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The Canadian Penning Trap (CPT) mass spectrometer is a device used for high-precision mass measurements on short-lived isotopes. It is located at the ATLAS superconducting heavy-ion linac facility where a novel injection system, the RF gas cooler, allows fast reaction products to be decelerated, thermalized and bunched for rapid and efficient injection into the CPT. The CPT spectrometer and its injection system will be described in detail and its unique capabilities with respect to its initial physics program, concentrating on isotopes around the N=Z line with particular emphasis on isotopes of interest to low-energy tests of the electroweak interaction and the rp-process, will be highlighted.

The dc oxygen-discharge cleaning of optical elements contaminated by synchrotron radiation has been studied for a variety of contamination levels, optical materials, electrode and reflecting-surface configurations, discharge powers, and exposure times. Cleaning with a proper electrode-surface configuration resulted in the removal of contaminant layers within 1 h even for highly contaminated elements. The reflectance of mirrors and the diffraction efficiency of gratings were almost completely restored after cleaning over the 4-40- eV energy range; the enhancement even amounted to 1 order of magnitude in some cases. This cleaning procedure did not cause any increased roughness; rather, it resulted in a reduced scattering level of contaminated elements. The removal of contaminants also led to a restoration of the grating blaze; essentially, this contributed to an improvement in the inside first-order efficiency around the blazed energy. From the results with controlled power and exposure time, it was shown that an optimum exposure is achieved within several minutes after the disappearance of visible contamination.

The Canadian Penning Trap (CPT) mass spectrometer, currently located at the Argonne National Laboratory (ANL), is designed to make precise mass measurements of a wide variety of nuclides with half-lives longer than 30 ms. The radioactive nuclides investigated here are produced through fusion-evaporation reactions using heavy-ion beams from the Argonne Tandem Linac Accelerator System (ATLAS). Once created, the nuclides of interest are separated from the beam using a gas-filled magnetic spectrometer. They are then stopped in a gas catcher filled with 150 Torr of helium, extracted and subsequently guided to a radio-frequency quadrupole ion trap where they are accumulated before being transferred to a high-precision Penning trap. This paper will discuss the mass measurement program underway at ANL using the CPT mass spectrometer with particular emphasis on the latest mass measurements obtained of proton-rich nuclides at A ~ 68 from the reaction of a 225 MeV 58Ni beam upon a 12C target.

A new synthetic retinoid, Am80, is effective in treating acute promyelocytic leukemia relapsed from all-trans-retinoic acid-induced complete remission (CR). We report here the long-term clinical outcomes of patients who achieved second CR with Am80. Of 24 evaluable patients, 14 achieved a second CR by Am80 therapy. Of those patients, 4 relapsed within 6 months, despite subsequent consolidation chemotherapy. Six patients underwent sibling or unrelated HLA-matched allogeneic bone marrow transplantation (BMT), and 4 are alive without relase for more than 49 months after achieving second CR. Four of 8 patients who did not receive BMT are alive without relapse for more than 49 months. Promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) fusion transcript was undetectable by reverse transcriptase-polymerase chain reaction in all living patients. Therefore, if patients achieve second CR with Am80 and HLA-matched donors are available, BMT is the treatment of choice. However, it is noteworthy that CR was maintained for more than 49 months in half of the patients who did not receive BMT.

An ion catcher as presented in this contribution is able to create cooled and very clean singly-charged ion pulses out of a ‘hot’ beam within a very short period of time. Precision measurements on shortlived radioactive nuclides become possible. This contribution describes experiments with a 252Cf fission source at the ‘gas-cooler’ at ATLAS (Argonne Tandem Linac Accelerating System) at the Argonne National Laboratories (ANL), Argonne, USA [1]. The system consists of a gas-cell to stop and thermalize the ions, two extraction radio frequency quadrupole structures (RFQ) to separate the ions from the buffer gas and a buncher RFQ to cool and accumulate the ions. The system and its performance is investigated with two independent measurements. The transported activity was measured to determine the efficiency of the system and time of flight measurements (TOF) were performed to determine the transported masses with respect to the transported activity.

