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PK/PD analysis was performed after percutaneous administration of insulin self-dissolving micropiles (SDMP) where chondroitin sulfate was used as a base. PK/PD model composed of 1-compartment open model with first-order absorption process and sigmoidal Emax model was used to simulate the time courses of both plasma insulin and glucose levels after percutaneous administration to dogs, 2.0 IU/dog. The Akaike’s information criterion (AIC) were 249.33 ± 13.00, though AIC was 259.55 ± 11.95 for the 2-compartment open model that was directly linked to sigmoidal E max model. The mean first-order absorption and elimination rate constants of insulin with SDMP were 7.59 ± 3.93 h − 1 (k 01 ) and 1.31 ± 0.66 h − 1 (k 10 ). For subcutaneous (sc) injection of insulin solution, k 01 and k 10 were 9.72 ± 5.67 h − 1 and 1.60 ± 0.45 h − 1 . PD parameter values from insulin SDMP were 148.5 ± 71.9 pg/mL for EC50 and 3.11 ± 1.41 for γ. These results suggested that insulin SDMP has almost the same PK characteristics as sc injection preparation.

Previously we have shown that both CD4+ T cells and CD8+ T cells produce histamine when activated with Con A. The aim of this study was to examine whether cytokine production by these cells is regulated by autosecretion of histamine.CD4+ and CD8+ T cells were separated from spleen cells of C57BL/6 mice and mice lacking the H1 receptor (H1R) or H2R, using anti-CD4+- and anti-CD8+-coupled magnetic beads, respectively.Depletion of the H1R resulted in decreases in the release of IL-2 and IL-10 from both CD4+ and CD8+ cells and increases in the release of IL-4 from CD4+ T cells and IFN-gamma from CD8+ cells. Mice lacking the H2R showed up-regulation of IFN-gamma secretion from CD8+ cells and of IL-4 from CD4+ and CD8+ T cells. Release of IL-2 and IL-10 from CD4+ as well as CD8+ cells was down-regulated in these mice. Both CD4+ and CD8+ T cell fractions synthesized histamine, which was enhanced in the H1R-deficient CD8+ T cells. Treatment of the cells with alpha-fluoromethyl-histidine, a specific inhibitor of HDC, or histaminase increased IFN-gamma from CD8+ cells, whereas it had no appreciable effect on IL-4 secretion from CD4+ cells.These results suggest that cytokine production by CD4+ and CD8+ T lymphocytes is regulated by autosecretion of histamine.

We have used a high temperature superconductor (HTS) SQUID in an unshielded environment to perform eddy current nondestructive testing measurement of a multi-layer aluminum structure. The sensor consists of an YBCO dc superconducting quantum interference device (SQUID). As a demonstration of the system's capabilities, subsurface defects in a multi-layer aluminum structure have been located and mapped using eddy current with no magnetic shielding around the specimen.

A high-T/sub c/ superconductive fluxgate magnetic sensor utilizing sintered YBa/sub 2/Cu/sub 3/O/sub 7-x/ core is constructed and applied to detect a flaw in an aluminum plate. The magnetic sensor successfully works in an unshielded environment. An electric current was supplied to an aluminum plate directly. A slit (0.2 mm width, 30 mm length), which is considered as a flaw, on an aluminum plate is successfully detected with this sensor, even though the slit is covered with another aluminum plate. The sensor can detect the flaw with its direction perpendicular to the electric current in the sample. It's supposed that the sensor can determine the length of the flaw larger than the diameter of the detection coil. These results suggest that the sensor has a potential for nondestructive evaluation of non-magnetic metals such as aluminum alloys, and also for their multi-layered structures.

Basic theoretical analyses to detect undesirable foreign metal pieces in the meat being processed have already been carried out. In this study, taking the low conductivity of meat into account, a double-layered spherical sample structure which enables easy analyses was selected. In order to detect these conductive materials, analyses of the difference in the impedance of a circular coil with, and another one without, a double-layered spherical conductor were made. In this way, a new formula for obtaining the electromagnetic properties of a double-layered spherical sample was derived. The process of deriving the new formula is explained. The calculated value was compared with the experimental value. Their values had a close correlation.

We describe the design and fabrication of thin-film Nb gradiometers with integrated DC SQUIDs for use in non-destructive evaluation (NDE) and biomagnetism. Issues of sensitivity, imbalance and field response are considered. Results are presented from eddy-current NDE in an unshielded environment of aluminium plates with sub-surface flaws, and from biomagnetic measurements of spinal and peripheral nerve evoked fields.

