Development of bacterial species-specific DNA probes based on ribosomal RNA genes using PCR.
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Bacteriological Techniques↗
Biomedical subjects
M Maher
Publications and source records attributed to M Maher.
Paclitaxel, cisplatin, and cyclophosphamide in human ovarian cancer: molecular rationale and early clinical results.
The three most active types of agents in the treatment of cancer of the ovary are platinum compounds (cisplatin or carboplatin), bifunctional alkylating agents (cyclophosphamide, melphalan, etc), and the recently developed natural product paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). In an effort to improve long-term disease-free survival in patients with advanced disease, we have developed a three-drug regimen consisting of cisplatin, paclitaxel, and cyclophosphamide. Granulocyte-colony stimulating factor is given as bone marrow support using a flexible dosing approach. The molecular basis for this approach is founded in the positive molecular interactions between cisplatin and bifunctional alkylating agents and between paclitaxel and DNA-damaging agents. Cisplatin and cyclophosphamide damage DNA by two very different mechanisms; the respective importance of DNA strand "kinking" versus DNA strand "cross-linking" may explain the positive cell kill interaction between these two drugs. Paclitaxel appears to markedly slow the repair of DNA lesions caused by DNA-damaging agents, which may include radiation-induced lesions, cisplatin adducts, and cyclophosphamide cross-links. Clinical data to date from several different groups strongly suggest that these molecular interactions translate into positive clinical benefit in human ovarian cancer. Preliminary data from our clinical trial show that these three agents are well tolerated in the doses administered and that this combination shows exceptional promise as a possible therapeutic advance in this disease.
Antineoplastic Combined Chemotherapy Protocols↗
Theory M: A restructuring process.
Through the Nursing Incentive Reimbursement Award (NIRA) Program initiated by the New Jersey Department of Health, a medical center tested, over a two-year time frame, the impact of a staff-developed "Theory M" nursing model. Three nursing units served as control groups and one as the experimental group that incorporated the following features: restructuring of a nursing unit through the redefinition of roles; modifying nurse staffing patterns to change existing ratio of RNs to NAs; incorporating matrix management principles; developing, implementing and evaluating training and educational programs; and renovating a nursing unit.
Health Care Reform↗
Acute midgut volvulus following laparoscopic cholecystectomy.
A case of midgut volvulus forty eight hours following laparoscopic cholecystectomy is reported.
Acute Disease↗
Thoracoscopic esophagectomy in Pakistan.
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Developing Countries↗
Effect of cooking on the concentration of toxins associated with paralytic shellfish poison in lobster hepatopancreas.
The hepatopancreases from lobsters (Homarus americanus) obtained from two locations in eastern Canada (Gaspé and Bay of Fundy) were analysed for paralytic shellfish poisons (PSP) before and after the shellfish were cooked by boiling or steaming. Forty-five lobsters from each location were divided into three groups of 15. Two of the groups were boiled or steamed while the third was uncooked for comparison purposes. The hepatopancreases of all lobsters were individually analysed for total PSP toxicity using the standard mouse bioassay procedure. Individual toxins were determined in each sample using a high-performance liquid chromatographic procedure employing pre-chromatographic oxidation of the toxins to form fluorescent derivatives. The results demonstrated that boiling or steaming reduced total toxicity (measured as saxitoxin equivalents per hepatopancreas) by approximately 65% compared to values obtained from raw lobsters. Of the individual toxins studied, saxitoxin decreased by about 60% with both the cooking treatments while gonyautoxins 2 and 3 (combined) decreased by almost 100% in the Gaspé samples and by about 90% in the Fundy samples with the same cooking treatments. Trace amounts of saxitoxin or gonyautoxins 2 and 3 were detected in some samples of tail or claw meat before or after cooking. In vitro boiling of raw hepatopancreas for up to 30 min led to no change in total or individual PSP concentration, indicating that the toxins in cooked lobster are not removed through chemical decomposition but are leached out during the loss of water.
Animals↗
The ribosomal intergenic spacer region: a target for the PCR based diagnosis of tuberculosis.