The first observation of a magnetic circular x-ray dichroism (MCXD) at the Mn L2,3 core edges in antiferromagnetic LaMnO3 shows canted spin and orbital ( m(orb)) moments arising from lattice distortions. An L2,3-edge MCXD in ferromagnetic metals and insulators, La1-xSr(x)MnO3+delta, reveals that m(orb) of Mn strongly depends on x in the metallic regime but remains unchanged with the metal-to-insulator transition (x approximately 0.16). An O K-edge MCXD, which shows m(orb) of O caused by 2p-3d hybridization, is much larger in the ferromagnetic metal than insulator phases, sharply contrasting with m(orb) of Mn. Our findings indicate a close magnetism-lattice-hybridization coupling.

The Canadian Penning Trap (CPT) mass spectrometer has been modified and reassembled at the ATLAS facility of the Argonne National Laboratory. It is currently being commissioned there. With this apparatus we expect to be able to measure the masses of a wide variety of nuclides having half-lives greater that 0.1 s, to an accuracy of better than 10 ppb of the mass. The planned program of measurements is aimed at improving our knowledge of the nuclear mass surface in general and to provide precise mass data of relevance to tests of the Standard Model and fundamental symmetries. This report describes the current status of the instrument.

The Canadian Penning Trap mass spectrometer was designed to determine precisely the masses of stable and unstable isotopes. To date, such measurements have been carried out on approximately 60 short-lived species. A laser ablation ion source is also available to produce ions of stable isotopes, intended for use in calibrations, checks for systematic effects and for measurements involving stable isotopes. Mass ratios for the isotopes 194,195,196,198Pt relative to 197Au have been determined to a precision of better than 3 × 10−8. These measurements were motivated, in part, by the long-standing discrepancy between earlier mass measurements and the Atomic Mass Evaluations in the mercury region. The results also demonstrate the stability of the measurement system and set limits on the magnitude of systematic effects. No significant deviations from accepted values were found.

All-trans retinoic acid (ATRA) has been used as a potent differentiation drug for acute promyelocytic leukemia (APL). Although the mechanism of its effectiveness upon APL remains unclear, the PML-retinoic acid receptor alpha (RARA) chimeric protein produced by t(15;17) is assumed to underlie the sensitivity of APL cells to ATRA. There are two major isoforms of PML-RARA transcripts; short (S) and long (L), according to the breakpoints in the PML gene. We therefore compared the clinical variables, the response to ATRA and the prognosis between 28 patients with type S and 68 patients with type L. Patients were treated in multi-institutional trials with ATRA, and chemotherapy was combined when peripheral blasts and leukocyte counts increased during the therapy. The clinical features at diagnosis were similar between the two molecular subtypes, and there was no significant difference in remission induction rates; 86% for the type S group and 90% for the type L group. There was no statistical difference in overall survival and CR duration as well as disease-free survival (DFS). In newly diagnosed patients, predicted 2-year DFS was 66% for the type S group and 67% for the type L group. In refractory or relapsed patients, it was 19 and 23%, respectively. These data indicated that isoforms of PML-RARA fused transcripts affect neither the clinical features of APL nor the prognosis after treatment with ATRA.

Minimal residual disease (MRD) was prospectively monitored at the 10(-5) level by the reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-retinoic acid receptor alpha (RARA) transcripts from 27 acute promyelocytic leukemia (APL) patients who achieved complete remission (CR) with all-trans retinoic acid and chemotherapy (previously untreated patients, 15; refractory to chemotherapy or relapsed, 12). The RNA quality from bone marrow cells was firstly assessed by gel electrophoresis to avoid false negativity because of the fragility of the APL cells and the PML-RARA transcripts. In 12 of 15 untreated patients, RT-PCR became negative during consolidation and intensification therapy 4-16 months after the initiation of therapy, whereas it remained positive in nine of 12 refractory patients. At the end of therapy, RT-PCR was negative in 14 patients and positive in 13 patients. The former patients remained in CR at median follow-up of 9 months after the end of therapy. In the latter, however, 10 patients relapsed at a median of 5 months after the end of therapy. These results suggest that the RT-PCR assay can evaluate the quality of CR in APL and predict subsequent relapse.

