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Biomedical subjects

K Nishikawa

Publications and source records attributed to K Nishikawa.

At least 343 records · Page 19Linked to original sources
PubMed1994

Substrate specificity of tRNA (adenine-1-)-methyltransferase from Thermus thermophilus HB27.

tRNA (adenine-1-)-methyltransferase was purified to homogeneity from an extreme thermophile, Thermus thermophilus HB27, by several steps of column chromatographies. The molecular weight of this enzyme was about 60,000 as analyzed by SDS polyacrylamide gel electrophoresis. Km for E. coli tRNA(2Glu) was 100 nM and that for the methyl group donor, S-adenosyl-L-methionine, was 7.8 microM. The substrate specificity of the enzyme was investigated by using T7 RNA polymerase transcripts and tRNA fragments obtained by partial digestion with RNases. The enzyme was able to transfer the methyl group to the 3'-half fragment of E. coli initiator tRNA, however, the extent of methylation was elevated by more than five times when the 5'-half fragment was added and annealed to the 3'-half. This indicates that the main recognition site of the enzyme is within the 3'-half region of tRNA molecule, while the tertiary interaction between the T-loop and the D-loop is very effective for the adequate methylation reaction.

Base Sequence↗
PubMed1994

[Reproductive and developmental toxicity studies of lactitol (NS-4) (1)--Fertility study in rats by oral administration].

A study of fertility and fetal development was conducted in Sprague-Dawley rats. Male rats were given lactitol, a hepatic encephalopathy drug, orally from 63 days before mating to the end of mating period. Female rats were given from 14 days before mating to day 7 of pregnancy. The dose levels for both males and females were 0 (control), 0.7, 2.65 and 10 g/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. The decrease in food consumption in either male or female was observed in the intermediate and high dose groups. The high dose caused soft stool, diarrhea and increase in water consumption in either male or female. Moreover, the high dose caused salivation and suppression of body weight gain in male. In the pathological examination, the enlargement of cecum were observed in male of the intermediate and high dose groups. The increase in cecum weight were observed in male in all lactitol groups, and in female of the high dose group. Lactitol did not affect on copulation and fertility indexes in either male or female rats. Lactitol failed to affect on estrous cycle in female rats, and number of corpora lutea, implantations and preimplantation egg losses. In the fetal examination, lactitol did not affect on the development of live fetuses. The results show that no-effect dose levels of lactitol are less than 0.7 g/kg in male rats and 0.7 g/kg in female rats for general toxicity, and 10 g/kg for reproductive function in parent animals and fetuses.

Administration, Oral↗
PubMed1994

[Reproductive and developmental toxicity studies of lactitol (NS-4) (2)--Teratogenicity study in rats by oral administration].

A teratogenicity study of lactitol, a hepatic encephalopathy drug, was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 7 to day 17 of pregnancy. Twenty-two female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and thirteen pregnant rats per dose level were allowed to deliver naturally for postnatal examination of their offspring. The high dose of lactitol caused diarrhea or soft stool in pregnant rats. The food consumption of female rats decreased in the intermediate and high dose groups. The water consumption of female rats increased in the high dose group. The drug failed to alter the body weight of female rats. The weights of cecum of dams increased in the intermediate and high dose group. The high dose caused enlargement of cecum in dams. The drug failed to alter the numbers of corpora lutea and implantations, fetal mortality, the number of live fetuses, body weight of live fetus, sex ratio, and external, visceral and skeletal development of fetuses. Lactitol did not affect the delivery of dams, the number of live newborns, birth index, external development, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 10 g/kg for reproductive function in mother animals and their offspring.

Abnormalities, Drug-Induced↗
PubMed1994

[Reproductive and developmental toxicity studies of lactitol (NS-4) (4)--Perinatal and postnatal study in rats by oral administration].

