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PubMed2002

Etiology and pathogenesis of Kaposi's sarcoma.

OBJECTIVE: To provide an overview of the role for HHV-8 as the causative agent responsible for Kaposi's sarcoma, the molecular cross-talk between HHV-8 and HIV-1, and the ability of specific cytokines to influence the pathophysiology of this malignancy. PATIENTS: Normal human skin grafts were studied using a SCID mouse xenograft model system in which engrafted skin was injected intradermally with HHV-8 and/or HIV-1, and the subsequent induction of clinical, histologic, and viral titer changes were assessed in serial fashion. RESULTS: Following intradermal injection of HHV-8 into engrafted normal human skin, cutaneous lesions resembling Kaposi's sarcoma were created in numerous different grafts. These lesions were characterized by routine light microscopy as well as by immunophenotypic and molecular virological assessments. As several grafts injected with HHV-8 failed to develop Kaposi's sarcoma, we sought to determine whether another cofactor was required and this led us to uncover the ability of HHV-8 and HIV-1 to reciprocally influence each other using both in vitro and in vivo studies. Given the importance of various cytokines, the influence of scatter factor and IFN-gamma in the pathophysiology of Kaposi's sarcoma was also evaluated. CONCLUSION: Based on these in vivo studies using SCID mice engrafted with human skin and injected with HHV-8, we conclude that HHV-8 is the etiologic agent in Kaposi's sarcoma, and that HIV-1 and HHV-8 can influence each other involving both direct and indirect cross-talk mechanisms.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Output of triglyceride from the sebaceous gland and to the skin surface of cattle.

Radiolabelled fatty acids, when injected intradermally into cattle skin, were largely incorporated into the triglyceride and phospholipid fractions of the sebaceous gland lipids. Linoleic acid was incorporated into the triglycerides to a greater extent than oleic or palmitic acids, whereas the phospholipids had a greater affinity for palmitic acid. The peak uptake of linoleic acid into the glandular triglyceride fraction was at about 61 hours compared with 52 hours and three hours for oleic and palmitic acids. Radioactively 14C labelled triglycerides appeared on the skin surface within one day of intradermal injection of 14C linoleic acid. At an ambient temperature of 20 degrees C, a single output-peak occurred at nine days while at 35 degrees C two peaks at four and eight to nine days were observed. From the data an estimate of 6.5 days for the mean storage time of sebum triglycerides in the hair follicle canal at 20 degrees C has been made.

Animals↗
PubMed1980

The in vivo quantitation and kinetics of rabbit neutrophil leukocyte accumulation in the skin in response to chemotactic agents and Escherichia coli.

This report describes the in vivo quantitation of neutrophil accumulation at inflammatory sites in rabbits by employing 51Cr-labeled autologous rabbit blood neutrophils. These labeled neutrophils circulated with a half of 3.2 to 3.8 hours. They were found to localize with great specificity at skin sites injected intradermally with zymosan-activated plasma, synthetic chemotactic peptides (e.g., N-formyl methionyl leucyl phenylalanine), Escherichia coli-derived chemotactic factors, or whole E. coli. Contrary to reports utilizing in vitro assays, under in vivo conditions the synthetic chemotactic peptides caused significantly less neutrophil accululation than zymosan-aulation by high concentrations of N-formyl methionyl leucyl phenylalanine was observed. Kinetic studies of the accumulation of labeled leukocytes in the skin in response to intradermal injection of formalin-killed E. coli were performed. Nearly all of the leukocytes accumulated during the first 4 hours after E. coli injection with a peak rate of accumulation between 2 and 3 hours. Essentially no additional localization of leukocytes occurred at lesions which were 6, 8, or 24 hours old. These results demonstrate that 51Cr-labeled rabbit blood neutrophils can be utilized to quantitate the degree of neutrophil accumulation in inflammatory reactions as well as to study the hour by hour kinetics of this accumulation.

Animals↗
PubMed1995

From hyperplasia to frank breast neoplasia. Carcinogenesis. Immunoprevention.

