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Biomedical subjects

T Morimoto

Publications and source records attributed to T Morimoto.

At least 343 records · Page 19Linked to original sources

A simple biochemical approach to quantitate rough endoplasmic reticulum.

In this report we demonstrate that the changes in size of the rough endoplasmic reticulum (RER) can be determined by quantifying the membrane-bound ribosomal population separated by cell fractionation and sucrose density gradient analysis. Total cell membranes, rather than microsomes, were used as the source of membrane-bound ribosomes to eliminate potential losses during the preparation of microsomes. Bound ribosomes were assayed after quantitative release and recovery from total cell membranes using puromycin in the presence of high-salt buffer. Using this analysis, we demonstrate a 4.2-fold increase in RER in estrogen-treated male Xenopus laevis liver. Furthermore, we show that the ratio of the distribution of free to membrane-bound ribosomes in a nonsecretory cell line (HeLa) was 3.3, while this ratio in a secretory cell line (AR42J) was 1.2, indicating that cells active in secretion contain more RER. We suggest that this biochemical technique provides a simpler assay to detect changes in the size of the RER.

Animals↗

Relationship between atrial natriuretic peptide and plasma volume during graded exercise with water immersion.

To assess the relationship between atrial natriuretic peptide (ANP) and the reduction in plasma volume (PV) during exercise, we measured changes in PV and ANP in seven male volunteers during treadmill exercise in air (AE) and with water immersion (WE) together with time control studies of rest in air and in water. Blood samples were collected from a catheter in the antecubital vein at exercise intensities of 32, 49, 65, and 78% of peak oxygen consumption (VO2). Plasma ANP in AE increased significantly from the resting value [15 +/- 1 (SE) pg/ml] only at 78% of peak VO2 (29 +/- 5 pg/ml), whereas ANP in WE increased significantly at exercise levels of > 49% of peak VO2 and reached 68 +/- 9 pg/ml at 78% of peak VO2. Although PV in AE and WE decreased significantly with VO2 of > 49% of peak VO2 (P < 0.01), the decrease from the resting value in WE was significantly greater than that in AE of > 65% of peak VO2 (P < 0.01) and the decreases at 78% of peak VO2 were -9.7 +/- 0.8 and -6.1 +/- 1.7%, respectively. The difference in the decrease in PV between AE and WE at corresponding VO2 correlated strongly with that in the increase in ANP (r = -0.97; P < 0.01). These results are consistent with the hypothesis that ANP may be involved in the fluid shift from the intra- to extravascular space during exercise.

Adult↗

Effect of growth hormone on hepatic energy metabolism in normal rabbit liver.

Growth hormone (GH), which is well known as an anabolic agent in systemic protein metabolism but has catabolic effects on the carbohydrate metabolism in the liver, was administered to normal rabbit to investigate its effects on the hepatic energy metabolism. The changes in arterial ketone body ratio (AKBR: acetoacetate/3-hydroxybutyrate), which reflects the hepatic mitochondrial redox state ([NAD+]/[NADH]), after GH injection was studied as an indicator of the hepatic energy metabolism. GH was administered to normal rabbit at the doses of 50 micrograms/kg (GH-50 group), 100 micrograms/kg (GH-100 group) and 200 micrograms/kg (GH-200 group) by intravenous bolus injection. In the GH-50, GH-100 and GH-200 groups, AKBR decreased significantly from 1.40 +/- 0.09 to 0.94 +/- 0.05, from 1.19 +/- 0.11 to 0.83 +/- 0.14, and from 1.19 +/- 0.08 to 0.71 +/- 0.15 at 90 min, respectively. The energy charge of the liver decreased significantly 90 min after 200 micrograms/kg GH injection from 0.872 +/- 0.003 to 0.836 +/- 0.012 (p < 0.05). These results suggest that GH is associated with the deterioration of the hepatic energy metabolism, and that the administration of GH should be carefully weighed up in cases of damaged liver.

Animals↗

Rapid determination of the membrane potential of mitochondria in small biopsy specimens of the liver.

In liver transplantation, graft viability is ideally to be determined before implantation. Integrity of mitochondria may be a prerequisite to a viable graft. A new method is presented, which allows for the determination of the membrane potential of mitochondria (MPM; mV) in state 4 respiration within 50 min in 40-mg specimens, employing rhodamine 123 as a probe. Normal control showed a MPM of 239.2 mV. Storage in saline at 37 degrees C yielded an impaired MPM of 153.5 mV within 3 h. The cold storage at 1 degree C could preserve MPM at quasi-normal after 3 h but reduced it significantly after 24 h to 222.2 mV in saline (p < 0.005 vs. control) and 231.0 mV in UW solution (p < 0.05 vs. control): the difference between the 24-hour values was significant (p < 0.05).

Animals↗

Allopurinol effects in rat liver transplantation on recovery of energy metabolism and free radical-induced damage.

