[Gene diagnosis for patients with leukemia].
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Blotting, Southern↗
Biomedical subjects
K Kitamura
Publications and source records attributed to K Kitamura.
[GM-CSF.G-CSF].
The basic characteristics of granulo-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) are reviewed. The structure of the proteins and genes have been clarified. The clinical use of these hematopoietic growth factors are also discussed. Diseases for which these growth factors will be effective are follows, the granulocytepenic state after anti-cancer chemotherapy, aplastic anemia, bone marrow transplantation and so on. As these growth factors increase the granulocyte function, these proteins will be effective on the immunodifective state.
Agranulocytosis↗
Expression of paternal and maternal mitochondrial HSP70 family, hsc74, in preimplantation mouse embryos.
We have investigated the regulation of gene expression of a novel mitochondrial HSP70 family, hsc74 in preimplantation mouse embryos. We used a monoclonal antibody, anti-CSA, which reacts with only one of strain variants of the hsc74. By immunostaining with anti-CSA antibody, the hsc74 protein was constitutively detected in C3H embryos from 1-cell to blastocyst stage, but no signals were detectable in C57BL/6 embryos. To know the timing of paternal genome expression, we examined the expression of hsc74 in (C57BL/6 x C3H)F1 embryos. No positive signals were detectable in embryos before 8-cell stage. In early 8-cell stage weakly positive signals appeared in the peripheral region of the blastomeres. From late 8-cell stage, the protein was intensively detectable and was persistently expressed in all types of cells. We have also applied a sensitive methodology to distinguish genetic variants of hsc74 from C3H and C57BL/6 by reverse transcription polymerase chain reaction followed by single strand conformation polymorphism analysis. In (C57BL/6 x C3H)F1 embryos, the paternal transcripts were first detected in 4-cell embryos, while the maternal transcripts were constantly detectable. These results indicate that the transcripts and proteins of hsc74 were derived only from the maternal gene from 1-cell to 4-cell stages, and that from 4-cell stage the paternal gene is also transcribed, and the significant increase of the paternally derived protein occurred around late 8-cell stage.
Animals↗
Molecular forms of human brain natriuretic peptide (BNP) in plasma of patients on hemodialysis (HD).
Plasma brain natriuretic peptide (BNP) levels have been reported to increase in patients with heart failure and end-stage renal disease (ESRD); however, little is known about molecular forms of plasma BNP that increase in these diseases. In the present study, we analyzed the molecular forms of plasma BNP in ESRD patients of both before (pre-) and after (post-) hemodialysis (HD) state. The plasma extract was analyzed by gel filtration on a TSK-GEL G2000 SW column followed by a RIA for both BNP and atrial natriuretic peptide (ANP). In the pre-HD patients, a 14- to 2300-fold increase in plasma level of immunoreactive (ir-) BNP was observed when compared to normal controls. A ratio of BNP-32 to g-BNP (pro BNP) in plasma from the patients was much larger than that in plasma from normal subjects, indicating that the high plasma level of ir-BNP level in the patients on HD largely results from a marked increase in BNP-32. HD significantly (P < 0.01) lowered the plasma levels of both BNP-32 and g-BNP with a greater reduction in BNP-32 than in g-BNP. Whereas, a-ANP was a main molecular form of plasma ANP in both pre- and post-HD plasma. These results suggest that plasma BNP-32 plays an important role in the sodium-fluid balance and that secretion and metabolism of BNP may differ from those of ANP in the HD patients.
Adult↗
[A case of localized fibrous tumor of the pleura with bloody pleural effusion].
