Showing papers by "Memorial Sloan Kettering Cancer Center published in 1985"
2,505 citations
TL;DR: The entire 1,370-amino-acid sequence of the human insulin receptor precursor is deduced from a single complementary DNA clone, finding sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.
Abstract: We have deduced the entire 1,370-amino-acid sequence of the human insulin receptor precursor from a single complementary DNA clone. The precursor starts with a 27-amino-acid signal sequence, followed by the receptor α-subunit, a precursor processing enzyme cleavage site, then the β-subunit containing a single 23-amino-acid transmembrane sequence. There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.
2,140 citations
TL;DR: The practice and theoretical basis of pain measurement is reviewed and critically examined in the areas of animal research, human subjects laboratory investigation and clinical study, and subjective report procedures are evaluated in human laboratory and clinical areas.
Abstract: The practice and theoretical basis of pain measurement is reviewed and critically examined in the areas of animal research, human subjects laboratory investigation and clinical study. The advantages and limitations of both physiological and behavioral methods are discussed in each area, and subjective report procedures are evaluated in human laboratory and clinical areas. The need for procedures that bridge these areas is emphasized and specific issues are identified. Progress in the technology of pain measurement over recent decades is reviewed and directions for future work are suggested.
1,057 citations
TL;DR: The molecular cloning and characterization of a gene regulated by rIFN-γ in U937 cells as well as in human mononuclear cells, fibroblasts and endothelial cells is reported here and may be a member of a family of proteins involved in the inflammatory process.
Abstract: Interferons are a family of proteins first identified by their ability to induce cellular resistance to infection by many viruses. In addition to the antiviral properties it shares with the α- and β-interferons, γ-interferon (IFN-γ), a lymphokine secreted by activated T cells, activates macrophages, stimulates B cells, increases fibroblast and endothelial cell resistance to many non-viral intracellular parasites and modulates cell-surface proteins central to immune cell regulation1–13. To identify molecules involved in the IFN-γ response and characterize their modulation, we have isolated genes that are induced following recombinant IFN-γ treatment of U937 cells, a histiocytic lymphoma cell line with monocytic characteristics14,15. We report here the molecular cloning and characterization of a gene regulated by rIFN-γ in U937 cells as well as in human mononuclear cells, fibroblasts and endothelial cells. Messenger RNA from this gene is induced within 30 min of rIFN-γ treatment and demonstrates maximal (>30-fold) accumulation within 5 h. Increased transcription is partly responsible for this accumulation. This gene encodes a protein of relative molecular mass (Mr) 12,378 which has significant amino-acid homology to platelet factor-4 and β-thromboglobulin, two chemo-tatic proteins released by platelets on degranulation. This IFN-γ-inducible protein may be a member of a family of proteins involved in the inflammatory process.
910 citations
TL;DR: Changing attitudes toward the effective use of narcotic analgesics, the development of novel routes and methods of administration, and a clinical approach based on scientific principles and humane care offer the promise of improved management of pain in patients with cancer.
Abstract: Pain is one of the most feared consequences of cancer Control of pain from cancer should be possible with the approaches discussed above Changing attitudes toward the effective use of narcotic analgesics, the development of novel routes and methods of administration, and a clinical approach based on scientific principles and humane care offer the promise of improved management of pain in patients with cancer
876 citations
TL;DR: The human leukemic myeloblast HL‐60 and monoblast U937 cell lines have made important contributions to the disciplines of cancer, hematology, and immunology.
Abstract: The human leukemic myeloblast HL-60 and monoblast U937 cell lines have made important contributions to the disciplines of cancer, hematology, and immunology. As sources of leukemic cells, they have been used for the study of neoplasia and therapeutics. As sources of hemic cells, they have been used for biochemical and biological analysis of regulation and differentiation in myelopoiesis. When stimulated with immunomodulatory factors, the cell lines develop properties of host-defense effector cells. They are also a source of cytokines that affect other cell types.