Rat livers were orthotopically transplanted after 90-min cold ischemia (group 1) or after 20-min warm and 70-min cold ischemia without (group 2) or with (group 3) allopurinol treatment (AT) (50 mg/kg i.v. 10 min prior to warm ischemia into the donor, flush perfusates with 1 mmol/l). Recovery processes were followed up for 60 min of reperfusion. Liver tissue levels of ATP and total adenine nucleotides were restored in group 1 to almost preischemic ranges within 15-30 min, remained significantly reduced by 30 and 20%, respectively, in group 2, and recovered with AT within 60 min in group 3 to almost the same extent as in group 1. A massive increase in the tissue malondialdehyde concentration, indicative of lipid peroxidation, occurred in the beginning of reperfusion of warm-ischemically damaged donor livers, which in group 3 with AT tended to be less pronounced than in group 2 without AT. The GSSG/GSH ratio reflecting intracellular oxidant stress averaged 3.3 x 10(-3) in group 1 between 15 and 60 min reperfusion. In group 3 AT resulted in comparably low values averaging 3.8 x 10(-3), while in warm-ischemically damaged livers without AT of group 2 this ratio was significantly and continuously elevated averaging 5.8 x 10(-3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

The effect of thyroid hormone treatment on the gene expression and enzyme activity of rat liver sodium-potassium dependent adenosine triphosphatase.

The effects of thyroid hormone (T3) treatment on liver Na,K-adenosine triphosphatase (Na,K-ATPase) at the levels of subunit messenger RNA (mRNA), enzymatic activity, and enzyme content were studied in euthyroid rats injected for 5 consecutive days with T3. Northern and slot blot analyses of polyadenylated mRNA revealed that T3 treatment coordinately increases the level of mRNA encoding the alpha 1- and beta 1-subunits, approximately 4- and 3-fold, respectively, above basal levels. To determine whether this increase in the subunit mRNA consequently results in an increase in the synthesis of the enzyme, a modified liver cell fractionation procedure was developed, and the subcellular fractions from control and T3-treated livers were examined biochemically. Western blot analysis and Na,K-ATPase assay demonstrated that T3 treatment resulted in a 2-fold increase in both the amount and activity of the enzyme. Furthermore, the Western blot analysis of endoglycosidase-H-treated membrane fractions revealed an increase in the amount of the precursor beta-subunit in the T3-treated liver rough microsomal fraction, suggesting that an increase in subunit synthesis contributes at least partially to the increase in the rat liver Na,K-ATPase by T3 treatment.

Animals↗

Effects of neuromedins and related peptides on the body temperature of rats.

Neuromedin B (NMB) and neuromedin C (NMC) are peptides found in the mammalian central nervous system, and their concentrations are particularly high in the hypothalamus. The amino acid sequences of these peptides are similar to that of bombesin, which is known to induce marked hypothermia not only in amphibians but also in mammals. The effect of neuromedins and related peptides on the body temperature regulation was examined in the rat under a thermoneutral environment. The findings indicated that NMC caused moderate hypothermia following intracerebroventricular administration, while the effect of NMB was meager, suggesting that these two neuropeptides possess different physiological functions in the brain.

Amino Acid Sequence↗

A simple construction of dual-slit red cell velocimeter.

A simple method of building a dual-slit red cell velocimeter is introduced. The basis of this technique is to utilize the body of a 35-mm photomicrography camera as the photometric device, exactly centering a pair of highly sensitive photodiodes on the film plane of the camera. By this arrangement, the microvascular image can be accurately focused on the sensing windows of the photodiodes. Because this velocimeter is not based on videophotometry, it was possible to measure red cell velocity up to 30 mm/s in the benchmark test. The maximum red cell velocity actually measured in the rat mesenteric microvessels (6.0 to 48 microns in diam) was 9 mm/s.

Blood Flow Velocity↗

Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs.

A novel ethylcellulose (EC) capsule which releases drug with a time-controlled fashion has been prepared. This capsule is composed of four parts, drug container, swellable substance, capsule body and cap. At the bottom of the body, micropores are made. As water penetrates through these micropores, the swellable substance such as low substituted hydroxypropyl cellulose (L-HPC) swells. When the cap made of water-insoluble macromolecular substance such as EC cannot persist the swelling pressure, the EC cap disintegrates and the drug in the container is released from the capsule. The lag-time is utilized for the delivery of drug to the colon. The release time of the drug from the capsule was measured both in vitro and in vivo experiments. In the case of an in vitro experiment, after 12mg of fluorescein as a model drug and 238mg of starch were filled into the container, caps having different thickness were attached to the capsule body and release study was performed. The release time of the drug was mainly dependent on the thickness of the cap. Using test capsules of which mean cap thickness were 39.1 +/- 2.3 (SE)microns, 63.1 +/- 5.0 microns and 75.6 +/- 4.1 microns, the in vivo release time was estimated after administration to beagle dogs. As a parameter, the peak time (tmax) when plasma fluorescein concentration reached to its maximum level was determined for the estimation of the release time of the drug from the capsule in the gastrointestinal tract. The in vivo tmax was well correlated with the cap thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The relationship between genotypes of HLA-DRB1 alleles and progression of bony destruction changes of rheumatoid arthritis].