A 25-year-old female came to our hospital with the chief complaint of right dorsal pain. On her initial chest X-ray, the tumor (5 x 3 cm) was recognized in the right lower lung field. The tumor grew rapidly during the three month period between the initial X-ray taken on her first visit and her getting admitted in the hospital. A preoperative diagnosis was done by percutaneous aspiration biopsy. Initial diagnosis of spindle cell tumor was made. Partial resection of right lower lobe with chest wall resection was carried out. There were about 500 ml of bloody pleural effusion. Macroscopically, the tumor was encapsulated, measuring 8.0 x 6.0 x 5.0 cm. The cross section was of a yellowish brown solid tumor. The histological diagnosis was of a low grade malignant fibrous mesothelioma. Only 14 cases of localized mesothelioma with pleural effusion including our case have been reported in Japan. She is still alive nine months after surgery. This patient should be carefully followed for the recurrence of the disease.
Adult↗
[General pharmacology of T-3761, a new oral quinolone antibacterial agent (1). Effect on the central nervous system].
General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the central nervous system were investigated in laboratory animals. The results obtained are summarized as follows. 1. T-3761 exerted no significant effects on spontaneous motor activity, motor coordination, pentobarbital-induced hypnosis, electroshock-, pentetrazole- or strychnine-induced convulsion, acetic acid-induced writhing responses, reserpine-induced hypothermia and ptosis in mice at oral doses of 100, 300 and 1,000 mg/kg. The same oral doses of T-3761 exerted no significant effects on body temperature and passive avoidance response in rats. 2. T-3761 had no effects on EEG in cats and spinal reflex in rats at intravenous doses of 10, 30 and 100 mg/kg. 3. Convulsions were not observed in mice after any oral combinations of T-3761 at a dose of 200 or 1,000 mg/kg with 14 different nonsteroidal anti-inflammatory drugs (NSAIDs) including fenbufen. 4. An oral combination of T-3761 even at a higher doses of 3,000 mg/kg with 4-biphenylacetic acid (BPAA) which is a principally active metabolite of fenbufen also did not induce convulsions in mice. 5. T-3761 did not inhibit GABA receptor binding in rat brain synaptic membranes at 10(-4) M in either the absence or presence of BPAA. These results suggest that T-3761 is an antibacterial agent which would be unlikely to produce any side effects on the central nervous system and to produce convulsion when combined with NSAIDs in clinical use.
Animals↗
[General pharmacology of T-3761, a new oral quinolone antibacterial agent (2). Effect on the respiratory and cardiovascular systems, autonomic nervous system and other functions].
General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the respiratory and cardiovascular systems, autonomic nervous system and other functions were investigated in laboratory animals. The results obtained are summarized as follows. 1. Respiratory and cardiovascular systems: Oral administration of T-3761 at doses of 100-1,000 mg/kg did not affect in conscious rats. But intravenous administration of T-3761 at doses of 10-100 mg/kg caused an increase in respiratory rate, induced hypotension, caused increase or decrease in heart rate and altered ECG patterns (elevation of T waves and reduction of voltage of QRS complexes, etc.) in anesthetized dogs. Intravenous administration of T-3761 at doses of 10-100 mg/kg showed respiratory rate increase or decrease, hypertension, heart rate decrease and ECG patterns changes (T waves elevation and extrasystole) in anesthetized rabbits. 2. Autonomic nervous system and smooth muscle organs: T-3761 increased the epinephrine-induced contraction of the isolated guinea pig vas deferens at concentration of 10(-5)-10(-4) g/ml. T-3761 decreased the acetylcholine-induced contraction of the isolated guinea pig ileum and epinephrine-induced relaxation of the isolated guinea pig trachea-chain at concentration of 10(-4) g/ml. T-3761 increased the norepinephrine-induced contraction of the isolated rabbit thoracic aorta at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg exerted slight mydriasis in mice. 3. Digestive system: T-3761 decreased the spontaneous motilities of isolated ileum and colon at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg inhibited gastric output and intestinal transit time in rats or mice. 4. Renal functions: Oral administration of T-3761 at a dose of 300 mg/kg increased Na+ excretion but did not affect PSP excretion in rats. 5. Hematological examinations: T-3761 showed no effects on resistance to hemolysis, blood coagulation and platelet aggregation in rabbits at concentration of 10(-6)-10(-4) g/ml. Oral administration of T-3761 at dose of 100-1,000 mg/kg did not affect bleeding time or blood glucose level in rats. 6. Miscellaneous effects: Intravenous administration of T-3761 at a dose of 100 mg/kg slightly inhibited the twitch tension of gastrocnemius in anesthetized rats. Oral administration of T-3761 at doses of 300-1,000 mg/kg exerted slight augmentation of carrageenin-induced hind paw edema in rats. From these results, it can be assumed that T-3761 had a wide safety margin as an oral antibacterial agent.
