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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 19 recordsLinked to original sources

Relationship between tissue content of TC-81 and relaxation of rat aorta.

This study dealt with the relationship between the relaxant action of TC-81, a new Ca2+ antagonist, and its distribution in rat aorta depolarized by high K+ (65.4 mM). The inhibitory effect by TC-81 on K(+)-induced contraction and 45Ca2+ uptake was strongly time-dependent. TC-81 and nicardipine, each 10(-9) M, produced gradual relaxation of high-K(+)-induced contraction. The tissue contents of TC-81 and nicardipine increased with time courses that reflected decreasing tension. Both the maximum tissue content of TC-81 and the maximum relaxation were significantly greater than those for nicardipine. Also, the relaxations produced by TC-81 and nicardipine were correlated with the logarithm of the content of each drug in muscle tissues. However, the dissociation of TC-81 from the tissues was slower than that of nicardipine. The data suggest that the action of TC-81 is closely related to a gradual distribution of drug into muscle tissue, resulting in a slow onset of action. Also, the saturation time of TC-81 was longer than that of nicardipine, thereby accounting for the greater relaxation with TC-81.

Animals

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues.

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Enzyme-Linked Immunosorbent Assay

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy.

A total of 71 consecutive patients with unresectable hepatocellular carcinoma were analyzed retrospectively to determine the significant prognostic factors. All the patients received systemic chemotherapy in a phase 2 study from 1980 to 1990, with no other anticancer treatment. Median survival time and 1-yr and 2-yr survival rates were 5.6 mo, 23% and 5%, respectively. By the univariate analysis, a performance status of 0-1 and tumor size less than 50% of the liver cross-sectional area were shown to be the factors most significantly favoring a better prognosis. By the multivariate analysis using the Cox proportional hazards model, a performance status of 0-1 (p less than 0.001), absence of tumor thrombus in the main portal trunk (p = 0.003) and age less than 60 yr (p = 0.036) were independent favorable prognostic factors. A prognostic index was calculated from these three factors according to the following equation: 1.8109 x (0 = performance status of 0-1 and 1 = performance status of 2-3) + 0.9322 x (0 = tumor thrombus absent in the main portal trunk and 1 = present) + 0.6996 x (0 = age less than 60 yr and 1 = age greater than or equal to 60 yr). This index was used to classify the patients into three groups with a good, intermediate and poor prognosis. The median survival times for these three groups were 9.8, 3.8 and 1.9 mo, respectively (p less than 0.01). The results of this study may be useful in the design and analysis of future clinical trials of systemic therapy for hepatocellular carcinoma.

Analysis of Variance

Kallikrein-producing cells in the rat pituitary and pineal gland.

By using an immunohistochemical technique, kallikrein-producing cells in the anterior pituitary of rats were identified to be the same as prolactin-producing cells. Kallikrein was localized at the Golgi apparatus, the rough endoplasmic reticulum and secretory granules. Kallikrein was also located in the perivascular cells of the pineal gland.

Animals

Assortative mating and grandparental transmission facilitate the persistence of a sign language.

Conditions for the persistence (i.e., protection from loss) of a sign language are investigated assuming monogenic recessive inheritance of deafness, assortative mating for deafness or hearing, and cultural transmission of the sign language to deaf individuals from their deaf parents and deaf maternal grandparents. A new method is introduced to deal with the problem of grandparental transmission in which the basic variables are the frequencies of triplets comprising a mother, a father, and their daughter of permissible phenogenotypes. Usual stability analysis is then done on the system of linear recursions in the frequencies of these triplets, derived on the assumption that signers (users of the sign language) are rare. It is shown that assortative mating is the most important factor contributing to persistence, but that grandparental transmission can also have a significant effect when assortment is as strong as observed in England and the United States.

Deafness

Selective reactivities of isocyanates towards DNA bases and genotoxicity of methylcarbamoylation of DNA.