640 citations
TL;DR: Treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation of inducing objective tumor regression in 53 to 89 per cent of the cases.
631 citations
TL;DR: R24 is an IgG3 mouse monoclonal antibody that identifies GD3, a prominent ganglioside on the surface of melanoma cells and other cells of neuroectodermal origin, which shows lymphocyte and mast cell infiltration, mast cell degranulation, and complement deposition.
Abstract: R24 is an IgG3 mouse monoclonal antibody that identifies GD3, a prominent ganglioside on the surface of melanoma cells and other cells of neuroectodermal origin. Twelve patients with metastatic melanoma were treated with R24 at three dose levels, 8, 80, or 240 mg/m2, over a period of 2 weeks. Peak antibody levels in the serum were dose related and ranged from less than 0.1 to 62 micrograms/ml. Inflammatory reactions (urticaria, pruritus, erythema, subcutaneous ecchymoses) were observed around tumor sites in patients treated at doses greater than or equal to 80 mg/m2. Tumor biopsies during and after treatment showed lymphocyte and mast cell infiltration, mast cell degranulation, and complement deposition. Side effects were mild and were readily controlled by antihistamines. Major tumor regression has been observed in three patients.
576 citations
TL;DR: Twenty of 89 consecutive patients with the acquired immunodeficiency syndrome (AIDS) in whom autopsies were performed over a 3 1/2 year period had a vacuolar myelopathy that was most severe in the lateral and posterior columns of the thoracic cord, providing a guide for antemortem diagnosis.
Abstract: Twenty of 89 consecutive patients with the acquired immunodeficiency syndrome (AIDS) in whom autopsies were performed over a 3 1/2-year period had a vacuolar myelopathy that was most severe in the lateral and posterior columns of the thoracic cord. Light and electron microscopy showed that vacuoles were surrounded by a thin myelin sheath and appeared to arise from swelling within myelin sheaths. Signs and symptoms referable to the spinal-cord lesions, including paraparesis, often accompanied by spasticity or ataxia (or both), were present in all five patients with marked pathological changes, in five of seven patients with moderate changes, and in two of eight patients with mild changes. Fourteen patients were demented. The clinical presentation was sufficiently distinctive to provide a guide for antemortem diagnosis. Possible causes of the vacuolar changes include uncharacterized viral infection or a metabolic derangement related to selective nutritional deficiency.
529 citations
TL;DR: This work has used Monte Carlo code (EGS) to compute photon spectra for a number of different linear accelerators and finds the mean photon energy to have a value lower than the generally perceived value of one-third the maximum energy.
Abstract: For accurate three‐dimensional treatment planning, new models of dose calculations are being developed which require the knowledge of the energy spectra and angular distributions of the photons incident on the surface of the patient. Knowledge of the spectra is also useful in other applications, including the design of filters and beam modifying devices and determination of factors to convert ionization chamber measurements to dose. We have used Monte Carlo code (egs) to compute photon spectra for a number of different linear accelerators. Both the target and the flattening filter have been accurately modeled. We find the mean photon energy to have a value lower than the generally perceived value of one‐third the maximum energy. As expected, the spectra become softer as the distance from the central axis increases. Verification of the spectra is performed by computing dose distributions and half‐value layers in water using the calculated spectra and comparing the results with measured data. We also examined the angular distributions of photons incident on the surface of the phantom. In currently used models of dose computations, it is assumed that the angular distribution of photons with respect to fan lines emanating from the source is negligible. Although the angular spread of photons with respect to the incident direction has been found to be small, its contribution to the diffuseness of the beam boundaries is significant.
520 citations
TL;DR: Two hundred episodes of fungemia that occurred at Memorial Sloan-Kettering Cancer Center between January 1, 1978, and June 30, 1982 are reviewed and compared with those seen from 1974 through 1977.
