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PubMed1992

Expression and cellular distribution of the alpha 1 gap junction gene product in the ocular pigmented ciliary epithelium.

The expression of four different gap junction (GJ) transcripts, corresponding to the alpha 1, alpha 3, beta 1 and beta 2 gene products, has been examined in the ciliary epithelium of human and bovine eyes, and in cultures of ciliary epithelial cells. Northern blot analysis revealed that alpha 1 mRNA, 3.6-kb in size, was the predominant transcript expressed in intact tissue and in cultures of pigmented ciliary epithelial cells (PE). No transcripts from the alpha 3, beta 1 or beta 2 gap junction genes were detected in intact tissue or ciliary epithelial cells as demonstrated by Northern blotting. When the levels of alpha 1 gap junction mRNA were compared between PE and NPE in primary cultures, a striking difference was observed in the level of alpha 1 transcripts: there was about a 6 to 8-fold increase in alpha 1 levels in PE cells, relative to the NPE cells. To verify the differential level of expression of alpha 1 GJ mRNA in the two cell types, indirect immunofluorescence localization studies were performed on semithin cryostat sections of ciliary processes. These studies revealed that alpha 1 gap junctions are present at the apical and lateral borders of PE cells, i.e. at the apical plasma membranes domains of PE-NPE cells, and at the lateral plasma membrane regions of PE-PE cells borders. Further analysis by immunoblotting confirmed that the 43 kD alpha 1 gap junction protein was the major gap junction gene product in the ciliary epithelium.

Animals↗
PubMed1996

Cell-attached patch clamping of the intact rabbit ciliary epithelium.

Following thorough removal of adhering aqueous humor, we have succeeded in patch clamping the intact rabbit ciliary epithelium in the cell-attached and inside-out excised-patch modes. Rapidly fluctuating currents ("chatter activity') were observed during recordings conducted for as long as 1 h. Chatter activity did not reflect seal instability since interconversion was noted between chatter activity and transitions between stable open and closed states, excision of patches into the bath was associated with substantial shifts in the reversal potential, and chatter activity could be triggered by sustained hyperpolarization, but was insensitive to stretch. The chatter channel was identified as cation-nonselective from the reversal potentials both in the cell-attached and excised-patch modes. The channel's kinetics were similar to those of the cGMP-activated phototransduction channel. The results of PCR amplifications of fragments in cDNA libraries from both human ciliary body and human nonpigmented ciliary epithelial (NPE) cells indicated that human ciliary epithelial cells transcribe message for the retinal phototransduction channel. The possible role of the phototransduction channel in expressing chatter activity was further explored by perfusing preparations with a known activator of that channel (cGMP) and with a known inhibitor (L-cis-diltiazem). Neither agent significantly affected chatter behavior. We conclude that: (1) this is the first demonstration of the feasibility of patch-clamping the intact ciliary epithelium; (2) the NPE cells display chatter activity arising from rapidly fluctuating transitions of a cation-nonselective channel; (3) NPE cells can transcribe message for the cation-nonselective phototransduction channel; and (4) if the observed chatter activity is from a homologue of the photo-transduction channel, the homologue is pharmacologically distinct.

Animals↗
PubMed1986

Serum beta 2-microglobulin as a marker of activity in systemic lupus erythematosus.

A prospective study of 62 patients with systemic lupus erythematosus (SLE) was performed in order to establish whether serum beta 2m could be a good marker of clinical activity. beta 2m was determined by radio-immunoassay and the values compared with a control group of healthy individuals. The mean value of beta 2m in the control group was 1.48 +/- 0.52 mg/l and 2.87 +/- 2.19 mg/l (p less than 0.001) in the SLE group, 4.53 +/- 2.89 mg/l in the 22 patients with active disease and 2.40 +/- 1.80 mg/l (p less than 0.001) in the 40 patients with inactive disease. High beta 2m values (greater than or equal to 3 mg/l) were observed in 64% of the patients with active SLE, VS. only 12% of the patients with inactive disease (p less than 0.001). Significant differences were also observed when beta 2m of the patients with inactive SLE was compared with the control group (p less than 0.001). The beta 2m with a sensitivity of 64%, a specificity of 87%, and an efficiency of 79% could be a good parameter to detect SLE clinical activity.

Adolescent↗
PubMed1989

Presence and significance of NK cells in glioblastomas.

A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.

Adult↗
PubMed1990

Immunohistochemical study of natural killer cells in tumor-infiltrating lymphocytes of primary intracranial germinomas.

