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Biomedical subjects

K Akagi

Publications and source records attributed to K Akagi.

At least 55 records · Page 3Linked to original sources
PubMed1998

[A single dose toxicity study of magnesium sulfate in rats and dogs].

A single dose toxicity study of magnesium sulfate by intravenous administration was conducted in rats and dogs. The results are summarized in the following. Magnesium sulfate was administered once at dose levels of 90, 130, 200, 300 and 450 mg/kg to Crj:CD(SD) rats at 6 weeks of age. Deaths occurred in the 200 mg/kg and above groups in both sexes. The LD50 values were 206 mg/kg for males and 174 mg/kg for females. In the surviving animals, in the 130 mg/kg and above groups, tonic convulsions, abnormal gait and tachypnea were seen. However, these signs disappeared gradually and all animals returned to a normal state by 15 min after dosing. There were no treatment-related changes in the body weight or gross pathology. Magnesium sulfate was infused for 6 hr at dose levels of 75, 300 and 1200 mg/kg (12.5, 50 and 200 mg/kg/hr) to female beagle dogs at 6 months of age. No deaths were observed in any of the dose groups and it was considered that the lethal dose level would be higher than 1200 mg/kg(200 mg/kg/hr). In the 1200 mg/kg group, vomiting, decreased spontaneous movement, staggering gait, prone position and flush of the conjunctiva and ear auricles were seen. However, these signs disappeared gradually and animals returned to a normal state by 1 hr after dosing. There were no treatment-related changes in the body weight, food consumption or gross pathology.

Animals↗
PubMed1998

[A 2-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs followed by 2-week recovery period].

A 2-week toxicity study of magnesium sulfate administered by a 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50, 100 and 200 mg/kg/hr in female beagle dogs was conducted, with 2-week follow-up observation after drug withdrawal. One of 2 animals in the 200 mg/kg/hr group died approx. 32 hr after the start of infusion. At the same time, the remaining 1 animal of the same group was sacrificed in a moribund state. Changes attributable to the treatment of magnesium sulfate were decreased food consumption and body weight gain, anemia, mild prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the animals treated with 100 mg/kg/hr. Furthermore, decreased calcium level was recorded in the animals treated with 50 mg/kg/hr or more. However, these changes disappeared after drug withdrawal, and reversibility was suggested. Judging from the mode of occurrence, since the change in calcium level observed in the group treated with 50 mg/kg/hr was slight, it was considered to be toxicologically insignificant. In conclusion, the nontoxic dosage level of magnesium sulfate was judged to be 50 mg/kg/hr under the condition of the present study.

Anemia↗
PubMed1998

[A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion in beagle dogs].

A 4-week toxicity study of magnesium sulfate administered by 24-hr intravenous infusion at the dosage levels of 0, 12.5, 50 and 100 mg/kg/hr in female beagle dogs was conducted. No death occurred in any group. Changes attributable to the treatment with magnesium sulfate were decreased food consumption and body weight gain, anemic change, increased urine volume, decreased serum calcium level, increased inorganic phosphorus level, slight prolongation of conduction time in electrocardiogram and tubular basophilia in the kidneys in the group treated with 100 mg/kg/hr. In addition, essentially similar changes were also observed at the same dosage level in the 2-week study of this drug, in which recoverability was recognized with 2-week follow-up observation after drug withdrawal. In conclusion, the nontoxic dosage level was judged to be 50 mg/kg/hr under the condition of the present study.

Anemia↗
PubMed1998

Analysis of cell kinetics after gamma-ray irradiation using an anti-BrdU monoclonal antibody.