Animals↗
Delayed or insufficient restoration of PML and PML-RAR alpha subcellular localization after exposure in vitro to retinoic acids in all-trans retinoic acid-resistant APL cells.
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Drug Resistance↗
[Studies on SY5555 in the field of pediatrics].
SY5555, a new oral penem, in the form of dry syrup (powder which is dissolved before use) was evaluated for its pharmacokinetics and clinical efficacy in pediatric patients. Oral administration of 5 mg/kg and 10 mg/kg of SY5555 in dry syrup resulted in respective maximum plasma concentrations of 1.08 +/- 0.38 micrograms/ml (n = 4) and 2.50 +/- 1.81 micrograms/ml (n = 4), half-lives (T 1/2) of 2.72 +/- 1.86 hours (n = 3) and 1.14 +/- 0.88 hours (n = 4), and urinary excretion until 6 hours of 4.7% (n = 1) and 3.86 +/- 2.01% (n = 4). Clinical efficacy was evaluable in 22 patients, and the overall efficacy rate was 100%. As for bacteriological efficacy, all 5 strains of pathogenic organisms identified were eradicated (eradication rate, 100%). No remarkable adverse reactions or abnormal laboratory values were observed.
Administration, Oral↗
[Diagnostic value of tissue polypeptide antigen in pleural effusions with malignant pleural mesothelioma].
There are no known tumor makers of malignant pleural mesothelioma. We measured the concentration of TPA in the pleural effusions from patients with malignant pleural mesothelioma and from patients with other pleural diseases, evaluate its clinical usefulness. The concentration of TPA was more than 7,000 U/l (mean: 18,600 +/- 9,867 U/l, n = 5) in all patients with malignant pleural mesothelioma, but it was less than 4,000 U/l in those with benign asbestos pleurisy and other benign pleural effusion (benign asbestos pleurisy 1,598 +/- 570, n = 5: p < 0.01, tuberculous pleurisy 1.37 +/- 759, n = 11: p < 0.01, others 2,497 +/- 2,152 n = 3: p < 0.05). The concentration of TPA in the pleural effusions was not significantly different between malignant pleural mesothelioma and lung cancer (12,287 +/- 17,070 U/l). However, in all patients with lung cancer and high TPA concentrations, cytologically malignant cells were detected in the pleural effusions. TPA was high in all five patients with malignant pleural mesothelioma, but cytologically malignant cells were detected in only one patient. Only in malignant pleural mesothelioma (not in other benign disease or in lung cancer) was the concentration of TPA more than 4,000 U/l, and no evidence of malignancy was obtained by cytological methods. These findings suggest that assessing TPA in the pleural effusion might contribute to the diagnosis of malignant pleural mesothelioma.
Adult↗
[Clinical study of ciclosporin in patients with aplastic anemia and pure red-cell aplasia].
We administered cyclosporine to patients with aplastic anemia and pure red-cell aplasia as a multicenter clinical trial. The cyclosporine was given by a dose of 6 mg/kg orally daily for 16 weeks. The efficacy of cyclosporin for aplastic anemia was 13.8% after 8 weeks, and 28.0% after 16 weeks. The severity of the disease was improved, and the amount of blood transfusion was reduced. The efficacy of cyclosporine for patients with pure red-cell aplasia was 60.0% at 16 weeks treatment. Adverse effects of cyclosporine were observed in some patients and the hirsutism was seen most commonly. In laboratory data, an increase of serum creatinine was seen but was transient. Our results showed that cyclosporine is an effective drug for treatment of aplastic anemia and pure red-cell aplasia.