SETTING: DNA Diagnostics, The National Diagnostics Centre and University College Hospital, Galway, Republic of Ireland. OBJECTIVE: To investigate the possibility of developing a DNA probe to distinguish the members of the Mycobacterium tuberculosis complex and develop an assay for the detection of M. tuberculosis in sputum. DESIGN: The ribosomal intergenic spacer regions from the members of the M. tuberculosis complex were sequenced and analysed for the ability of this region to provide sequence diversity for DNA probe development. RESULTS: The 100% sequence homology in this region precluded the development of a probe to distinguish the individual members of the M. tuberculosis complex. However it was possible to develop a DNA probe that could specifically detect only the members of the M. tuberculosis complex. CONCLUSION: A specific DNA probe was developed for the detection of the M. tuberculosis complex and its application to M. tuberculosis detection in sputum was demonstrated.
Base Sequence↗
Pseudosarcoma of the larynx: the value of ploidy analysis.
An 82-year-old male presented with a two-month history of hoarseness. A 2 cm pedunculated lesion was removed from the base of his epiglottis. Microscopy showed a polypoid atypical spindle cell lesion. Multiple levels failed to reveal an invasive squamous cell carcinoma. On the basis of haematoxylin and eosin stained sections the main differential diagnosis was a pseudosarcoma with an overlying dysplastic squamous mucosa or infiltrating spindle cell carcinoma. Immunohistochemistry showed positive staining for vimentin but no convincing staining with antibodies to cytokeratin and EMA. Ultrastructural analysis also failed to reveal epithelial characteristics. Ploidy analysis by static cytophotometry of the spindle cell proliferation revealed an aneuploid stem line with a DNA index of 1.67. On the basis of this the process was felt unlikely to be reactive and a diagnosis of a spindle cell squamous carcinoma was made. This diagnosis was subsequently supported by a clinical recurrence of the nodule at a six-month follow-up.
Aged↗
Early experience with leg lengthening by callotasis and chondrodiastasis.
Over a four year period, 20 segments in 16 patients were treated by lengthening by callotasis or chondrodiastasis. The indications for treatment were leg length discrepancy in 13 patients and short stature in three. Patients with leg length discrepancy were all treated by femoral lengthening; the mean length gained was 4.4 cm (range 2.5 to 6.Ocm). For patients with short stature, the mean femoral length gain was 10.0 cm (9.0 to 10.5 cm), and the mean tibial length gain was 8.0 cm (6.5 to 9.0 cm). The commonest problem was pin tract infection, but this always settled with antibiotic therapy. Most other complications were also successfully dealt with, and did not compromise the outcome of treatment. At the time of review, 13 of the 16 patients said they were very happy with the result; two patients were reserving judgement until completion of treatment, and, only one thought the treatment had been of no benefit. Our initial experience, with callotasis in particular, has been that it is a highly satisfactory method of limb lengthening, has an acceptable complication rate, and involves minimal hospitalization as compared with older techniques.
Adolescent↗
Diagnostic value of left ventricular dyssynergy patterns in ischemic and non-ischemic cardiomyopathy.
BACKGROUND: The distinction between ischemic and non-ischemic cardiomyopathy has important clinical implications. The objective of the present study was to investigate whether left ventricular dyssynergy patterns, detected by quantitative analysis of ultrasound images, differed in these two pathological processes. METHODS: Fifty-six consecutive patients with congestive heart failure (New York Heart Association functional class II-IV) secondary to depressed left ventricular systolic function (ejection fraction < or = 35% during diagnostic cardiac catheterization) were studied. Twenty patients were eliminated from further analysis because they met one or more exclusion criteria. The remaining 36 were divided into two groups based on the presence (ischemic cardiomyopathy) or absence (non-ischemic cardiomyopathy) of a > or = 50% narrowing of the luminal diameter in one or more coronary arteries. In all patients, a standard two-dimensional echocardiographic study was obtained. Apical four- and two-chamber views with optimal endocardial and epicardial resolution were selected for analysis, and the left ventricular contour was divided into six segments of interest. Optimal endocardial and epicardial resolution were defined according to an original internal quality score system. For each of the six segments of interest, regional ejection fraction and regional segmental thickening were estimated. Data analysis was then performed on the average values of regional ejection fraction and regional segmental thickening obtained across the entire left ventricular contour. In each patient, regional ejection fraction range and regional segmental thickening range were calculated by subtracting the minimum from the maximum value of regional ejection fraction and regional segmental thickening obtained across a left ventricular contour. RESULTS: Regional ejection fraction and regional segmental thickening did not differ significantly between the two groups. However, regional ejection fraction range and regional segmental thickening range were significantly greater in patients with ischemic cardiomyopathy than in patients with non-ischemic cardiomyopathy [28.32 +/- 11.17 versus 14.74 +/- 7.73% (P < 0.001) and 47.80 +/- 16.00 versus 24.64 +/- 9.39% (P < 0.001), respectively]. Overlap of findings was observed in 20% of the values for regional ejection fraction range but in only 14% of those for regional segmental thickening range. CONCLUSIONS: Patients with ischemic cardiomyopathy demonstrate a non-uniform dyssynergy that can be differentiated from a more uniform hypokinesis observed in those with non-ischemic cardiomyopathy. Computerized ultrasonic image analysis can distinguish characteristic dyssynergic patterns in patients with cardiomyopathy. Measurements of segmental wall thickening provide a more accurate assessment of regional function.
