold shift caused by kanamycin administration was investigated in dogs. In a series of monitoring of ABR against short-period auditory lesions, changes in the ABR waveform after intravenous administration of kanamycin were detected. These changes returned gradually and were reversible. The changes in ABR against long-period auditory function disorder were perceived by an increase in the ABR threshold. The ABR threshold shift occurred earlier in the high frequency sounds than in the lower frequency sounds. This is why amino glycoside antibiotics damage the cochlear hair cells in the basal layer and lead to the loss of hearing selectively for high frequency tones. These findings suggest that tracing of the ABR threshold by tone bursts could provide information that has a specificity for frequency in hearing tests and is a useful method in clinical veterinary medicine or/and toxicological tests.

Animals↗

PubMed1995

Studies on the factors affecting the recording of somatosensory evoked potentials induced by tibial nerve stimulation in dogs.

Since spinal cord abnormalities are often associated with lesion in the thoracic or lumber vertebrae, examination of Somatosensory evoked potential (SEP) induced by hind limb nerve stimulation will be useful. In the experiment, scalp recorded SEP in dogs by tibial nerve stimulation was studied on the distribution, the change of latency by body size and the influence of experimental compression to the spinal cord. Greatest response was got at Fz, and shorter latencies for SEP recorded on the ipsilateral stimulation side than from the contralateral side. The equation describing the regression line of the latency with the distance to the recording site from stimulating site was Y = 0.072X+13.23 and the regression was statistically significant. In the experimental study of compression to spinal cord, dorsal compression tended to be sensitive compared to the ventral compression. This study suggested that not only increase of latency but also reduction of amplitude could occur as a result of spinal cord disorders.

Animals↗

PubMed1994

[Investigation of nitroblue tetrazolium reduction of neutrophils in the dog infected with Hepatozoon canis].

Investigation of nitroblue tetrazolium (NBT) reduction of neutrophils was performed in the dog infected with Hepatozoon canis. No positive reactions were observed in the parasitized neutrophils by the resting and the stimulated NBT reduction tests. However, results of resting and stimulated NBT reduction tests apparently made no differences between non-parasitized neutrophils of the infected dogs and neutrophils of the non-infected dogs. These findings show that the parasitized neutrophil has no oxidative bactericidal capacity and the infected dogs had no-change in the host protective mechanism.

Animals↗

PubMed1993

[Bestatin therapy of chronic myelogenous leukemia].

We proposed a new approach to treat chronic myelogenous leukemia using a combination of busulfan and Bestatin. Twenty-three patients with Ph1 positive CML including 20 in the chronic phase and 3 in the accelerated phase, were treated with the combination therapy. Complete hematologic remission was obtained in all patients. Complete cytogenetic response (CCR) was obtained in 6 patients (26%), partial cytogenetic response (PCR) in 1 (4%), and minor cytogenetic response (MCR) in 6 (26%). In particular, of 13 patients in early chronic phase, 5 (39%) achieved CCR, 1 PCR, 3 MCR. Complete suppression of Ph1+clone was further confirmed by molecular analysis. Cytogenetic conversion to a normal diploid state persisted for 6-41+ months (median 22 months+). Three year survival rate was 86.6 +/- 9.0% (95% confidence limit). Furthermore, the long-term complete hematologic remission in the accelerated phase patients without progression of the disease may be indicative of a long-term survival. We conclude that Bestatin effectively controls CML and allows reappearance of diploid hemopoietic cells in some patients. The rationale for this combination therapy is that busulfan suppresses the proliferation of leukemic progenitors and decreases tumor burden to the level where Bestatin exhibits its antiproliferative effects. Bestatin is not merely antiproliferative but provides more complex biological properties capable of enhancing repopulation of normal residual stem cells.

Adult↗

PubMed1992

Clinical trials of bestatin for leukemia and solid tumors.

