HHV-6 in AIDS.
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Biomedical subjects
Publications and source records attributed to J McLaughlin.
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A complementation strategy was developed to define the signaling pathways activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of the kinase domain, and the Grb-2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently restored transformation activity only to the Bcr-Abl SH2 mutant. These data support a model in which Bcr-Abl activates at least two independent pathways for transformation. This strategy may be useful for discerning signaling pathways activated by other oncogenes.
c-Abl is a tyrosine kinase localized primarily in the nucleus. Previous assays for abl function rely on cellular transformation by abl mutants, which are cytoplasmic. Using a conditional overexpression strategy, we have developed a functional assay for c-abl. Overexpression of c-abl inhibits growth by causing cell cycle arrest. Growth suppression requires tyrosine kinase activity, nuclear localization, and an intact SH2 domain. Overexpression of dominant negative c-abl disrupts cell cycle control and enhances transformation by tyrosine kinases, G proteins, and transcription factor oncogenes. These findings suggest that c-abl acts as a negative regulator of cell growth. This growth suppressive activity is functionally similar to that of tumor suppressor genes such as p53 and Rb.
To confirm preliminary interpretive breakpoints for prototype 5 micrograms levofloxacin disks, 490 strains were tested in vitro using commercially manufactured disks. For in vitro susceptibility testing, 5 micrograms levofloxacin disks can be used with interpretive criteria of < or = 12 mm for resistant (MIC > or = 8.0 micrograms/ml) and > or = 16 mm for susceptible (MIC < or = 2.0 micrograms/ml). Proposed quality control limits for tests of levofloxacin are as follows: Escherichia coli ATCC 25922, zones 29-37 mm or MIC 0.008-0.03 microgram/ml; Pseudomonas aeruginosa ATCC 27853, zones 19-26 mm or MIC 0.5-2.0 micrograms/ml; Staphylococcus aureus ATCC 25923, zones 24-31 mm; Staphylococcus aureus ATCC 29213, MIC 0.06-0.25 microgram/ml and Enterococcus faecalis ATCC 29212, MIC 0.25-2.0 micrograms/ml.
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During late spring and early summer of 1993, national and international media called worldwide attention to a cluster of deaths in the southwestern United States. These patients succumbed to a rapidly progressive severe respiratory distress syndrome. After notification of state and national health agencies in mid-May, a major effort was launched to determine the cause of this often fatal respiratory distress syndrome, to advise the public on safety measures, and to determine the method of spread of this "mystery illness." Within weeks of recognition of the early cases, the Centers for Disease Control and Prevention announced the probable agent, a Hantavirus. This report details the response of pathologists, medical technologists, and other laboratory scientists to this new viral epidemic, with emphasis on activities that occurred within New Mexico.
A portable cardiac mapping system is used to improve the accuracy of diagnosis of acute ischaemic injury outside hospital. Patients presenting chest pain suggestive of myocardial infarction (MI) were mapped by attendant medical personnel operating from a mobile coronary unit. These first MI maps were compared against average normal maps using QRS and ST-T isointegral values. Discriminant function analysis performed on the parameters achieved a sensitivity of 90% and a specificity of 96%.
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The prognosis of patients with progressive multifocal leukoencephalopathy is poor, with few patients showing remission or surviving. We describe a 37-year-old man who developed progressive multifocal leukoencephalopathy in association with sarcoidosis. Despite treatment with cytarabine and acyclovir, he continued to deteriorate. Shortly following the addition of interferon alfa, he made a dramatic improvement, regaining full functional independence. The use of interferon alfa in addition to cytarabine in such patients offers a new therapeutic approach worthy of further trial.
Observations have been made on a patient with Friedreich's ataxia who died 52 years after the onset of symptoms. The pathology of the brain and spinal cord was typical of this disorder. Apart from loss of dorsal root ganglion cells, severe loss of secondary sensory neurons was observed, including the nucleus dorsalis in the spinal cord, the spinal and principal trigeminal nuclei and, in particular, the mesencephalic trigeminal nucleus in the brain stem. Morphometric studies on the first sacral nerve root and on the sural nerve at levels from midthigh to ankle revealed a distally accentuated axonal loss that predominantly affected larger myelinated nerve fibres. Regenerative activity was seen, mainly in the spinal root and proximally in the sural nerve. Relative myelin thickness, assessed by a g ratios, tended to be reduced. As teased fibre studies showed only limited evidence of demyelination/remyelination and of axonal regeneration, this therefore suggests the presence of a hypomyelination. The results confirm the presence of a distal axonopathy and provide no evidence that this is preceded by axonal atrophy.
