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Biomedical subjects

S Sakata

Publications and source records attributed to S Sakata.

At least 73 records · Page 4Linked to original sources

Synthesis of L-enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides.

L-Enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides were synthesized from D-xylose. Methyl 2,3,5-tri-O-benzyl-D-xylofuranoside 6 was converted to the corresponding xylitol 7, which was treated with MsCl and then Na2S to give 1,4-anhydro-L-4-thioarabitol 8. As previously reported, Pummerer rearrangement of 8 followed by glycosylation with a silylated thymine and N4-acetylcytosine derivative and deprotection gave the corresponding alpha- and beta-L-4'-thioarabinofuranosyl pyrimidine nucleosides.

Antimetabolites, Antineoplastic↗

Oxygen consumption and motility of mechanically unloaded myocardial slices.

We have recently established a new measurement system of myocardial O2 consumption per min (mVO2) of mechanically unloaded rat left ventricular (LV) slices (Yasuhara et al.: Am. J. Physiol. 270: H1063-H1070, 1996). Using this system, we have revealed that an increment in O2 consumption (delta mVO2) by electrical stimulation primarily represents mVO2 for Ca2+ handling in the excitation-contraction (E-C) coupling, though much smaller than that in the whole heart preparation. The much smaller delta mVO2 in the sliced myocardium than that in the whole heart is due to the much lower frequency of stimulation (60 bpm against 300 bpm). We consider that delta mVO2 does not contain mVO2 for residual crossbridge cycling from the results showing no effect of 2,3-butanedione monoxime on delta mVO2 despite the large decrease in mechanically unloaded contraction, which is expressed by the motility index. We also revealed that mVO2 without stimulation represents basal metabolism. The basal metabolism in rat myocardial slices, which is much higher than in other mammalian hearts, corresponds to that in the rat whole heart preparation. We finally obtained the results showing that sarcoplasmic reticulum (SR) Ca2+ pump blockers, thapsigargin and cyclopiazonic acid, did not reduce basal metabolic mVO2 but both of them reduced delta mVO2 maximally by 50-70% of control and markedly reduced the motility index. We conclude that myocardial O2 consumption (VO2) is composed of VO2 for E-C coupling and basal metabolism and does not contain VO2 for residual crossbridge cycling. Basal metabolic VO2 does not include VO2 for the SR Ca2+ pump, and at least two-thirds of VO2 for E-C coupling represents VO2 for the SR Ca2+ pump.

Animals↗

Anti-herpesvirus activity profile of 4'-thioarabinofuranosyl purine and uracil nucleosides and activity of 1-beta-D-2'-fluoro-4'-thioarabinofuranosyl guanine and 2,6-diaminopurine against clinical isolates of human cytomegalovirus.

Newly synthesized 4'-thio- and 2'-fluoro-4'-thioarabinofuranosyl purine and pyrimidine nucleosides were compared with the corresponding 4'-oxo type arabinosyl nucleosides for anti-herpesvirus and anti-cell proliferative potencies. 4'-Thioarabinosyl- and 2'-fluoro-4'-thioarabinofuranosyl 5-substituted uracils had selective antiviral activities, but were not superior to 4'-oxo nucleosides, except for the activity of 5-ethyl-uracil 4'-thio nucleosides against herpes simplex virus. Furthermore, 4'-thio substituted derivatives of sorivudine (BV-araU) and related compounds, and 2'-fluoro-5-methyl-arabinosyluracil exhibited reduced activity against varicella-zoster virus compared with the parent compounds. The 4'-thioarabinosyluracils, except for 5-methyluracil derivatives, were inactive against human cytomegalovirus (HCMV). 4'-Thioarabinofuranosyl guanine and diaminopurine had the most potent anti-HCMV and anti-proliferative activities, whereas arabinosyl guanine and diaminopurine had only marginal antiviral activity. 2'-Fluoro-4'-thioarabinofuranosyl derivatives of guanine (4'-thio-FaraG) and 2,6-diaminopurine (4'-thio-FaraDAP), however, had particularly high activity against all herpesviruses tested with anti-proliferative activity equipotent to that of arabinosyl guanine and diaminopurine. 4'-Thio- and 2'-fluoro-4'-thioarabinofuranosyladenines exhibited biological activities similar to that of arabinosyladenine. Both 4'-thio-FaraG and 4'-thio-FaraDAP had a 6-fold lower ED50 than ganciclovir against clinical isolates of HCMV. A ganciclovir-resistant isolate, obtained from a patient who had received long-term ganciclovir-treatment, was susceptible to 4'-thio-FaraG and 4'-thio-FaraDAP.

