Treatment of opportunistic infections.
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Biomedical subjects
Publications and source records attributed to J Feinberg.
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The incidence of intervertebral disc calcifications (IVDCs) was examined in 52 lumbosacral spines obtained sequentially at autopsy. The presence of calcific deposits was detected by fine-grain roentgenograms. The nature of these deposits was determined by wide-angle x-ray diffraction, and histologic observations were made. A high prevalence of IVDC, 18 spines of 52, some with multiple deposits, was noted. Calcium pyrophosphate dihydrate (CPPD) deposits were found in 3% of the spines and accounted for 29% of the 42 deposits analyzed. The CPPD deposits occurred at multiple disc levels (an average of four per spine), were diffuse, and involved a major portion of the disc (nucleus pulposus, annulus fibrosus, and endplate) but were not generally associated with histologic disc degeneration. Hydroxyapatite (HA) deposits occurred in 12% of the spines, most often in the nucleus pulposus and endplate. The HA deposits appeared as small punctate radiodensities. Roentgenographic evidence of degenerative changes, i.e., disc space narrowing, endplate disruption, desiccation, and osteophyte formation, were present in all but one of the spines containing HA deposits. An additional 19% of the spines had deposits that could not be characterized by x-ray diffraction but were very similar in roentgenographic appearance to HA deposits. No conclusions could be drawn on the relationship between the presence of HA or CPPD and collagen or hexosamine content.
After a 2-4 week no-treatment period, 24 patients (12 young, age 29-45 yr.; 12 elderly, age 65-81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91-120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low-dose (10 mg/day) were treated with a high-dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (less than or equal to 90 mm Hg). Low-dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately -15/-8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low-renin patients with essential hypertension.
Neurite promoting factors (NPF), fibroblast growth factor, and laminin were instilled inside autologous venous nerve conduits (AVNC) interposed across a 1 cm gap in the rat sciatic nerve. Axonal regeneration was measured electrophysiologically and histologically and was compared to control AVNC and autologous nerve grafts (ANG) in 45 rats. By 1 month, the AVNC group with NPF recovered an average nerve conduction velocity twice that of the ANG group (24 m/sec vs. 12 m/sec). The gastrocnemius muscle action potential of NPF grafts was twice that of the control AVNC and was similar to the ANG (1.63 mV vs. 0.87 mV). In subsequent months, the advantage of NPF disappeared; these grafts were grossly reduced to fibrous bands. Histological examination of these grafts at 5 months revealed a florid intraluminal fibrovascular proliferation, which appeared to be "choking off" the regenerating axons. It is suggested that more refined mixtures of NPF should be instilled inside AVNC so that the improved axonal regeneration is maintained while the late inhibitory fibrosis is avoided.
The expression of mRNAs for the RI alpha, RII alpha, and C alpha subunits of cAMP-dependent protein kinase has been studied in different ram germ cells. The sizes of the specific RI alpha, RII alpha, and C alpha mRNAs, observed in germ cells were 1.6, 2.0, and 2.6 kb, respectively. RI alpha and C alpha mRNAs were mainly expressed in primary spermatocytes. A postmeiotic expression predominating in early spermatids was unique to RII alpha mRNA. The location of RI, RII alpha, and C subunits in well-defined organelles of ram spermatids and epididymal sperm was assessed by immunogold electron microscopy. In spermatids, RI, RII alpha, and C were essentially present in the forming acrosome and, to a lesser extent, in the nucleus. During sperm epididymal maturation, the protein kinases disappeared from the acrosome and were detected in a variety of sperm functional areas, such as the tip of the acrosome, the motility apparatus, and the membrane network. The present study on subunits of cAMP-dependent protein kinase supports the concept that specific functions are attached to the different subunits in that it shows differential expression and differential subcellular localization in germ cells.
By using specific antibodies, we have shown by Western blots that dental tissues contain calmodulin, the 67 kDa calcimedin and calpactin II. Moreover, by immunogold electron microscopy, we were able to compare the intracellular distribution of these three calcium-binding proteins in secretory ameloblasts. They were all found in the cytosol of these cells but only calcimedin was detected in the mitochondria. Calpactin II was the only one present in secretory vesicles. Twice as much calmodulin and calpactin II were detected in cell bodies as in Tomes' processes, but calcimedin was more abundant in the latter. The presence of these calcium mediators in well defined areas of ameloblasts may indicate differential ways for these cells to regulate different calcium-dependent processes during enamel formation.
