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Biomedical subjects

R Wolf

Publications and source records attributed to R Wolf.

At least 19 recordsLinked to original sources

Co-expression of the natriuretic peptides (ANP, BNP, CNP) and their receptors in normal and acutely involuted rat thymus.

The natriuretic peptides (NP) ANP, BNP and CNP constitute circulating hormones as well as neuropeptides. The present investigation reveals that these peptides are also constituents of the immune system. BNP and CNP, in addition to ANP as previously communicated, are synthesized in the rat thymus. The NP seem to be produced by different types of thymic cells. Moreover, expression of NP is differentially affected by acute involution of the organ caused by dexamethasone (DEX). The concentration of BNP and CNP mRNA was not changed in gradually involuted thymi (i.e. at day 2, 3 and 4 after DEX administration). ANP mRNA was increased in parallel with the degree of involution (2-, 5- and 40-fold, respectively). The concentration of immunoreactive CNP (CNP-IR) was not affected by acute involution of the thymus (4th day after DEX); BNP-IR, however, was increased 2-fold and for comparison, ANP-IR as previously shown, was found 10-fold elevated. Our studies also revealed the presence of the specific mRNAs coding for the A-, B-, and C-type NP receptor in the thymus. The thymic NP system may be involved in the communication between the immune and neuroendocrine system.

Animals

Impact of clinicopathologic parameters on patient survival in carcinoma of the cervical esophagus.

BACKGROUND: The survival of patients with carcinoma of the cervical esophagus remains poor in spite of multimodality treatment and technical improvements in surgical resection and reconstruction. This study was undertaken to update our experience with cervical esophageal carcinoma and to identify factors that had an impact on patient survival and quality of life. PATIENTS AND METHODS: Clinical data encompassing 132 variables were collected on 67 patients with cervical esophageal carcinoma from 1980 to 1993. Statistical analysis was performed: independent Student's t-tests, Cox regression, Kaplan-Meier curves, and log rank analyses were used in the statistical evaluation. The mean age of the patients was 63 years (range 31 to 88). Dysphagia was the primary symptom in 86% of patients; 80% had received no prior treatment. The most common abnormal finding (21%) on physical examination was a neck mass. RESULTS: Curative resection was performed in 22 patients, 7 had palliative procedures, and 7 were found to be inoperable at exploration and received palliative treatment. Radiation with or without chemotherapy was definitive treatment for 10 patients, whereas 4 patients were treated with chemotherapy alone for cure, and 17 patients received palliative treatment. The mean survival following diagnosis was 17 months (range 1 to 96). Cumulative 5-year survival was 12%. CONCLUSIONS: Persistent disease, chemotherapy prior to presentation, and chemotherapy for cure remained as statistically significant parameters associated with decreased survival by multivariate analysis. There was a trend toward improved survival in patients treated with surgical resection.

Adult

Isotopic response.

BACKGROUND: The occurrence of a new skin disorder exactly at the site of another one, already healed and unrelated, was first described in 1955. In 1985, Wolf et al. recognized that we are dealing with a dermatologic phenomenon and established a precise definition for this phenomenon. Fifty-eight cases corresponding to the definition of this phenomenon have been reported until now. METHODS: The new phenomenon, for which the term "isotopic response" has been suggested, has been defined. Cases corresponding to the definition have been analyzed with special emphasis on the diseases involved, the time intervals, and the locations of the diseases. Eight new cases are described. RESULTS: A total of 58 cases of isotopic response have been described. The first disease in most of the patients was herpes zoster; in three cases it was herpes simplex, in two varicella, and in one, thrombophlebitis. The second disease, which appeared exactly at the site of the first, already healed disease, was in most reported cases a carcinoma (26 cases, in particular 15 cases of breast carcinoma, 5 basal cell carcinomas (BCC), 4 squamous cell carcinomas (SCC), 2 basosquamous carcinomas), or granuloma annulare (16 cases). Additional diseases were Kaposi's sarcoma (2 cases), pseudolymphoma (2 cases), sarcoid (2 cases), tinea (2 cases), tuberculoid and vasculitis granuloma (1 case), angiosarcoma, metastasis, Bowen's disease, lymphoma, leukemia cutis, and acne (1 case each). The diseases did not show any predilection for a particular location. The interval between the first and second disease was extremely variable (ranging from days to years) and showed no particular features. In the eight additional cases described in the present report, the first disease was herpes simplex (6 cases) or herpes zoster (2 cases). The second disease was viral warts (3 cases) or squamous cell carcinoma (2 cases). Additional diseases were furunculosis, contact dermatitis, and molluscum contagiosum (1 case each). CONCLUSIONS: The new term, "isotopic response," describes the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. It is suggested that the term "isotopic response" be included in the lexicon (glossary) of dermatology. Introducing the new term and classifying all the cases under a single key word, will make it possible to locate and collect them easily and to search for the mechanism underlying this phenomenon.