Antiviral Agents↗

Circadian rhythms of atrioventricular conduction properties in chronic atrial fibrillation with and without heart failure.

OBJECTIVES: We examined the circadian variations in atrioventricular (AV) conduction properties during atrial fibrillation (AF) by a technique based on the Lorenz plot of successive ventricular response (VR) intervals and analyzed their relations with clinical features. BACKGROUND: The VR interval in chronic AF shows circadian variation, which is attenuated in patients with an increased risk of death. Although the VR interval is determined by the dynamic processes in the AV node randomly stimulated by rapid atrial activity, the circadian variations of the AV conduction properties related to this mechanism are unknown. METHODS: In 48 patients with chronic AF, Lorenz plots were generated on overlapping sequential segments of 512 VR intervals in 24-h ambulatory electrocardiograms. For each scatter plot, the 1.0-s intercept of the lower envelope (LE1.0) of the plot and the degree of scatter above the envelope (root mean square difference from the envelope [scattering index]) were measured for estimating AV node refractoriness and concealed AV conduction, respectively. RESULTS: In all patients, a significant circadian rhythm was observed for the average VR interval, LE1.0 and scattering index, with an acrophase occurring at night. The mesor, amplitude and acrophase of LE1.0 and the scattering index closely and independently correlated with the corresponding rhythm variables of the average VR interval (partial r2 0.98, 0.86 and 0.68 for LE1.0 and 0.98, 0.92 and 0.92 for scattering index). The amplitudes of these measures were lower in patients with congestive heart failure (CHF) even after adjustment for the effects of age, duration of AF, medications, left atrial diameter and blood pressure (p < 0.01 for all). CONCLUSIONS: These results suggest that 1) both AV node refractoriness and the degree of concealed AV conduction during AF may show a circadian rhythm; 2) the circadian rhythms of these properties may independently contribute to the circadian variation of the VR interval; and 3) these circadian rhythms may be attenuated in patients with CHF.

Aged↗

The relationship between pentosidine and hemodialysis-related connective tissue disorders.

Dialysis-related amyloidosis (DRA), such as destructive spondyloarthropathy (DSA) and carpal tunnel syndrome (CTS), occurs in the connective tissues of patients on long-term hemodialysis (HD). Recently, it was suggested that advanced glycation end products (AGEs) and beta2-microglobulin (beta2m) modified with AGEs are related to DRA. The aim of this study is to elucidate whether serum levels of pentosidine, which is an AGE, relate to the occurrence of DRA in patients with long-term HD. 127 end-stage renal failure patients, with DSA or CTS and undergoing HD, were examined. Serum pentosidine was measured by the HPLC method with column switching. Beta2m and intact parathyroid hormone (i-PTH) were measured. Pentosidine levels were significantly elevated in the DSA, CTS, and DRA groups (patients in the DRA group had either DSA and/or CTS). There were no significant differences in the beta2m and i-PTH levels between any group. The duration of HD did not correlate with either pentosidine or beta2m levels, but did with i-PTH. Receiver-operating characteristic (ROC) analysis was performed to examine the discriminatory ability of pentosidine, beta2m, and i-PTH for DRA. The area under the ROC curve was the greatest for pentosidine. Serum beta2m levels were not related with the occurrence of DRA. The fact that serum pentosidine was higher in DRA than in non-DRA indicates that it has potential as an indicator of the occurrence of DRA in long-term HD patients.

Adult↗

Salivary amylase activity of rats fed a low calcium diet.

Wistar strain rats fed low calcium diets (1, 2, 3, 4, 6 and 8 weeks) exhibited changes in secretory function of whole saliva. In particular, there were changes in salivary flow rate, total salivary protein, amylase enzyme activity, salivary amylase content and the level of cyclic AMP in the parotid gland acinar cell. Although there were no changes for the first 3 weeks, the levels increased at week 4 and decreased at week 6. The wet weight of the parotid gland started to decrease at week 4. These results suggest that when fed low calcium diets for long periods of time, rats develop defective salivary secretion.

