Angiolymphoid hyperplasia with eosinophilia: successful treatment with pulsed dye laser using the double pulse technique.
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Adult↗
Biomedical subjects
G Gupta
Publications and source records attributed to G Gupta.
A prospective study of the impact of laser treatment on vascular lesions.
BACKGROUND: Vascular lesions, especially on exposed sites, can be unsightly and may cause significant psychological distress. Lasers are effective in treating such lesions, but relatively few studies have been performed looking at psychological scoring before and after laser therapy. OBJECTIVES: To assess the change in psychological distress in patients with vascular lesions following laser treatment. PATIENTS AND METHODS: A prospective study was performed with patients recruited over a 3-month period. Psychological distress was measured using subjective scores on a standard questionnaire before treatment and at a 6-month follow-up. Each patient was treated every 4-8 weeks with an appropriate laser by the same dermatologist until discharge. Forty-two patients were recruited with one of four diagnoses: telangiectasia, port wine stain (PWS), vascular spider or cherry angioma, which occurred mainly on facial or exposed sites. RESULTS: Following laser treatment, there was a significant decrease in subjective scores of patients with telangiectasia and vascular spiders. Patients with PWS showed objective improvement but this was not reflected in their subjective scores. Psychological distress had reduced significantly in patients with less severe vascular lesions. CONCLUSIONS: Laser treatment of minor vascular lesions leads to objective improvement, which is paralleled by psychological benefit, but objective benefit in PWS may not be perceived as beneficial by patients.
Adolescent↗
Capillaritis associated with interferon-alfa treatment of chronic hepatitis C infection.
We report the case of a 36-year-old man who was referred with an asymptomatic eruption that started on both lower legs. This started shortly after being commenced on interferon-alfa for chronic hepatitis secondary to hepatitis C. Clinically, the eruption was consistent with a capillaritis (pigmented purpuric dermatosis). Histology confirmed this to be lymphocytic vasculitis. Lymphocytic vasculitis is frequently identified in the salivary glands of patients who are hepatitis C positive. Although leukocytoclastic vasculitis confined to the skin is frequently reported with hepatitis C, lymphocytic vasculitis is rarely reported. We consider that the lymphocytic vasculitis in our patient occurred as a result of interferon-alfa treatment because of the strong temporal relationship between the onset of the skin eruption and drug therapy.
Adult↗
The novel beta-blocker, carvedilol, provides neuroprotection in transient focal stroke.
Increasing evidence supports a role for oxidative stress, proinflammatory cytokines, and apoptosis in the pathophysiology of focal ischemic stroke. Previous studies have found that the multi-action drug, carvedilol, is a mixed adrenergic antagonist, and that it behaves as an antioxidant and inhibits apoptosis. In the current study, the authors investigated whether carvedilol provides protection in focal cerebral ischemia and whether this protection is associated with reduced apoptosis and the downregulation of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin- 1beta (IL-1beta). Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) by an intraluminal filament technique. Carvedilol (1, 3, and 10 mg/kg) was injected daily subcutaneously 2 or 4 days before the induction of ischemia. Neurologic scores, infarct volumes, TUNEL staining, and mRNA levels of TNF-alpha and IL-1beta were assessed at 24 hours reperfusion. The effect of carvedilol on microvascular cortical perfusion was studied with continuous laser-Doppler flowmetry. Twenty-four hours after MCAO, carvedilol at all three doses reduced infarct volumes by at least 40% and reduced neurologic deficits on average by 40% compared with vehicle-treated controls when given 2 or 4 days before the induction of ischemia. This protection was not mediated by changes in temperature or blood flow. Treatment with all three dose regimens resulted in fewer TUNEL positive cells compared with controls. At 24 hours reperfusion, carvedilol decreased TNF-alpha and IL-1beta expression by 40% to 50% in the ipsilateral ischemic cortex compared with the contralateral controls. The results of the current study indicate that carvedilol is neuroprotective in focal cerebral ischemia and may protect the ischemic brain by inhibiting apoptosis and attenuating the expression of TNF-alpha and IL-1beta.
Adrenergic beta-Antagonists↗
Seasonal variations in daily sperm production rate of rhesus and bonnet monkeys.