The purpose of this study was to investigate whether immobilization stress would affect the cytotoxic activity of natural killer (NK) cells through the changes in norepinephrine release in the spleen. An in vivo microdialysis technique consisting of high-performance liquid chromatography with electrochemical detection was used to examine norepinephrine levels in the spleen of the conscious rat. The results of the physiological and pharmacological manipulations indicated that norepinephrine recovered in the dialysis solution was mainly derived from the nerve terminals of the splenic sympathetic nerve. Immobilization stress rapidly increased norepinephrine levels to 817.4 +/- 181.7% of baseline in conjunction with the suppression of NK cytotoxicity. Both the increased levels of norepinephrine and the immunosuppression of NK cytotoxicity by immobilization stress were significantly attenuated after surgical denervation of the splenic sympathetic nerve. The results suggest that immobilization-induced suppression of splenic NK cytotoxicity is mediated predominantly through enhanced activity of the splenic sympathetic nerve.

Ultrafine powders consisting only of an intermetallic compound were formed in the limited Cu-M (M=Al, Ga, Sn or Ge) systems by an evaporation method in which an arc plasma was used as a heat source to evaporate prealloyed Cu-based binary alloys. The limitation of the Cu-M systems is due to the criterion in which the ratio (R) of the vapor rate for molten M metal to that for molten Cu is in the range of 0.234 to 3.58. As R approaches 1.0, the resulting phase tends to coincide with the phases at high temperatures in the corresponding Cu-M equilibrium phase diagram. The compound particles obtained in the present study are Cu 9 Al 4 , Cu 9 Ga 4 , CuGa 2 , Cu 6 Sn 5 and Cu 3 Ge. The particles have a spherical shape and the particle size is below 180 nm

In this paper, an n-GaN metal-oxide-semiconductor (MOS) diode was fabricated using atomic layer deposited (ALD) Al 2 O 3 . Prior to Al 2 O 3 deposition, the n-GaN surface was treated with (NH 4 ) 2 S solution. As a result, interface state density of the treated n/n+-GaN MOS diode was significantly reduced compared to that without (NH 4 ) 2 S treatment.

Al-based amorphous and quasicrystalline alloys have been prepared by high-rate sputtering and melt-quenching, respectively. The Al 67 Cu 20 Mn 13 crystalline approximant phase also has been made by annealing the quasicrystalline counterpart. The formation of the localized magnetic moments of 3d metals in the Al matrix is difficult except for Mn. The ratio of the magnetic Mn atoms estimated from the saturation magnetization and the Curie constant in the quasicrystalline phase is smaller than that in the amorphous phase. In the crystalline approximant phase, the ratio is comparable to that in the amorphous phase, but the average magnetic moment of magnetic Mn atoms is much smaller than that in the amorphous and quasicrystalline phases

Four naturally occurring flavones (baicalein, quercetin, quercetagetin and myricetin) and two novel catechins [(-)-epicatechin gallate and (-)-epigallocatechin gallate, from the tea plant Camellia sinensis], which are known inhibitors of reverse transcriptase, were shown to induce mammalian topoisomerase II-dependent DNA-cleavage in vitro. The flavones differed from the catechins in causing unwinding of duplex DNA, but both classes of compound induced enzymic DNA breakage at the same sites on DNA. Moreover, the cleavage specificity was the same as that for the known intercalator 4′-(acridin-9-ylamino)methanesulphon-m-anisidide, suggesting that these agents trap the same cleavable complex. Analysis of some 30 flavonoid compounds allowed elucidation of the structure-function relationships for topoisomerase II-mediated DNA cleavage. For flavonoid inhibitors an unsaturated double bond between positions 2 and 3 of the pyrone ring and hydroxy groups at the 5, 7, 3′ and 4′ positions favoured efficient cleavage. Hydroxy substitutions could be tolerated at the 3, 6 and 5′ positions. Indeed, the absence of substituents at the 3′, 4′ and 5′ positions could be compensated by a hydroxy group at position 6 (baicalein). Similar requirements have been reported for flavonoid inhibitors of protein kinase C that act competitively with ATP, suggesting interaction with a conserved protein feature. Formation of the cleavable complex is a cytotoxic lesion that may contribute to the growth-inhibitory properties of flavones observed for three human tumour cell lines. These results are discussed in regard to the selectivity of antiviral agents.