Adult↗
Acquisition of NFKB1-selective DNA binding by substitution of four amino acid residues from NFKB1 into RelA.
The subunits of NF-kappa B, NFKB1 (formerly p50) and RelA (formerly p65), belong to a growing family of transcription factors that share extensive similarity to the c-rel proto-oncogene product. The homology extends over a highly conserved stretch of approximately 300 amino acids termed the Rel homology domain (RHD). This region has been shown to be involved in both multimerization (homo- and heterodimerization) and DNA binding. It is now generally accepted that homodimers of either subunit are capable of binding DNA that contains a kappa B site originally identified in the immunoglobulin enhancer. Recent studies have demonstrated that the individual subunits of the NF-kappa B transcription factor complex can be distinguished by their ability to bind distinct DNA sequence motifs. By using NFKB1 and RelA subunit fusion proteins, different regions within the RHD were found to confer DNA-binding and multimerization functions. A fusion protein that contains 34 N-terminal amino acids of NFKB1 and 264 amino acids of RelA displayed preferential binding to an NFKB1-selective DNA motif while dimerizing with the characteristics of RelA. Within the NFKB1 portion of this fusion protein, a single amino acid change of His to Arg altered the DNA-binding specificity to favor interaction with the RelA-selective DNA motif. Furthermore, substitution of four amino acids from NFKB1 into RelA was able to alter the DNA-binding specificity of the RelA protein to favor interaction with the NFKB1-selective site. Taken together, these findings demonstrate the presence of a distinct subdomain within the RHD involved in conferring the DNA-binding specificity of the Rel family of proteins.
Amino Acid Sequence↗
Blind peritoneal biopsy with other diagnostic parameters in diagnosis of ascites.
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Adult↗
Limiting the anatomic extent of upper thoracic sympathectomy for primary palmar hyperhidrosis.
Ninety-four consecutive patients undergoing bilateral sympathectomy of the upper part of the thorax for primary palmar hyperhidrosis were reviewed. The supraclavicular operative approach was used and a limited sympathectomy was performed from below T1 to above T3, denervating the palm only. Follow-up evaluation was complete in 86 patients at a median period of 31 months. All patients had complete and permanent relief of palmar hyperhidrosis. However, 19 had compensatory hyperhidrosis and this was the common cause of patient dissatisfaction. Although axillary denervation was not performed, axillary sweating was a problem postoperatively in only two patients. Significant morbidity was minimal; the only permanent disability was in one patient with Horner's syndrome. Upper thoracic sympathectomy is a safe and effective method of treatment for primary palmar hyperhidrosis. The low incidence of compensatory sweating may be explained by the limited extent of the sympathectomy. Axillary sweating is rarely a significant postoperative problem, and extensive sympathectomy to include axillary denervation is unnecessary and should be avoided to minimize compensatory hyperhidrosis.
Adolescent↗
Justification of a pharmacy intravenous admixture service in an Australian hospital.
The time and cost of i.v. admixture preparation by hospital pharmacy staff members in an established admixture unit was compared with that by nurses working on wards. The preparation time of antimicrobial admixtures was determined by using a stopwatch. The total cost of preparing an admixture by pharmacy and nursing staff was calculated by combining the respective labor costs (preparation time x average salary rates weighted for overtime) with the cost of disposable items. The mean +/- S.D. time for admixture preparation in the pharmacy was 3.38 +/- 0.38 minutes, whereas preparation by nurses required 14.37 +/- 1.55 minutes. The mean +/- S.D. total cost (in Australian dollars) of admixture preparation was $1.42 +/- 0.34 per dose, and $4.59 +/- 0.46 per dose, respectively. Centralization of admixture preparation would reduce the time required by 18.32 hours for every 100 admixtures prepared, equivalent to an annual cost avoidance of $112,420 for every 100 admixtures prepared each day. Centralizing the preparation of i.v. admixtures in a hospital pharmacy resulted in significant time savings and cost avoidance.
