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Biomedical subjects

H Hirakawa

Publications and source records attributed to H Hirakawa.

At least 19 recordsLinked to original sources

[Preparation of water-soluble hydronaphthoquinone derivatives and its application to the determination of hydrogen peroxide in clinical chemistry].

Several 1-alkoxy-2,3-dichloro-4-hydroxynaphthalene derivatives were prepared. These compounds were oxidized by hydrogen peroxide in the presence of a peroxidase to give 2,3-dichloro-1,4-naphthoquinone, which then reacted with various alkyl benzoylacetates to develop blue coloration with absorption maximum at greater than 600 nm. The color development reaction can be applied to the determination of appropriate serum constituents such as cholesterol.

Color

Establishment of an estrogen receptor-positive cell line (HMA-1) derived from human breast carcinoma.

We have established a novel human breast carcinoma cell line, HMA-1, derived from ascites of a female breast cancer patient. HMA-1 was shown to be an epithelial cell line with intracytoplasmic duct-like vacuoles, microvilli, desmosomes and tonofibrils in accordance with human breast cancer. The cell line demonstrated a good cell growth ability in monolayer fashion with a doubling time of 46 hr. Based on a whole cell binding assay the cell line contained estrogen receptor (1.45 x 10(-4) sites/cell). Tamoxifen, an anti-estrogen agent induced a dose-dependent decrease in the cell growth rate, but estradiol stimulated the cell growth. HMA-1 could be transplanted subcutaneously into BALB/c nude mice, and was able to cause tumors approximately two months after heteroinoculation. These results indicate that HMA-1 cell line may serve as a new human breast carcinoma cell line which could be utilized in the breast cancer research.

Adenocarcinoma

Effect of gentamicin intoxication on frog behavior.

Eighty micrograms of Gentamicin were injected into bull frogs' perilymphatic cistern for 3 days. Behavioral changes were evaluated together with morphology of the semicircular canal crista and the utricular macula. The behaviors evaluated were posture, walking, head stability, jumping and swimming. The earliest change of behavior was noticed one day after the last injection, and the changes tended to develop over the following 1 to 2 weeks. When the utricular macula was damaged, the frog tilted toward the damaged side. No tilting was observed when bilateral utricles were intact, or when bilateral utricles were equally damaged. Damage of the posterior (p.v.c.) and anterior vertical canal (a.v.c.) cristae resulted in instability of the head. Jumping ability also deteriorated when the p.v.c. and a.v.c. were damaged. These results indicate that p.v.c. and a.v.c. are involved in head stability and jumping function, while the utricle contributes to perception of gravity.

Animals

[The effect of organochlorine compounds on the induction of sister chromatid exchanges in cultured human lymphocytes].

In this study, first, we investigated the effect of 7,8-benzoflavone (ANF), mitomycin C (MMC), a well-known genotoxic compound, and ANF plus MMC on the induction of sister chromatid exchanges (SCEs) in human whole-blood cultures. Second, we examined the effect of mixture of organochlorine compounds, which very resembled their contamination of healthy people in its composition, on the induction of SCEs in the same blood culture system in order to clarify their genotoxicity as a whole. The following results were obtained. 1. ANF and MMC significantly enhanced the number of SCEs/cell at the concentrations of 4 x 10(-5) M and 10(-8)M, respectively. When both of the compounds were simultaneously added in the blood cultures, their effects on the induction of SCEs seemed to be additive. 2. Without ANF in the blood culture system, namely, an usual system of the SCEs experiment, we could not find a dose-response relationship between the concentration of the mixture of organochlorine compounds and the induction of SCEs/cell. With ANF, however, we observed a fairly good dose-response relationship between them. 3. In the whole-blood culture system with ANF, we found significantly great number of SCEs/cell at the level of twenty times higher concentration of the organochlorine compounds than the ordinary level. According to the results described above and of our other studies, 50% effective concentration (EC50, about 2 SCEs/cell higher than control SCEs/cell) of the mixture was considered to be about 5 times greater level over the general one.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzofurans

[Coplanar PCBs, PCDFs and PCDDs in the subcutaneous adipose tissue of Yusho patients and normal controls].