21 patients with AIDS and Kaposi's sarcoma were enrolled in an open therapeutic trial to determine the in vivo anti-retroviral activity of recombinant interferon-alpha (IFN-alpha). 8 (38%) showed a complete or partial anti-tumour response. The mean pretreatment CD4 count for the responders was 399 cells/microliter vs 154 cells/microliter for the non-responders. All 5 of the patients with more than 400 CD4 cells/microliter pretreatment showed a significant reduction in tumour, whereas none of the 7 patients with under 150 CD4 cells/microliter had any response. 5 of the 6 complete or partial responders with greater than 50 pg/ml of human immunodeficiency virus (HIV) p24 before IFN therapy showed a 75% or greater reduction by 12 weeks of therapy, with 3 patients having persistently negative HIV cultures. The anti-viral effects were also most pronounced in the patients with the highest CD4 counts. These data demonstrate the potential benefits, both anti-tumour and anti-retroviral, of treatment with IFN-alpha in the early stages of HIV infection and Kaposi's sarcoma.
Persons with rheumatoid arthritis, like those with other chronic illnesses, often demonstrate poor compliance with their treatment regimens. Numerous factors have been identified as influencing compliances, including various features of diseases and therapeutic regimens, and demographic and sociobehavioral features of patients. Perhaps the most significant factor is the physician-patient relationship. Because of the relatively high prevalence of rheumatoid arthritis and the numerous characteristics of the disease and its treatment which adversely affect compliance, this literature review deals with the effects of the patient-practitioner interaction on compliance with treatment programs for rheumatoid arthritis. Specifically, this review examined the reported effects of four components of the patient-practitioner interaction--pedagogical techniques, sharing of expectations, the patient's assumption of responsibility and affective tone. Based on this literature review, several suggestions are provided for the health professional regarding ways to enhance compliance through the interaction with the patient, and specific areas for further research are identified.
The implication of part of the C-terminal of actin (within the 285-375 sequence) in the interaction of serum gelsolin was investigated by the use of specific antibodies. These antibodies were directed against two or three discrete epitopes, one of which was specific for skeletal-muscle actin. Some of these epitopes were found to be near the serum gelsolin-actin interface. Thus it can be assumed that part of the C-terminal of actin is exposed at the barbed end of the actin filament. The interaction between tropomyosin and actin was also studied.
Calmodulin levels were measured in Zajdela hepatoma cells growing both in vivo and in culture, with respect to the distribution of the cells into G1 and S+G2 phases of the cell cycle and growth conditions. These levels, expressed on a per-microgram of protein basis, were significantly elevated at the G1-S boundary and maintained throughout the remainder of the cell cycle. This elevation of calmodulin took place independently of the culture conditions. Taken together with previous observations, these data suggest that a threshold concentration for calmodulin is required for progression through the cell cycle, DNA synthesis and cell division.
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Affinity-purified monospecific antibodies and indirect immunogold and immunoferritin labeling on ultra-thin sections of low-temperature Lowicryl K4M-embedded samples were used to study the redistribution of calmodulin in ram spermatids and epididymal spermatozoa at the electron microscopic level. Calmodulin appeared as an integral component of well-defined structures or organelles of these cells. In young spermatids, calmodulin was localized in the nucleus, cytoplasm, and developing acrosome. During spermatogenesis and epididymal maturation, calmodulin left the acrosome to reach the perinuclear substance and finally became concentrated in the post-acrosomal area of the head, although some calmodulin remained associated with the tip of the acrosome. Such a redistribution is consistent with the preferential location of Ca2+ in the post-acrosomal cytoplasm of ejaculated spermatozoa. Calmodulin was also observed in the flagellum associated with the plasma membrane and with the motility apparatus, between coarse fibers and axonemal microtubules. These changes in calmodulin distribution may account for the Ca2+-dependent regulation of spermatogenesis and sperm maturation. Calmodulin therefore appears to be a pleiotropic regulator of male gamete development and functions.
