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PubMed1990

Experimental pulmonary candidiasis.

The initial interaction of Candida albicans with pulmonary tissue of B6D2/F1 mice was investigated. The LD50 for mice challenged intravenously (IV) was approximately 3 X 10(5) yeasts, whereas the LD50 by the intratracheal (IT) route was in excess of 10(8) yeasts. Mice challenged IV died of progressive yeast growth in the kidneys. In contrast, mice challenged IT rapidly eliminated the entire inoculum by the first day after challenge. Resident pulmonary alveolar macrophages (PAM) killed upwards of 70% of C. albicans in an in vitro killing assay. At effector: target ratios favoring the effector cell population resident PAM were able to restrict the formation of yeast germ tubes to only 30% of the yeasts, whereas at equivalent ratios virtually all of the intracellular yeasts produced germ tubes. Evaluation of the ability of PAM, harvested from genetically different strains of inbred mice, to kill C. albicans in vitro showed that killing ability was a property of resident PAM from mice with the black 6 background. It was discovered that during the initial stages of infection in vivo, the expression of the F4/80 surface molecule was down regulated, and the expression of the Mac 1 surface molecule upregulated. There were no quantitative changes in expression of either Mac 2, Mac 3, Ly 5 or the 5C6 surface epitopes. Taken together, the data show that pulmonary tissue is quantitatively very resistant to C. albicans infection, because of the ability of resident PAM to rapidly phagocytize and kill yeasts. Killing of C. albicans by resident PAM may be a property of a subset of this mononuclear phagocyte population and was accompanied by alterations in the expression of surface molecules.

Animals↗

PubMed1989

Influence of scheduling on two-drug combinations of alkylating agents in vivo.

The effects of schedule and sequence on the survival of EMT6 tumor cell and bone marrow (CFU-GM) obtained after treatment using combinations of cyclophosphamide (CTX) and thiotEPA or melphalan (L-PAM) were examined and analyzed by isobologram methodology. On a single-injection schedule, when CTX and thio-tEPA were given simultaneously or thiotEPA was given prior to CTX, the result was slightly greater than additive tumor-cell kill. However, when CTX preceded thiotEPA by 4 h, there was less than additive cell kill. When the interval between the administration of the two drugs was 8 h, both sequences of the drugs produced greater than additive tumor-cell kill. Simultaneous administration of CTX and thiotEPA on a multiple-injection schedule resulted in sub-additive tumor-cell kill. On the multiple-injection schedule, extending the interval between injections of CTX and thiotEPA to 4 and 8 h resulted in increasing tumor-cell kill. With the 4- and 8-h intervals, no significant sequence-dependent difference in tumor-cell kill was obtained. The results of CTX and L-PAM combinations paralleled those of CTX and thiotEPA. Bone marrow (CFU-GM) survival was used as a representative normal tissue with which to compare tumor-cell survival after each treatment to obtain a measure of therapeutic effect. The trends for the ratios of bone marrow: tumor cell survival were the same for the treatment sequences of CTX with thiotEPA or L-PAM; however, greater magnitudes of differential tumor-cell kill were obtained with CTX L-PAM combinations. Using this measure, the greatest therapeutic effectiveness was seen with single-dose L-PAM or thio-tEPA followed 4 h later by CTX and with CTX given as a single or as multiple doses followed 8 h later by L-PAM or thiotEPA. Such data from tumor-model systems may be useful in the development of more effective alkylating agent regimens for use in the clinic.

Alkylating Agents↗

PubMed2004

Replication kinetics of different porcine circovirus 2 strains in PK-15 cells, fetal cardiomyocytes and macrophages.

In this in vitro study, the replication kinetics of porcine circovirus type 2 (PCV2) in porcine alveolar macrophages (PAM) and fetal cardiomyocytes (FCM), two target cells in vivo, was compared with that in PK-15 cells. Cultures were inoculated with either the postweaning multisystemic wasting syndrome (PMWS)-associated strain Stoon-1010 or the abortion-associated strain 1121. Viral proteins were visualized and virus production was determined. In PK-15 cells, the capsid protein was expressed between 6 and 12 hours post inoculation (hpi), it relocated to the nucleus between 12 and 24 hpi. At that time, Rep protein was also detected in the nucleus. This sequence of events also occurred in FCM and PAM but nuclear localized antigens appeared later (48 hpi) and in a lower percentage of cells. In PAM, clear differences in susceptibility were seen between pigs. In PAM from two out of five tested pigs, nuclear localized antigens were not detected, whereas in PAM from three other pigs they were seen in up to 20% of the antigen-positive cells. Virus production was observed in PK-15 but not in PAM or FCM cultures. In a second study, the replication kinetics of seven different PCV2 strains were compared in PK-15 cells. It was shown that the two abortion-associated strains had a different replication kinetics in comparison with PMWS or porcine dermatitis and nephropathy syndrome associated strains. With the abortion-associated strains, a higher number of infected cells was observed at 24 hpi and the percentage of infected cells with nuclear localised antigens was lower compared to that of other strains.