Australia↗
I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity.
The NF-kappa B transcription factor complex is comprised of two subunits, p50 and p65, that share significant homology to the rel oncogene. We have isolated a cDNA encoding a novel 66-kD rel-related protein, designated I-Rel. Unlike other rel-related proteins, I-Rel does not interact with DNA. I-Rel forms heterodimers with p50, however, and greatly attenuates its DNA-binding activity--an effect probably resulting from the presence of a domain inhibitory to DNA binding present within the 121 amino-terminal residues of I-Rel. In contrast, I-Rel does not associate with p65. Transfection experiments demonstrate that I-Rel suppresses NF-kappa B-induced transcription, probably through its association with p50. Expression of I-Rel mRNA is induced by mitogenic stimulation and accumulates after the appearance of p50 transcripts. Our findings suggest that p50 and I-Rel are components of a feedback pathway where expression of I-Rel may modulate indirectly the expression of genes responsive to the NF-kappa B transcription factor complex.
Amino Acid Sequence↗
Control of arteriolar resistance in heart failure. Partial attenuation of specific phosphodiesterase inhibitor-mediated vasodilation by digitalis glycosides.
BACKGROUND: The vasodilatory response to local specific type III phosphodiesterase inhibition with amrinone was evaluated before and immediately after local administration of digoxin in 14 patients with severe congestive heart failure (CHF). METHODS AND RESULTS: A 3F polyethylene catheter was inserted into the common femoral artery for drug administration and pressure monitoring. Mean blood flow velocity (MBFV) was continuously determined in the superficial femoral artery by transcutaneous Doppler ultrasonography. After intra-arterial administration of 10 mg amrinone, group MBFV increased from 7.7 +/- 1.4 to 16.0 +/- 2.1 cm/sec (p less than 0.05, n = 10). Local administration of 20 micrograms digoxin, which was infused over 20 minutes, did not alter group MBFV (i.e., 8.2 +/- 1.6 versus 7.6 +/- 1.5 cm/sec; p = NS, n = 10). The second administration of 10 mg amrinone, which immediately followed completion of local digoxin infusion, increased group MBFV but to a lesser extent than that produced by the first amrinone administration (i.e., 11.9 +/- 1.9 versus 16.0 +/- 2.1 cm/sec; p less than 0.05, n = 10). When placebo was administered instead of digoxin, group MBFV was similar after the first and second administrations of amrinone (i.e., 15.3 +/- 3.3 versus 15.6 +/- 3.8 cm/sec; p = NS, n = 4). CONCLUSIONS: Although local administration of digoxin did not significantly alter baseline vascular tone in patients with CHF, it substantially decreased the direct vasodilatory effect induced by specific type III phosphodiesterase with amrinone.
Aged↗
Portal vein thrombosis following sclerotherapy.
We present the case of a woman with idiopathic portal hypertension who underwent sclerotherapy for bleeding esophageal varices. She had a rebleed 27 months after complete eradication of esophageal varices. Endoscopy showed bleeding gastric varices. Ultrasonography, and later splenoportography, revealed a large thrombus in the right branch of the portal vein causing gross dilation of the portal and splenic vein. A proximal splenorenal shunt was done to decompress the portal system and hence gastric varices. Repeat endoscopy 4 weeks after surgery revealed complete disappearance of the gastric varices, while ultrasonography at 38 weeks showed marked decompression of the portal system with complete disappearance of the thrombus from the right branch of the portal vein. No new thrombus formation was seen.
Adult↗
Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.
The sequence reported in our 22 March 1991 report "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NFkappaB" [Science 251, 1490 (1991)], contained some errors. Resequencing under strong denaturing conditions revealed three insertions at nucleotide positions 1194, 1212, and 1220, which changed the AA sequence from RSAR-PRLGP to QISQASALAP (residues 372 to 380), thus accounting for some of the divergence in this region. A corrected sequence has been sent to GenBank.
Amino Acid Sequence↗