A new immunomodulating agent, bestatin (INN: ubenimex) has low toxicity after long-term oral administration and significantly modifies immunological responses. Prolongation of remission duration and survival was achieved in adult acute nonlymphocytic leukemia with bestatin immunotherapy combined with remission maintenance chemotherapy. Patients with myelodysplatic syndrome (MDS) and chronic myelogenous leukemia (CML) responded to bestatin, and it is noted that cytogenetic remission was obtained in CML. MDS and CML are thought to be a family of clonal malignant disorders in which malignant transformations occurs at the level of the pluripotent stem cell. Bestatin may be capable of modifying the biological-proliferative disequilibrium of the disease, and the therapy opens new and promising prospects in the treatment of both MDS and CML. Randomized controlled studies of bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck, and esophagus, and therapeutic benefits on disease free-interval or survival were observed in certain types of these cancers. However, the adjuvant activity of bestatin immunotherapy for these cancers should be further investigated to confirm its activity.

Humans↗

PubMed1992

Humoral immune responses of cats to feline infectious peritonitis virus infection.

Immunoperoxidase antibody (IPA) method as a titrating method of feline infectious peritonitis (FIP) virus (FIPV) was developed for titrating antibody to FIPV (IPA-titer). By this method the immune responses of the cats that had been infected with FIPV, were traced. The infected cats could be grouped into three types by their immune response to FIPV and clinical appearances. Type I cats lived for a long time, formed a major group among infected cats, had 160 to 1 x 10(4) IPA-titers, and showed healthy appearances without any changes both on autopsy and histopathologically. From among type I cats, type II cats appeared sporadically with rapid elevation of IPA titers to 3.2 x 10(5) and showing clinical signs of FIP, and died. Type III cats lived healthily for a long time with gradual elevation of IPA-titers to a plateau of about 1 x 10(5), then showed neuronal disorder of hind leg paralysis with the descending IPA-titers to 2 x 10(4), and died. Thus, typical FIP appeared as a hyper-immune disease. Other related problems are discussed.

Animals↗

PubMed1992

[Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia].

Clinical effects of KRN8601 (recombinant human granulocyte colony-stimulating factor:rhG-CSF) were studied in 26 patients with chronic neutropenia including 4 Kostmann's disease, 1 Shwachman's syndrome, 1 Lonsdale's syndrome, 1 glycogen storage disease Ib-associated, 6 chronic benign, 5 chronic hypoplastic, 2 cyclic, 4 autoimmune and 2 miscellaneous neutropenia. The patients were given rhG-CSF intravenously at doses of 20-540 micrograms/m2 or subcutaneously at doses 20-400 micrograms/m2, over the periods of 2-32 weeks. Increases in neutrophil counts occurred after rhG-CSF administration in 23 of the 26 patients. Patients with Kostmann's disease, Shwachman's syndrome and chronic hypoplastic neutropenia responded poorly compared to patients with other types of neutropenia. There were no serious side effects which caused interruption of the study. These results indicated a beneficial effect of KRN8601 in various types of chronic neutropenia.

Adolescent↗

PubMed1991

Application of mathematical model to multiple-dose experimental chemotherapy for fatal murine pneumonia.

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered for 7 days to mice with pneumonia caused by Klebsiella pneumoniae by using dosage regimens that would simulate multiple dosing in usual clinical treatments at dosing intervals of 8 or 12 h. Viable numbers of the bacteria in the lungs were measured at 12- or 24-h intervals. The mathematical model established in a previous single-dose study was applied in this study to explain the time courses of the changes in bacterial count over 7 days. However, because the error in viable count measurements was larger than that in the previous study, the time course of the changes in mean viable count was not regular and the viable count reduction rate changed during multiple dosing, and therefore it was difficult to explain the time course by repeated application of the mathematical model described previously. This study suggests that the changes in pharmacokinetic and pharmacodynamic parameters during multiple dosing need to be considered.

Animals↗

PubMed1991

[Combination therapy of chronic myelogenous leukemia with busulfan and bestatin].