The cell cycle was analyzed using double staining with an anti-bromodeoxyuridine (BrdU) monoclonal antibody and propidium iodide (PI). Changes in cell kinetics after irradiation were compared with those seen by the conventional PI-based DNA histogram method. The effect of irradiation on cell kinetics has been studied primarily by counting G2-arrested cells. By the present BrdU method, a rapid transition from G1 to S-phase was observed within 2 h of irradiation, followed by G1 block. Cells in the S-phase progressed to G2+M where they arrested, resulting in a decreased percentage of S cells (<5%). Release of G1 block occurred after 8 h, and G2+M cells returned to G1 after >18 h. The initial G1 arrest induced by irradiation was confirmed for the first time by the present BrdU-PI double staining.

Antibodies, Monoclonal↗
PubMed1998

Cell kinetic changes in cultured tumor cells after treatment with radiation and chemotherapy.

Flow cytometry instantaneously determines the percentages of cells in various cell cycle phases to rapidly evaluate effects of irradiation and anti-cancer drugs. We studied these using growth curve analysis and 5-bromodeoxyuridine propidium iodine (BrdU)-(PI) double staining. With conventional DNA histogram methods, determination of S phase fraction was difficult because of overlapping DNA content between G1 and early S phases and between late S and G2 phases. Double staining directly differentiated G1, S, and G2 + M phases. By double staining, rapid transition from G1 to S occurred within 4 h after irradiation or after the drug treatments, and initial G1 arrest induced by irradiation was confirmed for the first time.

Antineoplastic Agents↗
PubMed1998

[Analysis of tumor vascular density using the window chamber technique].

Vascular structure is indispensable for a tumor to maintain its growth. The structure also affects drug delivery over chemotherapy, and oxygen tension in the tissue during irradiation. Therefore, measuring the vascular density in the tumor will help to reach an expected level or to evaluate the effect of those therapies. Through previous observation, changes in vascular structure, like the vascular density, have been reported. However, the tissue was usually removed from the deceased animal and examined in the microscope. Not many studies have shown changes in one and the same animal's tissue. In this study, we used the dorsal flap window chamber technique, and observed changes in the development of vascular structure and vascular density in a tumor. Window chambers were attached to the backs of 3 rats, and they anesthetized every 24 hours for microscopic observation. Vascular growth in the tumor started 8 to 9 days after implantation. Their average vascular density was about 25%, and this ratio continued till necrosis started in the tumor. "Necrosis occurs in a tumor because its growth is so rapid that the vascular development can not maintain the same speed." This has been a kind of established theory. During observation, we recognized blood stagnation in vessels as the tumor grew, and the relationship between tumor size and its vascular density was significant (r = 0.926). Our data lead us to another conclusion that "Vascular growth is as fast as tumor growth, keeping a ratio of about 25%, but necrosis is caused by deficiency of blood flow circulation."

Animals↗
PubMed1998

[Prognosis of residual spleen after partial splenic embolization for the treatment of hypersplenism in cirrhosis].

The aim of this study was to elusidate the change in residual spleen volume after partial splenic embolization (PSE) in 43 cirrhotic patients with marked hypersplenism. Residual spleen volume was indicated as the rate (%) of residual spleen to initial spleen before PSE. Furthermore, the platelet count after PSE was observed in 23 patients followed up for 2 years. Residual spleen volume in patients with infarction rates of more than 80% (group A) had been maintained within 20 % even after 2 years, while they had obviously increased during the early stage after PSE in patients with infarction rates under 80% (group B), especially in patients with lower infarction rates (under 60%). Mean platelet count improved significantly in both groups after PSE (p < 0.001, respectively), but increased more in group A than in group B (p < 0.01). High fever and abdominal pain were observed in all cases of PSE. Other adverse effects such as pleural effusion and ascites that were frequent in group A were transient. These results suggest that PSE performed with a high infarction rate of the spleen provides effective, long-lasting results in the treatment of hypersplenism in cirrhosis.

Embolization, Therapeutic↗
PubMed1998

[A case of traumatic subacute subdural hematoma presenting symptoms arising from cerebral hemispheric edema].