We sequentially analyzed the immunoglobulin heavy chain variable (IgH V) region gene of leukemia cells obtained from a chronic myeloid leukemia (CML) patient who had three episodes of B-lymphoid crisis after bone marrow transplantation. Southern blot analysis using the JH probe showed different rearranged bands at each crisis, although the same rearranged bands of the BCR gene were observed. We amplified and sequenced the IgH V region gene of the leukemia cells by reverse transcriptase polymerase chain reaction (RT-PCR) using the primers corresponding to the consensus 5'VH and mu constant regions. The dominant leukemia clone at each crisis had a unique VH-D-JH rearrangement; VH4A (V79)-DLR2-J5 (clone-1), VH4B (DP70)-DK4-J6 (clone-2) and VH4A (V79)-DN4-J6 (clone-3) at the first, second and third crises, respectively. Further analysis by PCR amplification using the consensus 5'VH and clone-specific primers revealed that clone-1 underwent VH4--VH3 replacement at the second crisis, and that clone-3 was already in existence at the first crisis. Moreover, the DN4-J6 joining clone, in which the sequence was the same as that of clone-3, was identified at the first and third crises by PCR amplification using primers corresponding to the region upstream of the DN4 segment and DN4-J6 boundary of clone-3. These observations suggest that multiple clones were generated from the progenitor cells of blast crisis, which were transformed at a very early stage of B-lymphocyte ontogeny, by continuing rearrangement mechanisms of the IgH genes, and that the dominant clone at each crisis was undergoing change.

The platelet membrane glycoprotein (GP)Ib/IX complex is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX, and functions as a platelet receptor for von Willebrand factor. All three subunits are reported to be requisite for efficient surface expression of the complex. The absence of the GPIb/IX complex on platelet membrane is the hallmark of a congenital qualitative platelet disorder, termed the Bernard-Soulier syndrome (BSS). We describe here the molecular basis of a novel variant phenotype of BSS in a female patient, designated as BSS Kagoshima. Her platelets completely lacked the surface expression of GPIb alpha, but expressed a residual amount of GPIb beta and GPIX. Unexpectedly, her platelets and plasma contained a truncated GPIb alpha polypeptide with an apparent molecular weight of 116 kD (under nonreducing conditions). The amounts of truncated protein were 23% and 60% of the normal values in platelets and plasma, respectively. The abnormal protein contained a normal amount of sialic acid as demonstrated by digestion with neuraminidase. DNA sequencing analysis showed a homozygous single nucleotide substitution from the serine codon (TCA) to a nonsense codon (TAA) at residue 444 in the GPIb alpha gene. The mutant gene generated a truncated GPIb alpha molecule lacking the transmembrane region and cytoplasmic tail. Her parents were heterozygotes for the mutation. These findings suggest that this type of truncated GPIb alpha was produced, normally glycosylated, and subsequently secreted into the plasma. Furthermore, the truncated GPIb alpha might be associated with the process of the surface expression of incomplete GPIb/IX complex, GPIb beta and GPIX.

All-trans retinoic acid (ATRA)-therapy against acute promyelocytic leukemia (APL) is epoch-making in the sense of the first success in both tumor-differentiation therapy and molecule-targeted therapy. Kouseishou APL-study group performed three clinical studies to refractory APL with ATRA from 1990 to 1993. Complete remission (CR) was obtained in 82%, 88% and 78% of 22, 41 and 46 patients, respectively. Molecular diagnosis of the t (15;17) translocation was possible using Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR).

We treated 70 acute promyelocytic leukemia (APL) patients with daily oral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemotherapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p0.01);100/microliters in 17 out of 18 CR cases, andor = 200/microliters in all failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/microliters, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. Morphological evidence of differentiation was noted in all CR cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 20-month predicted disease-free survival rate is 76% for cases achieving their first CR with ATRA. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage, and high serum triglyceridemia.

We treated 70 patients with acute promyelocytic leukemia (APL) with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in 2 multi-institutional prospective studies. Of 63 evaluable patients, 21 were resistant to initial induction chemotherapy, 10 were resistant to salvage chemotherapy after relapse, 17 were in the first relapse, 4 in the second relapse, 4 in the third relapse, and 7 were previously untreated. In the first study with ATRA from China, 18 (82%) of 22 evaluable patients achieved CR within 8 to 53 days with a median of 29 days. Initial peripheral leukemia cell counts were significantly less in the CR cases (p0.01). They were less than 100/mm3 in 17 of 18 CR cases, and more than 200/mm3 in all failure cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 16-month predicted continuing CR rate is 60%. Based on the first study, in the second study with ATRA from Hoffmann-La Roche AG, if initial peripheral leukemia cell counts were more than 200/mm3, chemotherapy was first given and then ATRA was started. Of 41 evaluable patients, 36 (88%) achieved CR within 11 to 91 days with a median of 34 days. Of 3 patients who received preceding chemotherapy due to high leukemia cell counts, 2 achieved CR. Morphological evidence of differentiation was noted in all CR cases, with Auer rods in mature segmented neutrophils in 13 cases. The clinical signs of DIC decreased rapidly within a few days and disappeared in CR cases. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage and high serum triglyceridemia.

