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Histamine metabolism in delayed type hypersensitivity--comparative analysis with cellular infiltrates.

We examined the dynamic changes of histamine metabolism and infiltrating cell populations in lesional sites of representative cutaneous delayed type hypersensitivity (DTH), including dinitrochlorobenzene (DNCB) allergic dermatitis, purified protein derivative of tuberculin (PPD) reaction, and keyhole limpet homocyanin (KLH)-induced cutaneous basophil hypersensitivity. The concentration of histamine increased with time in all DTH reactions examined, though the time course varied among these reactions. In DNCB allergic dermatitis, the maximum content of the amine at 3 days after the initiation was about three times that of the control baseline. In PPD reaction, the maximum content and the time course were almost similar to that in DNCB allergic dermatitis. However, in KLH-induced cutaneous basophil hypersensitivity the maximum content was about ten times that in DNCB allergic dermatitis or PPD reaction, and was observed earlier, on the 2nd day. There was no remarkable change in the activities of histamine-degrading enzymes in these reactions. There was little infiltration of mast cells, while time-dependent changes of the basophil infiltration were almost parallel those of the histamine concentration in all these reactions. Basophils in DNCB allergic dermatitis showed a piecemeal degranulation, while those in either the PPD reaction or KLH-induced cutaneous basophil hypersensitivity remained intact. These results clearly suggest that the increase of histamine concentration in cutaneous DTH depends on the number of basophils infiltrating the lesional sites, even if the regulatory mechanisms of the activation of the cells differ among the DTH reactions.

Animals↗

Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas.

To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of 3H-thymidine-labeled infiltrating cells (3H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the 3H-index is moderately elevated in stage I and high in stage III. The 3H-index is within normal range in dermal infiltrate of Sézary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benign cutis. In parapsoriasis en plaques two groups can be distinguished: in the small-plaque variant (chronic superficial dermatitis) the 3H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

Adult↗

Reactivity of monoclonal antibody BE 2 in different stages of mycosis fungoides and in benign dermal infiltrates.

The cutaneous infiltrate in mycosis fungoides (MF) is predominantly composed of T4-positive T-cells. Attempts to distinguish the early stages of this condition from benign inflammatory infiltrates using anti-T3, T4 and other T-cell-associated antibodies have hitherto been unsuccessful. Recently a monoclonal antibody BE 2 has been described as selectively reacting against leukemic cells in patients with cutaneous T-cell lymphoma. To investigate whether the BE 2 antigen is differentially expressed in different stages of MF and benign dermatoses, thus facilitating diagnosis, especially of early MF, the reactivity of monoclonal antibody BE 2 against cutaneous infiltrates from such conditions was assessed. In the early stages of MF only a small number of reactive cells was present. In benign inflammatory infiltrates, especially in those that clinically and histologically were hardly distinguishable from early MF, BE 2 reactivity was essentially the same as in eczematous-stage MF. Lesions from plaque and tumor stage MF contained large numbers of BE 2-reactive cells. Our results indicate that expression of BE 2 is associated with the stage of a given MF lesion and is essentially identical in early MF and eczematous lesions with a similar histopathological appearance.

Antibodies, Monoclonal↗

Histiocytic necrotizing lymphadenitis without granulocytic infiltration.

Twenty-seven cases of an unusual necrotizing lymphadenitis previously described only in Japan are reported as occurring in West Germany (23 cases), Iran (1 case), Italy (1 case), Korea (1 case) and Spain (1 case). The lesion frequently develops in the cervical lymph nodes of young women. It is characterized by infiltration of the cortex and/or paracortex by large collections of proliferating histiocytes and is devoid of granulocytes. Complete or, more often, incomplete necrosis of lymphoid tissue is seen in all cases. In cases with incomplete necrosis, the histiocytes are interspersed with pyknotic cells and nuclear debris. Based on the histological findings, the term "histiocytic necrotizing lymphadenitis without granulocytic infiltration" is proposed. Lesions to be considered in a differential diagnosis are malignant histiocytic neoplasms and necrotizing lymphadenitis with granulocytic infiltration, which is seen in lupus erythematosus and bacterial infections. The aetiology of histiocytic necrotizing lymphadenitis without granulocytic infiltration is still unclear. Some clinical and histological features indicate the possibility of an underlying viral infection.

Adult↗

Cutaneous infiltrates of histiocytosis X contain plasminogen activator-bearing epidermotropic dendritic cells different from Langerhans cells.