A perinatal and postnatal study of lactitol, a hepatic encephalopathy drug was conducted in Sprague-Dawley rats. Female rats were given lactitol orally at dose levels of 0 (control), 0.7, 2.65 and 10 g/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats per level were allowed to deliver naturally for postnatal examination of their offspring. The high dose caused diarrhea or soft stool in dams. The high dose suppressed the body weight of dams during the perinatal period. The food consumption of dams decreased in the intermediate and high dose groups. The water consumption of dams increased in the high dose group. The high dose caused enlargement of cecum and increase of weights of cecum in dams. The drug failed to affect the delivery of dams and gestation index. However, high dose caused prolongation of gestation period. Two dams in the high dose group failed to nurse their all newborns during early lactation. The drug did not affect the number of live newborns, birth index, external appearance, body weight, viability index, weaning index, and sex ratio of weanlings. Nor did lactitol have any adverse effect on the postnatal development of the first (F1) generation offspring, such as differentiation, emotionality, motor ability, learning ability or reproductive performance. Nor did lactitol have any adverse effect on the second (F2) generation offspring. The results show that the no-effect dose levels of lactitol are 0.7 g/kg for general toxicity in mother animals, 2.65 g/kg for reproductive function in mother animals, and 10 g/kg for their offspring.

Administration, Oral↗
PubMed1994

Color Doppler sonography of hepatic tumors with a galactose-based contrast agent: correlation with angiographic findings.

OBJECTIVE: The purpose of this study was to evaluate the clinical usefulness of a galactose-based, IV sonographic contrast agent for assessing tumor vascularity and diagnosing hepatocellular carcinoma. SUBJECTS AND METHODS: We used color Doppler sonography with the sonographic contrast agent to examine 22 patients with 26 hepatic nodules (18 hepatocellular carcinomas, four hemangiomas, two adenomatous hyperplasias, and two metastatic tumors). In all 26 lesions, intratumoral arterial flow signals were examined before and after IV injection of the sonographic contrast agent at three concentrations (200, 300, and 400 mg/ml), and the findings on color Doppler sonograms of each lesion were correlated with angiographic findings. RESULTS: Conventional color Doppler sonograms showed flow in nine hepatocellular carcinomas (50%) and one hemangioma (25%). When the contrast agent was used, color Doppler sonograms showed intratumoral arterial flow in 11 hepatocellular carcinomas (61%) and one hemangioma (25%) at a concentration of 200 mg/ml, in 14 hepatocellular carcinomas (78%) and 1 hemangioma (25%) at 300 mg/ml, and in 15 hepatocellular carcinomas (83%) and two hemangiomas (50%) at 400 mg/ml. The detectability of intratumoral arterial flow was improved by the contrast agent, especially in hepatocellular carcinomas smaller than 30 mm in diameter. Angiography revealed neovascularization or staining in 15 hepatocellular carcinomas, four hemangiomas, and none of the adenomatous hyperplasias or metastatic tumors. Among 15 angiographically hypervascular hepatocellular carcinomas, the detection rate of intratumoral arterial flow with contrast-enhanced color Doppler sonography was 73% at 200 mg/ml, 93% at 300 mg/ml, and 100% at 400 mg/ml. No intratumoral Doppler signals were depicted with the use of contrast agent in any angiographically undetected tumors. CONCLUSION: Preliminary findings on contrast-enhanced color Doppler sonograms correlate well with angiographic findings for evaluating tumor vascularity. This noninvasive technique may be useful in diagnosing hypervascular hepatocellular carcinomas.

Adenoma↗
PubMed1994

[Mandibular reconstruction using a vascularized osteocutaneous scapular flap].

Composite tissue defect of the mandible following the surgical resection of head and neck neoplasma or osteoradionecrosis causes functional and cosmetic disorders. Mandibular reconstruction is, therefore, necessary to obtain satisfactory results. The introduction of microvascular surgery has made it possible to transfer various types of vascularized bone grafts and this technique is considered one of the most reliable procedures for mandibular reconstruction. Recently it has been reported that an osteocutaneous scapular flap is useful for mandibular reconstruction. We have performed, over the last 2.5 years, 13 mandibular reconstructions using a vascularized osteocutaneous scapular free flap, and successful results have been achieved. The features of this flap are as follows: 1) it provides a consistent blood supply to the bone and the skin and has a constant vascular pedicle; 2) since the skin island and bone flap have separate pedicles, three-dimensional reconstructions are facilitated; 3) if needed, two skin flaps can be elevated; 4) the skin island is not so bulky; 5) the lateral border of the scapula provides highly vascularized bone of thick cortical density and osteotomies are safely performed; 6) using an angular branch based on thracodorsal artery, a bi-pedicled scapula bone can be raised and two completely vascularized bone segments can be transferred with a single pedicle. Thus, a vascularized osteocutaneous scapular flap has proven very useful for complex mandibular reconstructions.

