A retrospective cross-sectional study on the risk factors and survival outcome of End Stage Kidney Disease patients receiving regular maintenance haemodialysis with COVID-19 infection in Hospital Enche' Besar Hajjah Khalsom, Kluang.

INTRODUCTION: COVID-19 pandemic has affected healthcare services around the globe as hospitals were turned into designated hospitals to accommodate high risk groups of patients with COVID-19 infection including end stage kidney disease (ESKD) patients. In Malaysia, there was insufficient data on COVID-19 infection among ESKD patients. This study aims to determine factors and survival outcomes associated with COVID-19 infection among ESKD patients in a designated COVID-19 hospital in Malaysia. METHODS AND MATERIALS: A retrospective cross-sectional study involving 80 haemodialysis (HD) patients recruited from March 2020 till March 2021. Patients' information and results was retrieved and evaluated. Risk factors affecting the COVID-19 mortality were analysed using a one-way analysis of variance (ANOVA) and binary logistic regression. RESULTS: The mean age of the patients was 54 years who were predominantly Malays (87.5%) and living in rural areas. Majority of them had comorbidities such as diabetes mellitus (71%) and hypertension (90%). The most common presentations were fever (46%) and cough (54%) with chest radiographs showing bilateral lower zone ground glass opacities (45%). A quarter of the study population were admitted to the intensive care unit, necessitating mechanical ventilation. This study found that 51% of the patients were given steroids and 45% required oxygen supplementation. The COVID-19 infection mortality among the study population was 12.5%. Simple logistic regression analysis showed that albumin, Odd Ratio, OR=0.85 (95% Confidence Interval, 95%CI: 0.73, 0.98)) and absolute lymphocyte count OR=0.08 (95%CI: 0.11, 0.56) have inverse association with COVID-19 mortality. C-reactive protein OR=1.02 (95%CI: 1.01, 1.04), lactate dehydrogenase OR=1.01 (95%CI: 1.00, 1.01), mechanical ventilation OR=17.21 (95%CI: 3.03, 97.67) and high dose steroids OR=15.71 (95%CI: 1.80, 137.42) were directly associated with COVID-19 mortality. CONCLUSION: The high mortality rate among ESKD patients receiving HD was alarming. This warrants additional infection control measures to prevent the spread of COVID- 19 infection among this vulnerable group of patients. Expediting vaccination efforts in this group of patients should be advocated to reduce the incidence of complications from COVID-19 infection.

A rare presentation of ectopic thyroid gland at right axilla.

The thyroid gland and its hormones play important roles in organ development and in the homeostatic control of physiological mechanisms in human beings. As a result of embryogenic descent of thyroid gland, it commonly resides along the midline - from tongue to mediastinum (90%). Ectopic thyroid gland is a rare occurrence, with extra-lingual ectopic thyroid gland being even rarer. Thus, there is a concern for malignant metastasis. Madam H, a 56-year-old healthy woman presented to the Hospital Sultanah Nora Ismail, Johor, Malaysia in April 2020 with an increasing size of right axilla mass and history of weight loss. She was having right axilla mass for the previous 7 years but only noticed the increase in size about 1 year ago. She has no other constitutional symptoms. A tru-cut biopsy performed demonstrated a benign ectopic thyroid tissue. Thyroid function test showed primary hypothyroidism. Serum Chromogranin A and other thyroid antibodies were within the normal value. Further radiological imaging showed the normal thyroid gland at neck, with no signs of distant malignancy. There was no other axillary, mediastinal or hilar lymph node enlargement. She was started on regular T. L Thyroxine 100mcg daily and given regular follow-up in endocrine clinic. Benign ectopic thyroid gland is an unusual finding. As such, follow up is needed with possibility of carcinomatous transformation such as papillary carcinoma should be considered.

Hypothalamic-pituitary fungal infection causing panhypopituitarism.

