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P Rácz

Publications and source records attributed to P Rácz.

At least 19 recordsLinked to original sources

1H spin-spin relaxation in normal and cataractous human, normal fish and bird eye lenses.

A systematic study on nuclear spin-spin relaxation of water protons in human, fish and bird eye lenses/lens nuclei is reported. The purpose of this study is to clarify the real nature of the relaxation processes not describable as a single exponential decay. The characterization of the spin-spin relaxation by a single exponential is commonly used both in literature and in MRI diagnostics. However, in our opinion, this single exponential decay hypothesis is an oversimplification that can lead to the loss of essential information. Our measurements were performed by Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences on human, carp, chicken and turkey eye lenses/lens nuclei. Several hundreds of CPMG echo amplitude were detected and the time-dependence of their decay was determined by careful fitting procedures. Our results clearly rule out the single exponential decay hypothesis for eye lenses: at least two or three decaying components are observed. These phenomena need further investigations: it should be decided which of the relaxation parameters, T2I-s and A(i)-s gives the most characteristic physiological or pathological information. It is claimed that the amplitude ratio of the bound and the free water fraction carries the most characteristic information. During the cataract formation the weight of free water is raised by more than 25%.

Aged↗

Circadian intraocular pressure management with latanoprost: diurnal and nocturnal intraocular pressure reduction and increased uveoscleral outflow.

Based on their mechanism of action, the most frequently used ocular hypertensive agents, the beta-blockers, cannot be assumed to reduce IOP during sleep. The need for drugs that reduce IOP around-the-clock is underscored, however, by the fact that inadequate nocturnal ocular perfusion pressure is considered to be one of the likely causes of glaucomatous optic neuropathy especially in some cases of normal tension glaucoma. The studies reviewed here demonstrate that latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue, applied once a day at a concentration of 0.005%, maintains a statistically highly significant IOP reduction around-the-clock. The magnitude of this IOP reduction was found to be essentially identical during the day and at night, both in patients maintained on timolol and in those not receiving other glaucoma medication. Latanoprost-induced IOP reduction was also found to be associated with increased uveoscleral outflow in normotensive volunteers, both during the day and at night. These circadian studies suggest that this new ocular hypotensive agent can be expected to be particularly useful for the medical management of some forms of glaucoma, such as normal tension glaucoma, when the cause of the glaucomatous damage cannot be linked specifically to diurnal IOP abnormalities.

Administration, Topical↗

Around-the-clock intraocular pressure reduction with once-daily application of latanoprost by itself or in combination with timolol.

OBJECTIVE: To determine whether once-daily, in the morning, topical application of the new ocular hypotensive prostaglandin analogue, latanoprost, yields nocturnal intraocular pressure (IOP) reduction similar to its diurnal IOP reducing efficacy. STUDY DESIGN AND PATIENTS: Placebo- controlled, randomized, and double-masked study on hospitalized patients with ocular hypertension or glaucoma. Patients in group 1 (n=9) were maintained on twice-daily applications of 0.5% timolol maleate. Patients in group 2 (n=10) terminated their timolol treatment 3 weeks before the beginning of the study. In both groups the test drug (0.005% latanoprost) and its vehicle (placebo) was applied by hospital staff every morning for 9 days. MEASUREMENTS: After 4 days of ambulatory treatment, patients were hospitalized, and IOP values were obtained in the supine and sitting positions with a handheld electronic tonometer (Tono-Pen XL, Bio-Rad, Glendale, Calif) and a Goldmann's applanation tonometer, covering every 2-hour interval, around the clock, but not more than at four time points per day during a 5-day period. RESULTS: The mean nocturnal IOPs (Goldmann's applanation tonometer) collected for 5 days were mean +/-SEM 17.9+/-0.6 vs 20.2+/-0.6 mm Hg and 16.8+/-0.3 vs 20.6+/-0.5 mm Hg for the study vs the control eyes in group 1 and group 2, respectively. These nocturnal IOP reductions were statistically significant (P<.001, two-tailed paired Student's t test). The differences between diurnal and nocturnal IOP reductions (handheld electronic or Goldmann's applanation tonometer) were minimal (>0.3 mm Hg) and statistically not significant (P>.31, two-tailed paired Student's t test). CONCLUSION: Once-daily latanoprost treatment provides uniform circadian (around-the-clock) IOP reduction by itself, or in combination with timolol.