The reactivities of methyl isocyanate (MIC) and phenyl isocyanate (PIC) with DNA, and the genotoxicity of MIC were investigated. MIC and PIC reacted with the exocyclic amino group of deoxycytidine, deoxyadenosine and deoxyguanosine to produce carbamoylated products. The reactions of both isocyanates with deoxycytidine were 2 and 4 orders of magnitude higher than with deoxyadenosine and deoxyguanosine, respectively. To explore the genotoxicity of MIC, M13mp9 RF DNA was modified with MIC and then introduced into E. coli. The plaque-forming efficiencies of DNA decreased with increasing dose levels, and the decreases were more pronounced in Uvr endonuclease-deficient strains (uvrA, uvrB and uvrC) than in the Uvr endonuclease-proficient strain, JM103. The differences in survival in JM103 and uvr- strains suggest that the methylcarbonyl adducts can be removed by the uvr excision-repair system. Modification of M13mp9 RF DNA with MIC induced MIC-dose-related, SOS-dependent mutations in the beta-galactosidase locus. These results demonstrate the genotoxic response of MIC-modified DNA in E. coli.

Carbamates

Differential scanning calorimetric studies on bovine serum albumin: III. Effect of sodium dodecyl sulphate.

Measurements of differential scanning calorimetry (d.s.c.) have been made on the complex bovine serum albumin (BSA)--sodium dodecyl sulphate (SDS) under various conditions. There are two peaks P1 and P2 in the d.s.c. curve for BSA at pH 7 and in the absence of NaCl, indicating the presence of the heat-induced transition of BSA. There are three peaks P1, P2 and P3 in the curve for the system with the molar mixing ratio SDS/BSA = 1. With the increase in the amount of SDS, the peak P3 grows at the expense of P1 and P2. There is only a single peak P3 in the curve for the systems SDS/BSA > 7, and no peak at SDS/BSA = 50 and 100. There is a single peak P12 in the curve for BSA at pH 7 and in the presence of 0.05 M NaCl, indicating that the heat-induced transition is suppressed. There are two peaks P12 and P3 for the systems SDS/BSA = 1-5; the area ratio of the peak P3 to P12 increases with the increase in the amount of SDS. There is only a single peak P3 when SDS/BSA > 7, and no peak at SDS/BSA = 50. It is concluded that the peak P3 is a product of SDS regardless of the presence or absence of NaCl. Values of thermal denaturation temperature (Td) and enthalpy (delta H) of thermal denaturation indicate that the complex AD12 (A = BSA, D = SDS) is in the most thermostabilized state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of voluntary exercise on bone growth and calcium metabolism in spontaneously hypertensive rats.

The effects of voluntary exercise on bone length and calcium metabolism were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. They were classified into voluntary exercise or sedentary group. Systolic blood pressure (SBP), bone length, urinary calcium excretion, plasma calcium and parathyroid hormone levels (PTH) were measured for analysis. SBP of the trained SHR (T-SHR) was significantly lower than that of the nontrained SHR (NT-SHR) at 10 and 11 weeks of age, but the trained Wistar rats (T-WR) and the nontrained Wistar rats (NT-WR) had similar SBP throughout the experimental period. The T-SHR had significantly longer bones in the extremities and the trunk than the NT-SHR, whereas the T-WR had similar or shorter bones than the NT-WR. The PTH level at 12 weeks of age was significantly lower in the T-SHR than in the NT-SHR. The urinary calcium excretion of the T-SHR was greater than that of the NT-SHR, but the food intake (calcium intake) of the T-SHR was also greater. The urinary calcium excretion and food intake of the T-WR and NT-WR were similar. No noticeable differences were observed in the plasma calcium level between the T-SHR and NT-SHR, the T-WR and NT-WR. From these results it is suggested that the abnormal calcium metabolism in the SHR is improved in some degree by voluntary exercise.

Animals

No inhibitory effect of increased serum magnesium upon pressor response to infused calcium.

OBJECTIVE: The purpose of this study was to determine whether the pressor effect of infused calcium is inhibited by increased serum magnesium. DESIGN: Intravenous infusions of calcium, magnesium, and calcium+magnesium were performed in 10 subjects and the effect upon haemodynamic variables was investigated. METHODS: Intra-arterial blood pressure and heart rate were recorded during i.v. infusions of magnesium, calcium and calcium+magnesium. Cardiac output and serum concentration of electrolytes were measured before and after the infusions. Total peripheral vascular resistance (TPVR) was calculated from: mean blood pressure/cardiac output. RESULTS: Magnesium infusion increased serum magnesium, but did not change blood pressure, cardiac output or TPVR. Calcium infusion increased serum calcium and elevated both blood pressure and TPVR with no change in cardiac output. Calcium+magnesium infusion increased both serum magnesium and calcium, showing elevation of blood pressure and TPVR with no change in cardiac output. Changes in haemodynamic variables caused by the calcium+magnesium infusion were similar to those caused by the calcium infusion alone. CONCLUSIONS: These results suggest that increased serum calcium elevates blood pressure and TPVR through arterial vasoconstriction by arterial smooth muscle contraction, but increased serum magnesium does not induce arterial vasodilation.