Adult↗
PubMed1994

[Transurethral hyperthermic treatment in patients with benign prostatic hypertrophy].

Transurethral hyperthermic treatment was performed on 30 patients with benign prostatic hypertrophy (BPH). Two patients had a urethral catheter because of urinary retention. The prostate was heated transurethrally. The treatment consisted of 3-8 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before and 1-5 weeks after the last hyperthermia session; subjective symptoms score, and as objective data residual urine volume and uroflowmetry. The symptoms score improved in 25 (83%) patients. Of 2 patients with a catheter, the catheter could be removed from 1 patient. Although there was no change in prostatic volume, significant decreases in residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

Aged↗
PubMed1994

[Quantitative flow-cytometric analysis of CD34-positive stem cells in peripheral blood stem cell harvests].

The percentage of CD34-positive cells (the CD34-positive rate) in peripheral blood stem cell harvests (PBSCH) was determined using two color flow cytometric methods, i.e., representation in a histogram (the histogram method) and the two-dimensional side scatter-fluorescence representation (the SSC-FL method). For all samples examined, the CD34-positive rate obtained using the histogram method was higher than that obtained using the SSC-FL method. This finding was probably due to the fact that some monocytes non-specifically reacted with anti-CD34 monoclonal antibody, and the histogram method could not distinguish these non-specifically stained cells from CD34-positive precursor cells. On the other hand, the SSC-FL method seemed to yield a more accurate measurement of the percentage of CD34-positive cells in PBSCH samples. Based on this finding, it is recommended that the histogram method, which is currently used at most commercial laboratories, be reviewed in favor of the SSC-FL method when the CD34-positive cell rate of PBSCH is to be determined.

Adolescent↗
PubMed1994

Sequential changes in stem cell markers in peripheral blood and leukapheresis samples after injections of recombinant human granulocyte colony-stimulating factor in patients with urogenital malignant solid tumors: a preliminary study.

In order to evaluate the mobilization effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on peripheral blood stem cells (PBSCs), rhG-CSF was given to patients with urogenital malignancy before chemotherapy. Markers for the stem cells, such as colony forming unit-granulocyte/macrophage (CFU-GM) and burst forming unit-erythrocyte (BFU-E), were sequentially monitored in peripheral blood and leukapheresis samples. Five patients, including a 13-year-old boy, were given 5 micrograms/kg rhG-CSF subcutaneously: the pediatric case for four consecutive days and the adult cases for six consecutive days (53-72 years of age). None of the patients had received chemotherapy within the four weeks prior to the start of the rhG-CSF series. PBSC collections were performed on the fifth day in the pediatric case and on the fifth and seventh days in the adult cases. Progenitor cells were monitored by methyl-cellulose cell culture techniques. CFU-GM on day 5 of the rhG-CSF series in peripheral blood increased 14- to 53-fold compared with samples taken immediately before the series. CFU-GM in the leukapheresis products on day 5 was greatest (70 x 10(3)/kg) in the pediatric case and least (14 x 10(3)/kg) in the oldest patient's case. The totals of the CFU-GM collected by two phereses in the adult cases were 21-73 x 10(3)/kg and the totals of CD34 positive cells were 0.6 to 1.4 x 10(6)/kg. The data suggest rhG-CSF to induce sufficient PBSCs for bone marrow rescue into the peripheral blood without any preceding chemotherapy. The patient's age may, however, be a contributory factor in using this method.

Adolescent↗
PubMed1994

[An approach to home therapy for cancer pain patients].