Plasminogen activators (PA) play an important role in cell migration and tissue degradation. Considering the strong epidermotropism of atypical mononuclear cells in histiocytosis X (HX) skin infiltrates leading to intraepidermal abscess formation, it was the purpose of this study to look for tissue-type PA (t-PA) and/or urokinase-type PA (u-PA) on HX cells. Four monoclonal antibodies against PA were used, employing the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique on cryostat sections from four patients with HX. Twenty percent to 40% of infiltrating cells in the epidermis expressed the t-PA antigen. t-PA+ cells were present in the follicular centers of human tonsil, absent in normal epidermis and scanty in cutaneous infiltrates from mycosis fungoides and lupus erythematosus. Double labeling with anti-PA and T6 (CD1) or S100 protein revealed some of the HX cells to express both antigens (t-PA+ CD1+ or t-PA+ S100+). We conclude that cutaneous infiltrates of HX contain PA+ dendritic cells which are different from normal Langerhans cells and which may be responsible for the strong epidermal alterations in HX.

Aged↗

Acute human pyelonephritis: leukocytic infiltration of tubules and localization of bacteria.

The fine structural details of how leukocytes appear in the lumen of tubules and the localization of bacteria in the tubulo-interstitial space were studied by light and electronmicroscopy in renal cortical biopsy specimens from three patients with acute pyelonephritis. The cells of interstitial infiltrates infiltrated and sometimes disrupted the cortical collecting tubules preferentially, while inflammatory infiltration of the proximal and distal convoluted tubules occurred more rarely. Since the emigration of tubular wall-localized individual leukocytes into the lumen was not observed even in long series of thin sections, focal inflammatory disruption of the uriniferous ducts was considered to be the morphological basis of the intratubular accumulation of leukocytes. The structural simplicity of the collecting tubular cells is suggested to be the reason for their preferential involvement in the drainage of the interstitial suppuration, although a role for specific carbohydrate receptors cannot be excluded. The bacteria were usually found within the neutrophilic granulocytes and macrophages of the interstitial infiltrates, and within and among the cells of leukocyte casts. Additionally, pure bacterial colonies were noticed in the lumen of a few collecting tubules. The problem of the adherence of the bacteria to the surface of the tubular cells is discussed.

Acute Disease↗

Characterization of the mononuclear infiltrate in Bowen's disease (squamous cell carcinoma in situ). Evidence for a T cell-mediated anti-tumour immune response.

We investigated the dermal inflammatory infiltrate and the expression of HLA-DR and beta 2-microglobulin on the tumour cells in 8 Bowen's disease (BD) using a series of monoclonal antibodies. The inflammatory infiltrate was classified as mild, moderate or heavy. The infiltrate in all cases consisted mainly of T cells (55 +/- 21%) and where the T helper (TH) subset predominated over the T suppressor/cytotoxic (TS/C) subset (TH/TS/C ratio of 2.4 +/- 1.0). The mean percentage of HLA-DR positive cells was 58 +/- 18%, Langerhans cells (LC) 4 +/- 1% and Leu-M5 positive cells (monocytes/macrophages) 9 +/- 2%. The mean percentage of B cells and natural killer (NK) cells was 4 +/- 5% and 1 +/- 2% respectively. B cells and NK cells did not invade any of the tumours. In the 5 BD with moderate or heavy infiltrate, TH cells, TS/C cells and Leu-M5 positive cells did invade the tumour. In the tumour area where there was invasion, the number of LC was increased and HLA-DR was expressed on the cells. beta 2-microglobulin was generally expressed on the tumour cells of BD. We concluded that there is evidence for a T cell-mediated anti-tumour immune response which may account for the infrequent invasive growth in BD.

Adult↗

Ultrastructural observations on cytotoxic effector cells infiltrating pancreatic islets of low-dose streptozocin treated mice.

The aim of this study was to observe the ultrastructural events, during the onset of diabetes mellitus in the low-dose streptozocin (LDS)-treated mouse model with emphasis on the infiltrating elements. Forty male C57 BL/6J mice were given 40 mg/streptozocin on 5 consecutive days and killed 5, 6, 7, 8, 9, 10, 15, and 18 days after the first injection. Results demonstrated that islet infiltration occurring in LDS-treated mice is characterized by a very early pre-infiltration state in which mononuclear phagocytes in islet capillary vessels were considerably increased in number. A new histopathological time sequence for the early insulitis is described, in which attraction of blood mononuclear phagocytes into the islet capillary lumen is the first step. During the successive stage, occurring on days 6-8 we observed that mononuclear phagocytes migrate through capillary and venule walls into the islet parenchyma, where they differentiate into tissue macrophages. It was only later (step 3) that these macrophages acquired novel properties, typical of their "activated state" and started to phagocytose islet beta-cell debris. These data suggest that during the pre-infiltration and early insulitis the mononuclear phagocyte system plays a key role in the onset of LDS diabetes.