A quantum flux parametron (QFP), a single quantum flux superconductive device that has a potential of up to 100-GHz switching with nW-order power dissipation, is considered. The potential of the QFP and key technologies when QFPs are applied to a Josephson supercomputer are described. Switching speed, stability, and power dissipation of a QFP are discussed. QFP gates, circuits, and systems are next described. Then, ultra-fast clock distribution using a standing wave is explained. High-speed operation at more than 10 GHz and 10/sup 14/ error-free operations per QFP have been demonstrated. Finally described is a high-density packaging scheme by three-dimensional integration, which is very important for ultra-high speed circuits because the propagation delay becomes dominant in such circuits. >

In order to solve the problems of old QFP (quantum flux parametron) logic and to improve the operating margin, a QFP logic uses various circuits including a flux regulator, activation/signal amplifiers, a variable activated QFP (VAQ), and a dual-input-multiplexer gate (D-gate). The detailed designs and experimental results of these circuits are discussed. New QFP logic adopts a novel QFP, which can transfer I/O signals between two stacked chips directly by its I/O transformer. The prototype model of three-dimensional circuits by this kind of QFP is described.

The detection of the flux quanta trapped in a large area superconductor by scanning a SQUID pickup coil is discussed. For this purpose a gas floating technique has been developed. In this technique, the supplied gas flow supports the coil while the coil scans the superconductor surface in liquid helium. The applicability of the gas floating technique is examined, and it is shown that this technique can be utilized even in liquid nitrogen or liquid helium. Measurements of magnetic field distribution over several superconductors in liquid helium are reported. By scanning the pickup coil over the superconductor, changes in the magnetic field, which come from the flux trapped in the superconductor, are observed. Furthermore, the background variation during sample rotation and displacement is reduced to about 2.4 Phi /sub 0/. The minimum detectable flux is shown to be less than Phi /sub 0/. These results show the possibility of using this technique in the detection of trapped flux quanta in superconductors.

Several subharmonic generators are presented, the larger of which consists of four shift registers connected serially around a loop. Low-frequency operation was demonstrated for four different devices using one, two, three, and four shift registers, respectively. The circuits presented use a standing wave for powering the QFPs, guaranteeing that all the QFPs are perfectly synchronized and that no power is consumed in the clock lines. If all the QFPs along a clock line are to be power within 20% margin, the maximum operating frequency is limited by the clock lines' length. Concerning the high-speed operation, a frequency divide-by-two circuit was able to work at a clock frequency of 8 GHz. For checking that no error occurs during the operation of the QFPs, a four-bit shift register was used. The latter device was able to work at frequencies up to 3.1 GHz, and all of the four-bit patterns were stored during experimental times of the order of one hour without observing the occurrence of an error. Thus, about 10/sup 14/ error free operations per QFP were demonstrated.

A magnetic flux sensing device that is made by using two DC SQUIDs is presented. The DC SQUIDs are of familiar characteristics, magnetically coupled by a common coil, and are turned into the voltage state by a single DC current source. As the DC SQUIDs are magnetically coupled, the magnetic flux noise generated by one of the DC SQUIDs is sensed by the other and vice versa. By making a differential measurement across both DC SQUIDs, the magnetic flux noise detected by the DC SQUIDs can be added either constructively or destructively. This means that magnetic flux noise cancellation is possible, as demonstrated experimentally. The double DC SQUID configuration can also be used in the add flux noise mode, in which there is no loss of performance when compared with what is possible to obtain with a single DC SQUID. Another advantage of the two DC SQUID configuration is that the output impedance is twice as large as that of the DC SQUID with Josephson junctions of the same critical current and shunting resistance. In the former configuration, the matching to room temperature electronics is simplified.

2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) was found to be an efficient substrate for DNA polymerase beta when activated DNA was used as the template.primer. Under the optimized reaction conditions with activated DNA, the rate of the incorporation of ddGTP into DNA was almost equal to that of the corresponding normal substrate dGTP. The Km value for ddGTP (1.8 microM) was smaller than that for dGTP (7.8 microM). In contrast, ddGTP was not utilized as a substrate for DNA polymerase gamma with any of the activated DNA and (dC)n.(dG)12-18 as the template primer. Other DNA polymerases such as DNA polymerase alpha, E coli DNA polymerase I and retroviral reverse transcriptase could poorly utilize ddGTP as a substrate. Some of the kinetic properties of DNA polymerase beta revealed toward ddGTP are also described. Since DNA polymerase beta plays a role in DNA repair, the present results predict possible appearance of cytotoxicity or clinical side effect(s) of 2',3'-dideoxyguanosine (ddG), known as a potent inhibitor of human immunodeficiency virus, when ddG is administered to the patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex.