A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence and distribution of these cells in a series of nine primary intracranial germinomas. In all of these tumors, IOT-10-positive NK cells were found in small numbers, mainly distributed among the tumor cells. The data obtained in the present study suggest that the presence of NK cells in primary intracranial germinomas can be influenced by factors other than the mere quantity of tumor-infiltrating lymphocytes.

Brain Neoplasms↗
PubMed1990

Papillary pineocytoma. Case report.

A case of papillary pineocytoma is presented. It is necessary to be aware of this unusual histological type of pineocytoma in order to make a differential diagnosis among other types of papillary tumors that arise in the pineal region.

Brain Neoplasms↗
PubMed1990

Cerebral metastasis from angiosarcoma of the heart. Case report.

A case of secondary cerebral angiosarcoma in a 30-year-old man is presented. The patient had previously undergone heart transplantation for treatment of the primary tumor. Only a few cases of cerebral metastasis from angiosarcoma have been recorded in the literature; the present case is the first reported case diagnosed after heart transplantation.

Adult↗
PubMed1999

Expression of vascular permeability factor in craniopharyngioma.

OBJECT: The expression of vascular endothelial growth/permeability factor (VEG/PF) has recently been correlated with the presence of tumor-associated cysts in some intracranial tumors. The purpose of this study was to evaluate a possible relationship between the presence of VEG/PF and the formation of cysts in craniopharyngiomas. METHODS: The expression of VEG/PF was studied in histological specimens from a series of 12 craniopharyngiomas. In this series, the tumors were classified as presenting a mainly solid pattern with small macroscopic cysts (four patients) or a mainly cystic pattern (eight patients). The mainly solid tumors containing small macroscopic cysts showed little or no VEG/PF positivity, which was mainly present in tumor cells surrounding cysts. Nevertheless, mainly cystic craniopharyngiomas showed a moderate or high degree of VEG/PF positivity in tumor cells. CONCLUSIONS: These findings indicate that the predominance of a cystic or solid macroscopic appearance of craniopharyngiomas may be influenced by the degree of VEG/PF expression within the tumor cells.

Adult↗
PubMed1999

Vascular endothelial growth/permeability factor in spinal cord injury.

OBJECT: Predicated on the hypothesis that this cytokine can contribute to the development of vascular hyperpermeability, leading to tissue edema after trauma, the purpose of this study was to determine the presence in tissue of vascular endothelial growth/permeability factor (VEG/PF) after experimental spinal cord injury. METHODS: The presence of VEG/PF was studied at 8 hours and 2, 8, and 14 days after a traumatic injury in adult Wistar rats. Studies were conducted in which a monoclonal antibody to the VEG/PF was used. Strong VEG/PF immunoreactivity was detected in the walls of pial and intramedullary vessels and in reactive astrocytes 8 hours posttrauma and was unchanged on Days 2 and 8. By Day 14, immunoreactivity decreased, and most of the arterioles from the pia and gray matter showed no mural VEG/PF. CONCLUSIONS: The authors' present findings suggest a role for this cytokine in the development of tissue edema after spinal cord trauma and point to the possible usefulness of a therapeutic approach to spinal cord injury based on blocking the cell expression of VEG/PF or its physiological effects.

Animals↗
PubMed2004

Comparison of different cooling regimes within a shortened liquid cooling/warming garment on physiological and psychological comfort during exercise.

The aim of this study was to compare the effectiveness of different cooling regime intensities to maintain physiological and subjective comfort during physical exertion levels comparable to that engaged in during extravehicular activities (EVA) in space. We studied eight subjects (six males, two females) donned in our newly developed physiologically based shortened liquid cooling/warming garment (SLCWG). Rigorous (condition 1) and mild (condition 2) water temperature cooling regimes were compared at physical exertion levels comparable to that performed during EVA to ascertain the effectiveness of a lesser intensity of cooling in maintaining thermal comfort, thus reducing energy consumption in the portable life support system. Exercise intensity was varied across stages of the session. Finger temperature, rectal temperature, and subjective perception of overall body and hand comfort were assessed. Finger temperature was significantly higher in the rigorous cooling condition and showed a consistent increase across exercise stages, likely due to the restriction of heat extraction because of the intensive cold. In the mild cooling condition, finger temperature exhibited an overall decline with cooling, indicating greater heat extraction from the body. Rectal temperature was not significantly different between conditions, and showed a steady increase over exercise stages in both rigorous and mild cooling conditions. Ratings of overall comfort were 30% higher (more positive) and more stable in mild cooling (p<0.001). The mild cooling regime was more effective than rigorous cooling in allowing the process of heat exchange to occur, thus maintaining thermal homeostasis and subjective comfort during physical exertion.

