Elastic scattering of 65 MeV positive and negative pions from nickel isotopes.
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Biomedical subjects
Publications and source records attributed to D Wright.
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A genomic library was prepared with DNA from a genetically enriched mouse cell line in which amplified copies of the adenosine deaminase (ADA) gene account for over 5% of the genome. Overlapping cosmid clones encompassing the entire ADA structural gene were isolated from this genomic library and used for subsequent structural and functional analyses. Nuclease protection and primer extension analyses served to identify the location of multiple transcription initiation sites at the 5' end of the structural gene. Promoter activity was found by functional analyses to reside within a 240-base-pair fragment which contains the transcription initiation sites. Sequences upstream of the transcription initiation sites are very G + C rich (77%) and include a 22 nucleotide stretch of deoxyguanylate residues and two potential Sp1 transcription factor-binding sites. Comparison of the mouse and human ADA gene promoters revealed the presence of several regions that are highly conserved with regard to both sequence content and location and may represent genetic elements which are involved in ADA gene expression.
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The white rot fungus Phanerochaete chrysosporium degraded DDT [1,1,-bis(4-chlorophenyl)-2,2,2-trichloroethane], 3,4,3',4'-tetrachlorobiphenyl, 2,4,5,2',-4',5'-hexachlorobiphenyl, 2,3,7,8-tetrachlorodibenzo-p-dioxin, lindane (1,2,3,4,5,6-hexachlorocylohexane), and benzo[a]pyrene to carbon dioxide. Model studies, based on the use of DDT, suggest that the ability of Phanerochaete chrysosporium to metabolize these compounds is dependent on the extracellular lignin-degrading enzyme system of this fungus.
Three different 15-kilobase rat genomic clones that contained sequences colinear with U3 RNA were isolated. These inserts hybridized only to U3 RNA in a mixture of total cellular 4-8 S RNA labeled in vivo which showed that genes or pseudogenes for most other small RNAs were absent in these U3 DNA clones. DNA sequence analysis showed that the three subcloned genes contained full-length U3-coding sequences but each had sequence variations, insertions, and/or deletions when compared to rat U3A or U3B RNA. Two of these pseudogenes contained poly(A) sequences on the 3'-end and were flanked by 6-15-nucleotide long direct repeats. None of the three clones was transcribed when injected into Xenopus oocyte nuclei. One clone was a template for a small RNA slightly larger than U3 RNA, but this transcript was not related to the U3 RNA sequences. The structural features of two of these three U3 DNAs are supportive of the hypothesis that some pseudogenes arose from RNA-mediated DNA synthesis and insertion into the genome at random sites (Van Arsdell, S. W., Denison, R.A., Bernstein, L.B., Weiner, A.M., Manser, T., and Gesteland, R.F. (1981) Cell 26, 11-20). This is the first instance where full-length, colinear, U3 RNA pseudogenes have been isolated and characterized.
Twenty-four patients with locally advanced (19 patients) or metastatic (5 patients) tumors were treated in a Phase I study combining constant intravenous infusions of iododeoxyuridine (IUdR) and hyperfractionated radiation therapy. IUdR was given as a constant infusion for 12 hours/day for two separate 14-day infusion periods in most patients. The dose of IUdR was escalated from 250 to 1200 mg/m2/12-hour infusion in this study. The initial tumor volume was treated to 45 Gy/1.5 Gy BID/3 weeks followed by a cone-down boost to 20-25 Gy/1.25 Gy BID/2 weeks after a planned 2-week break. THe IUdR infusion preceded the initial and cone-down irradiation by 1 week. Local acute toxicity (within the radiation volume) was uncommon and few patients required an alteration of the planned treatment schedule. Two patients developed late local toxicity with one patient showing clinical signs of radiation hepatitis and another patient developing a large bowel obstruction that required surgical bypass. Dose-limiting systemic toxicity was confined to the bone marrow with moderate to severe thrombocytopenia developing on Day 10-14 of infusions at 1200 mg/m2/12 hours. Mild stomatitis and partial alopecia occurred in some patients at this dose level. No systemic skin toxicity was seen. Pharmacology studies revealed steady-state arterial plasma levels of IUdR of 1 to 8 X 10(-6) M over the dose range used. In vivo IUdR incorporation into tumors was studied in three patients with high-grade sarcomas using an anti-IUdR monoclonal antibody and immunohistochemistry and demonstrated incorporation in up to 50-70% of tumor cells. The preliminary treatment results, particularly in patients with unresectable sarcomas, are encouraging. In comparison to our previous experience with intravenous bromodeoxyuridine, this Phase I study of IUdR shows less systemic toxicity (especially to skin), higher (2-3X) steady-state arterial levels, and comparable in vivo tumor cell incorporation.