There is strong evidence that in advanced cases of breast fibrocystic disease, the risk of cancer is elevated. Cyclic breast glandular hyperplasia is commonly associated with mastodynia and/or breast fibrocystic disease. The administration of progestins, antiestrogens and/or local progesteron, results in some cases in a desensibilisation, accompanied by loss in responsiveness to hormonal therapy. Out of 167 patients (pts) suffering from mastodynia and/or breast fibrocystic disease with positive delayed-type hypersensitivity (DTHS) reactions to a pharmaceutical Placenta Suspension (PS), when injected intradermally, in 87 pts. who failed to respond to hormonal therapy, a vaccine preparade from PS admixed with an adjuvant (BCG), was administrated in one intradermal injection (0.1). In all the pts. recruited into the study, a complete remission of the symptoms occurred and in the majority of cases lasted throughout the 12 month follow-up period. The essential factor of relative hyper-estrinism, initiates breast epithelial hyperplasia and also increases stromal ground substance, which has the propensity to fibrous reorganisation. A true or relative hypoxia results, as a consequence of connective tissue sclerosis and epithelial thickness, constituting a supplementary factor for further epithelial proliferation. The risk of gene faults is greater when hypoxia operates at cell viability level and for long enough duration. Within the frame of persistent multicellular proliferative potential, a basic shift in energy metabolism is accompanied by appearance of fetal isoenzymes and of membrane glycoproteins, that induces a host immunological reaction (emphasised by PS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Loss of cutaneous delayed hypersensitivity reactions in nevus anemicus. Evidence for close concordance of cutaneous delayed hypersensitivity and endothelial E-selectin expression.

BACKGROUND: The relationship of adhesion molecules in the dermis to immunologically mediated cutaneous inflammation can be understood by focusing on a serendipitous phenomenon: a lack of dermatitis within the margins of a nevus anemicus (NA) in generalized contact dermatitis. The expression and induction of endothelial and epithelial adhesion molecules with intradermally injected cytokines were investigated. OBSERVATIONS: Nevus anemicus without dermatitis lacked histopathological changes consistent with inflammatory cellular infiltration. The surrounding skin of the dermatitic lesion expressed HLA-DR, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin on endothelial cells, and HLA-DR and ICAM-1 in the epidermis. However, the skin of the NA lacked endothelial E-selectin and epidermal HLA-DR and ICAM-1 expression. Interferon gamma, injected intradermally, induced endothelial and epidermal HLA-DR and ICAM-1 expression in the NA and surrounding normal skin. While interferon gamma strongly induced E-selectin expression on endothelial cells in normal skin, it failed to induce endothelial E-selectin expression in the NA. CONCLUSIONS: This study suggests that vessels in the NA do not respond normally to proinflammatory cytokines, at least at the level of E-selectin expression. The absence of keratinocyte ICAM-1 and HLA-DR expression in the NA lesion in contact dermatitis is likely caused by the absence of infiltrating lymphocytes, rather than by the intrinsic unresponsiveness of keratinocytes to interferon gamma. Among the endothelial cell adhesion molecules in delayed hypersensitivity, E-selectin appears to be indispensable in recruiting circulating T lymphocytes to the skin.

Antigens, CD↗
PubMedDate not supplied

Skin blood flow changes following intradermal bradykinin injections measured by laser Doppler flowmetry: comparison with weal and flare.

Intradermal injections of normal saline and different concentrations of bradykinin were made into the forearms of healthy volunteers. Cutaneous blood flow was recorded just outside and over the centre of the weals by laser Doppler flowmetry (LDF), and flare area and weal volume were measured. There were concentration-related changes in the mean LDF output adjacent to the weal, flare area and weal volume. LDF recordings performed over the centre of the weals, however, failed to show any dose-response relationship. When similar concentrations of bradykinin were injected intradermally and the skin response measured by the above parameters, there was less variation in the mean LDF output adjacent to the weal than flare or weal measurements. The non-invasive technique of LDF is a useful, objective and sensitive technique of quantifying the skin blood flow changes induced by intradermal bradykinin and provides an alternative method of quantifying skin response to intradermal bradykinin to measurement of flare or weal sizes.

Adult↗
PubMed2003

Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patients.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients. METHODS: Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc-99m tin colloid, with a larger particle size (0.4-5 microm), rather than sulfur colloid and colloidal albumin. RESULTS: The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P = 0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False-negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P < 0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%). CONCLUSIONS: A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc-99m tin colloid with a large particle size than by subdermal injection.

Axilla↗
PubMed2000

Sentinel node localization in breast cancer patients using intradermal dye injection.

In a series of 161 consecutive breast cancer operations, intradermal injection of Patent Blue was used to localize the sentinel node (SN). The surgical localization rate was 60%. Including the blue lymph nodes found by the pathologist, localization rate was 70%. After the first 103 operations, the surgical procedure was changed, resulting in a localization rate of 83%. Ten surgeons participated, but only one had previous experience with SN dissection. The others experienced a steep learning curve. Metastasis was found in 42 of 97 SNs (43%). In 15 cases (36%) metastasis was recognized only after step-sectioning and immunohistochemical staining for cytokeratin. In one case a benign epithelial inclusion was found. The sentinel node was false negative in 9.1% of cases. The consensus from the literature is that the best results are achieved using a combination of dye and isotopic techniques.