We demonstrated the clinical effectiveness of combination therapy with Busulfan and Bestatin in 13 patients with Philadelphia chromosome positive chronic myelogenous leukemia, including 9 in chronic phase and 4 in acute phase. Sequential cytogenetic studies and molecular analysis of the breakpoint cluster regions were performed every 2 months. Complete hematologic remissions were observed in all 13 patients. Five minor cytogenetic responses, 2 partial cytogenetic remissions and 2 complete cytogenetic remissions were observed. All of the 4 patients in early chronic phase achieved cytogenetic remission and in 3 of them there was a complete disappearance of rearranged restrictive fragments of the bcr gene. In contrast, 4 of the 5 patients in late chronic phase failed to achieve cytogenetic remission and only 1 achieved minor cytogenetic response, suggesting excellent effects, particularly in patients with early disease. It is clear from this pilot study that combining Bestatin with Busulfan is an effective way to reduce or eliminate Ph1 positive clone and to maintain this status.

Adult↗

PubMed1991

[Studies on the change in the levels of serum ferritin, serum iron and total iron binding capacity caused by aging and sex difference].

Sex difference and aging change of serum ferritin concentration in normal subjects were studied with their relations to serum iron concentration, total iron binding capacity (TIBC) and other hematological parameters. The subjects of this study were the stuff of our hospital (113 males and 330 females) and some old patients without having any diseases of internal medicine (11 males and 23 females), 477 in all. Serum ferritin level was 108.0 +/- 57.8 ng/ml in men and 26.4 +/- 22.7 ng/ml in women, which showed the significant difference between the sexes. In terms of the changes in serum ferritin level by aging, serum ferritin level increased with age from twenties to fifties in the men. On the other hand, it remained low in the women to their forties and its changes by aging were not observed, though it abruptly increased in the women after 50 years of age. The low levels of serum ferritin, iron, transferrin saturation (Fe/TIBC) and hemoglobin of red blood cell were often observed in the women aged from 18 to 45, but rarely found in the women after 50 years of age. According to this fact, the low level of serum ferritin in the young women are considered to be related to the menstruation. Significant correlation between serum ferritin and serum iron or transferrin saturation was shown both in men and women, while that between serum ferritin and hemoglobin of red blood cell was shown only in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

[A double-blind, cross-over clinical trial of recombinant human G-CSF on neutropenia induced by chemotherapy for non-Hodgkin's lymphoma].

A double-blind, placebo-controlled, cross-over clinical trial of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was conducted in 46 patients receiving intensive chemotherapy for non-Hodgkin's lymphoma. Each patient received 2 cycles of CHOP therapy. rG-CSF (2 micrograms/kg/day) or its placebo was given subcutaneously to each patient for 14 days from 2 days after initiation of the chemotherapy, in a cross-over fashion. rG-CSF significantly increased the absolute neutrophil counts (ANC) at nadir, and reduced the number of days with ANC less than 1,000/mm3 and also the number of days for recovery to ANC greater than or equal to 2,000/mm3. Bone marrow examination showed a significant increase in the number of myeloid cells after rG-CSF treatment. 12 infective episodes were observed during placebo cycles, while 6 infective episodes were observed during rG-CSF cycles. No serious side effects were observed. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for non-Hodgkin's lymphoma.

Adult↗

PubMed1990

[Clinical effect of recombinant human G-CSF on neutropenia induced by chemotherapy for non-Hodgkin's lymphoma].

A clinical trial of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was conducted in 66 patients receiving intensive chemotherapy for non-Hodgkin's lymphoma. Each patient received 2 cycles of CHOP therapy, and one cycle of them was performed with rG-CSF treatment and another one without rG-CSF treatment, in a cross-over fashion. rG-CSF (0.4, 2, 5, 10 micrograms/kg/day) was given intravenously or subcutaneously to each patient for 14 days from 2 days after initiation of the chemotherapy. rG-CSF increased the absolute neutrophil counts (ANC) at nadir, and reduced the period of neutropenia with ANC less than 1,000/mm3 and also the period for restoration to ANC greater than or equal to 2,000/mm3 after initiation of chemotherapy. These effects were remarkable at doses of more than 5 micrograms/kg/day intravenously and 2 micrograms/kg/day subcutaneously. Fourteen infective episodes were observed during the cycles of chemotherapy without rG-CSF treatment, while 7 infective episodes were observed during the cycles with rG-CSF treatment. rG-CSF was well tolerated. These results demonstrated that rG-CSF was effective in neutropenia induced by cancer chemotherapy at a intravenous dose of 5 micrograms/kg/day and a subcutaneous does of 2 micrograms/kg/day.