Adult↗
[Induction of protective immune responses by a chimeric soluble protein from a recombinant BCG vector candidate vaccine to HIV-1].
We have been isolated HIV strains from blood specimens of HIV infected individuals in Japan for these 6 years. The number of specimens tested reached approximately 1,700 that ninety percent of them were from hemophiliacs repeatedly injected blood products from the United States. More than 300 of field HIV were successfully isolated from the samples. The isolation rates has decreased to 30 percent in 1993 from 40 percent in 1992, suggesting that treatment with anti-HIV drugs such as AZT and/or ddI may be effective to HIV-infected individuals. Further, both of the viral and genomic sequences of HIV were classified to be clade B virus. The clinical isolates that expressed IHIGPGRAFY sequence at the center of the HIV-V3 domain were found to be neutralized by an anti-clade B-V3 monoclonal antibody, mu 5.5. By individual levels, when asymptomatic seropositives have progressed to disease-states, neutralization core motif of GPGR in approximately 6% of the viruses has changed to GPGG and hydrophilic amino acid changed to hydrophobic amino acid, correlating the loss of binding activity to PND-peptide of Japanese Consensus virus. Further, rapid progressors to HIV-induced diseases showed decreased activity of the binding antibody. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein, and established the PND-peptide secretion system in BCG. The recombinant BCG inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide followed by passive transfer of the DTH by the systemic route.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Vaccines↗
[Tibial nerve somatosensory evoked potentials: studies on latency variability as a function of subject height and age].
Scalp-recorded somatosensory evoked potentials (SEP) to posterior tibial nerve stimulation were studied in healthy volunteers (27 males and 25 females) aged 15-67 years. Age alone was not correlated with SEP latencies, except for P 60 latency, but multiple regression analysis with two independent variables (height and age) showed that not only height but also age is a significant parameter in determining the optimal clinical limits for individual SEP latencies, and may increase the diagnostic sensitivity of absolute SEP latencies. There was no gender difference in the latencies of SEP in multiple correlation analysis involving height and age. A negative correlation tended to be found between height and age in adult subjects, although this is thought to be a characteristic of Japanese, it may show the necessity of renewing regression models at intervals of 5 or 10 years.
Adolescent↗
[Spontaneous rupture of the ureter caused by metastatic ureteric tumor: a case report].
Spontaneous rupture of the right upper ureter caused by metastatic ureteric tumor in an 80-year-old man is reported. He was admitted to our hospital with right lower abdominal pain. Ultrasonography showed mild right hydronephrosis and a low echogenicity mass under the right kidney. Drip infusion pyelography and abdominal computerized tomography showed extravasation of contrast medium around the right upper ureter. Retrograde pyelography was unsuccessful because of edema of the bladder wall. Right ureterocutaneostomy was performed under the diagnosis of spontaneous rupture of the right ureter. The right ureter was completely obstructed 3 cm below the point where it crossed the common iliac artery. At this site, the ureteric wall was hard, thickened, and adherent to the surrounding tissue. The lesion was a metastatic adenocarcinoma. The origin of the tumor could not be found, but pancreatic cancer was suspected on the basis of elevated CEA and PSTI levels. He died of peritonitis carcinomatosis at 8 months after surgery. Thirty three cases of spontaneous rupture of the ureter and 60 cases of metastatic ureteric tumor have been reported in Japan. However, our patient is the first reported case of spontaneous rupture of the ureter caused by a metastatic ureteric tumor in the Japanese literature.
Adenocarcinoma↗
[Surveillance of hyperlipidemia among young adults in an occupational setting].