Aged

Another "paraben paradox".

BACKGROUND: To test the reliability and reproducibility of the patch test with a paraben mix, we added a second paraben mix allergen to our standard tray and compared the results achieved with these two allergens. METHODS: Two hundred and fifteen consecutive patients, undergoing patch testing with a standard series, were simultaneously tested with an additional paraben mix (i.e., each patient was tested with two paraben mix allergens) supplied by two different companies. RESULTS: Twelve patients (5.6%) showed a positive reaction to one or two paraben tests. Five patients showed a positive reaction to one paraben test (paraben-a), and five others to the second paraben test (paraben-b). Only two patients out of 12 with positive reactions to parabens showed a reaction with both of the two parabens. The parabens appear to be overrepresented in our study compared to other series. There was no correlation between the results of the tests with the two different parabens used. CONCLUSIONS: Patch testing with a paraben mix cannot be considered an appropriate and reliable method for detecting paraben allergies. It is recommended to test routinely with a paraben screening series instead of the paraben mix.

Allergens

On the primary functions of melatonin in evolution: mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals.

Melatonin is widely abundant in many eukaryotic taxa, including various animal phyla, angiosperms, and unicells. In the bioluminescent dinoflagellate Gonyaulax polyedra, melatonin is produced in concentrations sometimes exceeding those found in the pineal gland, exhibits a circadian rhythm with a pronounced nocturnal maximum, and mimics the short-day response of asexual encystment. Even more efficient as a cyst inducer is 5-methoxyptryptamine (5MT), which is also periodically formed in Gonyaulax. In this unicell, the photoperiodic signal-transduction pathway presumably involves melatonin formation, its deacetylation to 5MT, 5MT-dependent transfer of protons from an acidic vacuole, and cytoplasmic acidification. According to this concept, we observe that cyst formation can be induced by various monoamine oxidase inhibitors and protonophores, that 5MT dramatically stimulates H(+)-dependent bioluminescence and leads to a decrease of cytoplasmic pH, as shown by measurements of dicyanohydroquinone fluorescence. Cellular components from Gonyaulax catalyze the photooxidation of melatonin. Its property of being easily destroyed by light in the presence of cellular catalysts may have been the reason that many organisms have developed mechanisms utilizing this indoleamine as a mediator of darkness. Photooxidative reactions of melatonin, as studied with crude Gonyaulax extracts and, more in detail, with protoporphyrin IX as a catalyst, lead to the formation of N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) as one of the main products. Photochemical mechanisms involve interactions with a photooxidant cation radical leading to the formation of a melatonyl cation radical, which subsequently combines with a superoxide anion.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine

Effects of an endogenous inhibitor of nitric oxide synthesis on postcapillary venules.

The objective of this study was to determine whether an inhibitor of nitric oxide (NO) synthase (NG,NG'-dimethyl-L-arginine; L-DMA) that is produced by vascular endothelium elicits the inflammatory responses induced by synthetic analogues of L-arginine such as NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration, leukocyte-platelet aggregation, and albumin leakage were monitored in rat mesenteric venules exposed to different concentrations of either L-DMA or L-NAME. Increases in leukocyte adherence (7- to 9-fold) and emigration (3- to 5-fold), platelet-leukocyte aggregation, mast cell degranulation, and an enhanced albumin leakage (30-50%) were observed within 30 min after exposing the microvascular bed to either inhibitor; however, leukocyte emigration and albumin leakage responded more intensely to L-NAME than to L-DMA. The microvascular alterations and mast cell degranulation were attenuated by addition of L-arginine to the superfusate. These results suggest that the L-DMA is capable of eliciting an inflammatory response at concentrations detected in plasma under certain pathological conditions.