Abstract: Two hundred episodes of fungemia that occurred at Memorial Sloan-Kettering Cancer Center between January 1, 1978, and June 30, 1982, are reviewed and compared with those seen from 1974 through 1977. The total number of episodes of fungemia per year increased by 30.6%, episodes per 100 new lymphoma and solid tumor patients increased by 73% and 95%, respectively, and episodes per 100 new leukemia patients decreased by 50%. Fungemia also occurred earlier during hospitalization, and embolic skin lesions were a common early sign of Candida tropicalis fungemia. Mortality was not significantly different with and without amphotericin B therapy in fungemic patients with leukemia, lymphoma, or aplastic anemia (51 of 70 vs. 21 of 24) or solid tumors (29 of 36 vs. 29 of 43); however, some patients appeared to benefit from combination therapy with amphotericin B and flucytosine. The prevalence of disseminated candidiasis at autopsy was the same in treated (11 of 15) and untreated (8 of 11) patients with leukemia, lymphoma, and aplastic anemia, but it was significantly lower in treated (none of 8) than in untreated (5 of 11) patients with solid tumors. Fungal infection remains an important cause of morbidity and mortality in patients with cancer, particularly neutropenic patients with leukemia and lymphoma who are receiving broad-spectrum antibiotic therapy, patients receiving total parenteral nutrition, and patients with solid tumors in whom abdominal surgery is performed [1-23]. A recent review of fungemic patients seen at our hospital between 1974 and 1977 documented a marked increase in the frequency of fungemia and a high mortality rate. Of particular note was that mortality was high whether or not amphotericin B was given; 81% of patients treated with amphotericin B for fungemia due to Candida albicans or Candida tropicalis died despite therapy [14]. Partly because of results such as these, our approach to therapy has changed. We now give am
TL;DR: Two genes encoding steroid 21-hydroxylase, a cytochrome P-450 enzyme, have been located within the HLA major histocompatibility complex, and restriction mapping and hybridization analysis showed that there are two 21-OHase genes, each located near the 3' end of one of the two C4 genes.
Abstract: Two genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor: oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10], a cytochrome P-450 enzyme, have been located within the HLA major histocompatibility complex. Congenital adrenal hyperplasia due to 21-OHase deficiency is a common inherited disorder of cortisol biosynthesis which is in genetic linkage disequilibrium with certain extended HLA haplotypes. These haplotypes include characteristic serum complement allotypes. A series of cosmid clones was isolated from a human genomic library by using a probe encoding part of the fourth component of complement, C4. These clones also hybridized with a probe encoding most of human 21-OHase. Restriction mapping and hybridization analysis showed that there are two 21-OHase genes, each located near the 3' end of one of the two C4 genes. Hybridization with probes specific for the 5' and 3' ends of the 21-OHase gene showed that the 21-OHase and C4 genes all have the same orientation. The 21-OHase genes 3' to C4A and C4B carry T aq I fragments of 3.2 and 3.7 kilobases (kb), respectively. Both of these fragments are found in genomic DNA of most individuals. In DNA from an individual with the severe, "salt-wasting" form of 21-OHase deficiency who was homozygous for HLA-A3;Bw47;C4A*1;C4B*Q0(null); DR7, the 3.7-kb Taq I fragment is absent, whereas hormonally normal individuals homozygous for HLA-A1;B8;C4A*Q0;C4B*1;DR3 do not carry the 3.2-kb Taq I fragment. These data suggest that the 21-OHase "B" gene (3.7-kb Taq I fragment) is functional, but the 21-OHase "A" gene (3.2-kb Taq I fragment) is not.
TL;DR: In this paper, a hierarchical logistic regression model is proposed for studying data with group structure and a binary response variable, where the group structure is defined by the presence of micro observations embedded within contexts (macro observations).