Animals↗

PubMed2006

Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate.

BACKGROUND: There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. METHODS: (99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM. RESULTS: Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 +/- 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of (99m)Tc-PAM increased after 24 h of application to 2.4 +/- 0.15, 1.53 +/- 0.09, 7.94 +/- 0.99, and 13.2 +/- 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 +/- 0.03 and 0.22 +/- 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 +/- 0.07 and 0.16 +/- 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h. CONCLUSIONS: The results indicate that the bone uptake of (99m)Tc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.

Administration, Topical↗

PubMed2006

Clinical and densitometric efficacy of the association of interferon alpha and pamidronate in the treatment of osteoporosis in patients with systemic mastocytosis.

Osteoporosis accompanying severe mastocytosis leads to numerous compressed vertebrae. We treated four patients (mean age 52 years) with severe osteoporosis and mastocytosis proven by bone marrow biopsy (more than 40 mast cells/mm3), according to the following protocol: interferon alpha (IFN) 3 million units (MU) three times a week, reduced to 1.5 MU three times a week in the event of intolerance, and pamidronate (Pam) 90 mg/month in infusion. This treatment was given for 2 years. It was followed by Pam alone at a dose of 90 mg/month. After 3 or 4 years of treatment, no patient presented new vertebral or extravertebral fractures. The mean increase in bone mineral density (BMD) with IFN and Pam was 16.05+/-6.12% at the spine, 5+/-2.24% at the femoral neck, and 4.12+/-3.03% for the whole body; the increase or loss of BMD with Pam alone was +0.2+/-2.13% at the spine, -2.25+/-2.78% at the femoral neck, and -0.1+/-3.35% for the whole body. In one patient, the IFN dose was halved because of a flu-like syndrome, and in another IFN was discontinued at one year for the same reason. The association of IFN and Pam led to a major increase in bone marrow density in osteoporosis with concomitant mastocytosis and this gain was then maintained by monthly infusions of Pam.

Adult↗

PubMed1987

Peptidyl-glycine alpha-amidating monooxygenase is present in islet secretory granules of the anglerfish, Lophius americanus.

Anglerfish islet secretory granules have been examined for the presence of an enzyme which could perform C-terminal amidation of glucagon-like peptide II and possibly anglerfish peptide Y. Using [125I]D-Tyr-Val-Gly as substrate, a peptidyl-glycine alpha-amidating monooxygenase (PAM) was detected in islet secretory granule lysates. The enzyme is active between pH 6.0 and 8.5 and exhibits maximal activity near pH 7.0. The islet PAM requires Cu2+, ascorbate, and molecular oxygen for activity. Other divalent metal ions and redox cofactors were tested and found to be inactive in the assay. Even though added Cu2+ and ascorbate are required for detecting islet PAM activity, when these factors were incubated with substrate in the absence of secretory granule lysate, no activity was observed. It was also found that the addition of higher than optimal concentrations of either Cu2+ or ascorbate inhibited amidating activity. The results demonstrate that a PAM is present in secretory granules of anglerfish islet tissue. The characteristics of the islet PAM are similar to those of PAMs identified and characterized in other tissues which produce bioactive C-terminally amidated peptides.

Animals↗

PubMed1983

Decreased pulmonary alveolar macrophage bactericidal activity in splenectomized rats.