Daily sperm production (DSP) rate was estimated in adult male rhesus and bonnet monkeys to evaluate seasonal changes in the gametogenic activity of the testes. Three monkeys of each species were castrated during breeding and non-breeding seasons and DSP rate was estimated by enumerating the homogenization-resistant spermatid nuclei of steps 13 and 14. Results indicated a significant reduction in the DSP rate per testis during the non-breeding season in two species, along with a marked decline in the testis weight. However, the gametogenic capacity of seminiferous tubules did not appear to be markedly affected during non-breeding season, as the DSP rate per gram parenchyma of testis was only marginally reduced. The seasonal changes in DSP were much more pronounced in the rhesus than in the bonnet monkey. The feasibility of circanual rhythm in DSP of sub-human primates to form a baseline for the study of reproductive function in male is discussed.
Animals↗
Cutaneous leucocytoclastic vasculitis caused by cyclosporin A (Sandimmun)
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Adult↗
Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation.
Increased total fat mass (FM) and visceral fat (VF) may account in part for age-associated decrease in hepatic insulin action. This study determined whether preventing the changes in body fat distribution abolished this defect throughout aging. We studied the F(1) hybrid of Brown Norway-Fischer 344 rats (n = 29), which we assigned to caloric restriction (CR) or fed ad libitum (AL). CR (55% of the calories consumed by AL) was initiated and used at 2 mo to prevent age-dependent increases in FM and VF. AL rats were studied at 2, 8, and 20 mo; CR rats were studied at 8 and 20 mo. VF and FM remained unchanged throughout aging in CR rats. AL-fed rats at 8 and 20 mo had over fourfold higher FM and VF compared with both CR groups. Insulin clamp studies (3 mU. kg(-1). min(-1) with somatostatin) were performed to assess hepatic insulin sensitivity. Prevention of fat accretion resulted in a marked improvement in insulin action in the suppression of hepatic glucose production (HGP) (6.3 +/- 0.3 and 7.2 +/- 1.2 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 8.3 +/- 0.5 and 10.8 +/- 0.9 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The rate of gluconeogenesis (by enrichment of hepatic uridine diphosphate glucose and phosphoenolpyruvate pools by [(14)C]lactate) was unchanged in all groups. The improvement in hepatic insulin action in the CR group was mostly due to effective suppression of glycogenolysis (4.4 +/- 0.3 and 4.9 +/- 0.3 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 5.8 +/- 0.6 and 8.2 +/- 1.0 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The results demonstrated the preservation of hepatic insulin action in aging CR rats. Therefore, body fat and its distribution are major determinants of age-associated hepatic insulin resistance.
Adipose Tissue↗
Aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats.
Increase in fat mass (FM) and changes in body composition may account for the age-associated impairment in insulin action on muscle glycogen storage. We wish to examine whether preventing the increase in FM abolishes this defect seen with aging. We studied the novel aging model of F1 hybrids of BN/F344 NIA rats fed ad libitum (AL) at 2 (weighing 259+/-17 g), 8 (459+/-17 g), and 20 (492+/-10 g) mo old. To prevent the age-dependent growth in FM, rats were caloric restricted (CR) at 2 mo by decreasing their daily caloric intake by 45% (weighing 292+/-5 g at 8 mo, 294+/-9 g at 20 mo). As designed, the lean body mass (LBM) and %FM remained unchanged through aging (8 and 20 mo old) in the CR rats and was similar to that of 2-mo-old AL rats. However, 8- and 20-mo-old AL-fed rats had three- to fourfold higher FM than both CR groups. Peripheral insulin action at physiological hyperinsulinemia was determined (by 3 mU x kg(-1). min(-1) insulin clamp). Prevention of fat accretion maintained glucose uptake (R(d); 29+/-2, 29+/-2, and 31+/-4 mg x kg LBM(-1) x min(-1)) and glycogen synthesis rates (GS, 12+/-1, 12 +/-1, and 14+/-2 mg x kg LBM(-1) x min(-1)) at youthful levels (2 mo AL) in 8- and 20-mo-old CR rats, respectively. These levels were significantly increased (P<0.001) compared with AL rats with higher %FM (R(d), 22+/-1 and 22+/-2 and GS, 7+/-1 and 8+/-2 mg x kg LBM(-1). min(-1) in 8- and 20-mo-old rats, respectively). The increase in whole body GS in age-matched CR rats was accompanied by approximately 40% increased accumulation of [(3)H] glucose into glycogen and a similar increase in insulin-induced muscle glycogen content. Furthermore, the activation of glycogen synthase increased, i.e., approximately 50% decrease in the Michaelis constant, in both CR groups (P<0.01). We conclude that chronic CR designed to prevent an increase in storage of energy in fat maintained peripheral insulin action at youthful levels, and aging per se does not result in a defect on the pathway of glycogen storage in skeletal muscle.