Amylases↗

Unloaded skeletal muscle O2 uptake decreases with decreased venous PO2 at high-frequency stimulation.

The aim of the present study was to clarify the effects of O2 diffusion limitation resulting from hypoxic interventions on O2 uptake (V.O2) in unloaded (that is, near-zero initial force) and loaded skeletal muscle in a high-frequency stimulation. We measured V.O2, muscle venous PO2 (PvO2) and initial force in gastrocnemius-plantaris muscle in situ of anesthetized dogs: (1) during hypoxic hypoxia at 1 Hz tetanic stimulation, and (2) during hypoxia induced by the perfusion with high O2-affinity erythrocytes (having a low value of PO2 at 50% saturation of hemoglobin (P50)) at 4 Hz twitch stimulation. Averaged unloaded V.O2 during normoxia was 10.2 ml.min-1.100 g-1 at averaged blood flow of 74 ml.min-1.100 g-1 (n = 6). Hypoxic hypoxia of a decreased O2 delivery (arterial O2 concentration x flow) significantly decreased both unloaded and loaded V.O2 with a decrease in PvO2 (p<0.05). The unloaded V.O2 was reduced to 8.5 ml.min-1.100 g-1. Low P50-hypoxia decreased V.O2 at high and low initial force conditions with a decrease in PvO2 (p<0.05) at the same O2 delivery. If these decreases in V.O2 correspond with a decrease in V.O2 at zero initial force (unloaded V.O2), the unloaded V.O2 value is calculated to be 7.57 ml.min-1.100 g-1 from V. O2-initial force data. Despite the different conditions of O2 delivery, the unloaded V.O2 decreased by both hypoxia showed similar values. Thus the decreased unloaded V.O2 does not seem to be derived from only the limited O2 delivery. Some other factors such as the limitation of O2 diffusion may contribute to the decreased V.O2.

Animals↗

[Limited operation for lung cancer: wedge resection using stapling device].

We employed wedge resection using stapling device for peripheral, clinical stage I lung carcinoma in selected poor-risk patients. Out of 10 patients, four developed local recurrence and one had the second primary in the same lobe resected. Compared with patients having lobectomy with 91% of a recurrence free rate in three years, those who underwent wedge resection had the lower rate of 53%. We conclude that wedge resection using stapling device cannot be an acceptable procedure even for poor-risk patients.

Adenocarcinoma↗

[Analyses on the long-term prognosis of surgical treatment for primary lung cancer in the elderly patients of 75 or over years old: how should be treated the non-recurrent death?].

We analyzed the long-term prognosis in 68 elderly (75 years old or over) patients with primary lung cancer. The 5- and 10-year survival rates were 56.5% and 10.2%, respectively. There were 33 deaths due to 16 recurrences (REC) and 17 non-recurrences (NREC). Thirty-three dead patients were divided into two groups; patients with less than 5-year follow-up period (group A) and patients with 5-year or over follow-up period (group B). In group A, the REC/NREC ratio was 15/6, and in group B, the REC/NREC ratio was 1/11. The mortality due to non-recurrence was significantly (p < 0.05) higher in group B. In conclusion, we recommend to include non-recurrent death in the survival rates, because it is impossible to clear the cause of death, strictly.

Aged↗

[Effects of deep halothane and isoflurane anesthesia on cerebral as well as coronary metabolism].

Mongrel dogs were subjected to halothane or isoflurane to examine the relationship between systolic blood pressure and cerebral as well as myocardial metabolism. The oxygen and hydrogen ion balances in the brain were not disturbed in either group to the systolic blood pressure level of 70 mmHg and were well maintained in the isoflurane group below this level. The myocardial oxygen balance was not aggravated in either group, whereas, the myocardial hydrogen ion balance was disturbed in the halothane group at the systolic blood pressure level between 70 mmHg and 50 mmHg though it was preserved in the isoflurane group. These findings demonstrate that the systolic blood pressure not disturbing oxygen and hydrogen ion balances in the brain and myocardium is 70 mmHg during halothane or isoflurane anesthesia, while isoflurane anesthesia becomes advantageous at the systolic blood pressures below this level. While the myocardial metabolism is less affected by lowering of blood pressures than the cerebral metabolism, it seems important to secure cardiac functions to maintain metabolism in both organs.