Adult↗
PubMed2005

Evaluation of the antitumor activity of interleukin-12 in an experimental murine model of colorectal cancer induced by 1,2 dimethyl-hydrazine (DMH).

OBJECTIVE: Interleukin 12 (IL-12) is a cytokine that may enhance the proliferation and cytotoxic activity of T lymphocytes and natural killer (NK) cells. A relationship between extensive intratumoral infiltration of NK cells and longer survival rates in colorectal cancer (CRC) patients was previously noted. Preliminary evidence suggests that the combined administration of IL-12 and IL-2 may produce additive immunomodulatory activity. The purpose of this study was to determine whether the systemic administration of IL-12 (+/- IL-2) may induce an immune response against CRC as induced by 1,2-dimethylhydrazine (DMH). METHODS: Sixty-five 6-week-old Wistar rats were treated with weekly subcutaneous injections of DMH for 26 weeks at a dose of 20 mg/kg of body weight. Once tumoral induction was over, the animals were randomly allocated to one of three groups: I, control; II, intraperitoneal injections of IL-12; III, intraperitoneal injections of IL-12 combined with IL-2. At 30 weeks, all surviving animals were sacrificed. We studied the following parameters in each rat--number of tumors, size of tumors, and total tumoral volume. Tumor samples were studied using the monoclonal antibody CD 57 for the detection of NK cells. The extent of NK infiltration was classified as small, less than 50 NK cells/50 high-power field (HPF); moderate, 50 to 150 NK cells/50 HPF, and extensive, more than 150 NK cells/50 HPF. RESULTS: Thirty-five rats died before completion of the carcinogen exposure, and 30 rats were randomized (10 each group). In group II, 2 animals died during treatment. All rats in groups I and III developed tumors, while in group II two rats (25%) were tumor-free. Moreover, only one rat in group II developed multiple neoplasms, in contrast with group I and group III, where six rats (60%) and seven rats (70%), respectively, had more than one tumor. We found statistically significant differences in the mean number of tumors found in group II when compared to group I (p = 0.028) and group III (p = 0.019). Other parameters measured, such as biggest tumor size and total tumoral volume were found to be lower in group II, although no statistical differences were found between groups. Only 10% of rats in group I showed moderated/extensive NK cell infiltration, vs. 60% of rats in group II (p = 0.077) and 70% in group III (p = 0.02). CONCLUSION: The administration of DMH to rodents provides a reliable and consistent means of inducing CRC that may be suitable for the evaluation of anti-cancer therapies. Our findings suggest that IL-12 is effective against the development of experimental CRC. Its antineoplastic effect could be attributed to the stimulus of this cytokine on the intratumoral infiltration of NK cells.

1,2-Dimethylhydrazine↗
PubMed1998

The placebo effect in ambulatory blood pressure monitoring.

The reduction of clinic blood pressure by placebo tablets in clinical trials of antihypertensive drugs is well established and health authorities require a placebo arm in these trials in order to know how much of the total reduction of blood pressure is attributable to the drug. Most authors now favor the hypothesis that, in contrast to clinic blood pressure measurements, ambulatory blood pressure monitoring (ABPM) is not subject to a placebo effect. Scientific evidence so far shows that ABPM recordings are affected by a negligible and clinically irrelevant placebo effect in short-term trials. Nevertheless, the results of the SYST-EUR study suggest that placebo treatment induces a reduction of blood pressure in old patients with isolated systolic hypertension even when blood pressure is measured by 24 h ABPM, and raise the question of whether a placebo arm is required in clinical trials when ABPM is used to measure changes in blood pressure. In this article, the evidence supporting and contradicting the hypothesis that placebo exerts an effect on ABPM and the possible explanations for the discrepancy are reviewed. My position is that clinical trials on antihypertensive drugs using ABPM should be designed with the same standards as those using clinic blood pressure measurements; that is, randomized, double-blind, placebo-controlled studies. This should be an absolute requirement in long-term trials. Short-term trials lasting no more than 12 weeks, particularly those focused on examining average changes in 24 h diastolic blood pressure, may be designed without a placebo arm.

Journal Article↗
PubMed1976

[Obstruction and normal rechannelization of the ureter in the human embryo. Relations to stenoses and congenital ureteral valves].