Recently, in consideration of cost performance and improvement in quality of life (QOL) of the patient, the significance of home care and outpatient treatment has also been recognized in Japan. A terminal cancer patient who had local recurrence in the pelvic region after surgery for rectum carcinoma, was treated for cancer pain by us with a continuous epidural infusion of morphine by means of a prolonged operating continuous infusion device. The treatment made home therapy possible and allowed the patient to return to normal social activities. Based on this case, the significance of and issues regarding home therapy are discussed in this study.

Costs and Cost Analysis↗
PubMed1994

Quantitative localization of angiotensin II receptor subtypes in spontaneously hypertensive rats.

Angiotensin II (Ang II) receptors were labelled by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand in the kidney, adrenal gland, thoracic aorta, and hindbrain of adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ang II receptors were differentiated into subtypes by susceptibility to subtype 1 (AT1) and subtype 2 (AT2) antagonists. In both rat strains, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors in glomeruli, proximal tubules, and the outer medulla. AT1 receptors were predominant in the thoracic aorta. The nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DM10), area postrema, and spinal trigeminal nucleus (Sp5) contained exclusively AT1 receptors, whereas the nucleus of the inferior olive contained AT2 receptors predominantly. Significant differences in receptor density were observed between SHR and WKY. The adrenal cortex, renal outer medulla, NTS, DM10, and Sp5 displayed higher AT1 receptor density in SHR than in WKY. These results indicate that expression of AT1 receptors is regulated differently in important targets of Ang II in SHR, and suggest that altered regulation of AT1 receptor expression may be relevant to the pathogenesis of hypertension in SHR.

Adrenal Glands↗
PubMed1994

Pharmacological profile of a novel nonpeptide angiotensin II subtype 1 receptor antagonist, TCV-116.

TCV-116, an angiotensin II (AII) receptor antagonist, is a prodrug that is converted in vivo to the active form, CV-11974. CV-11974 selectively and competitively inhibited the specific binding of [125I]AII-(Sar1,lle8) to All subtype 1 (AT1) receptors in rabbit aortic membranes (Ki = 0.64 nM) and insurmountably inhibited the AII-induced maximal contractile response of rabbit aortic strips (pD'2 = 9.97). TCV-116 inhibited the AII-induced pressor response in rats (ID50 = 0.069 mg/kg. p.o.). In spontaneously hypertensive rats (SHR), TCV-116 had a sustained antihypertensive effect (ED25 = 0.68 mg/kg, p.o.). Repeated oral administration of TCV-116 (1 mg/kg) to SHR once daily for 2 weeks reduced blood pressure by 30-50 mmHg over 24 h. The antihypertensive effects of TCV-116 correlated well with the inhibition of AII-induced contractile responses of aortic strips prepared ex vivo after administration of TCV-116. TCV-116 had sustained effects in both 2 kidney, 1 clip hypertensive rats and in 1 kidney, 1 clip hypertensive rats, but had no effect in DOCA/salt hypertensive rats. Unlike enalapril, TCV-116 had no potentiating effect on the incidence of cough induced by citric acid in guinea pigs. These results suggest that TCV-116 is a promising antihypertensive agent with once daily administration.

Angiotensin Receptor Antagonists↗
PubMed1994

Differential expression of homeobox-containing genes Msx-1 and Msx-2 and homeoprotein Msx-2 expression during chick craniofacial development.

The expression pattern of chick Msx-1 and Msx-2 homeobox genes in craniofacial primordia was examined by in situ hybridization using cRNA probes. Both genes were expressed in the distal region of the facial primordia, where the distribution of Msx-2 expression was restricted distally within the Msx-1 expression domain. On the contrary, Msx-2 expression in the lateral choroid plexus and cranial skull was broader and more intensive than Msx-1 expression. Our findings suggest that these two genes cooperate to play differential roles in craniofacial development. Msx-2 protein was detected immunohistochemically, and its localization essentially corresponded to the mRNA expression pattern, substantiating the involvement of Msx-2 protein as a transcriptional regulator in developing limb and face.