The organism most frequently encountered in postsplenectomy sepsis is Streptococcus pneumoniae, which is thought to invade via the upper respiratory tract. This study assesses the phagocytic and bactericidal activity of pulmonary alveolar macrophages (PAM) in normal, splenectomized, and one-third splenectomized autotransplanted rats at 8 weeks of age, 7 weeks post surgery. The PAMs from both the splenectomized and control rats all expressed the same ability to phagocytose latex beads and Fc-receptor-mediated phagocytosis of SRBC. In the bactericidal assay, bacterial growth, after 1 hr without macrophages, was 31 X 10(3) colony-forming units (CFU). In the presence of PAMs from splenectomized rats, the colony count was 22 X 10(3) (P less than 0.2). Bactericidal activity was highly evident when PAMs from control and autotransplanted rats were assayed, with CFU of 11.3 X 10(3) and 14.6 X 10(3), respectively (P less than 0.001, P less than 0.002, respectively). It is concluded that antibody-dependent and independent phagocytic activity of PAMs is unimpaired in splenectomized rats as compared to controls. The defect in rats splenectomized at 1 week of age resides in poor pneumococcal bactericidal activity of PAMs and is almost completely corrected by ip autotransplantation of one-third of the spleen.

Animals↗

PubMed1985

Effects of HI-6 and pralidoxime on neuronal RNA in thalamic cholinergic sites.

Quantitative azure B-RNA cytophotometry was employed to compare effects of the oximes HI-6 and pralidoxime (2-PAM) to those of atropine sulfate (AS) on neuronal RNA metabolism in the thalamic ventrobasal nuclear complex (VBC) and nucleus reticularis (NR). The ability of these compounds to mitigate soman (pinacolyl methylphosphonofluoridate)-induced neuronal RNA alterations (i.e., VBC-RNA depletion/NR-RNA elevation) in these muscarinic cholinergic sites was also determined. Generally, HI-6 (125 mg/kg, i.p.) and 2-PAM (43.2 mg/kg, i.m.) elicited similar patterns of neuronal RNA changes, i.e., diminution of VBC-RNA and NR-RNA with oximes alone; partial amelioration of soman (1.5 LD50, s.c.)-induced VBC-RNA loss; and slight or no effect on soman induced NR-RNA accumulation. HI-6 produced more severe RNA reduction than 2-PAM in both brain regions of non-poisoned rats, whereas 2-PAM was more effective in reversing the effects of soman in these two regions. The muscarinic antagonist, AS, also produced VBC-RNA depletion and partially counteracted the VBC-RNA loss in soman intoxicated rats. Unlike the oximes, however, AS resulted in NR-RNA accumulation and it also antagonized soman induced NR-RNA elevation. Neither oxime reactivated soman inhibited brain acetylcholinesterase but HI-6 did reactivate appreciable plasma cholinesterase. The overall data suggest that HI-6 and 2-PAM do exert pharmacologic actions on cholinergic neurons in the rat CNS. However, the greater effectiveness of HI-6 over 2-PAM in countering lethal actions of soman does not appear to be correlated with oxime mediated restoration of neuronal RNA levels in these two cholinergic regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Pharmacokinetics of pralidoxime chloride in the rat.

The pharmacokinetics of pralidoxime chloride (2-PAM) was studied in rats. Different groups of rats were given an intramuscular injection of 2-PAM at one of three doses (20, 40, or 80 mg/kg). This range of doses is used commonly in studies concerned with the efficacy of 2-PAM against poisoning by potent organophosphorus inhibitors of cholinesterase enzyme. Individual, sequential blood samples were collected during the course of the experiment. From these blood samples the plasma concentrations of 2-PAM were determined over time for each animal. Next the relationship of plasma concentration to time was expressed in terms of a standard pharmacokinetic model. Estimates of various pharmacokinetic parameters were calculated using an open, one-compartment model: volume of distribution (Vd), maximal plasma concentration (Cmax), elimination rate constant (k10), absorption rate constant (k01), area under the curve (AUC) and clearance (CL). Of the pharmacokinetic estimates, only Cmax and AUC were found to be statistically significant (p less than 0.0001) when compared across all the doses; these pharmacokinetic estimates were highly correlated with doses with r = 0.998 and r = 0.997, respectively. However, when AUC and Cmax were normalized by dividing through by dose, no significant differences were found in the transformed data. The results of this study in rat indicate that the pharmacokinetics of 2-PAM is linearly related to dose in a range employed in therapeutic studies of 2-PAM.

Animals↗

PubMed1989

The relationship between oxime-induced reactivation of carbamylated acetylcholinesterase and antidotal efficacy against carbamate intoxication.