3,4,3',4'-tetrachlorobiphenyl (T4CB), 3,4,5,3',4'-pentachlorobiphenyl (P5CB) and 3,4,5,3',4',5'-hexachlorobiphenyl (H6CB) [Co-PCBs] in the subcutaneous adipose tissue of seven Yusho patients and eight normal controls were determined to assess the contribution in the risk caused by the Yusho causual agents (PCBs, PCDFs, PCDDs and Co-PCBs) by using high resolution gas chromatography/high resolution mass spectrometry in selected ion monitoring mode. 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of the Yusho patients at the levels, of 6 to 29 ppt, of 32 to 130 ppt and of 160 to 1,140 ppt, respectively. The TCDD-Eq (Equivalents) value calculated by TCDD-TEfs (Toxic Equivalent factors) was from 8 to 30 ppt. On the other hand, 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of normal controls at the levels, of 3 to 9 ppt, of 41 to 280 ppt and of 47 to 200 ppt, respectively. The TCDD-Eq value calculated by TCDD-TEfs was from 9 to 57 ppt. In the Yusho patients, the average TCDD-Eq value calculated by TCDD-TEfs of the residual Co-PCBs, PCDFs and PCDDs was 17, 491 and 24 ppt, respectively. Therefore, we concluded that the typical symptoms for the Yusho patients are caused mostly by PCDFs.

Adipose Tissue

[Therapeutic trial for promotion of fecal excretion of PCDFs and PCBs by the administration of cholestyramine in Yusho patients].

Any effective therapy for elimination of causal agents remaining in Yusho patients was not found until now. To know the profile of fecal excretion of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs), the amounts of PCDFs and PCBs in the stool of six Yusho patients with the typical symptoms were determined. The stool samples of Yusho patients were collected in 1989. PCDFs, i.e., 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PnCDF), 1,2,3,4,7,8- and 1,2,3,6,7,8-hexachlorodibenzofurans (HxCDFs), 1,2,3,4,6,7,8-heptachlorodibenzofuran (HpCDF) and octachlorodibenzofuran (OCDF) were detected in all of the samples. PCDFs found in the stool samples were mostly PnCDF and HxCDFs. Of PCDFs detected, PnCDF and HxCDFs contributed to 42 +/- 4.7% and 43 +/- 5.5% as mean +/- SE, respectively. The fecal excretion of PnCDF and HxCDFs in Yusho patients was 720 +/- 490 pg/day and 790 +/- 620 pg/day as mean +/- SE, respectively. On the other hand, the fecal excretion of PnCDF and HxCDFs in normal controls was 32 +/- 13 pg/day and 47 +/- 5.2 pg/day as mean +/- SE, respectively. The fecal excretion of PnCDF and HxCDFs in Yusho patients was about 23 times and 17 times each higher than that in normal controls. The fecal excretion of PCBs in Yusho patients and normal controls was 400 +/- 430 ng/day and 150 +/- 39 ng/day, respectively, as mean +/- SE. In order to promote the excretion of these toxic chemicals in the stool of Yusho patients, the patients were continuously administered with cholestyramine, an anion exchange resin, at a dose of 4 g, 3 times a day, for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzofurans

[Bone marrow transplantation for pediatric solid tumor].

Bone marrow transplantation permits the use of greatly intensified cytoreductive therapy for cancer. Since 1981, fifteen children with disseminated solid tumor were treated by this method (6 Nb1, 6 Lymphoma, 1 PNET, 1 Hb1, 1 YST.). Eight out of 15 (53%) have been alive and well 2-96 (median 45) months after BMT. Though toxicity is severe, high dose chemo-radiotherapy using BMT after reaching complete remission with well scheduled induction chemotherapy and surgery is concluded as a treatment of choice for pediatric malignant solid tumor in advanced stage.

Bone Marrow Transplantation

[Improved therapeutic effect of sequential immunotherapy with cyclophosphamide, large doses of OK-432 and recombinant interleukin-2 in breast cancer patients with disseminated metastatic liver tumors].

It has been generally agreed that the prognosis of widely spreaded "surgically unresectable" metastatic liver tumor originated from breast cancer is very poor. We reported here the result of clinical efficacy of sequential immunotherapy with intra-tumoral injection of large dose OK-432, after oral administration of cyclophosphamide during 7-10 days, and continuous perfusion of purified human recombinant interleukin-2 (rIL-2) from hepatic artery for the breast cancer patients with unresectable metastatic liver tumors. In all of 3 cases, metastatic liver tumor revealed overwhelming tumor reduction more than 50% of preoperative total tumor burden evaluated by computed tomography. Only 1 day after operation, large doses of OK-432 was injected intratumorally, both activity of Natural Killer (NK) cells and lymphokine activated killer (LAK) cells in peripheral blood lymphocytes were 5-20 folds augmented in all clinical trials. Serum tumor markers, i.e., Carcinoembryonic Antigen (CEA) and CA15-3, were rapidly decreased in all cases, respectively. Our clinical data indicate that intratumoral injection of large dose OK-432 and continuous administration of rIL-2 via hepatic artery, pretreated with cyclophosphamide, were clinically effective immunotherapy for reduction of metastatic liver tumor.