Aging↗
The role of nickel in oral disease.
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Adolescent↗
Acute nitrobenzene poisoning.
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Child, Preschool↗
Interaction between aging and syndrome X: new insights on the pathophysiology of fat distribution.
Increased fat mass (FM), and in particular a specific increase in visceral fat (VF), may account for the age-associated decrease in insulin action and the development of Syndrome X. Utilizing chronic caloric restriction (CR) with aging in a rodent model, we dissociated the effects of VF and FM, and demonstrated that the decrease in VF accumulation was sufficient to prevent the marked decrease in hepatic insulin action. This suggests that the typical increase in VF with aging, rather than aging per se, determines hepatic insulin resistance. To directly assess the role of VF, we studied rats after surgical removal of VF or sham operation. Surgical extraction of VF (which accounts for approximately 10% of total fat) improved hepatic insulin action by more than twofold. We studied the role of fat-derived peptides in the regulation of body composition and insulin action. While VF extraction resulted in decreased gene expression for leptin and TNF-alpha in the subcutaneous adipose, administration of leptin selectively decreased visceral fat (approximately 60%), and enhanced the action of insulin on inhibiting hepatic glucose production (approximately 80%). Thus, the cause-effect relationship between the age-related increase in VF and the decrease in hepatic insulin action may involve the failure of leptin to "cross talk" with other fat depots to regulate fat distribution.
Adipose Tissue↗
Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth.
Several angiogenesis inhibitors are fragments of larger proteins that are themselves not active as angiogenesis inhibitors. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In the present study, we examined whether the full-length calreticulin molecule shares the antiangiogenic and antitumor activities of vasostatin. Similar to vasostatin, calreticulin selectively inhibited endothelial cell proliferation in vitro, but not cells of other lineages, and suppressed angiogenesis in vivo. When inoculated into athymic mice, calreticulin inhibited Burkitt tumor growth comparably with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids inhibited endothelial cell proliferation in vitro and Burkitt tumor growth in vivo comparably with vasostatin. An internal calreticulin fragment encompassing amino acids 120-180 also inhibited endothelial cell proliferation in vitro and angiogenesis in vivo comparably with calreticulin and vasostatin. These results suggest that the antiangiogenic activities of vasostatin reside in a domain that is accessible from the full-length calreticulin molecule and localize to calreticulin N-terminal amino acids 120-180. Thus, calreticulin and calreticulin fragments are inhibitors of angiogenesis that directly target endothelial cells, inhibit angiogenesis, and suppress tumor growth. This information may be critical in designing targeted inhibitors of pathological angiogenesis that underlies cancer and other diseases.
Angiogenesis Inhibitors↗
Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells.
CD4(+) T cells play a critical role in generating and maintaining immune responses against pathogens and alloantigens, and evidence suggests an important role for them in antitumor immunity as well. Although major histocompatibility complex class II-restricted human CD4(+) T cells with specific antitumor reactivities have been described, no standard method exists for cloning the recognized tumor-associated antigen (Ag). In this study, biochemical protein purification methods were used in conjunction with novel mass spectrometry sequencing techniques and molecular cloning to isolate a unique melanoma Ag recognized by a CD4(+) tumor-infiltrating lymphocyte (TIL) line. The HLA-DRbeta1*0101-restricted Ag was determined to be a mutated glycolytic enzyme, triosephosphate isomerase (TPI). A C to T mutation identified by cDNA sequencing caused a Thr to Ile conversion in TPI, which could be detected in a tryptic digest of tumor-derived TPI by mass spectrometry. The Thr to Ile conversion created a neoepitope whose T cell stimulatory activity was enhanced at least 5 logs compared with the wild-type peptide. Analysis of T cell recognition of serially truncated peptides suggested that the mutated amino acid residue was a T cell receptor contact. Defining human tumor Ag recognized by T helper cells may provide important clues to designing more effective immunotherapies for cancer.