Thirty-three patients with advanced Hodgkin's disease were treated with a combination chemotherapy consisting of vincristine 1 mg/m2 iv on day 1, 8, cyclophosphamide 500 mg/m2 iv on day 1, procarbazine 100 mg/m2 p.o. day 1-7, and prednisolone 40 mg/m2 p.o. day 1-7. Twenty patients received this regimen every 4 weeks (VCPP II regimen). Furthermore, we conducted higher dose intensive VCPP II-2 regimen which was repeated every two weeks for thirteen patients. Complete response rate of both regimens was 63% (VCPP II 45%, VCPP II-2 85%). The median duration of CR was 37 + months. Leukopenia, neurotoxicity and gastrointestinal toxicity were commonly observed but were clinically manageable. These results indicate that high dose intensive chemotherapy is effective for achieving high CR rate for advanced Hodgkin's disease.

N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex) was administered orally, to patients with myelodysplastic syndromes (MDS) and acute leukemia derived from MDS, in a multi-institute study. Out of 77 patients evaluated, one achieved a complete remission, three a good response and two a partial response while 71 failed to respond to a daily oral administration of 30 mg ubenimex. The overall response rate was 7.8% (95% confidence limits; 3.6-16.0%); 7.0% (3.0-15.4%) in 71 MDS and 16.6% (3.0-56.3%) in acute six leukemias derived from MDS. Responses continued for six to 24 (median 10.5) weeks. No serious hematologic, biochemical or clinical toxicity was encountered, except for gastro-intestinal (GI) toxicity in one patient. The present study demonstrated ubenimex not to be generally beneficial for patients with MDS, and not to be recommended as a standard treatment for the disease.

N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex) was administered orally, to patients with myelodysplastic syndromes (MDS) and acute leukemia derived from MDS, in a multi-institute study. Out of 77 patients evaluated, one achieved a complete remission, three a good response and two a partial response while 71 failed to respond to a daily oral administration of 30 mg ubenimex. The overall response rate was 7.8% (95% confidence limits; 3.6-16.0%); 7.0% (3.0-15.4%) in 71 MDS and 16.6% (3.0-56.3%) in acute six leukemias derived from MDS. Responses continued for six to 24 (median 10.5) weeks. No serious hematologic, biochemical or clinical toxicity was encountered, except for gastro-intestinal (GI) toxicity in one patient. The present study demonstrated ubenimex not to be generally beneficial for patients with MDS, and not to be recommended as a standard treatment for the disease.

For the purpose of obtaining the optimal dose of adriamycin (ADM) in hepatic intraarterial one-shot administration, phase I-II study was conducted in 14 patients with various liver cancers. The starting dose of ADM was 20 mg/m2 (4 patients) and the doses were escalated to 40 mg/m2 (5 patients), 60 mg/m2 (4 patients) and 80 mg/m2 (3 patients). One patient with salivary gland cancer showed PR for the liver metastasis. Major toxicity was leukopenia. With a dose of 40 mg/m2, 3 out of 4 patients showed nadir of WBC counts below 4,000/mm3 (2,400, 2,900, 3,100), 60 mg/m2 (1,100, 1,500, 2,200 and 2,700), and 80 mg/m2 (900, 1,200, and 1,400). Nadirs of WBC counts were observed from 9 to 15 days after the one-shot administration, and recovered above 4,000/mm3 in 1 to 3 weeks. Plasma concentrations of ADM from the peripheral vein were determined by HPLC in 12 patients, 14 courses. The curves of ADM plasma levels after 20 and 40 mg/m2 bolus injections were almost the same, and in patients treated with 60 and 80 mg/m2 the curves were also quite similar, but higher in the plasma levels, comparing with in patients with 20 and 40 mg/m2. There might be a limit of ADM tissue absorption, and above the doses 60 mg/m2, ADM might be overflowed, followed by side effects, especially leukopenia. Upon these data of venous plasma concentrations of ADM and leukopenia, the optimal dose of ADM in the hepatic intraarterial one-shot administration seemed to be 40 mg/m2.