This study was conducted to contribute to the improvement of occupational health surveillance. The subjects of the study were 461 young male workers born between April 1959 to March 1969, who worked at two plants in Tokyo, and who do not usually undergo examination of blood lipid levels at a routine health check-up program. The screening procedure was mainly based on the second report of the National Cholesterol Education Program Expert Panel (Adult Treatment Panel, ATP II). The proportion of the subjects with low HDL-cholesterol level (< 35 mg/dl) was 5.2% for workers in their late twenties (W20) and 8.4% for those in their early thirties (W30). For high LDL-cholesterol (130+ mg/dl), the proportion (underestimated due to non-fasting blood collection) was 7.2% for W20 and 13.5% for W30, and the difference was statistically significant (p < 0.05). Among subjects with low HDL, the proportion of subjects with total cholesterol (TC) being < 200 mg/dl was 94% (15/16) for W20 and 54% (7/13) for W30. This implies that it is difficult to detect subjects with low HDL from values for TC only especially among W20. Hence it is useful to examine HDL in combination with TC. Among subjects with TC being 200-239 mg/dl, the proportion (underestimated) of the subjects with high LDL was 40% for W20 and 26% for W30, and ATP II procedure would fail to incorporate most of them into a treatment program. Thus, accurate estimation of LDL is necessary for subjects with TC being 200+ mg/dl. Relationships of high HDL (60+ mg/dl) to exercise as well as low HDL to obesity (p < 0.05) were found among both age groups. The high prevalence of LDL and HDL abnormality found among the study subjects would imply that it is necessary to initiate evaluation of hyperlipidemia at younger ages and also ATP II procedure needs to be modified for proper surveillance.
Adult↗
[A case of acute myelogenous leukemia accompanied with myelofibrosis and megakaryocyte-like giant bizarre blasts].
A 45-year-old man was admitted with high fever and leukocytosis in August 1993. The diagnosis of acute myelogenous leukemia (AML; M2) was made on the basis of morphological, cytochemical and immunological characteristics of the blasts in the bone marrow. The induction therapy with BHAC, daunorubicin, 6-MP was unsuccessful in achieving remission; the bone marrow biopsy specimen revealed the proliferation of the remaining leukemic cells and massive fibrosis accompanied with unusual megakaryocyte-like giant bizarre cells. These megakaryocyte-like giant cells were positive for myeloperoxidase and CD34, but not GPIIIa and factor VIII, indicating that those were derived from myelogenous stem cells. Following the low-dose Ara-C therapy, improvement of fibrosis and disappearance of these giant cells were observed in the bone marrow. After the reinduction therapy with high-dose Ara-C and MIT against markedly increased blasts, the patient died of systemic fungal infection. The presence of myelofibrosis and giant atypical blasts might allow resistance to therapy and poor prognosis.
Antineoplastic Combined Chemotherapy Protocols↗
Pharmacological and physiological significance of ion channels and factors that modulate them in vascular tissues.
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Animals↗
Expression of G alpha i2 mimics several aspects of LPS priming in a murine macrophage-like cell line.
Priming of macrophages with low concentrations of lipopolysaccharide (LPS) enhances the ability of substances that act through heterotrimeric G proteins to stimulate immune cell functions. Although LPS-induced alterations in the expression and functions of G proteins of the alpha i family have been reported in hematopoietic cells, their effects on subsequent steps in LPS priming of macrophages have not been defined. To study the role of G alpha i2 in priming of macrophages by LPS, we expressed a mutant, activated form of alpha i2 (alpha i2Q205L) in P388D1 cells, and compared its effects on PAF-dependent C alpha signalling and arachidonic acid release to those in cells treated with LPS. In control P388D1 cells, treatment with LPS (100 ng/ml) for 1 hr increased the amount of alpha i2 protein 2-fold. Both LPS treatment and expression of alpha i2Q205L increased the rate of PAF-induced C alpha influx across the cell membrane and arachidonic acid release, although neither altered release of C alpha from intracellular stores by PAF. Expression of alpha i2Q205L is sufficient to mimic the effects of LPS on the PAF-induced C alpha i signal and enhanced arachidonic acid release. Consequently, although increasing the expression of alpha i2 may not be the sole mechanism by which LPS enhances signalling by PAF, increased alpha i2 expression can account for the alterations in PAF-induced C alpha i regulation, and arachidonic acid release in LPS-primed P388D1 cells.
Animals↗