Prognostic factors in superficial bladder cancer.
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Biomedical subjects
Publications and source records attributed to L Anderson.
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Eight anionic disaccharide precursors of lipid A accumulate at 42 degrees C in 3-deoxy-D-manno-octulosonic acid-deficient temperature-sensitive mutants of Salmonella typhimurium. These compounds comprise a series of lipids based on the minimal structure, O-[2-amino-2-deoxy-N2,O3-bis(3-hydroxytetradecanoyl)-beta-D-glucopyranos yl] -(1----6)-2-amino-2-deoxy-N2, O3-bis(3-hydroxytetradecanoyl)-alpha-D-glucopyranose 1,4'- bisphosphate (designated lipid IVA) that differ from each other by the presence of an additional phosphoethanolamine moiety (IIIA), or an aminodeoxypentose moiety (IIA), or both (IA). A homologous set of metabolites is further derivatized with a palmitoyl function; these are designated IVB, IIIB, IIB, and IB (Raetz, C. R. H., Purcell, S., Meyer, M. V., Qureshi, N., and Takayama, K. (1985) J. Biol. Chem. 260, 16080-16088). The attachment of the palmitoyl moiety, known to be on the reducing terminal GlcN residue by mass spectrometry, was determined to be O-beta of the N2-linked beta-hydroxymyristoyl group of that residue of IVB by 13C NMR and two-dimensional 1H chemical shift correlation spectroscopy experiments. 31P NMR indicated the presence of diphosphodiester moieties in IIIA, IIIB, and IA and monophosphodiester moieties in IIA and IA. Selective 1H decoupling of the 31P spectrum of IIIA demonstrated that the O-diphosphoethanolamine moiety is attached to the O4' position in IIIA. On the basis of the observed 31P chemical shifts it was concluded that the aminodeoxypentose is located at position 1 in IIA and IA, while diphosphoethanolamine is most likely located at O-4' in IA and IIIB, as in IIIA.
The ferric chloride-catalyzed glycosylation of hydroxy compounds by protected 2-acylamino-2-deoxy-beta-D-glucopyranose 1-acetates is described. In addition to known glycosides from the reaction of alcohols with 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-beta-D-glucopyranose (3), ally (and other alkyl) beta-glycosides were obtained from the N-benzoyl, N-phenoxyacetyl, N-methoxyacetyl, N-chloroacetyl, and N-phthaloyl congeners of 3. The latter compounds, except for the N-phthaloyl derivative, gave oxazolines in the absence of an alcoholic reactant. Compound 3 and the related N-benzoyl, N-chloroacetyl, N-acetyl-3,4,6-tri-O-benzyl, and N-acetyl-4-O-acetyl-3,6-di-O-benzyl derivatives were coupled to one or more protected sugars to form protected, beta-linked disaccharides. Coupling at the 6-positions of acceptors proceeded smoothly and gave 67-80% yields. For successful coupling at positions 3 and 4, long reaction times and multiple additions of glycosyl donor were required, and yields ranged from 60% to as low as 30%. 1,3,4,6-Tetra-O-acetyl-2-(chloroacetamido)-2-deoxy-beta-D- glucopyranose appeared to be the most reactive glycosyl donor in this series. The reaction of 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-alpha-D-glucopyrano)[2,1- d]-2-oxazoline (derived from 3) with allyl alcohol was catalyzed by ferric chloride, and oxazolines were detected as intermediates in some of the glycosylations of protected sugars.
Rat brain mitochondrial Ca2+ uptake and release were examined in the presence of amiloride (3,5-diamino-6-chloro-N-(diaminomethylene)-pyrazinecarboxamide) and nineteen amiloride analogues. Amiloride, an inhibitor of Na+-Ca2+ exchange in plasmalemma membranes, did not affect energy-dependent Ca2+ uptake, whereas several other analogues were inhibitors. Similarly, amiloride did not alter Ca2+ release in the presence or absence of Na+. However, some analogues were found that stimulated and others that inhibited Ca2+ release. While many of these analogues reduced mitochondrial respiratory control ratios, two analogues were identified which inhibited Ca2+ uptake but did not alter mitochondrial respiratory control. Similarly two analogues were identified which inhibited Ca2+ efflux without affecting respiratory control.