Abstract: A hierarchical logistic regression model is proposed for studying data with group structure and a binary response variable. The group structure is defined by the presence of micro observations embedded within contexts (macro observations), and the specification is at both of these levels. At the first (micro) level, the usual logistic regression model is defined for each context. The same regressors are used in each context, but the micro regression coefficients are free to vary over contexts. At the second level, the micro coefficients are treated as functions of macro regressors. An empirical Bayes estimation procedure is proposed for estimating the micro and macro coefficients. Explicit formulas are provided that are computationally feasible for large-scale data analyses; these include an algorithm for finding the maximum likelihood estimates of the covariance components representing within— and between—macro-equation error variability. The methodology is applied to World Fertility Survey data...
TL;DR: One documented clinical feature was a predilection for proximal versus distal colonic cancer in both CFS and HSSCC kindreds, which clarifies the need for instituting effective surveillance earlier to detect the predominantly proximal colonic cancers.
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is comprised of the following: the cancer family syndrome (CFS), or Lynch syndrome II, which shows early-onset proximal colonic cancer predominance and other associated extracolonic adenocarcinomas, particularly endometrial carcinoma; and hereditary site-specific colon cancer (HSSCC), or Lynch syndrome I, which shows all of the same characteristics, except for extracolonic cancer. Nine families with CFS and two with HSSCC provided the resource that was tested for biomarkers (see companion article). All families were meticulously evaluated for genealogy and cancer verification. Biologic specimens were obtained during field visits to areas of closest geographic proximity to the families. Cancer education and recommendations for surveillance/management were provided to patients and their physicians. Additionally, 40 families (about 3000 individuals) with either CFS or HSSCC have been ascertained. Syndrome cancers were restricted to direct-line relatives as opposed to nonbloodline relatives, arguing against involvement of environmental factors. One documented clinical feature was a predilection for proximal versus distal colonic cancer in both CFS and HSSCC kindreds. This has important clinical significance in that it clarifies the need for instituting effective surveillance earlier to detect the predominantly proximal colonic cancers.
TL;DR: Pulmonary function tests, in particular the diffusing capacity and the difference between rest and exercise alveolar-arterial oxygen tension, were helpful in screening for pulmonary diseases.
TL;DR: The highest nausea and vomiting scores were seen during the period from 48 to 72 hours after administration of cisplatin, with acceptable correlation between patient scores and observer ratings.
Abstract: Although many trials have evaluated the severity and treatment of nausea and vomiting immediately after cisplatin administration, no studies have focused on vomiting occurring more than 24 hours after chemotherapy--delayed emesis. Two consecutive trials were undertaken to evaluate the incidence, course (trial 1), and severity (trial 2) of delayed nausea and emesis and to develop methods to study these conditions. Eighty-six patients receiving cisplatin (120 mg/m2) for the first time were entered. On the day of cisplatin treatment, all received intravenous (IV) metoclopramide (3 mg/kg X 2 doses) plus dexamethasone (20 mg IV X 1 dose) with either diphenhydramine (50 mg IV) or lorazepam (1.0 to 1.5 mg/m2). Sixty-two percent of patients experienced no vomiting during the 24 hours immediately after administration of cisplatin. Overall, 93% of studied patients experienced some degree of delayed nausea or vomiting from 24 to 120 hours after cisplatin. In trial 1, the incidence of delayed vomiting ranged from 21% to 61% and delayed nausea from 24% to 78% in 58 patients. The highest incidence of both delayed nausea and emesis occurred during the period from 48 to 72 hours after administration of cisplatin. Patients who had no emesis during the initial 24 hours after cisplatin were less likely to experience delayed emesis. The severity of delayed nausea and vomiting was evaluated in 28 patients in trial 2. The amount of delayed nausea and vomiting was assessed daily by patients using a visual analogue scale and by an observer rating. The highest nausea and vomiting scores were seen during the period from 48 to 72 hours after administration of cisplatin, with acceptable correlation between patient scores and observer ratings. Although the nausea and vomiting occurring 24 or more hours after cisplatin administration is not as severe as that seen during the initial 24 hours after administration of cisplatin in patients not receiving antiemetics, it is a common condition that merits both further study and specific treatment.