A system to measure the high frequency MR curve of thin films was developed. Two problems had to be solved to realize MR measurement at frequencies above several MHz, namely, to produce a high amplitude magnetic field and to develop electrodes less sensitive to inductive high frequency noises than the conventional four probe electrodes. These problems were solved by making use of the resonance of a coil with a ferrite core connected in parallel with to a capacitor, and by contacting patterned thin film electrodes to the sample surface with a suitable pressure. The result was an appreciable reduction of inductive noises. Using the resonance circuit and electrodes we could obtain AMR curves of Permalloy films at frequencies up to 1.8 MHz in a field of 110 Oe pp.

Background and purpose: Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke. Methods: Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study. Results: The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907–8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P = 0.0510), and combined TT and TA genotypes (OR = 8.768, P = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes. Conclusions: The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.

This paper describes an approach of motion compensation by using laser range finder for biped walking robots with structural deformation. The response force received from ground environment is one of important indexes to realize stable walking for biped robots. For more reliable walking under various environments, this paper focuses on the walking motion with considerations of structural deformation. That is, hip joint deformation is observed by laser range sensor mounted at the hip of robot, and the deviation of ZMP trajectory is calculated by using the observed structural deformation, and the motion compensator is designed in order to recover ZMP deviation. The validity of the proposed approach is confirmed by several numerical and experimental results.

The effects of BD-40, a pyrido-pyrrolo-isoquinoline analogue of ellipticines, and its 2-acetylated derivative (BD-84) and in vitro DNA synthesis catalyzed by purified preparations of various DNA polymerases were examined. The major conclusions are: (1) Both BD-40 and BD-84 strongly inhibit the DNA synthesis by DNA polymerase or reverse transcriptase with poly(rA) · oligo(dT) as the template · primer. (2) Both compounds moderately inhibit the DNA synthesis by DNA polymerase α or E. coli DNA polymerase I with activated DNA. However, the DNA synthesis by DNA polymerase β is resistant to inhibition by BD-40 and slightly sensitive to that by BD-84. (3) BD-84 is more inhibitory than BD-40 in DNA syntheses by various DNA polymerases except in those by DNA polymerase α and terminal deoxyneuclotidyltransferase to which both compounds are similarly inhibitory. (4) Kinetic analyses revealed that the observed inhibitions are due to competition between the drug or the drug-bound template · primer and the free template-primer for the same binding site of the enzyme.

A traditional Kampo drug, Sho-saiko-to, composed of several herb extracts, differentially inhibited the activities of reverse transcriptase and human cellular DNA polymerases α and β. Reverse transcriptases from murine leukemia virus and human immunodeficiency virus were inhibited by over 80% and 50%, respectively, in the presence of 100 μg ml Sho-saiko-to, whereas DNA polymerase α was much less sensitive to inhibition by this drug than were the reverse transcriptases. DNA polymerase γ was not inhibited by this drug at concentrations of up to 500 μg ml . Only DNA polymerase β was moderately inhibited by Sho-saiko-to. Thus, it has been shown that the inhibition by Sho-saiko-to is relatively specific for reverse transcriptase and that the drug contains as yet unidentified inhibitory substance(s) for reverse transcriptase. Sho-saiko-to / reverse transcriptase inhibitor / AIDS.

The activity of DNA polymerase alpha was strongly inhibited by low concentrations (less than 1 microM) of 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) in the presence of Mn2+, although the incorporation of [3H]ddGTP into the product DNA was not detectable under the same reaction conditions. ddGTP competitively inhibited the incorporation of [3H]dGTP into the DNA. The Kis of DNA polymerase alpha for ddGTP were as low as 0.035 microM with activated DNA and 0.044 microM with (dC)n.(dG)12-18 as respective template.primers. By increasing [3H]ddGTP concentration (greater than 1 microM), however, it became an efficient substrate for DNA polymerase alpha. Under the assay conditions with activated DNA as the template.primer and Mg2+ as the divalent cation, the maximum incorporation rate of [3H]ddGTP reached 14.5% when compared to that of the corresponding normal substrate [3H]dGTP. These results indicate that the observed inhibition of DNA polymerase alpha activity by low concentrations of ddGTP in the presence of Mn2+ cannot be explained by the incorporation of ddGTP followed by chain termination of the growing DNA, and the results also support the previously presented hypothesis that the inhibition is caused by competition between the dideoxynucleotide inhibitor and its corresponding deoxynucleotide substrate at the same enzyme binding site. Thus ddGTP acts as an inhibitor or a substrate for DNA polymerase alpha depending on its concentration and the species of divalent cation. Some of the kinetic properties of DNA polymerase alpha connected with ddGTP are also described.