From 1973 to 1980, 1,427 cancer patients were treated by the Brachytherapy Service, Radiation Oncology Department of Memorial Sloan-Kettering Cancer Center (MSKCC) with I-125 permanent interstitial implantation. Concern has been expressed with regard to the possible toxic effects of the low average photon energy (28 kev) of I-125 on bone, secondary to its increased absorption in these tissues because of the photoelectric effect. In an attempt to address this concern with respect to cortical bone, we reviewed pertinent data on those patients whose site of implant was at close proximity to osseous tissue in the pelvic, chest wall and head and neck regions. The review included 74 sites in 58 patients having no prior history or clinical evidence of any pathologic or metabolic bony disorder. Long term (greater than 1 year) follow-up was available in over 50% of the cases, with 10 patients followed more than 4 years. Local control rate for the 74 implanted sites was 93%. The implanted activity ranged from 1.6 to 48.8 mCi and the implanted volume from 0.5 to 152 cm3. At this follow-up range, there appears to be no excessive osseous toxicity either clinically or radiologically with I-125 permanent implantation.
Carcinoma of the endometrium is the most common malignancy of the female genital tract. In early stage endometrial cancer, surgery remains the primary mode of treatment while radiation therapy plays an adjuvant role. Prophylactic vaginal radiation has been shown to reduce significantly the incidence of vaginal recurrences. Between the years 1969-1976, 330 patients with FIGO Stages I and II endometrial cancer were treated according to a standard departmental policy in which 40 Gy of external radiation was given to high risk Stage I and all Stage II patients in combination with surgery and intravaginal radiation. Stage I was considered high risk if the tumor was of high grade or exhibited deep myometrial invasion. Vault radiation was delivered with a remote afterloading technique to a point .5 cm from the surface of the applicator; a total dose of 21 Gy was delivered in three fractions spaced two weeks apart over four elapsed weeks. With this regimen, the mucosal surface received a total equivalent dose of 40 Gy. These treatments were given on an outpatient basis without the need for any sedation or analgesics. All patients, regardless of stage, grade, or depth of myometrial invasion received adjuvant post-operative vaginal radiation. The minimum follow-up was 5 years, with a median follow-up of 8.5 years. The overall pelvic and/or vaginal recurrence rate was 2.7%. The incidence of vaginal complications was 3.7%. It appears that the remote afterloading treatment (RAT) for vaginal radiation is a very cost-effective therapeutic alternative, which produces minimal early or late complications and gives complete protection from radiation exposure to the medical staff. The advantages of a remote afterloading technique in delivering vaginal vault radiation in endometrial cancer are discussed in this paper.
The metabolic degradation and the kinetics of the cerebral uptake of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.
A differential pulse polarographic method has been developed for the determination of formaldehyde, by means of its kinetic current, in noxythiolin solutions. The assay conditions have been optimized so that the noxythiolin decomposition reaction was not affected. The method had the advantage of rapidity with an analysis time of about 10 min per sample. Thus formaldehyde was determined in noxythiolin solutions prepared and stored under typical clinical conditions. The low concentrations of formaldehyde present in all solutions were insufficient to account for the known cidal action of noxythiolin. There must therefore be some doubt that the mode of action of noxythiolin is simply due to formaldehyde produced as a result of the decomposition of noxythiolin in aqueous solution.
The availability of a rapid and highly specific polarographic method of analysis for formaldehyde enabled investigation of the rate of formaldehyde release from noxythiolin solutions and actual concentrations of formaldehyde in solutions during clinical use and storage. The antimicrobial activity of noxythiolin solutions, equivalent pure formaldehyde solutions and N-methylthiourea individually or in combination was examined against standard bacteriological strains and clinical isolates. Several interesting observations were made. Clinical isolates were found to be relatively susceptible to noxythiolin in contrast to laboratory strains. The growth phase of the organism radically affects activity, early exponential phase cells being susceptible to 1.0% noxythiolin. Levels of formaldehyde detected in fresh noxythiolin solutions are extremely low and would not appear to be solely responsible for the antimicrobial activity observed.