Over an 18-year period we have diagnosed nodular lymphoid polyposis of the intestinal tract in 6 patients. The site of the polyposis, which was due to prominent lymphoid hyperplasia, was ileal (3), colonic (2), and rectal (1). The diagnosis was made following complications arising from the polyps, which included recurrent intussusception (2), rectal prolapse (1), intestinal or pseudointestinal obstruction (2), and rectal bleeding (1). Immunoglobulin staining was performed on all the bowel specimens and in every case secretory IgA was present on the mucosal surfaces and IgG and IgA were seen in the lamina propria, thus excluding immunodeficiency in these patients. Viral studies were performed in 3 patients and all were positive. In one patient Echovirus II was seen in tissue homogenate from a mesenteric lymph node and in another, adenovirus type II was cultured from lymphoid polyps of the rectum. A further patient had positive serological tests for adenovirus. Thus it appears that nodular lymphoid hyperplasia is part of the generalized lymphoid hyperplasia associated with viral infections in infancy and childhood. Immunodeficiency states as a cause of the lymphoid hyperplasia should always be excluded by estimation of serum immunoglobulins.
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Eight subjects suffering from bilateral sensorineural hearing losses with recruitment were fitted binaurally with two-channel compression hearing aids, worn behind the ear. After they had worn the aids for some time, measures of speech intelligibility were compared for two conditions: listening unaided, and listening aided. the dynamic range for speech, defined as the difference in level between the speech reception threshold in quiet and the highest comfortable level for speech, was substantially increased in the aided condition for seven of the eight subjects (the exception was a subject with almost normal low-frequency hearing). Speech reception thresholds were also measured in two levels of background noise ('babble'), 60 and 75 dB SPL. Seven of the eight subjects showed a reduced speech reception threshold (i.e. an improvement) in the aided condition for at least one of the two noise levels, although the size of the improvement differed considerably from one subject to another. The subjects were also given a battery of psycho-acoustical tests in an attempt to better characterise their hearing loss, and to gain more insight into individual differences. Results of measurements of frequency selectivity, frequency discrimination, temporal acuity and temporal masking are described and related to the measures of speech intelligibility.
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Training for the management of violent behavior, on the part of both hospital security officers and other staff members, is essential if violence and inappropriate behavior, and their consequences, are to be successfully dealt with. The laws and practices centering around the concept of training negligence are discussed fully in this article.
"Peer pressure" and "everyone is doing it" have been used as excuses for some drug-taking behavior for too long. We must look harder into reasons for drug use and neither accept these concepts nor teach our young people that this is what is really happening.
Neuromedin K, a decapeptide isolated from porcine spinal cord and suggested to have tachykinin-like activity in vitro, produced reciprocal hind-limb scratching when injected intrathecally to mice. Neuromedin K was 20-60 times less potent in producing scratching (on a molar basis) than substance P, kassinin, eledoisin or physalaemin. The activity of neuromedin K was blocked by the substance P antagonist [D-Pro2D-Trp7.9]substance P at doses of antagonist which effectively blocked the activity of the other tachykinins. These data provide the first evidence for tachykinin-like activity of neuromedin K in the central nervous system.
Eleven patients with peripheral bronchial carcinoma had computerised tomographic (CT) scans before operation. The resected specimens from six of these patients showed mild centri-acinar emphysema. Preoperatively the two groups had not differed significantly in spirometric findings or lung volumes. The frequency distribution curves of EMI numbers within the lung fields of patients who proved to have centri-acinar emphysema differed significantly from those of the group who did not, there being more pixels in the EMI range -450 to -500 in the emphysematous group (p less than 0.001). Detailed assessment of lung density by CT scanning may be useful in the diagnosis of emphysema in life.
This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL-1 production by adherent mononuclear cells [AMC]; and IL-2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 X 10(6) W163 ( a dimethylhydrazine [DMH]-induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL-1 and IL-2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P less than 0.05) which correlated with a fall in both IL-1 and IL-2 generation (r = -0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL-1 = 0.9% and IL-2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation.
Hereditary dysphasic dementia is described in terms of its clinicopathological, ultrastructural, and transmissibility characteristics. Its mode of inheritance is autosomal dominant, and its clinical manifestations of progressive dementia and severe dysphasic disturbances are expressed in late adulthood. Complete neuropathological examination of four patients reveals findings typical for Pick's disease (asymmetrical focal cerebral atrophy), Alzheimer's disease (profuse neuritic plaques), and paralysis agitans (neuronal depigmentation, depletion, and Lewy body formation in substantia nigra) in addition to a striking but nonspecific spongiform degeneration of superficial cortical layers. This unique combination of gross morphological and histopathological features qualifies hereditary dysphasic dementia as a distinct entity, but its precise relationship to the well-recognized adult cortical dementias has been difficult to establish by conventional classification methods. This disorder and other unusual dementing illnesses may be best considered as part of a Pick-Alzheimer spectrum of cortical neuronal degenerations.