1,25 Dihydroxy-vitamin D3 (1,25 (OH)2 vit D3) in the treatment of idiopathic myelofibrosis.
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Biomedical subjects
Publications and source records attributed to A Miller.
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Ingestion of a foreign body rarely produces symptoms. We report a patient who presented with oculosympathetic paresis. We believe this is a previously unrecorded manifestation of foreign body ingestion.
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A randomized prospective double-blind study of thymopentin was performed upon 24 severely burned patients to evaluate its efficacy in correcting postburn immunologic abnormalities and preventing infectious morbidity and mortality. Patients in the treated group received 50 milligrams of thymopentin daily for the first two weeks after injury and three times weekly thereafter until the patient was no longer at risk for having infections develop. The placebo group received saline solution intravenously. The rate of infectious complications was recorded. Immunologic tests used at least weekly were: white blood cell counts, OKT4 to OKT8 ratios, lymphocyte blastogenesis and neutrophil bactericidal index. There were no differences noted in patient mortality, infectious complications or antibiotic use. There were two significant differences noted among the immunologic tests. First, there was a decreased lymphocyte blastogenic response in the treated group at two weeks after injury without a difference in T4 to T8 ratios. Second, there was less leukopenia during the first week after injury in the treated group.
One hundred twelve patients with early (FIGO stage I and II) ovarian carcinoma had a second-look laparotomy performed after comprehensive surgical staging and randomization into clinical protocols. Of the 95 patients who were asymptomatic before second-look laparotomy, only 5% had positive findings. In contrast, 53% of the 17 patients with findings that suggested recurrence or bowel obstruction had disease at second-look laparotomy. Overall, only 13% of the entire group of 112 patients had recurrent disease at second-look laparotomy. Asymptomatic patients with early ovarian carcinoma who have undergone careful initial surgical staging followed by appropriate adjuvant therapy can be spared a routine second-look operation.
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Ak- or Ek-restricted T cells, generated by immunization with a 23-amino-acid peptide of hen egg-white lysozyme (amino acid 74-96), showed a strict correlation between the minimal peptide determinant recognized and the Ia molecule restricting recognition. All Ak-restricted clones obtained from six independently derived lines recognized determinants contained within peptides 74-86, while Ek-restricted clones recognized determinants within 85-96. This correlation was true whether B10.A mice (Ak, Ek) were immunized with peptide 74-96 or with each of the two smaller peptides (74-86 or 85-96). Furthermore, a T cell response could be obtained to peptide 74-86, but not to peptide 85-96 in B10.A (4R) mice, which express only the Ak molecule. Thus, an Ia molecule-associated selectivity exists in the choice of T cell determinants even within this small 23-amino-acid peptide antigen. Significant differences were noted, however, in the boundaries of the minimal peptide determinants recognized within peptide 74-96 by Ak- or Ek-restricted T cells, in comparison to those recognized by Ab-restricted T cells. These results indicate that interaction of the same peptide with distinct Ia molecules results in recognition of unique aspects of the antigenic determinants by the T cell receptor.
The specificity of C57BL/6 T cells reactive to peptide aa 74-96 of hen egg-white lysozyme (HEL) was analyzed by using a panel of synthetic peptides of varying lengths from this region. It was found that peptide 74-96-reactive T cells induced by native HEL (aa 1-129) or its denatured fragment L2 (aa 13-105) recognized two distinct but overlapping determinants contained within aa 74-90 or aa 81-96, respectively. Peptide 74-96 itself induced both peptide 74-90-and peptide 81-96-specific T cells. Thus, a choice was made between these two potential T cell determinants on peptide 74-96, depending on which immunogen was used. Interestingly, the ability of both peptide determinants aa 74-90 and aa 81-96 to stimulate peptide 74-96-reactive T cells was partly dependent on the presence of residues within the overlap region (aa 81-90), suggesting that this region may play an important role in Iab-restricted T cell activation. This was further supported by the poor immunogenicity of shorter peptides 74-86 or 85-96, lacking residues from the overlap region in B6 mice. These two short peptides were nevertheless capable of eliciting T cell responses in B10.A mice, suggesting that the importance of this overlap region in obtaining a response to peptide 74-96 is related to the MHC haplotype.
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A randomized clinical trial was conducted in women with bulky (suboptimal) Stage III and Stage IV ovarian carcinoma, using doxorubicin (Adriamycin) and cyclophosphamide with or without cisplatin. There were 440 evaluable cases, of which 227 had measurable disease. One hundred twenty of these latter patients were treated with cyclophosphamide and doxorubicin (CA), while 107 received cyclophosphamide, doxorubicin and cisplatin (CAP). The clinical complete response (CR) rate for CA was 26% (31/120) compared with 51% (55/107) for CAP (P = less than 0.0001). Of 23 CRs receiving CA who had a second-look laparotomy, only four were negative; of 39 CRs receiving CAP and a second-look, 13 were negative (not statistically significant). The response duration for patients with measurable disease (median 14.6 versus 8.8 months), progression-free interval for all patients (13.1 versus 7.7 months), and survival for patients with measurable disease (19.7 versus 15.7 months) showed a statistically significant advantage for CAP; however, there was no difference in survival of patients with nonmeasurable disease. Toxicity was more severe with CAP but was tolerable. Thus, the addition of cisplatin improves the chemotherapy of advanced ovarian carcinoma.
