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At least 487 records · Page 27Linked to original sources
PubMed1991

Construction and physiological characterization of glyceraldehyde-3-phosphate dehydrogenase overproducing transformants of Aspergillus nidulans.

The construction and characterization of glyceraldehyde-3-phosphate-dehydrogenase (GPD) overproducing transformants of Aspergillus nidulans and their behaviour in acetate-limited continuous cultures and glucose-grown batch cultures are described. The A. nidulans acetamidase deletion strain MH1277 was transformed with the homologous gpdA gene on a vector with the homologous acetamidase-gene (amdS) as a selection marker. Transformant A1 contains about nine integrated copies of the gpdA gene, and shows a proportional gene-dosage GPD production of about 22% of the total soluble cell protein. Compared to the wild-type MH1277, A1 has higher growth yields and reaches higher specific growth rates on both acetate and glucose, which could be due to the key position of GPD in glycolysis and gluconeogenesis.

Acetates↗
PubMed1988

Phase I study of weekly-administered iproplatin [cis-dichloro-trans-dihydroxy-bis-isopropylamine platin (chip, JM9)].

Iproplatin [cis-dichlor-trans-dihydroxy-bis-isopropylamine platinum (CHIP, JM9)] is a new antineoplastic platinum analogue with an octahedral conformation. It has more water solubility than does cisplatin and was found to have less neurotoxicity and nephrotoxicity in experimental animals than cisplatin. Like cisplatin, it has been demonstrated to have a broad spectrum of activity in experimental tumor systems. A phase I study of iproplatin was conducted in 28 patients (12 with melanoma, 8 with sarcoma, 6 with breast cancer, and 2 with colon cancer). All patients had failed prior chemotherapy. Four consecutive doses of iproplatin were administered at weekly intervals followed by a rest period of two weeks for hematologic recovery (one course). One hundred forty-two weekly doses were administered with all patients except three receiving at least one full course. The weekly starting dose of 40 mg/m2 was increased to 120 mg/m2 given over 30 minutes without hydration. Myelosuppression predominantly thrombocytopenia, was the dose-limiting toxicity at weekly doses of greater than or equal to 95 mg/m2 per course. With iproplatin doses 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median granulocyte counts were 2.6 x 10(3)/mm3, 2.2 x 10(3)/mm3, and 1.8 x 10(3)/mm3, respectively. Similarly, at iproplatin doses of 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median platelet counts were 144 x 10(3)/mm3, 99 x 10(3)/mm3, and 31 x 10(3)/mm3, respectively. Mild to moderate nausea and vomiting were observed in the majority of patients. No significant neurotoxicity, nephrotoxicity, or ototoxicity was observed. Objective tumor regression was not observed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMedDate not supplied

Pupil abnormalities on the first postoperative day after cataract surgery.

Most, if not all, ophthalmologists strive to achieve a round pupil after cataract surgery with posterior chamber lens implantation. The presence of pupil abnormalities and iris modifications is cosmetically undesirable and may affect the quality of postoperative vision. The pupillary motility may be changed which will in turn affect both pupillary light reflexes and pupillary dilatation during fundus examination. In this paper, we prospectively studied 2 groups of patients who underwent uncomplicated cataract surgery with posterior chamber lens implantation; 100 patients who had planned extracapsular cataract extraction (ECCE), and 130 patients who underwent phacoemulsification. On the first postoperative day, we found a 16% rate of pupil abnormalities in the group which underwent ECCE surgery while only 5.3% of the phacoemulsification group had pupil abnormalities. There were different causes in which the two groups. The most common cause of pupil abnormality after ECCE was due to iris sphincter rupture, whereas the most common cause after phacoemulsification was due to iris trauma during phacoemulsification. These pupil abnormalities are the direct consequence of factors in surgery and we suggest ways to minimize the occurrence of such abnormalities in cataract surgery.

Cataract Extraction↗
PubMed1983

Concentration of vinblastine in human intracerebral tumor and other tissues.