The relationship between genotypes of HLA-DRB 1 alleles and the progression of bone destruction of RA patients was assessed. The genotypes of the HLA-DRB 1 alleles were determined in 329 Japanese patients with seropositive RNA by polymerase chain reaction and allele-specific oligonucleotide probe techniques. We regarded HLA-DRB 1* 0101, 0401, 0404, 0405, 1001 and 1402 as susceptible alleles of RA and classified the patients into three groups. The s/s group consisted of those with susceptible factors in both of the HLA-DRB 1 alleles. The s/n group was made up of those having one susceptible factor and one non-susceptible factor. The n/n group consisted of those possessing two non-susceptible factors. The grading of radiographic change that was evaluated by Larsen's criteria compared with the genotyped results. In the result, the median years taken to development to grade III, IV and V were significantly shorter in the s/s groups compared with that in the s/n and n/n groups. Thus, genotyping of HLA-DRB 1 can be a useful prognostic market in the progression of bone destruction of RA.

Adult↗

[Improvement of recurrent lung metastasis of breast cancer by Zoladex and cyclophosphamide].

The patient was a 38-year-old woman who was diagnosed as having right breast cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy. Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2 years and 4 months, pulmonary metastasis was diagnosed from elevated tumor markers and chest X-P. After the relapse, treatment with goserelin acetate (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the lung had shrunk in size, and after 5 months partial remission (PR) was evaluated from improvements in chest X-P and normalization of tumor markers, This PR condition continues at present. A case report is presented of a patient with premenopausal recurrent breast cancer in whom good results were obtained by concomitant administration of Zoladex and CPA.

Adenocarcinoma↗

Analysis of functional abnormalities uncovered during preoperative evaluation of donor candidates for living-related liver transplantation.

Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.

ABO Blood-Group System↗

Evaluation of the effect of pancreatic resection in advanced pancreatic cancer with special reference using hospital-free survival as a measure of quality of life.

Comparisons of surgical procedures and the identification of prognostic factors in pancreatic cancer were carried out on 158 patients who underwent surgery in Aichi Cancer Center from 1975 to 1991 for advanced pancreatic ductal adenocarcinoma. Survival and 'hospital-free survival (HFS), which we consider the best general means of measuring quality of life (QOL) in such severe and often fatal disease, were identified as primary end points, and the effect of pancreatectomy, compared with palliative surgery (by-pass operation, etc.) for TNM Stages III and IV pancreatic cancer was evaluated. Both survival and HFS were significantly longer in the group of patients who underwent pancreatectomies (R group, n 25) compared to the group without pancreatic resection (NR group, n 35) in Stage III cases. In Stage IV cases, however, no significant difference was observed between the R (n 12) and NR (n 86) groups. From these results, we conclude that an extensive pancreatic resection against Stage III pancreatic cancer may improve prognosis. For Stage IV pancreatic cancers, however, aggressive surgery might not always be beneficial either for survival or for QOL.

Carcinoma, Ductal, Breast↗

The frequency of 4977 base pair deletion of mitochondrial DNA in various types of liver disease and in normal liver.

Using a polymerase chain reaction (PCR) method, we tested for the hepatic mitochondrial DNA (mtDNA) deletion in 40 hepatic tumors (28 hepatocellular carcinomas [HCCs], 9 other malignant tumors, and 3 benign tumors) and in the livers of 71 patients, including 16 pediatric patients with end-stage liver disease who underwent living related donor liver transplantation and 16 liver donors. A 4977 base pair (bp) deletion of mtDNA was detected in 36 of 55 specimens of non-tumor portions of adult liver (65.5%). However, none of the specimens obtained from cirrhotic livers of the 16 pediatric patients younger than 13 years of age had the 4977 bp deletion. The frequency of mtDNA deletion was significantly decreased compared with normal liver in HCCs (7 of 28) and other malignant liver tumors (2 of 9). The frequency of this deletion was unrelated to the presence of liver cirrhosis, patient's gender, hepatitis B virus surface antigen status, and hepatitis C virus antibody status.

Adolescent↗

Clinicopathological study on pineocytoma.

Six cases of pineocytoma, which had developed in the parenchyma of the adult pineal body, were examined immunohistochemically and under an electron microscope, after the malignancy of each case had been determined using our classification. One case was rated as grade 1 showing a lobular structure and resembling the normal pineal body. Two cases were rated as grade 2 without a lobular structure but with pineocytomatous rosettes (P-rosettes). Two cases were rated as grade 3 without P-rosettes but with few mitotic figures. One case was rated as grade 4 with marked cellular pleomorphism, numerous mitotic figures and necrotic foci. When examined immunohistochemically, neuron-specific enolase was positive but glial fibrillary acidic protein was negative in all cases. Under an electron microscope, all cases showed abortive synapses, and clear or dense core vesicles. These findings allow us to make two conclusions. First, pineocytoma is always a tumor of neuronal lineage, regardless of their grade of malignancy. Second, the grade 4 pineocytoma should be distinguished from the type of tumor classically called "pineoblastoma." That is, the former seems to be a biologically dedifferentiated tumor, while the latter seems to be biologically undifferentiated tumor.

Adult↗