Adrenergic beta-Antagonists↗

Maintained intraocular pressure reduction with once-a-day application of a new prostaglandin F2 alpha analogue (PhXA41). An in-hospital, placebo-controlled study.

To eliminate uncertainties about compliance, 15 patients with glaucoma (intraocular pressure [IOP] > 22 mm Hg and < 40 mm Hg) were hospitalized to participate in a clinical trial of the ocular hypotensive effectiveness of the new prostaglandin F2 alpha analogue prodrug, PhXA41 (13,14-dihydro-17-phenyl-18, 19, 20-trinor-PGF2a-isopropyl ester; latanoprost [World Health Organization generic name]). At 9 PM on each of five consecutive days, one of the investigators applied one drop of a 0.006% solution of PhXA41 (representing approximately 2 micrograms of PhXA41 per treatment) to one eye of nine patients and one drop of placebo to one eye of six patients. This was followed by an evaluation of potential local side effects at 9:30 PM. Complete examinations, including tonometry (Goldmann), were also performed at 8 AM and 8 PM on days 1 to 6, as well as at noon and 4 PM on days 1, 2, and 6. Except for mild conjunctival hyperemia in two PhXA41-treated eyes (once each at 8 AM), no side effects were observed or reported by any patient. Starting with the first IOP measurement after the first treatment (8 AM on day 2), IOP was reduced by 20% to 30% in the eyes treated with PhXA41. This reduction was highly significant (P < .01 at 12 time points and P < .05 at the remaining two measurements) throughout the study. The IOP reduction did not become attenuated during the 23 hours after treatments. At 11 hours after the last treatment, the mean (+/- SD) IOP difference between PhXA41-treated and contralateral control eyes was -5.5 +/- 2.8 mm Hg, as compared with -6.1 +/- 1.8 mm Hg 12 hours later. PhXA41 must, therefore, be regarded as an excellent candidate for use as a once-a-day glaucoma medication.

Adult↗

Human Kupffer cells infected with HIV-1 in vivo.

Blood monocytes as well as cells of the macrophage-phagocytic system in several tissues are targets for HIV-1 in vivo and in vitro. However, the data on HIV-1 infection of liver macrophages/Kupffer cells (KCs), which make up the main pool of fixed-tissue macrophages, is controversial. We therefore studied HIV-1 infection of KCs in vivo. Blood and liver tissue was obtained from seven AIDS patients shortly after death. Liver tissue was minced before processing. Cell suspensions were further purified by density gradient centrifugation, stained with anti-CD14 (blood monocytes) or anti-macrophage 25F9 (KCs), and separated by fluorescence-activated cell sorting (FACS). These highly purified cell populations were then analyzed for HIV-1 proviral DNA by the polymerase chain reaction (PCR). By performing PCR on FACS-purified cell populations, we could show that both KCs and peripheral blood monocytes were HIV-1-infected in 3 of 7 patients. KCs harbored HIV-1 proviral DNA only if peripheral blood monocytes were infected. These data show that KCs of the liver are infected with HIV-1 in vivo.

Acquired Immunodeficiency Syndrome↗

Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA.