Since 1984 several prospective randomized clinical trials have been reported that the disease-free survival for BMT in first remission was superior to chemotherapy for AML. However, there raise two main controversies about these conclusions. First, in last several years intensive consolidation therapy was applied and nearly 50% of patients are reported to be alive 5 years. Second 10% to 50% BMT scheduled patients were excepted mainly because of their condition. On the contrary, about ALL, even these several years, age is the still main risk factor independently of therapy. Reports with good 5 year disease free survival all due to their patients' youth. The prognosis of ALL patients age 30 or more are poor and BMT seems to be a first choice in first-remission in patients under age 40. Only large-scale prospective randomized study among patients with or without HLA-identical donors will give the answer to this important issue.

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 18, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.

The near-normal reflectivity of single-crystal ${\mathrm{TiSi}}_{2}$ from 0.01 to 8 eV and the dielectric functions obtained by Kramers-Kronig (KK) analysis are presented. The effect of an oxide overlayer on the optical properties is also considered. The low-energy response is discussed in terms of the Drude model; the higher-energy spectrum is interpreted on the basis of available information about the electronic structure. A comparison is made with the optical properties of pure Ti and other refractory-metal silicides.

Stereospecific polymerization of vinyl alkyl ether was studied; various kinds of compounds, such as metal oxides, metal halides, metal oxyhalides, metal sulfate complexes and organometallic compounds-Lewis acid complexes, being used at low temperature or room temperature. The relationship between the structures of catalysts and the stereoregularities of polymers is discussed, and it is found that tetrahedral compounds which have one active edge are especially useful for making the stereoregular polymers at room temperature. Also, the shorter the length of active edge, the more suitable the catalyst is for stereospecific polymerization. On the basis of these experimental results, a mechanism of stereospecific polymerization of vinyl alkyl ether is proposed.

The rate of polymerization of t-BuEO by t-BuOK in DMSO is about one-tenth that of propylene oxide. The slow rate of propagation was accompanied by considerable chain transfer. In the absence of solvent, the polymer obtained was crystalline, different from the isotactic form and therefore must be syndiotactic. The NMR spectra indicate the isotactic polymer exists in solution preferentially in the skew1 form, while syndiotactic is about 60% skew1, 40% skew2. Amorphous polymer accompanying isotactic exists about 50% in the trans conformer, by NMR data.

An attempt was made to summarize the activity of magnesium halides in the polymerization of vinyl ethers. Bulk polymerization was carried out at temperatures of 0–80°C. Methyl, ethyl, isopropyl, and isobutyl vinyl ethers were used as monomers, and the relative reactivities of these monomers were compared. Except for the fluoride, magnesium halides had mild activity. Within a given group, the overall activation energies of polymerization decrease with increasing weight of halogen. On the other hand, the molecular weight of polyvinyl ethers obtained from this group of catalysts increases with decreasing weight of halogen. In addition, some differences were observed between the diethyl ether complex and the dioxane complex of magnesium bromide.

Magnesium compounds, especially Grignard reagents were studied as catalysts in the polymerization of vinyl ethers. The Grignard reagent and diethyl magnesium possessed no activity for polymerization of vinyl ether. However, if the Grignard reagent is combined with some sort of third substances, it shows good activity. For these substances, oxygen, aldehydes, some metal oxides, and halogenated hydrocarbons seemed to be effective. The molecular weight of the polyvinyl ether obtained from this combined catalyst system is markedly higher than those of polymers obtained with the Friedel-Crafts type of catalyst, but the polymer of vinyl ether obtained from this mixed catalyst possesses little crystalline structure. The possible mechanism of the polymerization with this mixed catalyst is thought to be a cationic initiation type, because the true active species are regarded to be intermediate compounds which are analogous to magnesium halides or alkoxymagnesium halides. In this connection, alkoxymagnesium halides and magnesium oxide were examined. They had a good activity for polymerization but did not yield a high polymer.

One hundred and six patients with advanced breast cancer were treated with chemoendocrine therapy consisting of adriamycin (40 mg/m2) i.v. on day 1 and cyclophosphamide (130 mg/m2) i.v. daily for 5 days every 3 weeks, ftorafur (500 mg/m2) and tamoxifen (40 mg) orally daily. Of 82 evaluable patients, 16 showed complete response (20%), 32 partial response (39%), 32 no change (39%), and two progressive disease (2%). The overall response rate was 59%, and the median duration of response was 16.3 (3.5-67+) months with a median survival time from the start of chemoendocrine therapy of 25.5 (3.5-67+) months. The median survival time of responders (32.5 months) was significantly longer than that of non-responders (15.3 months). The major toxicities were hair loss, G1 symptoms, and hematological toxicity, but these were clinically well tolerated. No serious cardiac, renal or liver damage was seen. These results indicated that the addition of tamoxifen to the ACF regimen increased the number of complete responses and prolonged the survival time of responders.