Novel nondestructive evaluation measurements made using niobium dc superconducting quantum interference devices with integrated asymmetric first-order gradiometers are described. Comparative theoretical and experimental studies of their spatial response have been described, and it is shown that the gradiometric response makes operation possible in an unshielded and electromagnetically noisy environment. As a demonstration of their capabilities, subsurface defects in a multilayer aluminum structure have been located and mapped using induced eddy currents at 70 Hz, with no magnetic shielding around the specimen or cryostat.

We describe an eddy current nondestructive evaluation system using a low-temperature superconductor magnetic field sensor in an electromagnetically unshielded environment. The sensor comprises a niobium dc superconducting quantum interference device (SQUID) integrated with a first-order gradiometric pickup coil to reject spatially uniform interference fields but remain sensitive to flaw induced fields. We demonstrate its use in locating and mapping subsurface flaws in a multilayered aluminum structure using an eddy current excitation field at a frequency of 70 Hz, with no magnetic shielding around the specimen or cryostat.

The roles of histamine formed by the macrophage - T lymphocyte system were evaluated in the regulation of lymphocyte proliferation using mice lacking histamine receptors.Mice deficient in histamine type 1 (H1R), type 2 (H2R) or both receptors were employed to estimate possible intervention of the receptors in the histamine-dependent lymphocyte proliferation.Histamine was produced de novo by spleen cells. Con A-dependent T cell proliferation decreased when histamine produced in the culture was degraded by the addition of histaminase. The H2R-deficient mice also showed a significant decrease in the Con A-dependent T cell proliferation, whereas it was not modulated in the H1R-deleted mice. Consistent with the reduction in T cell proliferation, there was a significant down-regulation of the production of IL-2, a T cell growth factor, in the H2R-deficient mice. Con A-dependent IL-2 synthesis was abrogated by the addition of histaminase.Con A-dependent T cell proliferation is (up)regulated by histamine produced de novo through the H2R, suggesting that histamine is a newly found regulator of T cell proliferation.

ATM switches, which serve as nodes in ATM public backbone networks, are required to have a large capacity due to the increase of traffic. This paper proposes a large-scale ATM switch architecture providing 160 Gbit/s switching capability. It is such that the output buffered switch elements are expanded in square grids. Our switch architecture achieves non-blocking and multi-QoS guarantee. As a way to ensure multi-QoS, we employ a stop-shape-go (SSG) congestion control method and its performance is evaluated by simulation.

HoSb and DySb compounds have a very high specific heat peak below 10 K, and the measured specific heat of GdSb has a distinct peak at 25 K. Analyses have been conducted focused on the magnetic properties of these compounds to understand the difference between samples with sharp specific heat peaks and those with broad peaks. The magnetization of the samples was measured with a Vibrating Sample Magnetometer (VSM). The magnetic properties of HoSb and DySb are small above 100 K, while the magnetic property of GdSb exists up to near room temperature. Although further analysis is necessary, the data suggest that the differences in the specific heats between the materials is mainly due to differences in their magnetic properties.

In this paper, a simple control methodology for macro/micro manipulator system is proposed. The macro/micro manipulator system consists of a multi-link rigid body manipulator as a macro manipulator and a machining unit mounted on the end-effector of the macro manipulator as a micro manipulator. It is shown that the state equations of the proposed macro/micro manipulator system are identical with the singular perturbed system. A simple method of control system design of this system can be derived from the singular perturbation theory. Simulation results show that the proposed control scheme perfectly compensates the tracking errors. An experimental verification of the proposed control algorithm is shown by applications to electrodischarge machining. >

Basic theoretical analyses to detect undesirable foreign metal pieces in the meat being processed have already been carried out. In this study, taking the low conductivity of meat into account, a double-layered spherical sample structure which enables easy analyses was selected. In order to detect these conductive materials, analyses of the difference in the impedance of a circular coil with, and another one without a double-layered spherical conductor were made. In this way, a new formula for obtaining the electromagnetic properties of a double-layered spherical sample was derived. The process of deriving the new formula is explained. The calculated value was compared with the experimental value. Their values had a close correlation.