Administration, Oral

Interaction of excitatory and inhibitory stimuli on the action potential of the semicircular canal in the frog.

The posterior semicircular canal of the frog was sinusoidally stimulated by mechanical endolympathic flow. Interaction of the excitatory and the inhibitory responses was analyzed on the spike density histogram. When the oscillation started in ampullofugal direction, the evoked action potentials were readily suppressed by the following ampullopetal stimulus. When the oscillation started in ampullopetal direction, the action potential appeared slowly, indicating that the inhibitory response has a longer time course than the excitatory response.

Action Potentials

[An experimental study on the inhibitory response of the frog semicircular canal nerve].

The inhibitory response of the posterior semicircular canal (p.s.c.) ampullary nerve was studied in comparison with the excitatory response. The isolated p.s.c. of the bull frog was stimulated by the mechanical endolymphatic flow toward either the ampullofugal (AF, excitatory) or the ampullopetal (AP, inhibitory) direction. Three experiments were performed. 1) Experiment I: The influence of the endolymphatic K+ concentration. In both the high (50mM) and the low (2.5mM) K+ environment, the inhibitory response was smaller than the excitatory response. This was more pronounced in the low K+ environment. 2) Experiment II: The influence of the initial position of the cupula. The magnitudes of the responses when the cupula was moved from various positions were compared. When the same amount of stimulus was given in the same direction, the responses were equal regardless of the initial position of the cupula. The inhibitory response yielded a time constant approximately 2-3 times as long as the excitatory response. 3) Experiment III: The interaction of the AF and the AP stimulus. The influence of the inhibitory response upon the following excitatory response and vice versa, were studied by changing the timing of the stimulus onset. Both the action potential and the DC potential were recorded for comparison. The AP stimulus which immediately followed the AF stimulus suppressed the action potential and the negative DC potential was observed. On the other hand the AF stimulus which immediately followed the AP stimulus gave rise to the distinct positive DC potential but the action potential could hardly be evoked. That AF stimulus resulted in different responses between the action potential and the DC potential indicates that the DC potential recorded in this study is possibly a generator potential.

Action Potentials

Pathological studies and pathological principles on the management of extension injuries of the cervical spine.

Extension injury to the arthritic spine of elderly individuals involves rupture of the anterior longitudinal ligaments and disks at several levels, but no bony injury can be observed on X-ray. There are many small focal haemorrhages in the central portion of the spinal cord and the injury is often accompanied by incomplete paresis. As the injury is a stable injury with the posterior ligament complex being intact, it is only necessary to immobilise the cervical spine conservatively. Laminectomy is not indicated. In hyperextension injury of the rigid cervical spine and in momentary posterior dislocation observed in middle aged individuals, rupture of the anterior longitudinal ligament and disk is observed at a single site, but being spontaneously reduced, traumatic findings cannot be observed on X-ray. The spinal cord is crushed at the site of injury to bring about severe neural damage. When this type of injury is diagnosed or suspected, further damage may be inflicted on the spinal cord if skull traction is made with calipers in the extended position and the condition at the time of injury is reproduced. Therefore, the patient should be nursed in a shell or between sandbags in a neutral position or even in a position of slight flexion. In extension fracture dislocation with compression which resembles on X-ray a flexion injury, all of the three columns of the spine are destroyed to bring about an extremely unstable condition. As the spinal cord is extensively injured to involve several segments, decompression surgery for relief of neuroparalysis should not be performed when complete paralysis develops simultaneously with fracture dislocation. Therefore, it should be first treated conservatively with skull traction, and in cases where stability cannot be restored, surgical fixation of the spine should be performed.

Arthritis

Thoracolumbar fracture dislocation: a study of 30 patients.