When radiolabeled RNA was used for in situ hybridization, human immunodeficiency virus type 1 (HIV-1) RNA was found in high concentrations in germinal centers of lymphoid tissues from patients with HIV-1 infection. Most of the signal from hybridized probe was independent of specific cells, being found in the extracellular space of germinal centers in all lymphoid tissues examined from adult patients with Centers for Disease Control (CDC) class II and III disease or pediatric patients with CDC class P-2A disease. Lymphoid tissues from adult patients with CDC class IV infections or pediatric patients with CDC class P-2D disease (including autopsy material) lacked intact germinal centers, and HIV-1 RNA was then found only in rare, isolated cells, with some tissues having no detectable HIV-1 RNA. Thus, in the early stages of HIV infection, germinal centers serve as important reservoirs of free virus in the interstitial spaces, and this reservoir disappears as the germinal centers involute with advancing disease.

Adenoids↗

Immunocytochemical determination of antigen and epitope specificity of HIV-1-specific B cells in lymph-node biopsies from HIV-1-infected individuals.

Knowledge about B-cell dysfunction and HIV-specific antibody production is necessary for the understanding of both HIV-1-related immunopathology and the (vaccine-induced) humoral immunity involved in protection against AIDS. This paper describes the application of recently developed methods to detect epitope specificity of B cells in lymph-node biopsies with antigen-enzyme conjugates. Cryosections of five lymph-node biopsies from HIV-1-infected individuals and four control tissues were stained with a panel of HIV-1 antigen-enzyme conjugates: recombinant HIV-1 proteins (gp 160, gp 120 and p24), labelled with peroxidase, and synthetic peptides representing neutralizing epitopes from gp120 and gp41, labelled with alkaline phosphatase. Antibody-forming cells (AFCs) were detected in all the HIV-1-infected biopsies with gp160, gp120 and/or p24, in numbers up to 350 per section. AFCs producing specific antibodies against peptide 101 (SP 101), representing the neutralizing epitope 586-608 of gp41, were detected in one patient. These techniques allow correlation of in vivo function of B cells with lymph-node pathology, clinical stage of the disease and serological data. Their potential for the elucidation of HIV-related immunopathogenesis and the development of vaccines is discussed.

Amino Acid Sequence↗

Ultrastructural analysis of germinal centers in lymph nodes of patients with HIV-1-induced persistent generalized lymphadenopathy: evidence for persistence of infection.

Germinal centers play an important role in the pathogenesis of HIV-1-induced lymphadenopathy. Cell-free retrovirus particles, gag proteins of HIV-1, and cells expressing viral RNA can be detected in these areas of the lymph node. In the present study, the ultrastructural changes and the interactions of virus with different cell types of the germinal centers were investigated. We compared the alterations of lymph nodes obtained shortly after seroconversion with those seen in longstanding lymphadenopathy. The results demonstrated that germinal centers were already infected in the early phase of the disease. However, the number of cell free virions was low. During the course of the disease, large amounts of cell free virions accumulated in the germinal centers. The persistence of germinal center infection for up to 2 years was demonstrated by detecting retrovirus particles in repeated biopsy specimens. In addition, the presence of numerous small, moderately electron dense structures that might represent defective particles of HIV-1 and influence the course of the disease were described. HIV-1 was found to replicate in lymphocytes, macrophages, and follicular dendritic cells. Quite possibly, a genomic shift may occur at the time of transmission of the virus to a novel target cell, thus, germinal centers may be one of the anatomic sites where HIV-1 acquires the ability to develop into a variant with preferential tropism for a given cell type.

AIDS-Related Complex↗

Lymphadenopathy in HIV infection: histological classification and staging.

The histological alterations seen in HIV-related lymphadenopathy have been described with different terms by different authors. In order to facilitate comparisons of results from various laboratories, a group of pathologists of the European Lymphoma Study Group (later the European Association for Haematopathology) have proposed a histological classification for the evaluation of HIV related lymphadenopathy. Most observers agree that the morphological and immunohistochemical alterations in the follicles (germinal centres) are the most conspicuous and earliest changes seen. The follicular alterations were therefore used as the basis for the proposed classification. In addition, some features occasionally seen were also included, i.e. angioimmunoblastic hyperplasia, multicentric Castleman-like lesions, and vascular lesions, especially pretumorous and tumorous stages of Kaposi's sarcoma. The proposed classification was used by the members of the group of a collection of lymph nodes compiled from the various centres. The classification was shown to be reproducible and to have clinical relevance in staging of the patients. The prognostic relevance as to the survival of the patients has to be further substantiated by follow-up studies. The proposed classification offers a common terminology for the alterations previously described by different terms by various authors.