Animals↗
PubMed1994

Effects of TCV-309, a novel PAF antagonist, on circulatory shock and hematological abnormality induced by endotoxin in dogs.

We investigated the effects of TCV-309, a novel platelet activating factor (PAF) antagonist, on circulatory dysfunction and hematological abnormalities in experimental canine endotoxin (ET) shock. ET caused biphasic hypotension with a decrease in cardiac output (CO), left ventricular systolic pressure (LVP) and its dp/dt(max). The first hypotensive phase occurred within 15 min, and the second phase between 90 and 180 min following the injection of ET. Pulmonary vascular resistance (PVR) abruptly increased at 15 min with a partial recovery, and was then sustained at twice the basal value throughout the experiment. TCV-309 attenuated the hypotension, the decrease in CO, LVP and its dp/dt(max), and the increase in PVR. TCV-309 had no significant effect on the increase in TPR. The decrease in plasma fibrinogen and the increase in hematocrit and plasma lactate were significantly attenuated by TCV-309. These data suggest that PAF may be a key mediator leading to shock in sepsis.

Animals↗
PubMed1994

Assessment of testicular biopsy after cessation of maintenance chemotherapy in childhood acute lymphoblastic leukemia: a report from the Children's Cancer and Leukemia Study Group.

Among 484 male patients with acute lymphoblastic leukemia (ALL) registered into the protocols CCLSG 811, 841 and 874, from 1981 through 1990, 246 patients completed their protocols and were in continuous complete remission (CCR) for more than 3 years. One hundred and seven patients received bilateral testicular biopsies at the time of cessation of maintenance chemotherapy. Eight patients (7.5%) were found to have occult testicular leukemia (TL). Three of them did not receive any additional therapy and all suffered subsequent relapses; one bone marrow relapse and two testicular relapses. The other 3 patients received testicular radiation combined with an additional 2 years of chemotherapy, resulting in CCR for more than 6 years 10 months, 7 years 6 months, and 8 years 6 months. One with chemotherapy alone and another with radiation alone showed subsequent relapse. Overt TL after negative initial biopsy was developed in 3 (3.0%) of the 99 patients. All of them received testicular radiation with chemotherapy, resulting again in CCR for more than 1 year 0 months and 5 years 3 months; one patient showed relapse in testes and bone marrow after 3 years 8 months of CCR. These studies suggested that occult TL has an adverse prognostic significance unless retrieval chemotherapy is given and that performance of testicular biopsy at completion of maintenance chemotherapy is not contributory to prolongation of disease-free survival for males with ALL because the treatment employing testicular radiation plus retrieval chemotherapy for both occult TL and isolated overt TL after off-therapy is similarly very effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[A case of hydronephrosis caused by renal stones with elevated serum levels of CA-19-9 and CA-125].

A case of hydronephrosis caused by renal stones with elevated serum levels of carbohydrate antigens 19-9 (CA-19-9) and 125 (CA-125) is reported. A 74-year-old woman was hospitalized with pyelonephritis. The results of computerized tomography and endoscopy suggested that the patient did not have pancreatic or ovarian cancer, but laboratory tests were significant for serum CA-19-9 greater than 1,000 U/ml (normal less than 37) and serum CA-125 78 U/ml (normal less than 35), which are markers for such tumors. Abdominal X-ray films showed stones in the pelvis of the right kidney. Excretory urography showed that the right kidney was not functioning. Computerized tomography showed severe right hydronephrosis with a thin renal cortex. Complete obstruction of the ureteropelvic junction of the kidney was seen by retrograde pyelography. During percutaneous pyelography, aspiration of the pelvic urine was done, and the sample had a high concentration of CA-19-9 (250,000 U/ml), but no cancer cells. The patients underwent right nephrectomy. The pelvic urine was tested for both CA-19-9 and CA-125 this time, and both were high (190,000 U/ml and 5,100 U/ml, respectively). Pathological evaluation showed no evidence of a malignant tumor. The epithelium lining the renal pelvis was stained for both CA-19-9 and CA-125 using the avidin-biotin-peroxidase complex method. Serum levels of the markers returned to normal after nephrectomy.

Aged↗