Aged

Differences in responses to TC-81 among various arteries in dogs.

The vasodilation induced by TC-81 was investigated in vitro and in vivo. In helical strips of dog arteries precontracted with 65.4 mM KCl, TC-81, nicardipine, nifedipine, diltiazem, and papaverine produced concentration-dependent relaxation. The potencies of TC-81 were in the following order: basilar > coronary > femoral > renal > mesenteric arteries. The other drugs also showed a similar property of greater response in basilar and coronary arteries than in renal and mesenteric arteries. However, the difference in reactivity to TC-81 was greater. On the other hand, TC-81, nicardipine, and papaverine dose-dependently increased the blood flow in vertebral, coronary, and femoral arteries in anesthetized dogs. However, the blood flow in renal and mesenteric arteries was not changed or decreased. The decreases in vessel resistance induced by TC-81 were in the following order: vertebral > coronary > femoral > renal = mesenteric arteries, agreeing with the experimental results in vitro. These results suggest that Ca2+ antagonists have the pharmacological property of vasodilating cerebral and heart blood vessels more selectively than other arteries, and this property of TC-81 might be an advantage compared with other drugs.

Animals

[Evaluation of chlamydial IgM antibodies for clinical diagnosis].

Chlamydia trachomatis (C. trachomatis), C. psittaci, and C. pneumoniae are now well established as pathogens of respiratory infections including pneumonia. Serum samples from 223 infants and children with pneumonia, 31 patients with adult inclusion conjunctivitis, 16 parents of babies with neonatal inclusion conjunctivitis and others were tested for IgM antibodies to Chlamydiae. Diagnostic kits for chlamydial IgM antibodies (SeroELISA and IPAzyme) have been also evaluated for their diagnostic value. It was found that detection of specific IgM antibodies with SeroELISA has a diagnostic value in chlamydial pneumonias.

Adolescent

Molecular involvement of the pvt-1 locus in a gamma/delta T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation.

A highly malignant human T-cell receptor (TCR) gamma/delta+ T-cell leukemia was shown to have a productive rearrangement of the TCR delta locus on one chromosome 14 and a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on the other chromosome 14. Chromosome walking coupled with pulsed-field gel electrophoretic (PFGE) analysis determined that the TCR J delta 1 gene fragment of the involved chromosome was relocated approximately 280 kb downstream of the c-myc proto-oncogene locus found on chromosome band 8q24. This rearrangement was reminiscent of the Burkitt's lymphoma variants that translocate to a region identified as the pvt-1 locus. Sequence comparison of the breakpoint junctions of interchromosomal rearrangements in T-cell leukemias involving the TCR delta-chain locus revealed novel signal-like sequence motifs, GCAGA(A/T)C and CCCA(C/G)GAC. These sequences were found on chromosome 8 at the 5' flanking site of the breakpoint junction of chromosome 8 in the TCR gamma/delta leukemic cells reported here and also on chromosome 1 in T-cell acute lymphocytic leukemia patients carrying the t(1;14)(p32;q11) rearrangement. These results suggest that (i) during early stages of gamma delta T-cell ontogeny, the region 280 kb 3' of the c-myc proto-oncogene on chromosome 8 is fragile and accessible to the lymphoid recombination machinery and (ii) rearrangements to both 8q24 and 1p32 may be governed by novel sequence motifs and be subject to common enzymatic mechanisms.

Base Sequence

Effect of sleep on binaural interaction in auditory brainstem response and middle latency response.