Amino Acid Oxidoreductases

Pemphigus and dietary factors. In vitro acantholysis by allyl compounds of the genus Allium.

BACKGROUND: Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus in vivo and provoking acantholysis in vitro. We therefore suggested that plants, in particular those belonging to the Allium group, that contain several active compounds with stable disulfide and thiol groups in their molecule may cause the same. OBJECTIVE: To verify this hypothesis by investigating the in vitro acantholytic effect of three compounds of garlic. METHODS: Skin samples from donors were cultured in the presence of three compounds of garlic (i.e. allylmercaptan, allylmethylsulfide and allylsulfide) for 3 days. The skin samples were then processed for microscopic control for acantholysis. RESULTS: Results indicate that, indeed, the three garlic compounds tested are capable of inducing acantholysis in vitro. Focal and diffuse acantholysis was observed in the specimens from 4 out of 7 donors cultured in the presence of 6 and 9 mM of each of the allyl compounds for 3 days. Interestingly, tissues from a DR4+ donor proved to be more acantholysis prone than others, showing large blistering due to diffuse acantholysis, thus indicating that individual susceptibility plays a crucial role also in vitro. CONCLUSION: Garlic compounds with stable disulfide and thiol groups in their molecule are capable of inducing acantholysis in vitro. These findings lend further support to the theory that 'harmless' nutritional factors are capable of inducing acantholysis in vitro and possibly also in vivo. In view of these findings, it is suggested that nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing pemphigus.

Acantholysis

Microvascular responses to inhibition of nitric oxide production. Role of active oxidants.

The objective of this study was to assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte-endothelial cell adhesion and increased microvascular permeability observed in rat mesenteric venules after inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration and leakage of fluorescein isothiocyanate-labeled albumin were monitored in postcapillary venules before and after exposure of the tissue to L-NAME. H2O2 production in mesenteric tissue was monitored by using dihydrorhodamine 123 (DHR), the H2O2-sensitive fluorochrome. L-NAME elicited a rapid increase in both the rate of albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules. Treatment with either catalase or dimethylthiourea attenuated the L-NAME-induced oxidative stress, albumin leakage, and leukocyte-endothelial cell adhesion. Oxidation of DHR was enhanced in animals treated with either 3-amino-1,2,4-triazole (ATZ), an inhibitor of endogenous catalase, or a combination of ATZ and maleic acid diethyl ester, which depletes intracellular glutathione. Animals receiving a CD11/CD18-specific antibody to prevent leukocyte adhesion/emigration exhibited a reduced oxidation of DHR in response to L-NAME. These findings indicate that most of the H2O2 (and secondarily derived oxidants) generated in mesenteric tissue exposed to an inhibitor of nitric oxide production is due to accumulation of activated leukocytes.

Amino Acid Oxidoreductases

[Relation between plasma fibrinogen and the function of collateral coronary vessels].

The role of fibrinogen in LV function, especially after myocardial infarction, is still debated. We therefore investigated the relation between plasma fibrinogen, LV function and ischemic tolerance in 87 patients (average age 58.5 years) with proximal occlusion of the left anterior descending artery (LAD) and retrograde filling through noncompromised collaterals. Compared to a control group (n = 65; average age 57.0 years) study patients revealed significantly higher plasma fibrinogen levels (average 342.5 vs 316.1 mg/dl; p < 0.025) and a reduced ejection fraction (54.6 vs 75.5%; p < 0.0005). Study patients with collaterals were divided into three groups with increasing fibrinogen concentrations: Group I (n = 29) averaged 261 mg/dl (191-303), group II averaged 333.3 (304-362) and group III averaged 433.3 (364-742) (p < 0.0005). There were no significant differences regarding age, height, weight, number and age of previous infarctions and concomitant medical treatment; group III revealed a significantly higher proportion of women (21%) compared to group I (0%) (p < 0.005); group III also revealed significantly lower HDL-cholesterol and higher triglyceride levels compared to group I and group II, respectively (p < 0.05). Hematocrit, hemoglobin concentration, total and LDL-cholesterol showed no group differences. Group I with a low fibrinogen had the lowest endsystolic volume index (LVESVI) and highest ejection fraction (EF) (34.6 ml/m2 and 61.0%, respectively), whereas in patients of group II LVESVI amounted to 36.5 ml/m2 and EF to 57.3%, and in group III with the highest plasma fibrinogen levels LVESVI was 48.4 ml/m2 (group I, II vs III: p < 0.05) and EF 45.7% (group I, II vs III: p < 0.01). EF decreased exponentially with increasing fibrinogen concentrations (r = 0.5; p < 0.0005). Group III showed significantly higher LV enddiastolic pressures (19.1 mm Hg) compared to group I and II (14.6 and 14.4 mm Hg, respectively; p < 0.05). Fifteen patients in group I, 21 in group II, and 24 in group III showed akinetic LV wall segments (group I vs III: p < 0.0125). In addition, 21 patients in group I, 17 in group II, and only 10 in group III revealed exercise-induced myocardial ischemia (group I, II vs III; p < 0.05). In patients with ischemic ST-depression systolic rate pressure product (SRPP) at the onset of ischemic symptoms was 266.8 mm Hg x min-1 x 10(2) in group I, 246.8 in group II and 195.0 in group III (group I, II vs III; p < 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Scabies: the diagnosis of atypical cases.