Animals↗

Reticulin fibre content of bone marrow infiltrates of malignant non-Hodgkin's lymphomas (B-cell type, low malignancy)--a morphometric evaluation before and after therapy.

A morphometric study was performed on bone marrow infiltrates of non-Hodgkin's lymphomas (B-cell type, low malignancy) to evaluate the content of argyrophilic (reticulin) fibres in the various subtypes before and after therapy. In congruence with the corresponding lymph node lesions, subtypes consisted of lymphocytic lymphoma--chronic lymphocytic leukaemia (CLL, n = 39), centroblastic-centrocytic lymphoma (CB-CC, n = 35), lymphoplasmacytoid immunocytoma (LPI, n = 22) and finally hairy cell leukaemia (HCL, n = 21). In comparison with control specimens, morphometric measurements on trephine biopsies (initial staging procedure) disclosed a borderline or minimal increase in reticulin in CLL and moderate fibrosis in CB-CC and LPI, whereas HCL had the greatest increase in fibres. The marrow surrounding focal or patchy lymphoma infiltrates of CLL and CB-CC displayed no relevant changes in fibre density with respect to the control samples. Following chemotherapy, repeated trephine biopsies (restaging procedure) were obtainable from 38 patients. There was no significant decrease in the fibre content of CLL, CB-CC and LPI infiltrates. In HCL an incomplete reduction was recorded after interferon treatment. So-called benign lymphoid lesions may be distinguished from focal-patchy infiltrates of CB-CC and LPI not only by showing a central localization, but also by the absence of significant amounts of reticulin. However, considering the density of the reticulin fibres, a clear-cut discrimination of these lymphoid aggregates from an early nodal-central growth pattern of CLL is not feasible in many cases.

B-Lymphocytes↗

Pneumococcal antibody levels in patients with acute lung infiltrates.

We assessed the diagnostic value of serial serum antibody titers (IgG, IgM) to a polyvalent pneumococcal antigen preparation containing capsular polysaccharides from 14 different serotypes in the differential diagnosis between infectious lung infiltrates and lung infarction. A two-fold or higher change in antibody level, measured by means of an enzyme-linked immunosorbent assay (ELISA) was considered significant. Of 30 patients with pneumococcal pneumonia, 13 were infected with a Streptococcus pneumoniae serotype included in the vaccine (group A), five with a non-vaccine type (group B), and in 12 patients the S. pneumoniae serotype was not identified (group C). The sensitivity was 62% (group A). A heterotypic antibody rise was observed in one patient (group B). There was no difference in antibody rises between groups A and C. In 13 patients the pulmonary infiltrates were associated with different etiological factors (group D). The specificity determined in this group was 85%. The positive predictive value of an antibody rise was 89% (SD = 0.07) in pneumococcal pneumonia and a negative result signified in only 46% of the patients (SD = 0.10) that the pulmonary infiltrates were not associated with pneumococcal infection. Four patients suffering from pulmonary infarction had no antibody rise. Preliminary data of a current similar study, using a 23-valent antigen of pneumococcal capsular polysaccharides supported the aforementioned results. It is noteworthy that ten additional patients with lung infarction showed no seroconversion. The results suggest that serum antibody changes to a polyvalent pneumococcal vaccine may be of value in the differential diagnosis between infectious lung infiltrates and lung infarction.

Adult↗

Portal architecture: a differential guide to fatty infiltration of the liver on computed tomography.

Fatty infiltration of the liver, like fatty lesions elsewhere in the body, typically appears as low-density areas on computed tomography (CT). Fatty infiltration of the liver should be considered in the differential diagnosis of homogeneous low-density hepatic lesions regardless of distribution or size. As a physiologic rather than anatomic change, fatty infiltration of the liver characteristically leaves the portal venous architecture unaltered. Although fatty infiltration of the liver typically presents with complete or near complete involvement, other unusual patterns may be encountered. In these atypical cases, recognition of the normal portal structures on CT aids in correct diagnosis.