TL;DR: Postradiation osteogenic sarcomas most commonly arose in the bones of the pelvic and shoulder regions, and radiographically showed a destructive bone lesion with or without signs of radiation osteitis.
Abstract: Sixty-six patients with well-documented osteogenic sarcomas arising in bones and soft tissues after exposure to x-rays, which represent approximately 5.5 percent of all osteogenic sarcomas registered since 1921 at this institution, were studied. These secondary sarcomas occurred in equal proportion in both sexes, with the sixth decade of life being the most common age. In 42 patients, the bone had been normal at the time of irradiation, whereas in 24, the radiation was directed against an osseous tumor or tumor-like lesion. The median latent period was 10.5 years in both groups, ranging from 3.5 to 33 years. The radiation varied from diagnostic quality to 1 MeV x-rays. The dose was variable, but none was less than 2000 rads. Postradiation osteogenic sarcomas most commonly arose in the bones of the pelvic and shoulder regions. Histologically, the sarcomas were mostly of the fibrous type (46%) and radiographically showed a destructive bone lesion with or without signs of radiation osteitis. The cumulative disease-free survival rate at 5 years was 17%, with a median survival estimate of 1 year.
Journal Article•
TL;DR: Comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.
Abstract: Pretreating rats 24 hr earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P less than .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.
TL;DR: Most of the mycobacteria were serovar 4 (77%), and most (86%) produced a deep yellow pigment, but tended to be resistant to isoniazid, streptomycin, ethambutol, ethionamide, and rifampin.
Abstract: The Mycobacterium avium complex, only rarely described as an invasive pathogen in humans, has recently been reported to frequently cause disseminated disease in patients with the acquired immune deficiency syndrome Between February 1981 and February 1984 at Memorial Sloan-Kettering Cancer Center, 30 patients with acquired immune deficiency syndrome, 3 patients with leukemia, and 2 patients with congenital severe combined immunodeficiency syndrome developed disseminated M avium complex infection Mycobacteria were often found in multiple sites both antemortem and postmortem Blood cultures were a reliable method for detecting disseminated infection, and the new lysis blood culture systems provided an efficient technique for determining the number of organisms per milliliter of blood Acid-fast stains and cultures of fecal specimens were also helpful in diagnosing infection Most of the mycobacteria were serovar 4 (77%), and most (86%) produced a deep yellow pigment All isolates were susceptible to standard concentrations of clofazimine, cycloserine, and ansamycin, but tended to be resistant to isoniazid, streptomycin, ethambutol, ethionamide, and rifampin
TL;DR: It is concluded that bronchial carcinoid tumors are malignant and 10% of patients present with metastases and for patients with clinically localized tumors, the prognosis is determined by the size and histologic features of the tumor and the status of the regional lymph nodes, which must be assessed at thoracotomy.
TL;DR: Kaposi's sarcoma is a multifocal systemic neoplasm histologically characterized by proliferating fibroblastic and microvascular elements and is more frequent among whites and homosexuals than blacks and intravenous drug abusers.
Abstract: Kaposi's sarcoma is a multifocal systemic neoplasm histologically characterized by proliferating fibroblastic and microvascular elements. Initial signs include macules, papules, or nodules...
TL;DR: The microorganisms that regularly infect patients with the acquired immunodeficiency syndrome (AIDS) take advantage of defects in T-lymphocyte function, but others, such as Streptococcus pneumoniae and Haemophilus influenzae,take advantage of B-cell defects.
Abstract: The microorganisms that regularly infect patients with the acquired immunodeficiency syndrome (AIDS) have become well recognized. Most take advantage of defects in T-lymphocyte function, b...
TL;DR: It is difficult in the early stages of AIDS to separate reactive depression and psychomotor retardation from symptoms associated with central nervous system complications.