Anesthesia, Inhalation↗

[Ultrasound bone densitometry of os calsis].

In the last couple of years, Ultrasound bone densitometry (QUS: Quantitative ultrasound) have been developed which allow the assessment of fracture risk caused by osteoporosis. QUS are particularly promising since they are simple, inexpensive, portable, non-invasive and they do not subject the patient to any ionising radiation. Additional investigations that assess innovative QUS techniques in well defined research settings are important to determine and utilize the full potential of this technology for the benefit of early detection and monitoring of osteoporosis.

Adult↗

[Long-term survival in surgical cases of non-small cell lung cancer with mediastinal nodal involvement].

We studied long-result of the patients with mediastinal lymph node metastasis (N2) in lung cancer. From 1981 to 1991 in National Sanatorium Nishi-Gunma Hospital, we have performed a lobectomy or pneumonectomy with mediastinal lymph node dissection for 306 patients with non-small cell lung cancer. Six operative deaths were excluded (operative death rate: 2.0%). Of these, 53 patients (17%) were diagnosed as adenocarcinoma or squamous cell carcinoma with N2 disease pathologically. The patient consisted of 31 men and 22 woman whose ages ranged from 18 to 73 years, with a mean age of 58.1 years. The results were: Mean survival period was 39 month. Five-and 10-year survival rates were 18.9% and 12.6%, respectively. By motive of detection, the group of following other disease had a better prognosis than the group of having symptom. By pT-factor, T1 had a better prognosis than T3. By the number of nodal involvement level, 1 level had a better prognosis to compared to 3 or more than 4 levels. There were 10 patients of 5-year or over survivors after surgery, none of whom had primary site in left upper lobe. Analysis with a Cox's proportional hazard model demonstrated that the number of nodal involvement level was a useful factor in prognosis.

Adolescent↗

A facile, alternative synthesis of 4'-thioarabinonucleosides and their biological activities.

4'-Thioarabinonucleosides, which are potential antiviral agents, were synthesized from D-glucose. 1,4-Anhydro-4-thioarabitol (8), which can be derived from diacetone glucose in nine steps, was subjected to Pummerer rearrangement after protection of the hydroxyl groups to give 1-O-acetyl-4-thioarabinose (11), which was condensed with nucleobases to give 4'-thioarabinonucleosides. The 5-substituted-4'-thioaraU (6a-e) derivatives showed anti-HSV-1 activity (ED50 = 0.43-3.50 micrograms/mL). 4'-ThioaraG (6h) and 2,6-diaminopurine 4'-thioarabinonucleoside (4'-thioaraDAP, 6g) showed antiviral activity against several herpes viruses and were particularly potent against human cytomegalovirus (0.010 and 0.022 microgram/mL, respectively).

Antiviral Agents↗

Thoracoscopic closure of a congenital partial pericardial defect.

We describe our technique for performing direct thoracoscopic closure of a congenital partial pericardial defect, which was successfully employed in a 15-year-old boy. This is the first such report of a procedure that is noninvasive and may therefore become the treatment of choice for patients with a small congenital pericardial defect.

Adolescent↗

Ultrasound bone densitometry of os calcis in elderly Japanese women with hip fracture.

We evaluated 138 elderly patients (mean age 79 years) within 2 weeks after hip fracture (67 cervical and 71 trochanteric) using an Achilles ultrasound bone densitometer (Lunar Corporation, Madison, WI). The ultrasound variables of speed of sound (SOS in m/second), broadband ultrasound attenuation (BUA in dB/MHz), and stiffness (%) index were measured on the os calcis. Ultrasound densitometry also was done on 563 normal postmenopausal women to assess normal age changes. An elderly subgroup (n = 138) served as age-matched controls for the hip fracture group. Further subgroups of 33 patients and 33 controls were compared for lumbar spine and femoral neck BMD. There were no statistically significant differences between the hip fracture group and age-matched controls in height and weight, but each ultrasound variable was significantly lower for the hip fracture group (P < 0.0001). For the hip fracture group, SOS was 1470 +/- 19 m/second, BUA was 84.3 +/- 8.4 dB/MHz, and the stiffness index was 47.8 +/- 9.2%, whereas for the age-matched controls, SOS was 1486 +/- 27 m/second, BUA was 94.0 +/- 11.4 dB/MHz, and the stiffness index was 59.1 +/- 12.5%. There were no significant differences between cervical and trochanteric hip fracture groups. Logistic regression analysis showed that a change of the ultrasound values by 1 standard deviation (SD) changed the odds ratio for SOS, BUA, and stiffness index by 2.51, 3.24, and 3.60, respectively. Ultrasound variables, particularly stiffness, were good indicators of hip fracture risk.