Open reduction and wiring of the spinous processes were carried out in patients with a thoracolumbar fracture dislocation. Clinical and X-ray examinations were performed on 30 patients 5 or more years following operation. At the time of the initial examination, an anterior angulation of 30 degrees or more was noted in 18 patients, but only in 4 cases at the time of the follow-up examination. Anterior displacement of the vertebral bodies was seen in 30 patients, but it was found to be normal in 26 patients at the time of follow-up. There were 7 patients with lateral angulation of 5 degrees or more, but only 2 patients at the time of follow-up. Lateral displacement of 5 mm or more was observed in 10 patients, but only 3 patients could be seen at the time of follow-up. In comparison with spinal instrumentation with the use of large long metallic materials, wiring of the spinous processes has several advantages such as limited surgical invasion, firm fixation, no effect on spinal mobility and no need for repeat surgery for removal of metallic materials. It is an adequate alternative method for the internal fixation of rotational fracture dislocations of the thoracolumbar region of the spine, without fracture of the posterior wall of the vertebral body and pedicle fracture.

Adult

Five cases of ectopic liver and a case of accessory lobe of the liver.

Five cases of ectopic liver, two of retro-peritoneal cavity and three of gallbladder, and a case of accessory lobe of the liver, are reported. One of these cases with ectopic liver was accompanied by multiple cysts of the liver and kidney, and biliary microhamartoma, which was observed laparoscopically on the surface of the main liver and histologically proven in the ectopic liver.

Adult

Pancreatic biopsy under visual control in conjunction with laparoscopy for diagnosis of pancreatic cancer.

Two cases of histologically confirmed pancreatic cancer are reported. Histological diagnosis was obtained after pancreatic biopsy was carried out under visual control in conjunction with laparoscopy using pancreatic biopsy forceps designed by us. In Case 1, localized swelling of the pancreas was observed on abdominal ultrasonography (US) and computer tomography (CT) scan, and interruption of the main pancreatic duct was demonstrated by endoscopic retrograde cholangiopancreatography (ERCP). In Case 2, a pancreatic tumor was detected by abdominal US and CT scan, but ERCP findings were only those of chronic pancreatitis.

Adenocarcinoma

Laparoscopic observation of hepatic lobe atrophy.

From the standpoint of diagnostic laparoscopy, the frequency and etiological aspect of atrophy of a lobe of the liver was studied. The frequency of hepatic lobe atrophy was 5.3% among 1,208 laparoscopy cases at our department. Lobe atrophy of the liver can be seen not only in congenital anomaly, atrophic cirrhosis and malformation, as described in the OMED database of digestive endoscopy, but also in some other kinds of liver diseases including chronic hepatitis, idiopathic portal hypertension, primary biliary cirrhosis, drug-induced liver injury, scarred liver, autoimmune hepatitis and also in malignancies of other visceral organs. The disorders most frequently associated with hepatic lobe atrophy were idiopathic portal hypertension, and scarred liver, primary biliary cirrhosis, etc.

Atrophy

Structural and physiological change of the bullfrog semicircular canal due to gentamicin intoxication.

The effect of Gentamicin (GM) on the vestibular organ was studied using bullfrogs. The ototoxicity was compared among 3 different ways of administration, i.e., intraperitoneal (IP), intramuscular (IM) and intralabyrinthine (IL) injections. Morphological change of the posterior canal crista was observed by SEM. The posterior canal ampullary nerve action potentials (AP) were recorded, and were compared with SEM findings of the sensory epithelia. Morphological and physiological changes were severe in the order of IL greater than IM greater than IP. Morphological and physiological changes developed as the postinjection time elapsed. Morphological damage started at the narrow portion of the crista and developed towards the center and finally towards the periphery. Physiological change was already observed before the morphological damage. Physiological change tended to correlate with the morphological damage.

Action Potentials

[Reduction of 5-FU toxicity with improved nutritional status in tumor bearing mice].

This study was performed to determine the role of nutritional status as a determinants of 5 fluorouracil (5-FU) toxicity in a tumor bearing mice. After subcutaneous inoculation, of mammary tumor (81 B) mice were assigned randomly to two nutritional regimens, (1) 8% casein: D-mice, (2) 27% casein: N-mice. Mortality was increased significantly in D-mice (100%) compared with N-mice (0%) by administration of 5-FU (20 mg/kg). Intratumoral 5-FU concentration of D-mice was significantly lower than that of N-mice, 1 hour after i.p injection of 5-FU (100 mg/kg, 300 mg/kg). Both growth rate and intratumoral protein content of transplanted tumor was equivalent in two dietary group, N-mice and D-mice. Protein depleted status was associated with a significant reduction in Interferon production of spleen cells. Inhibition of cell proliferation in bone marrow and cytokine production were recognized in hypo-nutritional status. Thus, improved nutritional status reduced the morbidity and mortality associated with 5-FU treatment in tumor bearing mice.

Animals