Traumatic subacute subdural hematoma is a condition in which the major symptoms affecting prognosis most appear in the subacute stage after head trauma, while traumatic acute subdural hematoma is treated conservatively when the symptoms are mild. The cause of the major symptoms occurring in the subacute stage is mostly expansion of the subdural hematoma volume. The authors report a case of traumatic subacute subdural hematoma in which the cause of the major symptoms was cerebral hemispheric edema instead of expansion of the subdural hematoma volume. To our knowledge, only one similar case to the present case has been previously reported. A 44-year-old female fell from the stairs on July 21, 1995 and was suffering from headache. On July 23, she was admitted to our hospital because of generalized convulsion. On admission, she was drowsy but showed no convulsion. Head CT showed an acute subdural hematoma on the right side with a slight midline shift and no other abnormalities. She was treated conservatively because of the mildness of the symptoms and two days later became alert with no symptoms. Thereafter she only complained of occasional headache which was controlled with medicine. On August 3, she suddenly fell into coma. Head CT showed severe cerebral hemispheric edema on the right side without change of the subdural hematoma size. Emergency cerebral angiography showed no definitive abnormalities such as occlusion of the arteries or of the venous sinuses. Craniotomy associated with external decompression was performed. The hematoma was composed of red-brown jelly accompanied with some liquid component and had a thin black-brown outer membrane. While removing the hematoma, bleeding from a vein on the cerebral surface around the sylvian fissure was observed and this location was suspected to be the sources of the bleeding point. Postoperatively, she received steroid and barbiturate therapy associated with moderate hypothermia under hyperventilation. She tolerated this treatment well and left the hospital, on September 26, 1995 with only diplopia during downward gaze. Although the mechanisms of the cerebral hemispheric edema occurring in the subacute stage was unclear, a failure in the cerebral venous circulation arising from compression to the bridging veins, which may be hypoplastic, by the subdural hematoma was suspected to have been the cause.

Adult↗
PubMed1998

Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features.

We investigated the presence of K-ras gene mutation in plasma DNA and assessed its clinical value in patients with pancreatic adenocarcinoma. Mutations in codon 12 of the K-ras gene were examined by mutant allele-specific amplification method using DNA extracted from surgical specimens and plasma samples of 21 patients with pancreatic adenocarcinoma. K-ras gene mutation was detected in 15 of 21 (71%) primary tumors. In 9 of 15 (60%) patients with K-ras gene mutation-positive tumors, an identical mutation was detected in the plasma DNA. None of four patients with chronic pancreatitis or five healthy subjects had such mutations in plasma DNA. Tumors positive for K-ras gene mutation in plasma DNA were significantly larger (P = 0.04) and less likely to result in a curative cure after surgical resection (P = 0.09) than those negative for the mutation. Other clinicopathological features, including age, sex, histological type, mode of invasion, and metastasis, did not correlate with K-ras gene mutations in plasma DNA. Treatment resulted in disappearance of K-ras gene mutations in plasma DNA in six of nine (67%) patients. Three patients with a persistently positive K-ras gene mutation in pre- and post-treatment plasma samples were likely to show early recurrence or have a progressive disease. Our findings suggest that K-ras gene mutation can be detected in plasma DNA of patients with pancreatic adenocarcinoma. Detection of K-ras mutations in plasma may be clinically useful for evaluating tumor burden and efficacy of treatment.

Adenocarcinoma↗
PubMed1998

Effect of hyperthermia on transmembrane potential of HeLa cells--a flow cytometric analysis.

