Treatment of acute myelogenous leukemia.
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Biomedical subjects
Publications and source records attributed to S Slater.
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The tissue-distributions of heat shock proteins (HSP) identified by monoclonal antibodies ML-30, TB-78, CA-Str7-1, and MAB 72/73 have been examined in formalin-fixed and paraffin wax-embedded tissues from 10 normal pancreatic specimens and 92 cases of chronic pancreatitis. The chronic pancreatitis cases were divided by probable etiology into alcohol-related, postacute pancreatitis, or idiopathic. The HSP identified by ML-30 and CA-Str7-1 were constitutively expressed, with a regional distribution, by duct and ductular epithelial cells in all normal pancreatic tissues. The HSP detected by ML-30 were expressed uniformly throughout the cytoplasm of the majority of ductular epithelial cells in all cases of chronic pancreatitis, irrespective of suspected etiology, and in the ducts of all but two cases of alcohol-associated chronic pancreatitis. The HSP defined by CA-Str7-1 were identified in the majority of duct or ductular epithelial cells in most of the cases of chronic pancreatitis, although possible differential expression was observed with respect to etiology (ie, there seemed to be less HSP in cases of postalcohol pancreatitis). The HSP identified by TB-78 were not constitutively expressed by normal pancreatic tissues but were found in a few scattered epithelial cells in two of these cases. However, significant expression of these HSP were observed in most epithelial cells in a population of cases regarded as either alcohol-associated (0.05 > p > 0.02) or postacute chronic pancreatitis (0.01 > p > 0.001). The HSP identified by monoclonal antibody MAB 72/73 were either not demonstrable or were expressed at very low levels in both the normal and inflamed pancreatic tissues. Expression of the four groups of HSP molecules appeared to be differentially regulated both in normal pancreatic and in chronic pancreatitis tissues. These differences in expression may indicate different functions in normal tissues, with either a protective or a pathogenic role for these proteins in the diseased state. Our current findings support the hypothesis that expression of certain HSP, particularly those identified by TB-78, may be involved in the pathogenesis of distinct subtypes of chronic pancreatitis. Our data do not suggest that HSP are the primary targets of immune-mediated cytotoxic activity; nevertheless, enhanced expression of these molecules by pancreatic ductular epithelial cells does provide an environment in which increased amounts of endogenous intracellular peptides may be transported to the cell surface, thereby becoming potential targets of immune-surveillance and cell-mediated cytotoxicity. Conversely, HSP may play a protective role in such a manner that selected groups of pancreatic ductular epithelial cells withstand cytotoxic damage of chemical, metabolic, or immune origin, and for significantly increased periods of time than they would otherwise; HSP thereby conserve a population of "reserve" epithelial cells from which pancreatic regeneration might occur. Identification of distinct pathogenic groups, defined according to precise immunohistochemical criteria, might provide the basis of a functional assessment and hence allow development of biologically appropriate strategies for managing individual patients with chronic pancreatitis.
BACKGROUND: Infantile intussusception often presents with symptoms more common to less dangerous conditions, and diagnosis must be established as early as possible. Clinical diagnosis is often wrong and contrast enema is invasive. Sonography is painless and harmless and if it provides a reliable method of diagnosis or exclusion of intussusception, diagnostic delay will be avoided. METHODS: In the John Hunter Hospital, Newcastle, between 1993 and 1994, the names of all children referred for abdominal sonography with a degree of suspicion of intussusception were recorded, and the histories were subsequently reviewed. RESULTS: Fifty patients were studied. Forty-one patients had no sonographic evidence of intussusception and nine patients had positive findings. None of the 41 patients who had negative sonograms proved to have intussusception. The nine patients who had positive findings were subjected to air enema. In two patients the sonographic diagnosis was proved wrong. In the other seven patients it was confirmed. Thus there were two false positives and no false negatives. CONCLUSION: Sonography is a reliable aid to the clinical diagnosis of intussusception.
The seqA gene negatively modulates replication initiation at the E. coli origin, oriC. seqA is also essential for sequestration, which acts at oriC and the dnaA promoter to ensure that replication initiation occurs exactly once per chromosome per cell cycle. Initiation is promoted by full methylation of GATC sites clustered in oriC; sequestration is specific to the hemimethylated forms generated by replication. SeqA protein purification and DNA binding are described. SeqA interacts with fully methylated oriC strongly and specifically. This reaction requires multiple molecules of SeqA and determinants throughout oriC, including segments involved in open complex formation. SeqA interacts more strongly with hemimethylated DNA; in this case, oriC and non-oriC sequences are bound similarly. Also, binding of hemimethylated oriC by membrane fractions is due to SeqA. Direct interaction of SeqA protein with the replication origin is likely to be involved in both replication initiation and sequestration.
The initial clinical clue to the existence of a disorder of the thyroid gland often is the detection of a physical abnormality of the gland. Adequate palpation of the gland is an essential component of the evaluation of a suspected disorder of the thyroid gland. Provided herein are guidelines that others have found useful in improving their skill in this aspect of physical diagnosis.
We describe a phagemid-based system for rapidly generating chromosomal allele replacements in two steps. The system utilizes simple vector-determined selection procedures for each step and requires only that the target strain be male and sup+ (nonsuppressing for amber mutations).