AIDS-Related Complex↗

Immunohistochemical, electron microscopic and in situ hybridization evidence for the involvement of lymphatics in the spread of HIV-1.

To investigate the role of the lymphatic vessels and the sinus systems of the lymph node in the spread of HIV-1, we evaluated 15 lymph nodes from patients with persistent generalized lymphadenopathy (PGL). Fifteen lymph nodes taken from patients with follicular hyperplasia not related to HIV-1 infection served as controls. Immunohistochemical and in situ hybridization techniques revealed infected cells within the sinuses and the efferent lymphatics of the PGL lymph nodes. In contrast, infected cells could not be detected within the walls of the high endothelial venules nor in the areas immediately adjacent. The parenchymal side of the marginal sinus was lined by a discontinuous endothelium. Macrophages and lymphocytes were located within the gaps of this endothelium. More importantly, when the enlarged follicle extended as far as the wall of the marginal sinus, the processes of follicular dendritic cells could be seen extending through the gaps into the lumen of the sinus. This suggests that these cells could transport antigens (including HIV-1) from the sinuses directly to the germinal centers. In addition, HIV-1 particles within cytoplasmic vacuoles were seen in infected macrophages located in the submarginal zone. Positive cells were also found in the extrafollicular lymphoid parenchyma, especially in the area between the marginal sinus and the follicles. The observed distribution of the virus-positive cells within the PGL lymph nodes strongly implicates the lymphatic vessels in the spread of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Cadmium, lead and copper concentrations in normal and senile cataractous human lenses.

Cadmium, lead and copper concentrations were measured in normal and cataractous human lenses by atomic absorption spectrophotometry. The concentrations of all three elements were relatively higher in cataractous lenses compared with normals, and the ratios of cataract/normal concentrations were in the order Pb greater than Cd greater than Cu. The concentration of these trace elements also varied according to lense age. It is likely that the major source of cadmium is tobacco smoke while that of lead is the exhaust gases of motor cars.

Aged↗

Interferon alpha in the treatment of AIDS-associated Kaposi's sarcoma.

Twenty-three patients with biopsy-proven Kaposi's sarcoma and HIV infection were treated with recombinant interferon-alpha-2a (Roferon-A). Two dosage regimens were used: 21 patients received 18 X 10(6) units intramuscularly per day for 3 months, followed by injections of 18 X 10(6) units three times a week. The remaining 2 patients were treated with 2 X 18 X 10(6) units i.m. per day for 3 months. Three patients either refused further treatment or were lost to follow-up within the first few weeks. Thus, a median observation period of 7.5 months (range 1.5-17) was available for 20 patients. Within the first 3 months, 6 patients (30%) responded to treatment, 6 patients (30%) showed no progression, whereas in 8 cases (40%) progressive disease was noted. A similar rate of responders versus nonresponders was found after 6 months of observation. In progressive disease, interferon could be effectively combined with cytostatic drugs. Dose-dependent neurological and hematological side effects were observed in a few patients only. Opportunistic infections were diagnosed in 12 patients with a median onset of 6 months (range 1-10) after start of interferon treatment. The total number of lymphocytes expressing the CD4 antigen or the ratio of CD4 to CD8 positive cells were of prognostic value. These data suggest that interferon alpha is an active agent in the treatment of Kaposi's sarcoma, that it shows tolerable side effects and can be combined effectively with cytostatic drugs in case of progression.

Acquired Immunodeficiency Syndrome↗

Monoclonal antibodies to human immunodeficiency virus: their relation to the patterns of lymph node changes in persistent generalized lymphadenopathy and AIDS.