Three beta-lactamase inhibitors were combined with ampicillin in a fixed 2:1 ratio. The activity of ampicillin was enhanced by tazobactam and by clavulanic acid, and to a lesser extent by sulbactam when tested against fresh clinical isolates of Enterobacteriaceae. At a concentration of 8 micrograms/ml, ampicillin alone inhibited 49.6% of 2,434 consecutive isolates of enteric bacilli compared to 81% inhibited by ampicillin combined with tazobactam or clavulanic acid and 69.3% inhibited by the sulbactam/ampicillin combination. A four-fold or greater reduction in ampicillin MICs was observed in comparable numbers of isolates with all three combinations, but the most marked effects were seen with strains that were highly resistant to ampicillin.
In vitro studies in five different medical centers documented the susceptibility of 2,440 consecutive isolates of the Enterobacteriaceae against ampicillin-sulbactam disks of different potencies. For determination of MICs, both 2:1 or 1:1 ratios were used as long as the concentrations of sulbactam at the breakpoints remained the same, i.e. MIC < or = 16/8.0 micrograms/ml or < or = 8.0/8.0 micrograms/ml for the susceptible category. Disks containing 10 micrograms of ampicillin and 10 micrograms of sulbactam are still to be preferred with interpretive criteria of > or = 15 mm for susceptible and < or = 11 mm for resistant (MIC > or = 64/32 micrograms/ml or > or = 32/32 micrograms/ml). The reliability of the disk test actually diminished when the amount of sulbactam in the disk was increased.
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The role of self-care in the management of chronic illnesses is essential to successful patient care. This paper compares and contrasts self-initiated self-care practices of 51 Danish and 35 American persons with multiple sclerosis at various levels of disability. Respondents were asked about ways they managed their symptoms and problems during periods of non-medical contact--including methods of following the medical regimen; alternative treatments; use of lay-referral systems; and, sources of information regarding physical, psychological, social, and environmental dimensions of coping with the illness. The two groups of respondents varied regarding adaptation strategies and primary sources of information used. The ultimate aim, however, of using these strategies was similar; to gain control over uncertainty, dependency, and physical and emotional decline. This study suggests that the empowering role of self-initiated self-care strategies in chronic illness may transcend differences in health care systems.
The aim of the study was to provide a preliminary basis for advising women with cerebral palsy (CP) who choose to initiate pregnancy regarding the course of parturition and the outcomes for their newborn infants. The authors studied 22 women with CP who had 38 pregnancies at a mean age of 26 years. Eight pregnancies were electively terminated and two resulted in miscarriage. Of the 28 viable pregnancies, one resulted in a preterm stillborn infant and two in preterm liveborn infants. Delivery was vaginal in 18 cases and by cesarean section in nine (one pregnancy was lost to follow-up). Pregnancy outcomes were reassuringly normal in this small, select sample of women with relatively mild CP. Possible effects of pregnancy and childbirth on general adaptive skills or specific child-care skills of women with CP could not be assessed in this retrospective study.
Two cases of staphylococcus aureus septicaemia secondary to endometritis following endometrial destruction are presented. After surgical endometrial destruction, endometritis has been reported rarely, but there are no previous reports of staphylococcal septicaemia.
The c-ABL proto-oncogene is a predominantly nuclear localized tyrosine kinase. A random mutagenesis scheme was used to isolate c-ABL mutants whose expression produced a transformed phenotype in rodent fibroblast cells. An in-frame deletion within the central region of the last exon was identified in one ABL mutant. The mechanism of c-ABL oncogenic activation by mutation within the last exon differs both functionally and structurally from those of v-ABL and BCR/ABL. This class of ABL mutants shows increased tyrosine phosphorylation of cellular proteins in vivo but low levels of autophosphorylation. Last-exon ABL mutants are distinguished from v-ABL or BCR/ABL by their inability to transform primary bone marrow cells or support the growth of transformed pre-B cells. These findings define a new mechanism of oncogenic activation for the ABL kinase through mutations in the last exon which do not require amino-terminal deletions or mutations within the src homology regions.