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Growth factor-independent cell lines, including four lines characterized as macrophages, were isolated by infection of BALB/c mouse primary spleen cells with combinations of three retroviruses encoding v-myc, v-ras, and v-myc/v-raf. Proliferating cell lines were isolated only rarely, and after long crisis periods, following the introduction of myc and raf by infection with J2 virus, or of myc and ras by coinfection with myc309 and raszip6 viruses. However, sequential infections with all three viruses--myc plus ras cells reinfected with J2, or J2 followed by myc plus ras coinfection--resulted in rapid outgrowth of cell lines which grew at high growth rates to high densities. When cells were treated with anti-IgG F(ab')2/IL-4/IL-5 to specifically stimulate B cells, cell lines were isolated readily by infection with myc plus ras alone, J2 alone, or all three viruses. These cell lines arose after shorter crisis times and all grew at high growth rates and to high densities. Analysis of cell surface markers and immunoglobulin gene arrangement revealed no lymphoid characteristics in any of the lines. Four cell lines express all three macrophage markers analyzed (F4/80, Mac1, FcR), and many others are Mac1+ and/or FcR+. Out of 20 immortalized cell lines tested, 13 show clonal growth in soft agar, and 3/6 of these produced tumors in BALB/c mice, indicating that fully transformed cells may be isolated by these procedures. In at least one of the cell lines, integration of all three infecting viruses has occurred.
Thirty-eight solar keratoses from 32 patients were studied for expression of mutant p53 protein by an immunohistochemical technique. Twenty-eight of the 38 solar keratoses (73.7%) showed positive and variable nuclear labelling, whereas 10 specimens were immunonegative. The nuclear immunopositivity which was seen in all variants was mostly diffuse in distribution. The adjacent "normal" epidermis of 8 keratoses showed positive mutant p53 labelling. Eight of the keratoses were associated with invasive squamous cell carcinoma of which only two were immunopositive. Cytoplasmic labelling was never a feature. The study demonstrates that mutant p53 protein is commonly expressed in all variants of solar keratosis and that its expression correlates with atypical keratinocyte proliferation. It is proposed that the demonstration of mutant p53 in the adjacent normal epidermis may be a potential marker of early neoplastic transformation.
An Escherichia coli strain has been constructed that produces the copolymer poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) P(HB-co-HV). This has been accomplished by placing the PHB biosynthetic genes from Alcaligenes eutrophus into an E. coli fadR atoC(Con) mutant and culturing the strain in M9 minimal medium containing glucose and propionate. 3-Hydroxyvalerate incorporation is absolutely dependent on the presence of both glucose and propionate, and 3-hydroxybutyrate-3-hydroxyvalerate ratios in the copolymer can be manipulated by altering the propionate concentration and/or the glucose concentration in the culture. P(HB-co-HV) production can be accomplished by using a wide variety of feeding regimens, but the most efficient is to allow the culture to grow to late log phase in minimal medium containing acetate and then add glucose and propionate to initiate copolymer production. A broad range of propionate concentrations can be used in the culture to stimulate 3-hydroxyvalerate incorporation; however, the most efficient utilization of propionate occurs at concentrations below 10 mM. 3-Hydroxyvalerate molar percentages in the copolymer are relatively constant over the course of growth. The copolymer has been purified and confirmed to be P(HB-co-HV) by gas chromatography/mass spectrometry and differential scanning calorimetry.
Primary colonic lymphoma is an increasingly recognised complication of ulcerative colitis. We report the first known case of rectal lymphoma occurring after colectomy and ileorectal anastomosis in ulcerative colitis.
A recent broadening of family life cycle theory to include the various family norms deriving from ethnic differences, single parenting, divorce, and remarriage has not extended to the lesbian family experience. The need to articulate a lesbian family life cycle is underscored here with particular attention to the specific challenges and coping mechanisms of this particular family experience.
Almost 100% of 52 cattle tested from the southern areas of Zimbabwe were found to have antibodies reactive with Rickettsia conorii compared with less than 30% of 120 cattle from the north. Steers artificially infected with R. conorii isolated from Amblyomma hebraeum were found to show no hematological or biochemical signs of disease but did seroconvert. Clinical signs of infection were restricted to regional lymphadenopathy and dermal erythema, edema, and tenderness at the inoculation site. Rickettsemia was detectable for at least 32 days postinfection. Our findings indicate that cattle could be involved in the transmission of rickettsias by A. hebraeum and may serve as a reservoir of human tick-bite fever in southern Africa.
The effects of ribavirin, a broad spectrum antiviral agent, on the structure and function of normal human nasal epithelium have been studied in vitro, as has also the in vivo effect of treatment with nebulised ribavirin on nasal mucociliary clearance of saccharin in four patients. Ciliary beat frequency was measured by a photometric technique, and changes in epithelial and ciliary ultrastructure were assessed by transmission electron microscopy. Ribavirin solution at the recommended concentration of 20 mg/ml had no adverse effects on ciliary activity in vitro; at concentrations of 50 mg/ml and above it slowed ciliary beating significantly and at 60 mg/ml caused ciliostasis associated with epithelial disruption. Nasal inhalation of ribavirin at 60 mg/ml for up to 20 minutes, however, did not slow nasal mucociliary clearance, nor did it adversely affect the ciliary beating or structure of nasal ciliated epithelium examined in vitro immediately after inhalation.
Paracetamol in serum was assayed by a new enzymatic method, and the results compared with a high performance liquid chromatographic method. Results by the two procedures agreed well (t = 0.05). The correlation coefficient was 0.999, and the slope and intercept by Deming analysis were 0.975 and 0.003 mmol/l respectively. The enzymatic method represents a simple, accurate, precise and not too costly method with several advantages over many currently used techniques. It is eminently suitable for the smaller laboratory, and for use out of normal hours.
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A mixed acid-base disturbance in a long-standing insulin dependent diabetic resulting in a combination of hyperglycaemic ketosis with an alkalosis is reported, in which an analysis of the biochemical mechanisms involved helped to clarify the clinical problem.