Fatty Liver↗

Relationship between arachidonic acid metabolism, myeloperoxidase activity and leukocyte infiltration in a rat model of inflammatory bowel disease.

The relationship between 14C-arachidonic acid (14C-AA) metabolism, myeloperoxidase activity (MPO) and leukocyte infiltration was studied in a chronic model of inflammatory bowel disease, induced by a single intrarectal application of the hapten, trinitrobenzene sulphonic acid (TNB). The colonic damage produced by TNB was accompanied, after 12-36 hours, by a marked increase in MPO, which was directly correlated to leukocyte infiltration, assessed histologically. There was also a marked increase in the metabolism of 14C-AA, by homogenates of inflamed colon, to 12-, 15-HETE and 6-keto-PGF1 alpha as indices of lipoxygenase and cyclo-oxygenase metabolism respectively. However, a further increase in MPO-cellular infiltration, between 36-72 hours after TNB, was accompanied by a reduction in 12- and 15-HETE formation. The increase in MPO-cellular infiltration was maintained for up to 3 weeks, at which time both 12-, 15-HETE and 6-keto-PGF1 alpha formation had returned to control levels. These results suggest that these AA metabolites have a greater importance in the acute phase of the inflammatory response induced by TNB compared to the later chronic phase.

Animals↗

Detection of bone marrow infiltration by non-Hodgkin's lymphoma--comparison of histological findings, analysis of gene rearrangements, and examination by magnetic resonance imaging.

The histological examination of bone marrow specimens is one of the standard procedures in staging non-Hodgkin's lymphoma. To investigate the validity of a conventional unilateral iliac crest biopsy, we performed a prospective study comparing histological findings with analysis of gene rearrangements in bone marrow samples and magnetic resonance imaging of bone marrow. Twenty-seven consecutive patients with non-Hodgkin's lymphoma (ten with high grade, seventeen with low grade) were studied. In twelve patients, histological examination revealed bone marrow infiltration. Results of histology and magnetic resonance imaging were discordant in three of the twenty-seven patients. With magnetic resonance imaging, suspected infiltration was found in two patients without histological evidence for bone marrow involvement in the disease. In one patient, an infiltration was described by histology but MRI revealed no pathological findings. In this case, DNA analysis confirmed bone marrow infiltration by detection of a clonal rearrangement of the immunoglobulin heavy chain gene. Analysis of gene rearrangements was performed in ten patients. As examined by histology, five of them had bone marrow involvement in the disease and five had not. In all these cases, analysis of gene rearrangements confirmed the histological findings. Our data show that, despite the small volume of bone marrow specimens, the sensitivity of an iliac crest biopsy seems to be high in staging non-Hodgkin's lymphoma.

Adult↗

Infiltrated Cells in Experimental Allergic Encephalomyelitis by Additional Intracerebral Injection in Myelin-Basic-Protein-SensitizedB6 Mice.

We previously reported that murine experimental allergic encephalomyelitis can be induced by an additional intraperitoneal and intracerebral (i.c.) restimulation in resistant B6 mice after standard immunization with myelin antigens in complete Freund's adjuvant and Bordetella pertussis coadjuvant. Neutrophils infiltrated into perivascular spaces at 12 h, followed by mononuclear cells 24 h after i.c. injection. In this study, we report that the i.c. injection induced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The kinetic expression of ICAM-1 or VCAM-1 on brain endothelial cells paralleled the infiltration of neutrophils and mononuclear cells, respectively. The infiltrated lymphocytes also expressed very late antigen-4 (VLA-4) molecules. The microvascular endothelial cells were positive for VCAM-1, whereas the surrounding mononuclear cells were VLA-4 positive. Furthermore, we found a unique subpopulation of cells with characteristics of CD4(-)CD8(-)V(beta)8(+) markers. The kinetic studies of this population showed that these cells were transiently depleted from 12 to 24 h after i.c. challenge (before the development of clinical symptoms) in cervical lymph nodes. These CD4(-)CD8(-)V(beta)8(+) cells can be expanded by in vitro culture with myelin basic protein or IL-2. No significant changes of CD4(+)/CD8(+) cells were noted. CD4(+)CD8(-)CD3(+) cells were also found in brain by double histochemical stains and were the major infiltrating cells at 24 or 48 h after i.c. challenge.

Journal Article↗

Pulmonary infiltrations. Sign of severe acute pancreatitis.