Madam LPS, a 69 years old lady complained of left eye blurring of vision since January 2017. It was associated with left orbital swelling with chemosis, eye redness, epiphora, several episodes of self-limiting epistaxis and bilateral ophthalmoplegia. Other neurological examinations and cerebellar systems were intact. Magnetic Resonance Imaging (MRI) Brain and Orbit were performed, depicting a sellar mass with suprasellar extension with blood investigations results showed panhypopituitarism. She underwent bilateral orbital decompression. Trans-nasal endoscopic biopsy showed suppurative granulomatous lesion, which cultured Candida Albicans and Candida Galbrata. She was started on antifungal and hormonal replacement therapy for panhypopituitarism. Unfortunately, she did not respond well to treatment as repeated MRI Brain on December 2018 showed increase in size of sellar mass causing obstructive hydrocephalus and increasing size of left orbital lesion. She was counselled for another debulking surgery with a ventriculoperitoneal (VP) shunt. HPE taken were reported as chronic inflammatory process in favour to fungal infection. Pituitary infections may mimic pituitary mass. Some may exhibit symptoms of panhypopituitarism as well. Thus, physical examination, MRI brain imaging as well as HPE of biopsy are important aids to achieve diagnosis. Optimal treatment of fungal pituitary abscess includes transsphenoidal surgery combined with antifungal therapy.

Colorectal resection via natural orifice specimen extraction versus conventional laparoscopic extraction: a meta-analysis with meta-regression.

BACKGROUND: Studies have shown differences in postoperative outcomes between two minimally invasive extraction methods for colorectal lesions-natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic surgery (CLS). The aim of this study was to discover the major differences in NOSES and CLS to refine current practice. METHODS: Electronic databases were searched for articles comparing NOSES and CLS from inception till March 2020. Weighted mean differences (WMD) and odds ratio (OR) were estimated for continuous and dichotomous outcomes, respectively. Summary statistics were calculated using the DerSimonian and Laird random effects. RESULTS: Twenty-one studies (15 on malignant disease, 4 on benign disease, 2 on both) were included in this meta-analysis, totalling 2378 patients (1079 NOSE, 1299 CLS). NOSE was associated with decreased: intraoperative bleeding (WMD: - 10.652 ml; 95% CI: - 18.818 ml to - 2.482 ml; p < 0.001), pain score (WMD: - 1.520; 95% CI - 1.965 to - 1.076; p < 0.001), time to flatus (WMD: - 0.306 days; 95% CI: - 0.526 to - 0.085 days; p < 0.001), length of hospital stay (WMD: - 1.048 days; 95% CI: - 1.488 to - 0.609 days; p < 0.001), and total morbidity (OR: 0.548; 95% CI: 0.387 to 0.777; p = 0.001). Subgroup analyses showed significant differences between malignant and benign lesions for intraoperative bleeding (p = 0.011) and pain score (p = 0.010). Meta-regression analyses showed an association between the American Society of Anaesthesiologists (ASA) physical status classification III with pain (p = 0.03) and ASA III with time to flatus (p = 0.04). CONCLUSIONS: This meta-analysis and meta-regression demonstrated that NOSES had better postoperative outcomes compared to CLS. More comprehensive reviews should be conducted on the long-term outcomes specific to the extraction site to better inform clinical practice.

alpha-fetoprotein response predicts survival benefits of thalidomide in advanced hepatocellular carcinoma.