Amino Acid Sequence↗
The high-resolution structure of the triplex formed by the GAA/TTC triplet repeat associated with Friedreich's ataxia.
Expansions of the triplet repeat, GAA/TTC, inside the first intron of the frataxin gene causes Friedreich's ataxia (FRDA). It was of interest to us to examine whether the FRDA repeat forms an unusual DNA structure, since formation of such structure during replication may cause its expansion. Here, we show that the FRDA repeat forms a triplex in which the TTC strand folds on either side of the same GAA strand. We have determined the high-resolution NMR structures of two intramolecularly folded FRDA triplexes, (GAA)2T4(TTC)2T4(CTT)2 and (GAA)2T4(TTC)2T2CT2(CTT)2 with T.A.T and C+.G.C triads. T4 represents a synthetic loop sequence, whereas T2CT2 is the natural loop-folding sequence of the TTC strand. We have also made use of site-specific 15N-labeling of the cytosine residues to investigate their protonation status and their interaction with other protons. We show that the cytosine residues of the Hoogsteen C+.G pairs in this triplex are protonated close to physiological pH. Therefore, it appears that the triplex formation offers a plausible explanation for the expansion of the GAA/TTC repeats in FRDA.
Cytosine↗
Q-switched ruby laser in the treatment of labial melanotic macules.
BACKGROUND AND OBJECTIVE: The term, labial melanotic macule, refers to a benign entity. The Q-switched ruby laser (QSRL) has been used to treat such lesions but the numbers are small with relatively short follow-up. STUDY DESIGN/MATERIALS AND METHODS: Eight patients were treated with single pulses of the QSRL (694 nm, 20 nsec pulse duration, and 5 mm spot size) at 6.5 J/cm(2). Patients were followed-up for a maximum of 24 months to assess for recurrence. RESULTS: Five patients cleared with a single pulse of the QSRL, while three required a second treatment session. There were no side-effects reported. At follow-up, there was no recurrence of pigment. CONCLUSIONS: Treatment of labial melanotic macules with the QSRL produces excellent cosmetic results. No new pigment was detected at follow-up.
Adult↗
Effect of simulated sunlight on atrazine and metolachlor toxicity of surface waters.
Atrazine and metolachlor are the two most widely used herbicides in the United States; through non-point-source runoff both herbicides may cause toxicity to aquatic organisms. Toxicity changes were measured for atrazine and metolachlor in surface waters after exposure to simulated sunlight (0, 20, and 40 kJ/m2) using a Xenon Weather-Ometer. A Microtox toxicity test, using the marine luminescent bacterium Vibrio fischeri, was conducted on deionized, river, and bay water samples mixed with atrazine or metolachlor herbicide (12 mg/liter) after exposure to simulated sunlight. Microtox test (EC50%) results demonstrated that the toxicity decreased with increasing light intensity for both herbicides in river and bay water. These results also indicate that the toxicity of the bay water, with high concentrations of organic and suspended matter, was reduced, for both herbicides, compared with the toxicity of the river water, possibly through photodegradation of pesticides.
Acetamides↗
Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease.
T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis. These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection.
Adolescent↗
Changes in daily sperm production rate in rats under the influence of a potent antispermatogenic agent, CDRI 84/35.
CDRI 84/35, a potent nonsteroidal antispermatogenic agent, causes total sterility in rats by directly acting on germ cells while having no effect on Sertoli/Leydig cells. This study was conducted to evaluate the effect of the compound on gametogenic activity of testes and to identify stages of spermatogenesis that were affected. Adult male rats administered either compound 84/35 at minimum effective dose or estradiol (5 micrograms) or water only were killed on days 22, 41, and 64 of the treatment period to evaluate the effect on spermatid, spermatocyte, and spermatogonial stages, respectively. Daily sperm production (DSP) was measured employing a homogenization technique. Results showed a decline in testis weight and DSP with a drastic reduction (approximately 95%) in DSP in 84/35-treated rats on day 41 of the treatment period. Estradiol was more potent in reducing the testis weight; however, 84/35 had an edge over estradiol in reducing the DSP. After withdrawal of treatment for 120 days, a phenomenal recovery (> 90%) in DSP per gram parenchyma was noted in 84/35-treated animals. Results indicate a direct effect of estradiol on spermatogonia, whereas 84/35 seems to affect the spermatocyte stage.
Animals↗