Uptake of vinblastine into human cerebrospinal fluid, intracerebral tumor and autopsy tissues was quantitated radiochemically after separating vinblastine from its metabolites by high pressure liquid chromatography. Only low concentrations of vinblastine were found in cerebrospinal fluid from a single patient. A second patient who received a tracer dose of radiolabelled vinblastine prior to surgical resection of an intracerebral tumor had slightly less radioactivity in tumor than in temporalis muscle, but more in tumor than in edematous brain surrounding the tumor. The radioactivity in tumor increased gradually and exceeded concurrent plasma radioactivity by 2 hr after drug administration. A third patient died 4 hr into a planned 24-hr infusion of radiolabeled vinblastine. Highest vinblastine concentrations were found in organs with high blood flow such as kidney and heart. Intermediate concentrations were found in liver and lung, and low concentrations were found in prostate, gastrointestinal tract, spleen, muscle, bladder, and hepatic and lymph node metastases. A fourth patient died one month after receiving radiolabeled vinblastine. Highest concentrations were in liver and next highest concentrations were in intracerebral tumor. Moderately high concentrations were found in pancreas, thyroid, lung, spleen, ovary, kidney, and kidney metastases. Lowest concentrations were found in omental metastases, heart, breast, and brain. Vinblastine concentration decreased with increasing distance into brain from the brain metastases. Thus, vinblastine was not selectively localized in tumors. The concentrations in tumor did not reflect the concentration in the organ in which the tumor was located. There was no indication that uptake into intracerebral tumor was impaired. Cerebrospinal fluid and brain concentrations of vinblastine did not give any indication of the concentration attainable in intracerebral tumor.

Adult↗
PubMed1986

Fine structure of the malaria parasite Plasmodium falciparum in human hepatocytes in vitro.

Recent advances in the ability to culture the hepatic forms of mammalian malaria parasites, particularly of the important human pathogen Plasmodium falciparum have provided novel opportunities to study the ultrastructural organisation of the parasite in its natural host cell the human hepatocyte. In this electron-microscopic and immunofluorescence study we have found the morphology of both parasite and host cell to be well preserved. The exoerythrocytic forms, which may be found at densities of up to 100/cm2, grow at rates comparable to that in vivo in the chimpanzee. In the multiplying 5- and 7-day schizogonic forms of the ultrastructural organisation of the parasite bears striking resemblances to other mammalian parasites, e.g., the secretory activity and distribution of the peripheral vacuole system, but also homology with avian parasites, e.g., in nuclear and nucleolar structure and mitochondrial form. The latter homologies support earlier suggestions of the close phylogenetic relationship of P. falciparum with the avian parasites. Evidence is also presented showing the persistence of the cytoskeleton of the invasive sporozoite within the cytoplasm of the ensuing rapidly growing vegetative parasites.

Animals↗
PubMed1984

Central nervous system pharmacology of Baker's antifolate (NSC139105) in man.

Radiolabelled Baker's Antifolate (BAF) was administered to 6 patients undergoing surgical resection of intracerebral tumors. Levels of radioactivity in resected tumor and edematous brain adjacent to tumor were generally higher than levels in concurrent plasma samples and were generally comparable to levels in temporalis muscle. Levels in tumor cyst fluid were far lower than concurrent plasma levels and levels in surrounding tumor. Chromatography was performed on tumor from 2 patients and revealed that only a small proportion of the radioactivity represented unchanged BAF. The major metabolite present in tissues was 1 000 times less potent as an inhibitor of dihydrofolate reductase than was BAF. Five patients had cerebrospinal fluid (CSF) sampled following administration of tracer doses of radiolabelled BAF. Radioactivity levels were far lower in CSF than in plasma. Levels of radioactivity in the CSF were also far lower than levels in tumor and brain samples from other patients and were slightly lower than tumor cyst fluid levels. Two patients had CSF collected after they received therapeutic doses of BAF. In these patients, both CSF and plasma were assayed using a dihydrofolate reductase inhibition assay. As with tracer dose studies, CSF concentrations of BAF were substantially lower than were concurrent plasma concentrations. Thus it appears that only very low concentrations of BAF are attainable in human CSF and intracerebral tumor, although a metabolite which is a very weak inhibitor of dihydrofolate reductase attains high concentrations in tumor.

Antineoplastic Agents↗
PubMed1986

Clinical pharmacokinetics of 9, 10-anthracenedicarboxaldehyde-bis [(4,5-dihydro-1 H-imidazol-2-yl)hydrazone]dihydrochloride.

We studied the clinical pharmacokinetics of the anthracene derivative bisantrene using high-performance liquid chromatographic analysis. We administered the drug to ten patients at 120-250 mg/m2 IV; one of these patients also received a second dose of 120 mg/m2 6 weeks later, and another received 150 mg/m2 weekly for three doses. Bisantrene disappeared from the plasma biphasically, with an initial t1/2 of 0.6 +/- 0.3 h and a terminal t1/2 of 24.7 +/- 6.9 h after single doses. The apparent volume of distribution according to the area under the curve was 42.1 +/- 5.9 l/kg, and the total clearance was 1045.5 +/- 51.0 ml/kg/h. The 96-h cumulative urinary excretion was 3.4% +/- 1.1% of dose; thus, renal excretion was a minor route of elimination for this agent. Bisantrene pharmacokinetics in the patient who received a second dose after 6 weeks showed insignificant changes. However, in the patient who was given this drug weekly for 3 weeks, the plasma t1/2 of the drug during the terminal phase became increasingly longer, while the total clearance was significantly reduced. These results suggest that bisantrene may accumulate in the body and that caution is essential in the event of frequent administration.