Adult↗

PubMed1990

Application of mathematical model to experimental chemotherapy of fatal murine pneumonia.

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered in an experimental model of murine pneumonia caused by Klebsiella pneumoniae in a way which enabled us to approximate the serum antibiotic concentration time course in humans. Bacterial counts during the experiments were subjected to nonlinear least-squares analyses by using a mathematical model that explained the bacterial killing by the antibiotic concentration time course and other factors associated with antimicrobial potency and bacterial growth. Cefazolin gave a killing curve that changed synchronously with the drug levels in serum; in contrast, cefmenoxime gave a curve that was prolonged as compared with the change in the drug levels in serum. Multiple correlation coefficients were about 0.9, and the model worked well for bacterial count data. Parameters relating to antimicrobial potency of the drugs, bacterial growth rate, and drug distribution into the tissue were estimated numerically.

Animals↗

PubMed1990

Bestatin treatment of myelodysplastic syndromes (MDS) and the effects of bestatin on hematopoiesis in MDS.

A high remission rate (75%) was achieved in a preliminary study using bestatin in patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t). One of 2 patients with RAEB-t and 3 of 6 patients with RAEB obtained complete response. Two patients with RAEB achieved good response, but one with refractory anemia failed. Clonogenic marrow cell culture studies in patients with myelodysplastic syndromes have demonstrated intrinsic hematopoietic stem cell abnormalities, in particular defective erythroid colony formation. After bestatin treatment, these abnormalities as well as hematologic findings were markedly improved. The results suggest that bestatin has an enhancing effect on burst promoting activity production of helper (CD4 positive) T lymphocytes and the effect on hematopoiesis of bestatin may be mediated by T lymphocytes.

Aged↗

PubMed1990

Relative effects of xylazine-atropine, xylazine-atropine-ketamine, and xylazine-atropine-pentobarbital combinations and time-course effects of the latter two combinations on brain stem auditory-evoked potentials in dogs.

Brain stem auditory-evoked potentials (BAEP) were recorded in 4 dogs to analyze the relationship between acoustic stimulus intensities and peak latencies of each wave, and to investigate the relative effects of xylazine-atropine, xylazine-atropine-ketamine, and xylazine-atropine-pentobarbital combinations and the time-course effects of the latter 2 drug combinations on BAEP. Click stimulations fixed at a stimulus rate of 10/s and a frequency of 4 kHz were delivered at intensities ranging from 10- to 110-dB sound pressure level (SPL) in 10-dB steps for analyzing the relationship between the acoustic stimulus intensities and the peak latencies and at an intensity of 110-dB SPL for investigating the effects of the sedative and anesthetic drug combinations and their time-course effects on BAEP. Waves I to VI were identified with stimulus intensity of greater than or equal to 50-dB SPL. Wave VII was observed in some records, but was excluded from statistical analysis. As stimulus intensity was increased from 50- to 110-dB SPL, the latency decreased for all waves during xylazine-atropine-ketamine anesthesia. There were no statistically significant differences in the peak latencies of each wave in BAEP among xylazine-atropine, xylazine-atropine-ketamine, and xylazine-atropine-pentobarbital combinations 20 minutes after drug administration, except that the latency of wave VI during xylazine-atropine sedation was significantly (P less than 0.01) shorter than that detected during xylazine-atropine-ketamine or xylazine-atropine-pentobarbital anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