Allergen extracts contain a wide variety of allergenic determinants and the sensitization of allergic subjects is extremely heterogeneous. Specific immunotherapy is usually performed with multiple component extracts and it is therefore important to determine whether this treatment may elicit the onset of newly developed IgE sensitivities. By means of nitrocellulose immunoblotting technique, the IgE sensitivities of 20 patients were characterized before and after specific immunotherapy. Ten patients had a rush immunotherapy with a standardized orchard grass pollen extract and ten others underwent a rush immunotherapy with a 6-grass pollen allergoid. The allergenic profiles of the patients before and after immunotherapy were qualitatively similar. In some patients an increase of orchard grass pollen-specific IgE was observed and the allergenic profile was quantitatively different. These results suggest that rush immunotherapy with either an aqueous non-modified extract or an allergoid does not elicit the onset of new IgE sensitivities. Multicomponent allergenic extracts may therefore be used in the treatment of patients.
Brevin, an actin-severing protein present in serum from numerous mammals, has been purified to homogeneity from bovine serum, using hydrophobic chromatography as the last purification step. The physicochemical parameters of brevin have been established and some of them studied in the absence and presence of Ca2+. Brevin exhibits an apparent Stokes radius, Rs, of 3.4 nm, an intrinsic sedimentation coefficient S degrees 20, W, of 4.8 S and 4.4 S in the absence and presence of Ca2+ respectively, indicative of calcium-induced conformational change. The native molecular mass of brevin was found to be 68 kDa and the hydrodynamic data suggest that the protein is an asymmetric molecule. Sedimentation equilibrium studies demonstrated that Ca2+ affects the shape (asymmetry) of brevin without altering its molecular mass. Limited tryptic and chymotryptic digestion of brevin distinguishes the Ca2+-induced conformation from the EGTA one. No change in the electrophoretic migration of brevin was seen upon Ca2+ addition. Several isoforms were detected by two-dimensional gel electrophoresis. Brevin increases the rate of nucleation of actin but decreases the rate of elongation of the filaments and the steady-state viscosity of F-actin in substoichiometric amounts, as measured by viscometric assays under high shear conditions. Electron microscopic examination documents these effects. Brevin produces shorter actin filaments and binds to the 'barbed' end of filaments to which monomers add preferentially during elongation, as demonstrated by indirect immunogold staining of antibodies against brevin. Filament elongation occurs only at the slowly growing end. An enzyme-linked immunosorbent assay was developed and used to detect and quantify brevin and related proteins in extracts of different bovine cells and tissues. Liver and smooth muscles were found to contain the highest amounts of the severing protein.
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The changes in intracellular calmodulin levels and cAMP-dependent protein kinase activities have been studied in the testis of normally developing and hypophysectomized rats. It appears that the onset of spermatogenesis which occurs on the first days of the postnatal development, is associated with a major (over fivefold) increase in the calmodulin level and enhancement of the cAMP-dependent protein kinase activity. On the contrary, hypophysectomy of adult animals is associated with a progressive decline in the calmodulin level and a rapid and regular decrease in the cAMP-dependent protein kinase activity. Moreover, measurements of the intracellular calmodulin level and cAMP-dependent kinase activity of isolated testicular germ cells or epididymal spermatozoa have shown that testosterone, administered to hypophysectomized rats as subcutaneous implants, maintains the concentration of these regulatory proteins to normal values.
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Male rats received dorsal or median raphe electrolytic lesions or sham operations. Ten days later subjects received 3.0 g/kg ethanol or saline and were decapitated 30 minutes later. Both dorsal and median raphe lesions significantly increased corticosterone and non-esterified fatty acid levels. Ethanol significantly increased corticosterone and non-esterified fatty acid levels in rats with dorsal or median raphe lesions. Dorsal raphe lesions significantly attenuated the elevating effect of ethanol on corticosterone. These results confirm, in part, previous pharmacological studies and suggest the effects of ethanol on corticosterone, but not non-esterified fatty acid, involve serotonergic neurons.