Aged↗

Carbon isotopic fractionation associated with lipid biosynthesis by a cyanobacterium: relevance for interpretation of biomarker records.

For the cyanobacterium Synechocystis UTEX 2470, grown photoautotrophically to a logarithmic stage of growth, the total lipid extract is depleted in 13C by 4.8% relative to average biomass. Depletions observed for acetogenic (straight-chain) lipids range from 7.6 (hexadecanoic acid) to 9.9% (a C16 n-alkyl chain bound in a polar-lipid fraction), with a mass-weighted average of 9.1%. Polyisoprenoid lipids fall into two isotopic groups, with phytol, diplopterol, and diploptene depleted by 6.4-6.9% and bishomohopanol (produced from the extracts by the preparative degradation of bacteriohopanepolyol) depleted by 8.4%. Analysis of the pattern of depletions indicates that two carbon positions in each C5 biomonomer leading to polyisoprenoid products are probably depleted in 13C relative to average biomass. The depletion of bacteriohopanepolyol relative to other polyisoprenoids can be ascribed to changes that occur over the life of each cell: (1) the 13C content of carbon flowing to lipid biosynthesis decreases as the cell size increases and (2) a greater proportion of the bacteriohopanepolyol which, unlike other polyisoprenoids, is present mainly in the cytoplasm rather than in membranes and is synthesized when cells are larger. Chlorophyll a is depleted relative to average biomass by O.7%. Given the observed depletion of 13C in phytol, the heteroaromatic, chlorophyllide portion of chlorophyll must be enriched in 13C by 2.7%. This enrichment is large relative to that in chlorophyllides produced by eukaryotes and may be related to a parallel enrichment of 13C in cyanobacterial glutamic acid. As in many previous investigations of cyanobacterial lipids, long-chain n-alkanes (C22-C29) are found in the extracts. They are, however, enriched in 13C relative to biomass and have isotopic compositions suggesting that they are contaminants of petrochemical origin. Available results indicate that cyanobacterial lipids will be depleted relative to dissolved CO2 that has served as a carbon source by 22-30% and that a wider range of depletions will be characteristic of eukaryotic products. The absence of long-chain n-alkanes in cyanobacteria reduces the possibility that petroleum ever formed from pre-eukaryotic sedimentary debris.

Acetic Acid↗

Structure-activity relationship of the affinity of 5-substituted uracil nucleoside analogues for varicella-zoster virus thymidine kinase and their activity against varicella-zoster virus.

We investigated structure-activity relationships of 5-substituted uracil nucleoside analogues for their selective antiviral activity against varicella-zoster virus (VZV) and affinity for VZV thymidine kinase (TK). Anti-proliferative activity of the compounds was measured using human lymphoblastoid cells. Most 2'-deoxyribofuranosyluracil, arabinofuranosyluracil (araU) and 2'-deoxy-2'-fluoro-arabinofuranosyluracil derivatives showed selective anti-VZV activity as well as activity against herpes simplex virus types 1 and 2. 2'-Deoxyuridine derivatives showed higher affinity than the corresponding araU analogues. A correlation was seen between the 50% effective doses for VZV and the Ki values for VZV TK, except for 5-ethyl-2'-deoxyuridine and 5-ethyl araU that showed relatively high affinity for VZV TK without showing any activity against VZV. 5-Halogenovinyluracil nucleosides showed the highest affinity and the most potent and selective anti-VZV activity. 2'-Deoxy-2'-fluoro-arabinofuranosyluracil derivatives exhibited high anti-VZV potency though they showed relatively low affinity for VZV TK. Some 3'-deoxythymidine analogues having anti-human immunodeficiency virus activity were inactive against herpesviruses.

Antineoplastic Agents↗