The efficacy of the oximes pyridinium-2-aldoxime methochloride (2-PAM) and 1-[[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydro xyimino) methyl]pyridinium dichloride (HI-6), in combination with atropine (At), against lethality by either carbaryl (CA) or physostigmine (Phy) was investigated in rats. The protection by At, 8 mg/kg, iv, against CA intoxication was reduced by 2-PAM (22 mg/kg, iv) and HI-6 (50 mg/kg, iv) from a protective ratio (PR) of 6.6 to 3.5 and 2.3, respectively. However, in Phy-intoxicated rats, the administration, iv, of At alone, At + 2-PAM, or At + HI-6 at 1 min following Phy provided good protection and resulted in PRs of 7.2, 8.8, and 23.3, respectively. In experiments on decarbamylation of inhibited acetylcholinesterase (AChE), HI-6 and 2-PAM accelerated (p less than 0.05) the decarbamylation of Phy-inhibited AChE in vitro, and HI-6 decreased (p less than 0.05) the inhibition of whole blood AChE in Phy-intoxicated rats. These findings show that the protection was increased substantially by the use of either 2-PAM or HI-6 against Phy-induced lethality, whereas the use of oximes against carbaryl poisoning was contraindicated. Furthermore, even though CA and Phy are both N-methyl carbamates, the data indicate that there is no adverse interaction between 2-PAM or HI-6 and Phy.

Acetylcholinesterase↗

PubMed1994

Effect of selected cytokines on the replication of Corynebacterium pseudotuberculosis and ovine lentiviruses in pulmonary macrophages.

Opportunistic bacterial pathogens that induce monokine secretion by pulmonary alveolar macrophages (PAM) are frequently encountered complicating factors in lentivirus-associated pneumonias in ungulates and man. We examined the effect of selected cytokines on the replication of Corynebacterium pseudotuberculosis and ovine lentivirus (OvLV) in ovine PAM. Recombinant bovine (rBo) IL 1 beta, rBoIL-2, rBo interferon-gamma (IFN gamma) and rBoTNF alpha, alone and in combination at physiological doses had no apparent effect on the extracellular growth of C. pseudotuberculosis, compared with the growth of the pathogen in medium alone. Untreated ovine PAM, derived from bronchoalveolar lavage, were found to substantially reduce, but not eliminate the growth of C. pseudotuberculosis in culture. This bactericidal effect was neither enhanced nor inhibited by pretreatment of PAM with the recombinant bovine cytokines or low doses of LPS that induce monokines. In contrast, addition of rBoTNF alpha or rBoIL-1 beta, at physiological doses, at the initiation of, or on Day 4, after OvLV infection resulted in a significant increase in viral replication in PAM, as measured in an antigen capture assay for OvLV p25, compared with untreated infected cells. This effect was more pronounced with lower levels of infecting OvLV, and, in the case of TNF alpha, was abrogated by preincubation of the cytokine with specific anti-serum. Conversely, in most instances, inclusion of rBoIFN alpha in OvLV-infected PAM cultures resulted in a significant decrease in viral replication. These results suggest that these soluble mediators that are probably secreted in response to C. pseudotuberculosis infection may have little direct effect on the extra- or intracellular survival of the bacteria in the lung, but may modulate lentiviral replication and, by extension, disease expression, in sheep with dual infection.

Animals↗

PubMed1984

Modification of alkylating agent cytotoxicity by cisplatin.

The effect of cisplatin on the cytotoxicity of alkylating agents in the RIF-1 tumor both in vivo and in vitro was investigated. A single dose of cisplatin (1 mg/kg) enhanced the in vivo tumor killing by melphalan (L-PAM; 8 mg/kg). The effect was maximal when cisplatin was given between 3 hours before and 1 hour after injecting L-PAM; the enhancement was lost as the time interval increased. Similar results were obtained with cyclophosphamide (CYT; 75 mg/kg) and CCNU (50 mg/kg) although the enhancement was much less than that seen with L-PAM. The enhancement by cisplatin was constant at all L-PAM doses as measured by both cloning assay and regrowth delay. Measurements of white blood cell counts four days after drug administration suggests that a therapeutic gain can be achieved. Exponential and plateau phase RIF-1 cells grown in monolayer culture were also exposed to various L-PAM doses. A 1 hour pre-exposure to cisplatin (0.5 micrograms/ml) under aerobic conditions increased the cell killing by L-PAM. The results are discussed with reference to the possible reasons for the therapeutic gain.

Alkylating Agents↗

PubMed1991

Modulatory effects of interferon-gamma on the fibronectin receptor function of squamous cell carcinoma cells in vitro.