This paper presents a design of a low-voltage fully differential current-mode analog CMOS integrator using FG (floating gate)-MOSFETs. The performances of the proposed circuit are predicted by theory and SPICE simulations. The integrator covers the frequency range 4 MHz-800 MHz at a 1.5 V supply voltage and dissipates DC power of about 74 /spl mu/W. The proposed integrator was fabricated in a Motorola 1.2 /spl mu/m CMOS process through VDEC (VLSI Design and Education Center).

Materials including rare-earth and Sb compounds were developed as regenerator materials for a 4K GM refrigerator. Sb compounds have a remarkably large peak value of specific heat in the low temperature range. First, the heat capacities, thermal conductivity, and thermal expansion of HoSb, DySb and GdSb, which are anti-ferromagnetic with a large spin value in the low temperature range, were measured. Then, the results of these measurements were used to analyze the problems encountered when Sb compounds were used as the regenerative materials in a GM refrigerator.

The classification of 'Manic-depressive illness(MDI)' has been changing in this several years greatly. MDI is recently named as a 'mood(affective) disorder' according to the ICD and DSM diagnostic system. Since 1990, with ICD-10(WHO), and 1994, with DSM-IV(APA), practitioners have had at their disposal two(practically compatible) classifications of mental disorders containing operational criteria for diagnosis, and helpful in guiding clinical and therapeutic approach. In ICD-10, mood disorder belongs to the F3 category, and there are seven subcategories which were divided in to subclasses. The two other subclasses of 'F06.3 organic mood disorder' 'F41.2 mixed anxiety and depressive disorders' were set up additionally.

We report a case of synchronous presentation of thyroid cancer and testicular seminoma with lymph node metastasis. A 37-year-old man presented with right scrotal swelling and multiple lymph node swelling. We performed right radical orchiectomy, and histological examination revealed a seminoma of the testis. After systemic work-up for staging, we diagnosed the patient with multiple lymph node metastasis of the seminoma, and administered three cycles of bleomycin, etoposide, and cisplatin (BEP) therapy. Although the chemotherapy was very effective for the retroperitoneal and left cervical lymph node metastases, the right cervical tumor did not change. Retroperitoneal lymphadenectomy combined with right cervical lymph node dissection and hemi-thyroidectomy were performed on September 8, 1998. Pathological examination of the thyroid revealed papillary thyroid cancer and its right cervical lymph node metastasis. There was no evidence of viable cancer cells from either of the primary cancers in the retroperitoneal lymph node. Unresponsiveness to chemotherapy for metastatic lesions from testicular cancer might be a useful clue to detect primary tumors of other origins.

Prenyltransferases (prenyl diphosphate synthases), which are a broad group of enzymes that catalyze the consecutive condensation of homoallylic diphosphate of isopentenyl diphosphates (IPP, C5) with allylic diphosphates to synthesize prenyl diphosphates of various chain lengths, have highly conserved regions in their amino acid sequences. Based on the above information, three prenyltransferase homologue genes were cloned from a thermophilic cyanobacterium, Synechococcus elongatus. Through analyses of the reaction products of the enzymes encoded by these genes, it was revealed that one encodes a thermolabile geranylgeranyl (C20) diphosphate synthase, another encodes a farnesyl (C15) diphosphate synthase whose optimal reaction temperature is 60 degrees C, and the third one encodes a prenyltransferase whose optimal reaction temperature is 75 degrees C. The last enzyme could catalyze the synthesis of five prenyl diphosphates of farnesyl, geranylgeranyl, geranylfarnesyl (C25), hexaprenyl (C30), and heptaprenyl (C35) diphosphates from dimethylallyl (C5) diphosphate, geranyl (C10) diphosphate, or farnesyl diphosphate as the allylic substrates. The product specificity of this novel kind of enzyme varied according to the ratio of the allylic and homoallylic substrates. The situations of these three S. elongatus enzymes in a phylogenetic tree of prenyltransferases are discussed in comparison with a mesophilic cyanobacterium of Synechocystis PCC6803, whose complete genome has been reported by Kaneko et al. (1996).