Abstract: The acquired immunodeficiency syndrome (AIDS) and its related conditions are a public health problem of unprecedented proportions due to the debilitating and fatal nature of the disease, the sociocultural implications related to contagion, and its initial appearance in certain socially stigmatized groups. The ability of patients to tolerate the consequences of the disease depends on their psychological ability to cope based on emotional strength and the availability of social support. The psychological and social impact of AIDS may result in psychiatric symptoms similar to those seen in other life-threatening diseases, including anxiety, depression, and delirium. Neurologic complications are frequent, the commonest being an encephalopathy and dementia that is poorly understood. It is difficult in the early stages of AIDS to separate reactive depression and psychomotor retardation from symptoms associated with central nervous system complications. Guidelines are needed to manage the psychological problems posed by AIDS and its related conditions.
TL;DR: In an analysis of the genomic variation of AIDS retroviral isolates from patients living in New York, Alabama, and Zaire, restriction maps were constructed by using seven enzymes, each known to cleave the proviral DNA more than once, in conjunction with Southern blot analysis.
Abstract: In an analysis of the genomic variation of AIDS retroviral isolates from patients living in New York, Alabama, and Zaire, restriction maps were constructed by using seven enzymes, each known to cleave the proviral DNA more than once, in conjunction with Southern blot analysis. The maps of LAV, HTLV-III, and ARV-2 as deduced from their published nucleotide sequences were included in this analysis. The results demonstrated that (i) several "signature" restriction sites were common to all isolates; (ii) with the exception of LAV and HTLV-III, the North American and European isolates were all different from one another and showed no geographical specificity; (iii) the African isolates as a group were more diverse than those from North America and Europe; and (iv) the genomic variability was concentrated within the env gene.
TL;DR: The quintet of leg pain, weakness, edema, rectal mass, and hydronephrosis suggests plexopathy due to cancer.
Abstract: We studied 85 cancer patients with lumbosacral plexopathy and documented pelvic tumor by CT or biopsy. Three clinical syndromes were delineated: lower (L4-S1), 51%; upper (L1-L4), 31%; and pan-plexopathy (L1-S3), 18%. Seventy percent of patients had the insidious onset of pelvic or radicular leg pain, followed weeks to months later by sensory symptoms and weakness. The quintet of leg pain, weakness, edema, rectal mass, and hydronephrosis suggests plexopathy due to cancer. CT showed pelvic tumor in 96%. On myelography, epidural extension, usually below the conus medullaris, was seen in 45%. With treatment, only 28% of patients had objective responses on CT and 17% on examination.
TL;DR: These studies demonstrate that regulatory sequences closely linked to the β-globin gene are sufficient to specify a correct pattern of tissue-specific expression in a developing mouse, when the gene is integrated at a subset of foreign chromosomal positions.
Abstract: The globin gene family represents an attractive system for the study of gene regulation during mammalian development, as its expression is subject to both tissue-specific and temporal regulation. While many aspects of globin gene structure and expression have been described extensively1, relatively little is known about the cis-acting DNA sequences involved in the developmental regulation of globin gene expression. To begin to experimentally define these regulatory sequences, we have taken the approach of introducing cloned globin genes into the mouse germ line and examining their expression in the resulting transgenic animals2,3. Here we describe a series of transgenic mice carrying a hybrid mouse/human adult β-globin gene, several of which express the gene exclusively or predominantly in erythroid tissues. These studies demonstrate that regulatory sequences closely linked to the β-globin gene are sufficient to specify a correct pattern of tissue-specific expression in a developing mouse, when the gene is integrated at a subset of foreign chromosomal positions.
TL;DR: Teratoma with malignant transformation, when found in metastatic sites, appeared to be a poor prognostic pathologic variant in male patients with germ cell tumors.
