Cyclical Combination Chemotherapy for Advanced Breast Carcinoma

Twenty-five patients with advanced metastatic breast cancer were treated with the combination of methotrexate 60 mg/M² and 5-fluorouracil 700 mg/M² intravenously on the first and eighth days, and cyclophosphamide 100 mg/M² and prednisone 40 mg/M² by mouth daily for the first 14 days of a 28-day cycle. The patients had had no previous chemotherapy or extensive radiotherapy and all but two had not responded to hormonal therapy or endocrine ablation. The major metastatic lesions were: lung (12 patients), liver (four patients), bone (four patients), soft tissue (three patients), nodes (two patients). Seventeen of the 25 patients (68%) responded to treatment with seven complete remissions; these included patients suffering metastatic lesions in the lung, nodes, and soft tissue. The overall median duration of response was nine months (range 6-26 months). Toxicity was primarily haematological, but the group received an average of at least 75% of their calculated dose for each monthly cycle. Haematological toxicity was most pronounced in patients with liver dysfunction and bone marrow involvement. Out of eight nonresponders seven died, with a median survival of six months. Only six of 17 responders died, and the median survival in this group will exceed thirteen months. There was no correlation between the length of the metastasis-free interval after previous treatment and subsequent response to chemotherapy.     

Carcinoembryonic antigen and alpha1-fetoprotein in ulcerative colitis and regional enteritis

Sera were collected from 108 patients with inflammatory bowel disease and assayed for carcinoembryonic antigen (CEA) and alpha₁-fetoprotein (AFP). Seven (14%) of 51 patients with ulcerative colitis had a positive test for CEA and one of these had associated carcinoma of the colon. Ten (19%) of 52 patients with regional enteritis were also seropositive. The sera of 4 (9%) of 47 patients with ulcerative colitis and 2 (5%) of 41 patients with regional enteritis contained small amounts of AFP. Of two unclassified patients one had a positive CEA and the other a positive AFP. No serum was positive for both CEA and AFP. In addition, multiple samples were available for sequential analysis in eight CEA-positive patients but there was no apparent relationship between seropositivity and disease activity. Continued follow-up is now in progress to determine the significance of detectable fetal antigen levels in inflammatory bowel disease.     

Translocation of Photosynthate in Curly Top Virus-infected Tomatoes

Photosynthate translocation in single leaflets of healthy and curly top virus-infected tomatoes was investigated using ¹⁴C as a marker. The amount of radioactivity found in plant parts not exposed to ¹⁴CO₂ was substantially lower in diseased than in healthy plants. The time lag for the appearance of ¹⁴C in the petiole was considerably longer in the infected plants than in the healthy. The kinetics of disappearance of ¹⁴C from the lamina during the 24-hour period following labeling showed a strong retention of recent assimilates within the diseased leaf, not accompanied by increased immobilization into insoluble forms. Sucrose was the predominant compound participating in photosynthate transport in both healthy and diseased leaves. The amount of ¹⁴CO₂ fixed was approximately 40% lower in curly top virus-infected leaves than in healthy leaves.     

KINETICS OF IN VIVO CONVERSION OF γ-[3H]AMINOBUTYRIC ACID TO γ-[3H]HYDROXYBUTYRIC ACID BY RAT BRAIN1,2

Abstract— The appearance of γ-[³H]hydroxybutyric acid ([³H]GHB) in rat brain at various times after the intraventricular administration of [³H]GABA was determined. Radioactivity recovered as [³H]GHB was maximal 30 s after [³H]GABA administration and declined exponentially thereafter. From a linear transformation of the disappearance with time of [³H]GHB formed from [³H]GABA, the fractional rate of disappearance and turnover time of GHB were calculated. Administration of amino-oxyacetic acid (50 mg/kg i.p.) 1 h before [³H]GABA, reduced [³H]GHB formation, measured 4 min after [³H]GABA, to 28% of that found in control animals. This strongly suggests that GABA-transaminase catalyzes at least one step in the conversion pathway. [³H]GHB recoverable 4 min after [³H]GABA was unchanged when animals were pretreated with pyrazole (1.25–5.0 mmol/kg), diphenyl-hydantoin (25 and 75 mg/kg), phenobarbital (7.5–60 mg/kg), ethanol (1.25–5.0 g/kg), or morphine (2.5–10 mg/kg). Significantly more [³H]GHB could be recovered at several time points from animals which had been pretreated with 50 mg/kg i.p. of the convulsant 3-mercaptopropionic acid.     

Peptides in the cerebrospinal fluid of neuropsychiatric patients: An approach to central nervous system peptide function

This review highlights that essentially all of the recently discovered putative central nervous system (CNS) peptides and other peptide substances are measurable in human cerebrospinal fluid (CSF). Preliminary evidence also suggests that peptides in CSF may have an active regulatory role in relation to CNS function and behavior. Even if this is not the case, CSF peptides may prove to be a useful indirect marker of CNS peptide function and metabolism. Alterations in peptides have been reported in neurological and psychiatric illness, pain symptoms and their treatment, symptoms such as anxiety, and following treatment with CNS active drugs such as carbamazepine. CSF methodologies provide a strategy for the study of the interaction of classical neurotransmitters and peptide substances and their relationship to neural function and behavior in man. Assessment of peptides in CSF may supplement post mortem studies of peptide levels and receptor distribution and help lead to new diagnostic and treatment approaches in neuropsychiatric disorders.     

Isolation and Complementation Studies of Auxotrophic Mutants of the Lignin-Degrading Basidiomycete Phanerochaete chrysosporium

A variety of auxotrophic strains of Phanerochaete chrysosporium were isolated after treatment of conidia with UV and X rays. Complementation studies with these strains demonstrated heterokaryotic mycelia and conidia in this organism. Nuclear staining also showed that conidia can be mono-, di-, or multinucleate. Complementation tests allowed the separation of each auxotrophic class with the same phenotype into complementation groups.     

Metabolism of cyclopenta(cd)pyrene at the K-region by microsomes and a reconstituted cytochrome P-450 system from rat liver

Liver microsomes and reconstituted cytochrome P-450 systems purified from phenobarbital or 3-methylcholanthrene pre-treated rats metabolize cyclopenta(cd)pyrene at its K-region to $\text{trans}$-9,10-dihydroxy-9,10-dihydrocyclopenta(cd)pyrene. The rate of formation of the K-region product is from 5% to 25% that of $\text{trans}$-3,4-dihydroxy-3,4-dihydro-cyclopenta(cd)pyrene. The preference of microsomes and purified cytochromes P-450 for oxygenating cyclopenta(cd)pyrene at the ethylenic C(3)–C(4) position is explainable in part by the fact that the C(4) position has the greatest electron density in the highest occupied molecular orbital.