We previously showed that the in vivo invasion of a squamous cell carcinoma induced by the intradermal injection of tumor cells was significantly delayed after the IFN-gamma-producing gene transfer to tumor cells. With respect to the mechanism of the delayed invasion, it was suggested that the IFN-gamma might inhibit the adhesion of the cells to extracellular matrices (ECM) and the subsequent locomotion. Thus, we examined the effect of IFN-gamma on the adhesion of Pam-T cells to ECM. The attachment of Pam-T cells to fibronectin (FN) was significantly higher than that to laminin (LN), collagen type I (COL I) or collagen type IV (COL IV) substrata. The attachment to FN was significantly enhanced specifically by the IFN-gamma-treatment of the cells, although the attachment to LN, COL I or COL IV was not altered by IFN-gamma. Neither IFN-alpha nor IFN-beta had any effect on the attachment of Pam-T cells to FN. When Pam-T cells were treated with IFN-gamma together with a neutralizable anti-IFN-gamma antibody, this enhancement was completely abolished. Moreover, the attachment of IFN-gamma-treated Pam-T cells as well as non-treated cells to FN was blocked by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), but not by the control peptide Arg-Gly-Glu-Ser. Based on these results, we conclude that IFN-gamma specifically enhances the adhesiveness of Pam-T cells to FN substrata by the modulation of integrin activity.

Amino Acid Sequence↗

PubMed2005

Protective effect induced by atropine, carbamates, and 2-pyridine aldoxime methoiodide Artemia salina larvae exposed to fonofos and phosphamidon.

The acute toxicity of fonofos and phosphamidon on three age classes of Artemia salina was evaluated. An increase in toxicity of these organophosphorous (OP) insecticides was found following longer development of A. salina. The effects of pretreatment with the nonselective muscarinic antagonist atropine, the two reversible acetylcholinesterease inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating oxime 2-pyridine aldoxime methoiodide (2-PAM), as individual and combined pretreatments, on OP-induced lethality in 24 h Artemia were also investigated. The lethal action of both OP insecticides was prevented by pretreatment of 24 h Artemia with atropine and 2-PAM, while physostigmine proved ineffective against intoxication with both OP insecticides and pyridostigmine exhibited a low synergic effect. In both cases, the inhibitory effects of combinations of atropine (10(-5)M) plus 2-PAM were greater than those elicited by either drug alone, with the maximum protection afforded being 100%. Combined pretreatment of atropine (10(-5)M) plus physostigmine practically abolished the lethal effects induced by both insecticides. Pretreatment with 2-PAM (10(-6)M) plus physostigmine afforded maximal protection of 100% and 76% on the lethality induced by fonofos and phosphamidon, respectively. The data obtained suggest that the combination of atropine plus 2-PAM or physostigmine and the combined pretreatment of 2-PAM plus physostigmine are effective in the prevention of the lethal effects induced by fonofos and phosphamidon in A. salina larvae.

Age Factors↗

PubMed2006

Biological weighting functions as a tool for evaluating two ways to measure UVB radiation inhibition on photosynthesis.

To estimate the inhibitory effect of the changing UVB radiation (UVBR, 280-315nm) on earth's ecosystems, an understanding of its wavelength dependency is needed. The tool used for these estimations is the biological weighting function (BWF), whereby the inhibition of different wavelengths is calculated. BWFs were determined for three algae species from different classes, Phaeodactylum tricornutum (Bacillariophyceae), Dunaliella tertiolecta (Chlorophyceae) and Rhodomonas sp. (Cryptophyceae), using polychromatic irradiation, where the UVBR spectra were varied with cut-off filters. For each alga, BWFs were determined for two photosynthetic parameters; the quantum yield measured as fluorescence from Photo System II in a pulse-amplitude-modulation (PAM) fluorometer, and the fixation of (14)C-labelled carbon dioxide. The BWFs were calculated with the Rundel method, using the radiation data between 270 and 360nm with 1nm resolution. The results show that the UVBR damages were generally higher when using the carbon fixation measurements than when measuring with the PAM technique. When using PAM, P. tricornutum in particular had a sensitivity intermediate between the sensitive Rhodomonas sp. and the more tolerant D. tertiolecta, but was as sensitive as, or even more sensitive, than Rhodomonas sp. when using carbon fixation. D. tertiolecta was shown to be less sensitive when using both techniques and the inhibition of its photosynthesis was almost as high when using PAM as when using carbon fixation. We concluded that, although the PAM technique has advantages such as being cleaner and easier to use, it is unable to substitute the carbon fixation measurements. Not only are the algae less sensitive when measured with PAM than they are when measured as carbon fixation, the relationship between the effects on the algae measured with the two techniques also differs. As fixation of carbon dioxide integrates a larger part of the photosynthetic machinery, it should be favoured as a measure of photosynthesis.