The potential carcinogenicity of 3 azabenz(a)anthracenes was determined in vitro. The 3 compounds tested were 1-, 2-, and 9-azabenz(a)anthracene. The initial assay was chemical carcinogen-induced enhancement of anchorage-independent survival of Rauscher leukemia virus-infected Fischer rat embryo cells, 2FR(4)50 (2FR4). Cells treated with 2- and 9-azabenz(a)anthracene showed dose-dependent increased survival. After continued subculturing, the surviving cells from 2- and 9-azabenz(a)anthracene-treated cultures displayed morphological transformation and ability to grow in semi-solid medium. Mock-treated controls and I-azabenz(a)anthracene-treated cultures did not show either of these properties. These data suggest that certain azabenz(a)anthracenes are potential carcinogens.
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Single-channel conductance fluctuations are analysed for gramicidin A incorporated into binary-mixed black lipid membranes of charged phosphatidic acid and neutral lecithin in different molar ratios. At very low Ca++ concentrations in the electrolyte (i.e. in the presence of EDTA) homogeneous lipid mixtures are identified through their conductance and life time probability distributions for integral gramicidin pores. As for the pure lipid components, the conductance histograms each show a single maximum with regular width and for all channels a single mean lifetime is found. For Ca++-levels (10(-6) - 10(-5) M) that are close to the critical demixing concentration (approximately 10(-4) M) unusually broad conductance distributions and reduced lifetimes are found provided the PC content, chi, of the membrane is close to the critical mixture (chi crit approximately equal to 0.5). We interpret this as a first example of the coupling of a membrane function (the transport of ions) to a lipid matrix with locally fluctuating composition close to a critical demixing point. For cCA++ = 10(-2) M the conductance histogram of gramicidin A in an equimolar mixture of PA and PC shows two well-separated maxima. A correlation analysis between conductance and lifetime of the single pores shows that the two channel populations also differ significantly in their mean channel lifetime, tau *. This finding is interpreted as being direct evidence for Ca++-induced lateral phase separation in black lipid membranes, as has been postulated recently.
The study of 3,472 chest x-rays from four populations with different levels of exposure to asbestos and with different cigarette smoking histories shows that smoking in the general population does not produce pulmonary fibrosis recognizable on chest radiography. In the general population of Michigan, the prevalence of a radiographic pattern of fibrosis was 0.5 percent in men and 0.0 percent in women. In a Long Beach, California census tract population, the prevalences were 3.7 percent for men and 0.6 percent for women. Similarly, cigarette smoking does not enhance fibrosis when the exposure to asbestos has been as light as that in households of shipyard workers. Asbestosis was recognized in 6.6 percent of 137 shipyard workers' wives who have never smoked and 7.6 percent of 132 who had ever smoked. Cigarette smoking and asbestos appear to be synergistic in those occupationally exposed to asbestos (as insulators), since 7.2 percent of 97 nonsmokers and 20.5 percent of 316 ever-smokers showed fibrosis. This apparent synergy was also found in shipyard workers up to age 70 with 31 percent of nonsmokers and 43.3 percent of ever-smokers having fibrosis. There were increases of approximately 10 percent in the prevalence of fibrosis in cigarette smokers and nonsmokers for each decade after age 40.
We report the successful creation of ureteral strictures in primates and their successful management by balloon dilation 3 months later without ureteral stenting. This experimental work confirms the sporadic clinical reports of the effectiveness of balloon dilation in the management of ureteral strictures and suggests that ureteral stenting is not necessary for a successful result.
As an extension of an earlier investigation (J. Med. Chem. 1984, 27, 1431), we prepared a series of 3-substituted 5-[(hydroxyimino)methyl]-1,2,4-oxadiazoles and the corresponding 5-thiocarbohydroximic acid 2-(N,N-dialkylamino)ethyl S-esters. The compounds were evaluated in vitro as reactivators of phosphonylated electric eel and human erythrocyte (RBC) acetylcholinesterases (AChE). The compounds were characterized with respect to (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol/buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivating ethyl methylphosphonylated AChE. One compound was also tested for effectiveness in preventing AChE phosphonylation. All of the tested compounds significantly reactivate ethyl methylphosphonylated AChE: the 3-n-octyl- and 3-(1-naphthyl)-substituted aldoximes are as reactive (within a factor of 5-10) toward the inhibited enzymes as the benchmark pyridinium reactivators, 2-PAM and HI-6. All of the substituted thiocarbohydroximic acid S-esters are powerful reversible inhibitors of AChE's: the 3-n-octyl- and 3-(1-naphthyl)-substituted thiocarbohydroximates inhibit eel AChE to 50% initial activity at concentrations less than 5 microM. When added to an eel AChE solution at concentrations between 5 and 50 microM, the 3-phenyl-substituted thiocarbohydroximate effectively antagonizes AChE inhibition by ethyl p-nitrophenyl methylphosphonate (EPMP), suggesting the potential utility of this compound for preventing anti-AChE-agent poisoning.