The effect of hyperthermia on transmembrane potential was studied in HeLa cells in vitro using a 3',3'-dipentyl oxacarbocyanine [Di-0-C5(3)], a lipophilic cation probe that equilibrates across the plasma membrane according to the transmembrane potential. Uptake of the fluorescent probe was measured by flow cytometry. The flourescent intensity (FI) increased with increase in temperature, and the increase was statistically significant when the duration of heat treatment was 30 minutes or more. At each temperature studied the depolarization was higher after longer duration of heat treatment (p value: 41 degrees C < 0.05; 42 degrees C < 0.005; 43 degrees C < 0.001 and 44 degrees C < 0.001, respectively). The lack of significant depolarization after shorter duration of heating, particularly at lower temperatures could be due to the repair of membrane damage that could have occurred in the holding interval between heating and measurement. The results suggest that depolarization of membrane potential, i.e. increase in the intracellular cation concentration, can be considered as an indicator of cell injury by hyperthermia and may be mechanistically related to cell death by heat treatment. The technique may be suitable for studying repair of damage after hyperthermia.

Flow Cytometry↗
PubMed1998

[Effect on hepatic function of hepatic artery infusion chemotherapy using epirubicin and mitoxantrone for advanced hepatocellular carcinoma].

This study was designed to assess the effect of hepatic dysfunction from hepatic artery infusion (HAI) in advanced hepatocellular carcinoma (HCC). The patients were randomly assigned to receive epirubicin (n = 12, Epi group) or mitoxantrone (n = 14, Mito group) once every 4 weeks between 1992 and 1996. HCC patients were given 6-8 mg of mitoxantrone or 30-40 mg epirubicin. There was hepatic dysfunction in 27 patients after HAI, showing similarly elevated GOT, GPT, and total bilirubin. In the Epi group, the GOT value was slightly higher than in the Mito group, but it was not significant. After HAI chemotherapy, the GOT value showed a more than two-fold elevation. Six patients in the Epi group and 2 in the Mito group showed a significant difference. Our results indicated that mitoxantrone had less impact on hepatic function following HAI therapy.

Antibiotics, Antineoplastic↗
PubMed1997

Cre-mediated somatic site-specific recombination in mice.

Conditional mutant mice equipped with heterologous recombination systems (Cre/lox or Flp/frt) are promising for studying tissue-specific gene function and for designing better models of human diseases. The utility of these mice depends on the cell target specificity, on the efficiency and on the control over timing of gene (in)activation. We have explored the utility of adenoviral vectors and transgenic mice expressing Cre under the control of tissue-specific promoters to achieve Cre/lox-mediated somatic recombination of the LacZ reporter gene, using a newly generated flox LacZ mouse strain. When adeno Cre viruses were administered via different routes, recombination and expression of LacZ was detected in a wide range of tissues. Whereas in liverbeta-galactosidase activity was quickly lost by turnover of expressing cells, even though the recombined allele was retained,beta-galactosidase in other tissues persisted for many months. Our data indicate that the flox LacZ transgenic line can be utilized effectively to monitor the level and functionality of Cre protein produced upon infection with adeno Cre virus or upon crossbreeding with different Cre transgenic lines.

Actins↗
PubMed1997

Development of computer assisted orthosis design and manufacturing system for malformed ears.

Most cases of malformed ears in neonates can be treated by mounting a suitably shaped orthosis. Our objective was to develop a computer-assisted orthosis design and manufacturing system for the treatment of malformed ears. Also, we aimed to manufacture a first experimental orthosis made of nitinol shape-memory alloy wire. First, the target posttherapeutic auricular shape is input from computed tomography scans, and characteristic points and contours are extracted. The shape of the orthosis is then created by tracing the necessary contours automatically. Finally, the orthosis shape data are projected onto one or more approximate planes and autoconverted into numerical control (NC) data for plate groove processing. The nitinol shape-memory alloy wires are inserted in the groove and the shape is memorized by heat treatment. The shape of the manufactured orthosis can be memorized from the generated NC data within 1.0 mm of error. Stahl's ear in a 9-month-old baby was treated 7 months ago by mounting the orthosis manufactured by the system. The developed system allows the design and manufacture of orthoses made of nitinol shape-memory alloy wire for the treatment of malformed ears.