Binaural interaction (BI) in auditory brainstem response (ABR) and middle latency response (MLR) was measured in 14 adults with normal hearing in the awake and asleep states. The ABR and MLR were recorded with click stimuli given monaurally and binaurally. Four peak-to-peak amplitudes of the response waveforms were measured, and the BI was determined from the amplitude difference between the summed monaural and binaural responses expressed in percent of the summed monaural responses. The magnitude of BI was smallest in ABR (waves I'-V) and largest in the later component of MLR (Pa-Nb) in both the waking and sleeping states. BI values for the peak-to-peak amplitudes in the ABR and MLR were significantly lower (p less than 0.025) in the sleeping state than in the waking state.

Acoustic Stimulation

Radiotherapy for bone metastases of hepatocellular carcinoma.

Radiotherapeutic effects of 42 bone metastases in 26 hepatocellular carcinoma patients were retrospectively analyzed. Pain relief was observed in 79% of 37 bone metastases treated (29/37). Antitumor effects and improvement of paralysis were also observed in 88% (8/9) and 17% (1/6), respectively. The toxicities experienced were tolerable. Radiotherapy was an effective means of palliation in the treatment of hepatocellular carcinoma bone metastases.

Adult

[The positive rate of hepatitis C virus antibody detected by the second generation method in pregnant women and influence of pregnancy and delivery on HCV infection].

The C100-3 antibodies to HCV can be examined with a Chiron kit but only the antibody to non-structure-4 can be. The antibodies in sera of pregnant women were examined by a passive hemagglutination method (PHA), which is one of the second generation kits used in detecting antibodies to the hepatitis C virus. We studied the percentage of pregnant women in our hospital with antibodies to HCV, and tried to compare the C100-3 antibodies with PHA results in pregnant women. The results are as follows. 1) In the sera of 235 pregnant women both the PHA antibody and the C100-3 antibody were examined. Two women (0.85%) had the C100-3 antibody and 4 (1.7%) had the PHA antibody. 2) Two women positive for both PHA and C100-3 antibodies were positive for PCR during pregnancy. But 2 women positive for PHA only were negative for PCR during pregnancy and positive after delivery. So 4 women positive for PHA had HCV RNA. 3) Next, the sera of 1,198 pregnant women were examined by the PHA method, and nine women were positive. Only four of the 9 were positive for C100-3. 4) It is speculated that the positive rate for anti-HCV antibodies in the sera of pregnant women in Nagoya city is 0.75%. 5) There were 3 cases that were negative for PCR during pregnancy and positive after delivery. So it is speculated that HCV can be activated after delivery.

Adult

Long-term observation of neutralization antibody after enterovirus 70 infection.

There is the need for more information on the persistence of the immune response to enterovirus 70 (EV70) infection. In August 1984, an outbreak of acute hemorrhagic conjunctivitis occurred at a nursing home in Sapporo, Japan. During the subsequent 7 years, we have monitored the neutralization antibody of EV70 in 13 patients with acute hemorrhagic conjunctivitis and 15 persons with subclinical EV70 infection among the 108 persons in the nursing home. During the first one to two years, the neutralization antibody in 6 of the 28 subjects (21.4%) decreased to less than 1:8. Seven years later, the neutralization antibody had decreased to less than 1:8 in 92% of the subjects. There was an individual difference in the level of neutralization antibody titer against EV70. However, overall the antibody levels markedly decreased every year. It is important to remember that the neutralization antibody titer of EV70 decreases with the passage of time. Consequently, most of the patients who had acute hemorrhagic conjunctivitis will not have resistance against reinfection 7 years after the initial infection.

Adult

Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic inclusions comprising of aggregates of keratin.

A case of primary hepatic carcinoid tumor was recently encountered, which was argyrophil and showed positive reactions to serotonin, gastrin and pancreatic peptide in an immunohistochemical hormonal study. The tumor had unusual morphologic features. The neoplastic cells had a signet-ring cell appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma. Ultrastructural and immunohistochemical studies revealed the formation of the signet-ring cells to have been caused by the presence of cytoplasmic inclusions consisting of cytokeratins. Further investigation, using eight monoclonal antibodies recognizing cytokeratins of different molecular weights, showed the accumulated cytokeratins to be of low and medium molecular weights. The morphologic observations in this unusual case of hepatic carcinoid tumor are described and reported cases with similar features, for which we propose the term "signet-ring cell carcinoid," are reviewed.

Adult