Abstract: Pathology reports of over 580 male patients with germ cell tumors treated between 1972 and 1982 were screened for teratomas in which malignant transformation was apparent. The diagnosis was established in 17 cases. The median age was 28 years (range, 14-52). For patients with disease limited to the testis, the median survival has not been reached, with all five patients surviving disease-free at 22+ to 120+ months. Among the 12 patients with metastatic disease, the median survival was 30.5 months (range, 12-69). All 12 patients were treated with cisplatin-containing regimens. Six had complete responses either to chemotherapy alone or to chemotherapy plus resection of residual disease. Four of the six complete responders relapsed, and three died of progressive disease. One patient with sarcomatous differentiation was treated with a doxorubicin-based regimen and had a partial remission, which lasted 8 months. Teratoma with malignant transformation, when found in metastatic sites, appeared to be a poor prognostic pathologic variant in male patients with germ cell tumors.
TL;DR: The results of a search for sequences homologous to the per locus DNA in the genomic DNA of several species of vertebrates show an unusual, tandemly repeated sequence forming a portion of the 4.5-kb per transcript is homologously to DNA in chicken, mouse and man.
Abstract: The per locus has a fundamental involvement in the expression of biological rhythms in Drosophila. Mutations at this locus can shorten, lengthen or eliminate a variety of rhythmic activities that range from circadian behaviours, exemplified by eclosion and locomotor activities, to short-period behaviour such as the 55-s rhythm of courtship song. DNA from the per locus has been cloned, and we have used P-element-mediated DNA transformation to establish that a 7.1-kilobase(kb) HindIII fragment contains a functional copy of the gene. This transforming DNA contains a single transcription unit which gives rise to a 4.5-kb poly(A)+ RNA. Here we report the results of a search for sequences homologous to the per locus DNA in the genomic DNA of several species of vertebrates. An unusual, tandemly repeated sequence forming a portion of the 4.5-kb per transcript is homologous to DNA in chicken, mouse and man. Cloned DNAs from the mouse and Drosophila are related by long, uninterrupted tandem repetitions of the sequence ACNGGN. At the per locus, these tandem repeats are predicted to code for poly(Thr-Gly) tracts up to 48 amino acids long. These repeated sequences are also transcribed in the mouse. Several long tracts of poly(Thr-Gly) appear to be encoded by DNA cloned from the mouse.
TL;DR: It was concluded that combinations of metoclopramide plus dexamethasone plus diphenhydramine improve antiemetic control, facilitate the usage of higher doses of metclopramid, and decrease the incidence of treatment‐related side effects.
Abstract: A series of consecutive trials were undertaken to determine whether higher doses of intravenous metoclopramide and combinations of metoclopramide, dexamethasone, and diphenhydramine would improve antiemetic control or decrease treatment-related side effects in patients receiving cisplatin at 120 mg/m2. Metoclopramide and dexamethasone were studied because of their proven efficacy as single agents and their differing mechanisms of action and side effects. Diphenhydramine was used because of its possible antiemetic properties and its ability to control acute dystonic reactions. Two hundred fifty-five patients who had never received chemotherapy or antiemetics were observed in the hospital for the 24 hours following cisplatin administration. The addition of dexamethasone or dexamethasone plus diphenhydramine to intravenous metoclopramide 2 mg/kg produced both improved antiemetic control and a decrease in treatment-associated diarrhea (P = 0.002). The use of metoclopramide alone at a dose of 3 mg/kg for only two doses appeared as effective as 2 mg/kg for five doses. When dexamethasone and diphenhydramine were given with metoclopramide 3 mg/kg for two intravenous dosages, 81% of patients experienced no emesis and 93% had two or fewer vomiting episodes. The antiemetic results of this 2-hour "short-course" regimen were superior to metoclopramide 2 mg/kg, with (P = 0.002) or without (P = 0.0001) dexamethasone and diphenhydramine. It was concluded that combinations of metoclopramide plus dexamethasone plus diphenhydramine improve antiemetic control, facilitate the usage of higher doses of metoclopramide, and decrease the incidence of treatment-related side effects.