Recently there has been much interest in using immunohistology with monoclonal antibodies (MABs) against different cells of the immune system in lymph nodes (LNs) of patients with HIV infection. The panel of these MABs is becoming increasingly extensive. In this study we report on our finding that by using a limited number of properly chosen MABs, diagnostically and prognostically relevant parameters can be acquired. One hundred and twenty-one LN biopsy specimens from patients with HIV infection were reviewed and classified according to our expanded working classification and a fifth main type of LN lesion, the small lymphocyte follicular type, was added to our earlier classification. We propose that this new type represents a transitional form between the mixed follicular type and the follicular depleted type. In the follicular type of LN lesion there is no marked change in the number of CD4 cells within the follicles and in the extrafollicular parenchyma. The reaction against the major core proteins of HIV is always positive and the number of proliferating cells is very high. The positivity is weaker in the earlier cases and stronger in the older ones. The follicular dendritic cell (FDC) network shows degenerative changes. In the hypervascular follicular type the reaction pattern with these selected MABs is very similar to the one in the follicular type. In the mixed type there are hyperplastic follicles and regressively transformed follicles in the same node. The hyperplastic follicles show a pattern similar to those in the follicular type. However, the reaction with MABs against core proteins of HIV is often markedly stronger. The number of proliferating cells is decreased markedly. Some follicles show extensive FDC network destruction. CD4 cells within the follicles and in the extrafollicular parenchyma are decreased. The regressively transformed follicles contain very few proliferating cells and the reaction with MABs against core proteins is variable, being strong in some follicles and weak in others. The small lymphocyte type contains follicles consisting mainly of small lymphocytes. These lymphocytes are of the same phenotype as those in the primary follicles. In contrast to these, however, the numbers of CD4 and Leu 7+ cells are much decreased. The reaction with MABs to core proteins is weak and limited to the germinal centres (GCs). The number of proliferating cells is strongly diminished. The FDC network, however, is well developed in most follicles. In the follicular depleted LNs there are no follicles; however, in some LNs remnants of FDC can be seen.

AIDS-Related Complex↗

Freezing-thawing hysteresis. I. NMR detection in human lens.

Human eye lenses were investigated by 1H-NMR as a function of temperature around freezing. Wide hysteresis in line intensity and relaxation time has been found. The hysteresis behavior of the phase transition presents a useful possibility for investigating the structure of water in these materials.

Body Water↗

Freezing-thawing hysteresis. II. Investigation of human ocular tissues.

The freezing-thawing behavior of cataractous eye lenses and corneas was investigated by 1H-NMR. The corneas have shown hysteresis similarly to the normal lens. No hysteresis could be demonstrated in cataractous lenses. The transparency of lens seems to be correlated with the existence of the freezing-thawing hysteresis.

Body Water↗

Detection of coronavirus-like particles in homosexual men with acquired immunodeficiency and related lymphadenopathy syndrome.

Coronavirus-like particles were identified by electronmicroscopy in the feces of homosexual men. The particles banded at a density of 1.21 g/ml after cesium chloride density gradient centrifugation. To determine whether the presence of this virus might be related to clinical symptoms, several patient groups were studied prospectively. In 8 of 16 (50%) homosexual males with acquired immunodeficiency syndrome (AIDS) or unexplained lymphadenopathy syndrome (LAS), coronavirus particles were found. In contrast, such particles were found in none of 18 heterosexual controls and in only 3 of 20 homosexual males without AIDS or LAS. Thus, coronavirus excretion correlated significantly (2 alpha less than 0.01) with the clinical diagnosis of AIDS or with syndromes belonging to the AIDS-related complex. In addition, such particles identified in the serum of one patient with LAS and diarrhea suggest invasion and systemic spread of the agent and underline that this virus behaves differently from "common cold" human coronaviruses.

Acquired Immunodeficiency Syndrome↗