Adult↗
PubMed1975

Puritus vulvae: treatment by multiple intradermal alcohol injections.

A Preliminary report is presented on the use of multiple intradermal injections of absolute alcohol in the treatment of intractable pruritus vulvae. Twenty-five patients were followed up for over I year, and of these six (24%) were cured, and thirteen (52%) showed marked symptomatic improvement.

Adult↗
PubMed1990

Reducing the pain of intradermal lignocaine injection by pH buffering.

The effect of pH on the pain of administration and efficacy of 1% lignocaine was investigated in a prospective, double-blind, randomized study of 20 adult volunteers. Onset and spread of anaesthesia by intra-dermal injection were not altered, but there was a significant reduction in pain scores with a higher pH. Overall, pain scores appear to be more dependent on the speed of injection rather than alteration of pH.

Adolescent↗
PubMed1998

Bacillus Calmette-Guérin sequestered in the brain parenchyma escapes immune recognition.

We have previously shown that heat-killed bacillus Calmette-Guérin (BCG) injected into the brain parenchyma becomes sequestered behind the blood-brain barrier for months, apparently unrecognised by the immune system (Matyszak and Perry, 1995, 1996a,b). In this paper we have studied T-cell and antibody responses to purified protein derivative (PPD) at different times after intracranial injection of BCG or after the same dose of BCG was injected intradermally. We detected no antibody to PPD in the sera of animals which received intracranial injection, although there was a clear antibody response in the sera of animals injected intradermally, as shown using immunoblot analysis. The skin contact sensitivity to PPD was robust in animals which had received a previous intradermal injection of BCG. 72 h after a PPD injection, the injected site showed many MHC class II + macrophages and T-cells. However, the response in skin following PPD challenge, in animals injected intracranially (i.c.), was comparable with that of naive animals which had received no previous BCG challenge. The skin lesions in animals injected i.c. and in naive animals, were characterised by a small number of MHC class II + cells and rare T-cells. T-cell responses were also studied in an in vitro proliferation assay. The proliferative response was measured for cells isolated from the cervical lymph nodes and the spleen. Cells purified from the spleen and the cervical lymph nodes of animals injected with BCG i.c. showed no specific proliferative response to PPD. The response was comparable to that found in naive, uninjected animals. However, spleen and cervical lymph node cells from animals injected intradermally with BCG showed a significant proliferative response to PPD. These results show that a dose of bacteria injected into the brain parenchyma fails to prime the immune system even though the same dose injected subcutaneously will do so. This response to bacteria in the CNS differs from that previously reported for soluble proteins.

Animals↗
PubMed2004

Effect of protein kinase C blockade on phosphorylation of NR1 in dorsal horn and spinothalamic tract cells caused by intradermal capsaicin injection in rats.

We have previously reported that protein kinase A (PKA) is involved in the phosphorylation of NR1 subunits of N-methyl-d-aspartate (NMDA) receptors in dorsal horn neurons after intradermal injection of capsaicin (CAP). To see if protein kinase C (PKC) also participates in the phosphorylation of NR1, we used electron microscopic techniques to determine further where the phosphorylated NR1 subunits (pNR1) are expressed in the spinothalamic tract (STT) cells and immunohistochemistry to examine whether a PKC inhibitor, chelerythrine chloride, blocks the enhanced phosphorylation of NR1 on serine 896. The pNR1 subunits were in the soma and dendrites of STT cells and in presynaptic endings. Western blots showed that pretreatment with the PKC inhibitor caused a decrease in CAP-induced phosphorylation of NR1 protein. In immunofluorescence staining, the number of pNR1-like immunoreactive neurons was significantly decreased on the side ipsilateral to the injection when chelerythrine chloride was administered intrathecally before CAP injection. In addition, when STT cells were labeled by microinjection of the retrograde tracer, fluorogold (FG), into the thalamus, we found that the proportion of p-NR1-LI STT cells was markedly reduced after PKC inhibition. Combined with our previous findings, these results strongly suggest that NR1 subunits in spinal dorsal horn neurons are phosphorylated following CAP injection, and this phosphorylation is catalyzed by PKC, as well as by PKA.

Alkaloids↗