Conventional fixation for thin-section microscopy is insufficient to preserve many elements of cells and tissues. Actin filaments, for example, are destroyed during post-fixation in OsO4. In our search for a better fixative, we chose pellets of pure actin filaments as a very sensitive model system. In the present study, the potential of amines for improving aldehyde fixation was explored, and the results were compared to those obtained with the use of tannic acid. Aldehyde and amine were used together as an initial fixative, followed by aldehyde alone with postfixation in 1% OsO4 in buffer at 4 degrees C for 15 min, uranyl acetate en bloc stain, acetone dehydration, and embedding in Epox 812. Some primary monoamines improved the preservation of filaments; filaments were not broken beyond recognition by OsO4, as occurs when glutaraldehyde alone is used. Excellent preservation was seen when certain primary diamines were used. The quality of this fixation was superior to that obtained with tannic acid and was without the large increase in filament diameter that is seen with concentrations of tannic acid sufficient to protect filaments against osmium damage. The effects on filaments of the amines lysine, putrescine, ammonium, and arginine have been documented in detail, as we systematically varied all the major parameters normally considered in formulating fixation protocols.
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Na+-Ca2+ exchange in rat brain synaptosomal plasmalemma vesicles is reversibly inhibited by amiloride (3,5-diamino-6-chloro-N-(diaminomethylene)pyrazinecarboxamide++ +). This drug (pKa = 8.7) inhibits Na+-dependent Ca2+ uptake more effectively at basic pH values than at neutral pH values, indicating that the positively charged form of amiloride is the active moiety. Twenty amiloride analogues were examined for ability to inhibit Na+-Ca2+ exchange. These studies demonstrate that the 6-chloro group, the 5-amino substituent, and the carbonyl guanidinium moiety are essential for drug inhibition of Na+-Ca2+ exchange. N-Benzyl amiloride derivatives such as 3,5-diamino-6-chloro-N-(benzylamino-aminomethylene)pyrazinecarb oxamide (benzamil) and 3,5-diamino-6-chloro-N-(2-phenethylamino-aminomethylene)p yrazinecarboxamide are more potent inhibitors of Na+-dependent Ca2+ uptake than is amiloride. The amiloride analogue pattern of interaction with the Na+-Ca2+ exchange system is distinct from the inhibition patterns of the epithelial Na+ channel and the Na+-H+ exchange transport system.
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The effects of referral letters on increasing the likelihood of patients obtaining hypertension follow-up assessments are presented. Seventy-four patients with elevated diastolic blood pressure (between 95 and 120 mm Hg), who were administratively ineligible for longitudinal care from the Veterans Administration, were randomized into one of four groups: a patient letter; a physician letter; both patient and physician letters; or no letter (control group). No evidence of interaction between the patient and physician letters was found. Results revealed that nearly twice as many patients (63%) receiving the patient letter returned for a hypertension evaluation as compared with those who did not (33%). No difference was found between the physician letter and no physician letter conditions. These findings suggest that patient-directed referral letters can increase the likelihood of follow-up in both previously detected and newly detected cases.
The efficacy and safety of haloperidol, lithium carbonate, and placebo were critically assessed in 61 treatment-resistant, hospitalized children aged 5.2 to 12.9 years with diagnoses of conduct disorder, aggressive type. In this double-blind and well-controlled study, the optimal dosages of haloperidol ranged from 1.0 to 6.0 mg/day and those of lithium carbonate from 500 to 2,000 mg/day. For the assessment of behavioral changes and untoward effects, various rating scales were used in different settings. Both haloperidol and lithium carbonate were found to be significantly superior to placebo in decreasing behavioral symptoms. Although both medications were clinically effective, haloperidol was associated more often with untoward effects than was lithium carbonate.
Eight separate monoclonal antibodies to the Long strain of respiratory syncytial virus (RSV) were tested for their utility as rapid diagnostic reagents in immunofluorescence. Preliminary screening indicated that all 8 reacted with 11 field strains from three previous local RSV outbreaks and with 4 of 5 additional strains chosen because of their antigenic diversity by neutralization. Two monoclonal antibodies, one each directed against a surface glycoprotein and the nucleocapsid protein, were then compared, singly and combined, with a polyclonal antiserum as diagnostic reagents in 209 consecutive samples submitted to our diagnostic laboratory. Agreement between the two monoclonal antibodies was 100% and between them and the polyclonal serum was 98%. Sensitivity in relation to culture was 96-98%. Monoclonal antibodies are excellent immunofluorescent diagnostic reagents; antigenic diversity among RSV strains was not an impediment to their use in this study.
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