Adult↗
PubMed1985

Phase II trial of 5-fluorouracil, adriamycin and cisplatin (FAP) in advanced gastric cancer.

Twenty patients (15 male, 5 female) with nonresectable gastric adenocarcinoma were treated with FAP (5-fluorouracil 300 mg/m2 IV on days 1-5, adriamycin 50 mg/m2 IV on day 1, cisplatin 20 mg/m2 IV on days 1-5). Each course was repeated every 21 days. Eighteen patients were evaluable for response. The median age was 51 years, the range extending from 34 to 68. None had undergone chemotherapy. The median Karnofsky performance score was 80%. Nine (50%) partial responses (PR) and eight (44%) cases of stable disease (SD) were observed. One patient showed progression of the disease and died after 6 months. The median duration of response was 6+ months for PR and 6 months for SD. The median survival was 12 months. FAP toxicity was moderate, with the median WBC nadir 3.2 X 10(9)/l (range 0.7-4.2). One patient in PR died of septicemia. Nausea and vomiting were not dose-limiting. Neuropathy was mild in four and moderate in two patients. This FAP combination appears to be as effective with respect to response rate and duration as reported for 5-fluorouracil, adriamycin and mitomycin C (FAM).

Adenocarcinoma↗
PubMed1982

Clinical pharmacology of bruceantin by radioimmunoassay.

During the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2 beta) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2 beta on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration X time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

Antineoplastic Agents, Phytogenic↗
PubMed1986

A comparative study of bisantrene given by two dose schedules in patients with metastatic breast cancer.

Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m2 (37 patients) or an injection of 80 mg/m2 daily for 5 days (D x 5) (35 patients) every 3-4 weeks after stratification by performance status, dominant disease site, and response to prior doxorubicin therapy. All but one patient had received prior doxorubicin. Partial remission (PR) was achieved by 5 of 35 patients (14%) in the S arm and 7 of 35 patients (20%) in the D X 5 arm (P = NS). There were 4 patients who had primary refractoriness to doxorubicin but responded to bisantrene. The median number of courses was two for both arms. The median time to progression was 5 months for the responders in each arm and 3 and 4 months, respectively, for patients who showed no change in the S and D X 5 arms. Myelo-suppression was dose-limiting and greater for the D X 5 arm. Drug fever (34% versus 21% of courses; P = 0.02) and myalgia (22% versus 10% of courses; P = 0.02) were reported more often in the D X 5 arm; malaise was greater in the S arm. Grade 2-3 nausea and vomiting occurred more often in the S arm (40% versus 10% of courses; P less than 0.01). Significant hypotension that was not symptomatic occurred in 1 patient in the D X 5 arm. Phlebitis occurred in 3 patients without a central line. One patient who had previously received doxorubicin and mitomycin C developed heart failure, which was controlled with medication. Bisantrene is an effective drug for metastatic breast cancer that has incomplete cross resistance to doxorubicin, and there was no schedule dependency in this study.

Adult↗
PubMed1988

Post-transfusion purpura following open heart surgery: management by high dose intravenous immunoglobulin infusion.

We present three cases of post-transfusion purpura (PTP) developing in the immediate post operative period after open heart surgery. All had developed platelet specific antibodies and severe anaphylactoid reactions occurred to platelet transfusion in two cases. Treatment with high dose intravenous immunoglobulin (IV IgG) led to complete recovery in two patients one of whom demonstrated a marked biphasic response pattern to therapy. The other died from congestive cardiac failure. PTP is a potentially fatal complication which may well become more frequent with increasing blood product usage.

Aged↗
PubMed1995

Nature of abortive transformation in Saccharomyces cerevisiae.

Disruption mutagenesis by homologous recombination in Saccharomyces cerevisiae is carried out by transforming-DNA fragments containing the target gene disrupted by a selectable marker. A large number of transient (abortive) transformants are often formed that may hinder the isolation of integrants containing the gene disruption. We show that abortive transformants result from re-circularization of the linear transforming-DNA in vivo. Their number was greatly reduced when the cut DNA could not readily re-ligate, either by digestions that gave non-compatible or blunt ends, or by de-phosphorylation. In addition, true integrants could be readily distinguished from abortive transformants through replica plating onto selective media. Enhanced disruption-mutagenesis was also observed when non-compatible ends were generated in an ARS-containing insertion vector.

Aldose-Ketose Isomerases↗