BACKGROUND: Radiographic measurements do not always reflect the biological response of hepatocellular carcinoma to drug therapy. AIMS: To evaluate the clinical implications of tumour marker (alpha-fetoprotein) response in advanced hepatocellular carcinoma patients with thalidomide treatment. PATIENTS AND METHODS: Forty-two advanced hepatocellular carcinoma patients with baseline alpha-fetoprotein levels above 200 ng/mL and thalidomide therapy were included. Serum alpha-fetoprotein levels were measured every 4 weeks. alpha-fetoprotein response was defined as a 50% or greater reduction of alpha-fetoprotein levels for 4 or more weeks during treatment. Radiographic response was assessed by World Health Organization criteria; survivals were estimated by Kaplan-Meier method and prognostic factors were assessed by Cox's proportional hazard model. RESULTS: With intention-to-treat analysis, radiographic response and alpha-fetoprotein response were obtained in 7% (three of 42, 95% confidence interval: 0-15) and 24% (10 of 42, 95% CI: 10-38) of patients, respectively. All radiographic response was observed in alpha-fetoprotein responders. Multivariate analyses showed alpha-fetoprotein response was independent prognostic factor for both progression-free survival (relative risk = 0.394, 95% CI: 0.189-0.820, P = 0.013) and overall survival (relative risk = 0.241, 95% CI: 0.096-0.606, P =0.003), whereas radiographic response was not. CONCLUSION: alpha-fetoprotein response can more accurately reflect the biological response of advanced hepatocellular carcinoma to thalidomide therapy than radiographic response.

Anterior subfascial transposition of the ulnar nerve.

After anterior subfascial transposition, the ulnar nerve lies superficial to the flexor-pronator muscle group but deep to its fascia. Eight patients with cubital tunnel syndrome were treated with this method and reviewed retrospectively. The average age at the time of operation was 52 years. All patients had severe cubital tunnel syndrome based on Dellon's classification. The average follow-up period was 2 years and 9 months. Post-operative outcome assessment was based on the modified Bishop rating system. Six patients had excellent and two had good outcomes. All were back at work by the 5th post-operative week. There were no complications or recurrence of symptoms. Anterior subfascial transposition of the ulnar nerve is an effective method of surgical treatment for patients with severe cubital tunnel syndrome.

Overexpressed alpha3beta1 and constitutively activated extracellular signal-regulated kinase modulate the angiogenic properties of ECV304 cells.

ECV304, a spontaneously transformed cell line derived from the human umbilical vein endothelial cell (HUVEC) (Takahashi et al., 1990), has been developed as an in vitro angiogenesis model. In the present study, we further characterized the angiogenic properties of this cell line. Compared to HUVEC, ECV304 cells showed distinct features including a higher activity of cellular adhesion, slower but reproducible progression of angiogenesis on Matrigel, and resistance to apoptosis. Thus, the expression of integrin and activation of extracellular-signal regulated kinase 1/2 (Erk1/2), a downstream effector of the integrin pathway, were examined. Flow cytometry revealed that alpha3beta1 integrin was markedly upregulated in ECV304 cells, while alpha(v)beta1 and alpha5beta1 integrins were slightly downregulated. Consistent with this, the binding activity to collagen type IV and laminin, major extracellular matrices of Matrigel, was increased 1.4- and 1.9-fold in ECV304 cells, respectively. This tight binding may retard the initial stage of sprouting and migration in the angiogenesis of ECV304 cells. It has been further demonstrated that Erk1/2 is constitutively active in ECV304 cells, rendering them resistent to the inhibitory effect of PD98059 on proliferation. However, migration of both HUVEC and ECV304 cells was inhibited to a similar extent by PD98059 in a dose-dependent manner. Up to 50 microM of PD98059, no significant changes in cell binding and tubulogenesis on Matrigel was observed in ECV304 cells. In contrast, the tubulogenesis of HUVEC was severely impaired by PD98059. Elevated Erk1/2 activity in ECV304 cells was suppressed by dominant negative H-Ras, but not by cytochalasin D. These results suggest that the overexpression of alpha3beta1 integrin and the constitutive activation of Erk1/2 play a key role in the alteration of the angiogenic properties of ECV304 cells.

The significance of body weight change in non-Hodgkins lymphoma.