Alloys↗
PubMed1997

Calcium oscillations in single cultured Chinese hamster ovary cells stably transfected with a cloned human cholecystokinin (CCK)B receptor.

In Chinese hamster ovary cells stably expressing the cloned human cholecystokinin (CCK)B/ gastrin receptor, cholecystokinin octapeptide (CCK-8) evoked increases in [Ca2+]i monitored by digitized video imaging of fura-2 fluorescence ratios. At concentrations around 10 pM, CCK-8 elicited [Ca2+]i oscillations, which were blocked by elimination of extracellular Ca2+, by a phospholipase C inhibitor, U-73122, by a protein kinase C inhibitor, H7, as well as by phospholipase A2 (PLA2) inhibitors, ONO-RS-082 and aristolochic acid. At higher concentrations, CCK-8 induced a single biphasic [Ca2+]i rise consisting of a large peak followed by a lower sustained plateau, while the response turned into [Ca2+]i oscillation when the extracellular Ca2+ was eliminated or a PLA2 inhibitor was included. CCK-8 stimulated the release of arachidonic acid, and this was inhibited by aristolochic acid. Arachidonic acid caused an increase in [Ca2+]i which was dependent upon extracellular Ca2+. These results suggest that the activation of PLA2 might be involved, at least in part, in the Ca2+ influx that maintains the sustained plateau phase of [Ca2+]i as well as the [Ca2+]i oscillation when CCKB receptors are stimulated.

Animals↗
PubMed1997

Hypothalamic pilocytic astrocytoma presenting with intratumoral and subarachnoid hemorrhage.

A 45-year-old male presented with sudden onset of severe headache. Computed tomography and magnetic resonance imaging demonstrated an irregularly enhanced suprasellar mass with intratumoral and subarachnoid hemorrhage. The mass was removed in two operations. Histological examination of the tumor revealed pilocytic astrocytoma. The relatively rich vascularity and perivascular tumor cell proliferation observed in this benign lesion were probably the causes of this extremely rare association.

Astrocytoma↗
PubMed1997

Fatty liver in a case with heterozygous familial hypobetalipoproteinemia.

We herein present a case of fatty liver in a patient with heterozygous familial hypobetalipoproteinemia. A 34-yr-old male presented with abnormally elevated levels of transaminases and a fatty liver. He was asymptomatic, and the physical examination showed nothing remarkable. The serum total cholesterol, triglyceride, LDL-cholesterol, and apolipoprotein B levels all ranged from low normal to one-half normal. His other laboratory data were all in the normal range. The patient's body mass index measured was 25.7 kg/m2, and he did not demonstrate obesity. He had no history of alcohol consumption. It was thus thought that the fatty liver in this case might be associated with heterozygous hypobetalipoproteinemia. Heterozygous hypobetalipoproteinemia with a bright liver by ultrasound was also found in several of the patient's family members. Based on these rare findings, heterozygous hypobetalipoproteinemia should thus be considered as a possible cause in patients presenting with an unexplained fatty liver.

Adult↗
PubMed1997

[Partial splenic embolization for the treatment of liver cirrhosis with hypersplenism: assessment of clinical response and liver function].

We have evaluated the efficacy of partial splenic embolization (SE) in the treatment in 10 cirrhotic patients with marked hypersplenism. The mean infarction rate of the spleen was 84%. The change of spleen size, peripheral blood cell counts and liver function tests after SE were investigated during 3 years, and also 10 cirrhotic patients without SE were followed as control. The residual spleens after SE did not enlarged except 1 case with 65% infarction rate of the spleen. In these cases, the SE led not only to a sustained increase in both platelet and white blood cell counts but also to a significant improvement of hepatic function tests (hepaplastin test, total cholesterol and albumin) during observation period. On the other hand, these parameters tended to decrease in control patients without SE. This study suggests that SE performed with a high infarction rate of spleen is an useful therapy for hypersplenism in cirrhosis.

Adult↗