Study of 5 normal human embryos from 5 to 55 mm in length from vertex to coccyx, shows that the ureteric ducts, which in the first phases of development are permeable (embryos of 5-13 mm, Streeter's Horizons XIII-XVII, age from 28 +/- 1 to 35 +/- 1 days), constantly undergo a process of obstruction and a subsequent recanalization of their lumen, which takes place when the embryos measure from 14 to 22 mm. The processes begin in the middle zone of the ureters and progress proximally and distally until they cover its entire length. These ducts, which in embryos of approximately 17 mm in length form solid cords, are totally permeable in embryos of 23 mm. These modifications are of great importance for correct interpretation of the pathogenic mechanism of congenital ureteric strictures and valves.

Humans↗
PubMed1999

[Calcium pump changes in patients with essential arterial hypertension].

BACKGROUND: Transmembrane Ca2+ fluxes are mediated, at least in part, by the Ca(2+)-dependent ATPase. Thus, genetic or acquired abnormalities of this pump could explain the increase in free cytosolic Ca2+ content that has been observed in essential hypertensive patients. PATIENTS AND METHODS: We carried out a kinetic study of the Ca2+ pump in intact erythrocytes from 49 essential hypertensive patients and 27 normotensive healthy persons. We used Sr2+ as a calcium analogue to measure Ca2+ fluxes dependent of the Ca2+ pump. The intracellular concentrations of Sr2+ and Ca2+ were modified using the A-23187 ionophore in a Ringer isotonic solution. RESULTS: Hypertensive patients showed a significant increase of the maximal efflux rate for Sr2+ (Vmax) with respect to controls (6.6 [2.3] vs 5.2 [1.6] mmol/l cel/h; p = 0.006). Mean values of apparent dissociation constants for intracellular Ca2+ (KCa) were also increased in essential hypertensives (80.36 [53.46] vs 55.25 [15.13] mumol/l cel; p = 0.06). A significant correlation between Vmax and age (r = 0.342; p = 0.016), and serum creatinine (r = 0.446; p = 0.001) was observed. The KCa only correlated with serum creatinine (r = 0.402; p = 0.004). Using the KCa confidence interval of 99% as the higher normal limit, patients were segregated into two subgroups depending on normal KCa values (33 patients, 67.3%) or increased KCa values (16 patients, 32.6%). Age (50.8 [13.5] vs 43 [10.2] years; p = 0.02), serum creatinine (1.13 [0.17] vs 0.95 [0.17] mg/dl; p = 0.001) and serum uric acid (7.27 [3.32] vs 6.14 [1.49] mg/dl; p = 0.04) were higher in patients with increased KCa. Finally, patients with increased KCa also showed increased values of Vmax (9.13 [2.02] vs 5.38 [12.81] mmol/l cel/h; p < 0.0001). CONCLUSIONS: Essential hypertensive patients are heterogeneous regarding ion transport abnormalities, only affecting subgroups of hypertensive patients. We have observed abnormalities of the Ca(2+)-dependent ATPase in 33% of essential hypertensive patients. These patients are older and tend to exhibit higher values of serum creatinine and uric acid.

Adult↗
PubMed1999

[The effects of an oral calcium overload on the rat exocrine pancreas].

AIM: The possible induction of functional or morphologic changes in the exocrine pancreas of the rat by oral calcium overload was studied to determine the possible relationship to predisposition of acute pancreatitis over the acinar theory. MATERIALS AND METHODS: Oral chloride calcium (0.45 and 0.25 g/kg body weight/day) plus cholelecalciferol (300,000 UI/kg i.m.) were administered to male Wistar rats over 1 to 3 months. Half of each group, including a control were submitted to cholinergic stimulation with carbamylcholin. After anesthesia, blood and pancreatic tissue and duodenal fluid were extracted for enzymatic and ultrastructural studies. RESULTS: In the rats treated with high doses of calcium for 1 month greater tissue concentrations of amylase, lipase and trypsin were observed. Moreover, there was a greater trend to the presence of dilated ergastoplasm. In the rats treated with high doses over 3 months a lower enzyme concentration was observed in the animals not stimulated that in the control group. On stimulation with carbamylcholin, higher concentrations of enzymes were observed in tissue than in those not stimulated. This was accompanied by a lower number of exocytosis in this experimental group that in the control. CONCLUSIONS: A possible increase in the calcium concentration in the acinar cell may lead to dysfunction in the secretory mechanisms favoring the intracellular accumulation of digestive enzymes, predisposing intracellular activation, in the context of the acinar or lysosomal hypothesis of acute pancreatitis.

Administration, Oral↗