CONCLUSION: Pleural infiltrates are indicative of severe acute pancreatitis and a negative prognostic parameter for the course of the disease. BACKGROUND: The purpose of this study was to determine the frequency of pulmonary infiltrates in acute pancreatitis and their importance for evaluating the severity of the disease. METHODS: Incidence and localization of pulmonary infiltrates were evaluated in 140 patients with acute pancreatitis. Chest X-ray was obtained within 24 h, and a contrast-enhanced computed tomography within 72 h after admission. Ranson's prognostic parameters were estimated within the first 48 h. RESULTS: Patients with pulmonary infiltrates (n = 36, 26%) had a significantly higher Ranson's score and pancreatic necroses more frequently than patients without this complication, plus a higher mortality rate.

Acute Disease↗

Different modes of mesenteric infiltration displayed by two rat leukemias. A study by scanning and transmission electron microscopy and by microcinematography.

Infiltration of the mesentery after intraperitoneal implantation of two transplantable rat leukemias, the undifferentiated L5222 and the myeloid BNML, was studied by means of scanning and transmission electron microscopy, and microcinematography. In animals implanted with L5222 cells, contraction of the mesenteric mesothelium is a conspicuous feature. It occurs within the first 24h after implantation and influences decisively the course of infiltration. In contrast, The presence of BNML cells leads to mesothelial contraction only in the terminal stage and, therefore, exerts no direct effect on infiltration. In addition, the two leukemias differ with regard to their cellular motility. Whereas L5222 cells locomote within the mesentery, only stationary movements are recorded with BNML cells. Based on the different interactions with the mesothelium and cell motilities, two distinct modes of infiltrating the mesentery could be ascertained for the two rat leukemias.

Animals↗

The effect of local anaesthetics on epinephrine absorption following rectal mucosal infiltration.

This study was undertaken to investigate the effects of lidocaine and bupivacaine on epinephrine absorption following rectal mucosal infiltration, to assess the cardiovascular and metabolic effects of the absorbed epinephrine and to compare the systemic absorption of the local anaesthetics employed. Three groups of five greyhounds received 1.5 micrograms.kg-1 of epinephrine 1:200,000 in lidocaine 0.5 per cent, bupivacaine 0.5 per cent or 0.9 per cent saline. Plasma epinephrine, lidocaine, bupivacaine, lactate, glucose and potassium concentrations were measured at 1, 2, 5, 10, 15 and 30 minutes following infiltration. Plasma epinephrine concentrations were significantly higher in the lidocaine group at one and two minutes following infiltration. Plasma bupivacaine concentrations were significantly higher than plasma lidocaine concentrations throughout the study period. There were no significant differences in metabolic or biochemical indices within or between the three groups. A local vasodilatory action of lidocaine may enhance epinephrine absorption. Differences in hepatic uptake and rate of metabolism may explain the increased plasma bupivacaine measured. Lidocaine may be the local anaesthetic of choice for ano-rectal procedures, especially when large volumes of local anaesthetic are being infiltrated.

Absorption↗

Post-tonsillectomy infiltration with bupivacaine reduces immediate postoperative pain in children.

Pain management after tonsillectomy in children remains a dilemma for the anaesthetist. A previous study demonstrated that the administration of lidocaine 1% topical spray to the peritonsillar fossae before tracheal extubation provided considerable immediate postoperative pain relief in infants and children. However, the pain relief was of short duration. We were hopeful that the use of bupivacaine would offer more prolonged pain relief because of its pharmacological characteristics. Therefore, this study was designed to compare the effects of bupivacaine 0.5% with 1:200,000 epinephrine administered after tonsillectomy either as topical spray or submucosal infiltration on postoperative pain in children. Forty-three patients aged two to ten years were randomized into three groups after tonsillectomy was performed. Group (1) received 0.5 ml.kg-1 normal saline spray; (2) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine peritonsillar infiltration in a similar volume to Group 1 and; (3) received 2 mg.kg-1 bupivacaine 0.5% with 1:200,000 epinephrine spray to both tonsillar beds. The patients in each group were compared postoperatively with regard to the quality of pain control using the Objective Pain Score, and their analgesic requirements. Peritonsillar infiltration of bupivacaine provided superior immediate postoperative analgesia as reflected by lower recovery room pain scores (P < 0.05) and opioid requirements (P < 0.01). Ward pain scores and analgesic requirements were similar among groups. Peritonsillar infiltration of bupivacaine 0.5% with 1:200,000 epinephrine provides better post-tonsillectomy pain control in the immediate postoperative period than bupivacaine spray or placebo.

Anesthetics, Local↗