Efficacies of 8 antibiotics against Pseudomonas aeruginosa in the relation to serotypes and clinical sources were investigated on 50 strains isolated from patients at Nagoya Ekisaikai Hospital between August and September, 1986. Disk sensitivity test was carried out simultaneously for 5 antibiotics including piperacillin (PIPC), cefoperazone (CPZ), cefsulodin (CFS), ceftazidime (CAZ) and amikacin (AMK), using the single-disk method. We also examined changes in susceptibilities of P. aeruginosa to 5 antibiotics including PIPC, CFS, fosfomycin, gentamicin (GM) and AMK during last 4 years (1983-1986). The results are summarized as follows. 1. CAZ and AMK proved to have high antibacterial potencies, and their MIC80's (concentrations to inhibit growth of 80% of objective bacteria) were both 6.25 micrograms/ml. Following these two the order of potencies were; CFS, cefpiramide (CPM), PIPC, CPZ, netilmicin (NTL), and cefmenoxime (CMX). Sixty two percent of the strains of P. aeruginosa showed high resistances (MIC greater than 50 micrograms/ml) to CPM, CPZ, NTL and CFS, 58% to PIPC, and 2% to AMK. 2. With regard to serotypes, strains belonging to type E were less susceptible than those belonging to types G and I. Type E strains showed high resistance to all antibiotics except CAZ and AMK. 3. Strains obtained from pura and secreta were relatively susceptible, while those from urines were resistant, to these antibiotics tested, in general. 4. Good correlation between MIC's obtained with the agar dilution method (MIC less than or equal to 12.5 micrograms/ml) and these with the disk sensitivity test (greater than ¿ was observed. chi 2 statistical analysis showed that the results obtained with the 2 methods were closely related (P less than 0.01). 5. P. aeruginosa showed fairly high susceptibility to AMK through the recent 4 years (1983-1986). On the other hand, highly resistant strains against CFS, PIPC, FOM and GM increased rapidly during this period.

Eight patients with acute non-lymphocytic leukemia in adults refractory to Daunomycin (DM)-based conventional regimens were treated with AMSA-based regimens. Complete remission (CR) was obtained in 4 (50%) and partial remission (PR) in 2 (25%). The median time to CR was 26.5 days and 3 cases achieved CR in the first cycle. The median duration of CR was 8.3 months. Hematologic toxicity was severe and the nadir (median) of leukocytes and platelets was 0.15 x 10(3)/microliters and 15.5 x 10(3)/microliters, respectively. Other adverse effects were mucositis, nausea.vomiting and hepatotoxicity which occurred over 50%, while cardiac toxicity was not observed. This study indicates that AMSA is clinically non-cross-resistant to DM and considered to be an active drug for salvage therapy.

Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.

Clinical studies of combination therapy with chemotherapeutic agents and interferon (IFN) were performed. Seventeen patients with non-Hodgkin's lymphoma (NHL) and 2 patients with Hodgkin's disease (HD) were treated by combination chemotherapy (COPP or CHOP), and then received 300 X 10(4) U of alpha-IFN daily for 14 days. Complete remission was seen in 11 of 15 evaluable patients with NHL and both of 2 patients with HD. Myelosuppression such as leukopenia and thrombocytopenia was observed in half of the patients. Other side effects were fever, liver dysfunction, alopecia, and peripheral neuropathy. However, all these side effects were mild and well tolerated even in elderly patients.