In the current scabies pandemic, classic scabies is seen less frequently and special forms are becoming more common. The diagnosis of scabies has become, therefore, a challenge for clinicians. The well-known scabietic burrow is seen only very rarely today and, therefore, pathognomonic as it is, the diagnosis of scabies should not rely on this clinical sign. In our experience, examination of skin scrapings mounted on a slide with saline is the most practical bedside method and ideal for screening patients with suspected scabies. It is easy to perform, requires neither sophisticated tools nor special skill, and can be done in less than five minutes by every practitioner.

Animals

Expression of xenobiotic-metabolizing enzymes by primary and secondary hepatic tumors in man.

PURPOSE: To determine the immunohistochemical expression of xenobiotic-metabolising enzymes (XME) in normal livers, primary hepatocellular carcinomas (hepatomas) and secondary hepatic tumors from colonic primary tumors. METHODS AND MATERIALS: The expression of XME in primary (n = 16) and secondary (n = 21) hepatic tumors and patients with no malignancies (n = 20) were investigated using polyclonal antibodies raised against the following rat enzymes CYP1A1, CYP2B1, CYP2C6, CYP3A1, CYP4A1, cytochrome P-450 reductase, epoxide hydrolase and testosterone UDP-glucuronyl transferase. The rat cytochrome P-450 antibodies recognize various human isoenzymes within the same gene family. Immunohistochemistry was undertaken using the immunoperoxidase and alkaline phosphatase anti-alkaline phosphatase techniques. RESULTS: There was a reduction in the overall expression of all XME by tumor tissue compared to adjacent nonneoplastic liver cells (p = 0.008), more in livers with secondary tumors (p < 0.0001) and reduced expression of XME by hepatomas and secondary liver tumors compared to livers with no malignancy. A tendency for higher expression of all XME by nonneoplastic liver cells from patients with hepatomas relative to nonmalignant livers was observed, with significantly higher expression of CYP3A4/5 and testosterone UDP-GT enzymes (odds ratio 3.12; CI 1.59-6.10). CONCLUSION: The expression of XME by tumor tissue is reduced in primary and secondary hepatic malignancies. The expression of XME by nonneoplastic liver cells is higher in patients with hepatomas than patients with no hepatic malignancies. These alterations in XME activities may have important therapeutic implications in the response and toxicity to systemic anti-cancer therapy, due to altered pharmacokinetics. In addition, differential expression of these enzymes by normal and malignant cells may be important for the rational design of selective anti-tumor drugs.

Adult

P-selectin-dependent leukocyte recruitment and intestinal mucosal injury induced by lactoferrin.