Eukaryota↗

PubMed2006

Improvement of leukocyte functions in prematurely aging mice after five weeks of diet supplementation with polyphenol-rich cereals.

OBJECTIVE: We investigated the beneficial effects of diet supplementation with two types of cereals naturally rich in polyphenolic compounds on several functions of peritoneal leukocytes from prematurely aging mice (PAM). METHODS: Two-hundred sixty healthy mice, 8 wk of age, were recruited and their behavioral responses were tested in a simple T-maze to identify PAM. Then the mice were fed a diet supplemented with 20% (wt/wt) of two different cereal fractions, named B (wheat germ) and C (buckwheat flour), rich in polyphenols (gallic acid, catechin, p-hydroxybenzoic acid, vanillic acid, p-coumaric acid, sinapic acid, ferulic acid, quercetin, and rutin), or a standard diet (controls) for 5 wk. Several parameters of innate (adherence to tissues, chemotaxis, phagocytosis, microbicidal capacity, and natural killer activity) and acquired immune (lymphoproliferation and interleukin-2 release) responses were measured. RESULTS: The PAM control group showed worse immune functions (P < 0.001 to 0.05) compared with the non-PAM control group. The PAM group that received cereal B showed increases in phagocytosis (P < 0.01), microbicidal activity (P < 0.001 to 0.01), natural killer activity (P < 0.001) and lymphoproliferation in response to lipopolysaccharide (P < 0.01) and interleukin-2 release (P < 0.001), and the PAM group that received cereal C showed a similar pattern, with increases in macrophage chemotaxis (P < 0.01), phagocytosis (P < 0.01), microbicidal activity (P < 0.001 to 0.01), natural killer activity (P < 0.01), lymphoproliferative response to concanavalin A and lipopolysaccharide (P < 0.001), and interleukin-2 release (P < 0.001). CONCLUSIONS: Dietary supplementation with polyphenol-rich cereals appears to have a protective effect on immune cell functions in mice with premature senescence. Thus, regular intake of these compounds could delay normal aging and improve quality of life.

Aging↗

PubMed1985

Primary acquired melanosis of the conjunctiva.

Forty-one cases of conjunctival primary acquired melanosis (PAM) were studied to determine the frequency of progression to malignant melanoma and to establish prognostic parameters for progression to melanoma. Two subdivisions were identified: lesions with cytologically atypical melanocytes (PAM with atypia, 28 lesions, 68.3 per cent) and those lacking cytologically atypical melanocytes (PAM without atypia, 13 lesions, 31.7 per cent). None of the lesions of PAM without atypia progressed to melanoma. Thirteen of the 28 lesions of PAM with atypia (46.4 per cent) progressed to melanoma. Progression to melanoma was more frequent in the lesions of PAM with atypia if basilar hyperplasia was not the dominant histologic pattern (90 per cent progression, P = 0.02) or if any epithelioid cells were present (75 per cent progression, P = 0.02). It was not possible to determine which lesions were atypical on the basis of clinical appearance. Lesions at risk for the development of melanoma should be totally extirpated.

Biopsy↗

PubMed1985

Malignant melanoma of the conjunctiva.

One hundred thirty-one cases of conjunctival melanoma in which biopsies had been performed were studied to determine potential factors that might affect outcome in patients with these lesions. Two groups of lesions were identified: those associated with primary acquired melanosis (melanoma with PAM, 98 cases, 74.8 per cent) and those without primary acquired melanosis (melanoma without PAM, 33 cases, 25.2 per cent). The overall mortality rate in the 131 cases was 26 per cent (34 of 131); the mortality rate due to melanoma with PAM was 25.5 per cent (25 of 98), and that due to melanoma without PAM was 27.3 per cent (9 of 33). If PAM was associated with the lesion, the presence of atypical melanocytes within the epithelium (pagetoid invasion) was a sensitive indicator of subsequent metastasis. Tumor thickness may also be useful for predicting subsequent metastases. None of the histologic parameters studied proved useful for predicting outcome in patients who had melanomas without PAM. The presence or absence of nevi had no effect on prognosis.

Adolescent↗