Sequential response patterns to chemotherapy and radiotherapy in head and neck cancer: potential impact of treatment in advanced laryngeal cancer.
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Biomedical subjects
Publications and source records attributed to J Welch.
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Copper resistance in yeast is controlled by the CUP1 locus. The level of resistance is proportional to the copy number of this locus, which can be found in up to 15 tandemly iterated copies. To elucidate the molecular mechanisms controlling the amplification and expression of the CUP1, locus, we determined its full nucleotide sequence. We have also identified and mapped two transcription units within the basic amplification unit of CUP1 in laboratory yeast strains. One of those transcription units is inducible by copper and encodes a low molecular weight copper binding protein--copper chelatin. The increased production of chelatin, due to both gene amplification and induction of transcription, leads to increased resistance of yeast cells to copper ions.
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A prospective randomized study was conducted to determine the relative effectiveness, toxicity and tolerance of methotrexate (MTX) versus cisplatin (DDP) in patients with recurrent head and neck squamous cell carcinoma. Forty-four patients were randomized to receive either MTX, 40 mg escalated to 60 mg/m2 IV push weekly, or DDP, 50 mg/m2 6 hour infusion days 1 and 8 every 4 weeks. All patients had objectively measurable disease and a performance status greater than 60% (Karnofsky scale). All had been treated with surgery and/or radiotherapy. No patients had prior chemotherapy. Prior treatment, performance status, and site of primary disease were comparable in both groups. Complete and partial objective responses were achieved in 23.5% of the MTX group and 28.6% of the DDP group (P = 0.51). Median duration of response was 84 days in the MTX group and 92 days in the DDP group. Median survival of patients was 6.1 months with MTX and 6.3 months with DDP. Mucositis was noted in 38% of patients in the MTX group (P = 0.001) compared to none in the DDP group. Vomiting occurred in 87% of patients in the DDP group (P less than .0001) compared to 10% of patients in the MTX group. This study demonstrates that in the treatment of recurrent head and neck squamous cell carcinoma, MTX and DDP are equally effective, although MTX appears to be better tolerated.
CGS 7525A, a new tetracyclic compound, was evaluated for alpha 2 adrenoceptor antagonism in receptor binding assays and in behavioral and electrophysiological tests. 3H-Clonidine, but not 3H-prazosin, binding was potently inhibited in vitro by CGS 7525A. In vivo, CGS 7525A attenuated the suppressant action of clonidine on phenylquinone-induced writhing and on locus coeruleus neuronal firing rate. Mianserin was nearly equipotent with CGS 7525A in the 3H-clonidine binding assay, but considerably less potent in the measures of alpha 2 adrenoceptor antagonism in vivo. Both CGS 7525A and mianserin displaced 3H-spiroperidol binding from frontal cortex 5-HT2 binding sites. Although yohimbine resembled CGS 7525A in most respects, its activity at 5-HT2 binding sites was relatively low, CGS 7525A was not associated with any appreciable blockade of norepinephrine or serotonin uptake in vitro. Thus, CGS 7525A appears to be a promising new pharmacological tool for investigating the behavioral function of brain alpha 2 adrenoceptors.
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A device was developed to measure the evoked tensions of the rectus abdominis muscle which consisted of a fluid-filled reservoir wedged between the rectus abdominis muscle and a self-retaining retractor. The evoked contractions of the rectus muscle were compared with that of the tibialis anterior muscle in twelve dogs anaesthetised with pentobarbitone. Significantly greater amounts of tubocurarine were required to depress the response to train-of-four stimuli and the twitch tensions of the rectus muscle than the tibialis. The tibialis recovered faster, spontaneously or after neostigmine, than the rectus in eight of the animals; the opposite occurred in the other four. The present device can be useful during surgery for the evaluation of abdominal muscle tension.
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Considerable evidence has accumulated to implicate general anaesthetic agents as a cause of post-surgical immune depression. In the present study we evaluated the immuno-suppressive effects of three in vivo administered anaesthetic agents on cellular immune function in sub-human primates which did not undergo surgery. Normal rhesus monkeys received a minimal anesthetic dose of ketamine HCl, meperidine HCl, or sodium pentobarbital. Peripheral blood mononuclear cells were assayed for mitogen-induced lymphocyte proliferative responses and cell-mediated cytotoxicity (CC), including antibody-dependent CC, spontaneous CC and alloimmune CC. In vivo administration of the three agents caused significant reduction in lymphocyte functional capabilities. Within 30 min after administration of ketamine HCl or sodium pentobarbital, cytotoxic effector function was significantly depressed, with variable recovery occurring at 48 hr; cytolytic effector function was not impaired after meperidine HCl or in untreated controls. Ketamine HCl selectively suppressed effector function; mitogen-induced lymphocyte proliferative responses were not suppressed. Monkeys given meperidine HCl showed stable effector function and depressed lymphocyte proliferative function. Effects from sodium pentobarbital were non-selective, with reduced cytotoxic and proliferative lymphocyte functions. In summary, this study shows that intravenous anaesthetic agents are immunosuppressive in primates and exhibit disparate effects on afferent and efferent expressions of cellular immunity.
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The results of an epidemiological survey of facial clefting in the province of Manitoba which covered the years 1964 to 1977, inclusive, are reported. The mean annual incidence of total facial clefts was 2 in 1000 births; the incidence of cleft lip +/- cleft palate (CLP), and of cleft palate (CP), unassociated with a syndrome or two or more major malformations, was 1.05 in 1000 and 0.46 in 1000, respectively. Mennonite infants were over-represented in the CLP group and Amerindian infants in both the CLP and CP groups. These ethnic groups also had more familial cases and showed higher average coefficients of inbreeding. Recurrence rates among sibs were found to be influenced by the presence or absence of additional affected relatives and by the presence of malformations in the proband. It is possible that these latter two variables may not be independent.
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Nuclear and mitochondrial DNA replication were monitered during the development of synchronous yeast zygotes. Purified first zygotic buds were also analyzed. Nuclear DNA replicated discontinuously but coincidently with bud initiation, while mitochondrial DNA replicated throughout the zygotic formation and maturation period. First zygotic buds contained the diploid level of both nuclear and mitochondrial DNA.
A new device for collecting and administering blood by intraoperative autotransfusion consists of several novel features: a collection bag that is kept expanded by a vacuum and into which the blood is drawn by suction of a lesser degree than the outside vacuum, a crease in the collection bag that decreases turbulence and foaming, and separation of the infusion element from the retrieval system by a valve that allows pressure infusion and suction continously. The apparatus is inexpensive, quickly assembled, operated by wall suction or suction pump. We have had favorable experience with its use in animals.
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