Plasma concentrations of lactoferrin relevant to an inflammatory response are known to elicit leukocyte-endothelial cell adhesion in mesenteric venules. The objectives of this study were (1) to determine whether exogenously administered lactoferrin causes microvascular and mucosal injury in rat intestine and (2) to assess the contribution of adherent leukocytes to a lactoferrin-mediated injury process. Mucosal myeloperoxidase (MPO) activity and vascular protein clearance were monitored in the distal intestine of male Sprague-Dawley rats. Macroscopic erosive lesions of the mucosa and increases in mucosal MPO and intestinal vascular protein were observed 2 h following the lactoferrin infusion, results consistent with granulocyte accumulation and microvascular protein leakage. These lactoferrin-induced alterations were significantly attenuated in animals pretreated with a monoclonal antibody (mAb) directed against P-selectin but not by an E-selectin-specific mAb. In another series of experiments, leukocyte adherence/emigration and leakage of fluorescein isothiocyanate (FITC)-labeled albumin were measured in rat mesenteric venules using intravital video microscopy. Lactoferrin elicited increases in both leukocyte adhesion/emigration and albumin extravasation, which were attenuated by mAbs directed against P-selectin but not E-selectin. These observations indicate that (1) the lactoferrin released by activated neutrophils may lead to significant microvascular and mucosal injury or dysfunction and (2) the lactoferrin-induced injury is related to P-selectin-mediated adhesion of leukocytes to microvascular endothelium. Our results raise the possibility that neutrophil-derived lactoferrin contributes to the inflammatory response by promoting further granulocyte accumulation and activation and that mAbs to P-selectin may be therapeutically beneficial in inflammatory disorders.

Animals

Eosinophilic pustular folliculitis: a sterile folliculitis of unknown cause?

BACKGROUND: Eosinophilic pustular folliculitis (EPF) was initially defined as a sterile folliculitis of unknown cause. Because attempts to demonstrate bacterial organisms have been unsuccessful, and antibiotic therapy is usually ineffective, a bacterial infection is not considered a plausible causative factor for this disease. OBJECTIVE: Our purpose was to describe five patients with the clinical and histologic characteristics of EPF and to report the results of bacterial cultures. METHODS: Biopsy specimens were examined and pustules were cultured. RESULTS: In three of the five patients, Pseudomonas infection of the hair follicle was the cause of the disease as proven by repeated cultures and the response to specific therapy. Three patients had a systemic disorder known to cause immunologic alteration: AIDS in one and a myeloproliferative disorder in two. CONCLUSION: Although EPF was initially defined as a sterile folliculitis of unknown origin, three of our patients had an identifiable and treatable cause. We believe that these cases warrant the diagnosis of EPF.

Adult

Contact dermatitis in Israeli soldiers.

This report consists of an evaluation of 41 soldiers from the infantry, armored, and artillery division, who developed hand dermatitis from their contact with oils and fuel. A special "tailored" supplementary tray with five reagents relevant to their field of work and environment was performed. The reagents that were used were gun oil, hydraulic oil, automotive lubricant (oil) 20/50, white spirit, and car petrol (gasoline). Seven of the 41 patients (17%) showed one or more positive tests to the supplementary tray. The fact that none of the control group of 64 patients not exposed to these substances showed a positive result to the supplementary tray indicates that false positive results are, at least, not probable. It is suggested that soldiers with occupational hand dermatitis should be tested with supplemental aimed trays that are relevant to their work and environment, in addition to the standard trays.

Dermatitis, Contact

Pyruvate supplementation of a low-cholesterol, low-fat diet: effects on plasma lipid concentrations and body composition in hyperlipidemic patients.

The effects of the three-carbon compound pyruvate on plasma lipid concentrations and body composition were evaluated in hyperlipidemic patients consuming a low-cholesterol (165-180 mg), low-fat (22-24% of energy; 18-20% of energy as saturated fatty acid) diet (0.091-0.099 MJ.kg body wt-1 x d-1). After consuming the above diet for 4 wk, during which time plasma lipid concentrations decreased, 34 subjects were randomly assigned to receive either 22-44 g pyruvate (n = 17) or 18-35 g polyglucose (placebo, Polycose, n = 17), iso-energetically substituted for a portion of carbohydrate energy for 6 wk. Despite greater weight and fat losses with pyruvate (P < 0.05), plasma concentrations of cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride were not different between the two groups of subjects. We conclude that subsequent to diet-induced reduction in plasma lipid concentrations, pyruvate supplementation of a low-cholesterol, low-fat diet providing 6.7-7.6 MJ/d for 6 wk has no effect on plasma lipid concentrations but enhances body weight and fat losses.

Adipose Tissue