Twenty-eight patients with a metastatic breast cancer who have achieved a complete remission from a combination chemotherapy that included doxorubicin have been analyzed to ascertain the factors which affect the duration of the response and the survival time. The median duration of a complete remission was 26 months. Relapses occurred in 17 patients (61%), of which the median duration of the response was 18 months and 71% of the relapses occurred at the sites of the prior dominant disease. Most of the patients suffered a relapse while they were receiving maintenance chemotherapy. The number of metastasized organs were one or two in 89% of the patients. The dominant sites of the disease were mainly the visceral (61%) and soft tissue (29%), and the duration of survival was found to be longer in patients with a visceral metastasis. In the group of patients who experienced a recurrence 2 years or more after their operation showed a statistically longer remission and survival time than those who experienced a recurrence within 2 years. The duration of survival from the start of chemotherapy was 45.5 months for complete responders and 21 months for partial responders. This difference was statistically significant (p less than 0.001), though no difference was found between partial responders and "no-change" patients (18.5 months). The tendency towards a relapse at the site of the initial involvement and while receiving maintenance therapy suggests that the majority of patients with a metastatic breast cancer who achieved a complete remission with this combination chemotherapy still have a substantial subclinical residual tumor. Maintenance treatment should be investigated to ascertain the procedures and duration of therapy. Thus, these results have indicated that it is necessary to achieve a complete remission in order to obtain a long term survival.

Seventeen patients with advanced malignancy were treated with recombinant human granulocyte colony stimulating factor rhG-CSF (KRN 8601) infused intravenously over a period of 30 minutes once daily at the dose level/25 micrograms, 50 micrograms, 100 micrograms, 200 micrograms, 400 micrograms, 800 micrograms/m2 for 14 consecutive days, and the effect was compared to the period without rhG-CSF treatment. The maximum numbers of peripheral leukocyte (granulocyte) showed a dose-related increase and the nadir of leukocyte counts escalated with shortening of the period. After stopping infusion, the neutrophil count dropped to the base line level within two or three days. RhG-CSF did not affect other components of peripheral blood such as monocyte, lymphocyte, eosinophil, and hemoglobin value and platelet counts. Transient bone pain occurred in two patients receiving a dose of 800 micrograms/m2. The biochemical changes detected were increased total alkaline phosphatase activity in serum, which appeared in parallel with the increase of neutrophil numbers, and less elevation of total uric acid values. We conclude that an optimal dose of rhG-CSF is 100 micrograms/m2 (average maximum peripheral granulocyte count, 10799/microliters; nadir granulocyte count, 3772/microliters; period of neutropenia, 2.6 days), and rhG-CSF is useful for acceleration of neutrophil recovery and prevention of infection from chemotherapy.

We investigated in vitro synergistic activity of astromicin (ASTM) combined with beta-lactam antibiotics (cefsulodin (CFS), cefoperazone (CPZ), ceftazidime (CAZ), piperacillin (PIPC) and fosfomycin (FOM) against fresh clinical isolated Pseudomonas aeruginosa, which consisted of 13 CFS sensitive (MIC less than or equal to 3.13 micrograms/ml) and 19 CFS resistant (MIC greater than or equal to 400 micrograms/ml) strains according to the FIC index. Against CFS-sensitive P. aeruginosa, ASTM showed good synergistic activities when combined with PIPC (54%), CAZ (38%), CPZ (23%) and CFS (8%). Against CFS-resistant P. aeruginosa, ASTM also showed high synergistic activities when combined with CAZ (63%), CPZ (47%), PIPC (37%) and CFS (11%). Among the CFS-resistant P. aeruginosa, one clinical isolate showed a high sensitivity (MIC0.78 micrograms/ml) against ASTM alone.

Drug resistant phenomenon to antitumor agents remains a major problem in cancer chemotherapy. In this study, we attempted to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation (ABMT). The main regimen consisted of Cyclophosphamide 60 mg/kg/day and thio-TEPA 6 mg/kg/day which were infused for 3 consecutive days. Three patients with malignant lymphoma, four with breast cancer, two with gastric cancer and one with ovarian cancer. All of whom were refractory to conventional chemotherapies were treated. The overall response rate was 70%. Severe bone marrow suppression, mucositis and diarrhea were observed in all patients, but these were not life-threatening and clinically manageable. Furthermore, the administration of granulocyte colony stimulating factor (G-CSF) has significantly (p less than 0.05) shortened the duration of leukopenia, and has been judged to be useful for reducing severe infections and for shortening the period stayed in clean room. Our results indicates that high-dose chemotherapy with ABMT is an effective method for overcoming drug resistance.

Optical constants of several optical glasses and fused quartz between 7 and 23 eV are reported. After a brief description of the method of determining optical constants from the reflectances measured at two or more angles of incidence and the graphical analysis of data, the results are given in terms of n, k, n 2-k 2, and n kν, with some remarks on their accuracies. An absorption band was observed at about 14 eV in the fused quartz and two of the glasses examined and has been tentatively assigned to the characteristic electronic transition of SiO2.