BACKGROUND: The purpose of this study was to evaluate the effect of weight changes after completion of chemotherapy on the prognosis and survival of patients with intermediate and high grade non-Hodgkin's lymphoma. MATERIALS AND METHODS: A retrospective analysis of data on patients from the TCOG T1488 protocol, a phase II study using CHOP in the treatment of intermediate and high grade lymphoma. From September, 1988 to December 1994, 138 adult patients had complete weight data for analysis. Weight gain in lymphoma patients after therapy significantly correlated with improved survival (Logrank test p = .0031). In patients with initial B symptoms, weight gain after therapy correlated with survival (Logrank test p = .0039), female patients (odds ratio = 6.2) were less likely to gain weight on treatment. CONCLUSION: Weight gain after chemotherapy for lymphoma is a significant positive prognostic factor for survival.

Dietary biotin requirement for maximum growth of juvenile grass shrimp, Penaeus monodon.

A feeding trial was conducted to estimate the minimal dietary biotin requirement for juvenile grass shrimp, Penaeus monodon. Purified diets with eight levels (0, 0.2, 0.5, 1.0, 3.0, 6.0, 10.0 and 20.0 mg/kg) of supplemental biotin were fed to P. monodon (mean weight 0. 26 +/- 0.01 g) for 8 wk. Each diet was fed to three replicate groups of shrimp. Shrimp fed diets supplemented with biotin (0.2-20.0 mg/kg) had significantly (P < 0.05) higher weight gain, feed efficiency and protein efficiency ratio than those fed the unsupplemented control diet. Weight gain was high in shrimp fed 3. 0-10.0 mg biotin/kg diet and lowest in shrimp fed

The correlation of blood pressure, age and endothelin-1 binding sites in aortic smooth muscle cells of rats.

Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats at the ages of 4, 8, 12, 16 and 24 weeks were used to examine the effects of age on the density of endothelin-1 (ET-1) binding sites in aortic smooth muscle cells and systolic blood pressure (SBP). The SBP of the 3 different rat strains was measured, and the maximum binding value (Bmax) and dissociation constant (Kd) of ET-1 binding sites in smooth muscle cells of the thoracic aorta were determined. The results showed that the SBP and Bmax values of SHR, WKY and SD rats increased with age; the SBP and Bmax value at each corresponding age were significantly higher in SHR than in WKY and SD rats, however, there was no significant difference between WKY and SD rats. The relationship of age vs SBP, age vs Bmax, and Bmax vs SBP showed significantly positive correlation in all 3 rat strains. The regression line in the Bmax of endothelin binding sites against SBP in the 3 different rat strains presented a similar slope. These results indicate that SBP, which increased with age, could be related to an increased density of ET-1 binding sites on vascular smooth muscle cells in these 3 different rat strains.

Cross sectional study of use of alternative medicines in Chinese cancer patients.

The aim of this study was to ascertain the prevalence of alternative medicine consumption in Chinese cancer patients on active conventional treatment. A cross sectional survey of 100 consecutive advanced cancer patients admitted to a cancer clinical trial referral unit were personally interviewed by their assigned oncology research nurse using a specially designed questionnaire. The results showed that 64% of our patients used indigenous Chinese medication. In all age groups except the over-70s (P = 0.043), > 50% took such medication, more female (76%) than male (57.6%) patients (P = 0.323). Patients of all educational levels (P = 0.062) and religious backgrounds (P = 0.08) consumed alternative medicines. Duration of alternative medication consumption was less than three months in 50% of patients, with costs between US$40 and 2000/month for 70% of patients. Reasons cited for alternative medication consumption was hope that it might be of some benefit to their well being or disease control, and maybe even result in a miracle cure. Sources of advice on medication were mostly from strangers (by word of mouth), family, friends, the media, and infrequently from qualified professional Chinese doctors. Reasons for discontinuing such treatment were mostly given as lack of positive effect. In conclusion, Chinese cancer patients, willingly, rampantly and non-selectively seek out and consume alternative medications, with almost total ignorance of the medication consumed, oblivious to any potential side effects, and with little subjective benefit.

Intracellular signaling of tumor necrosis factor-alpha in brain microvascular endothelial cells is mediated by a protein tyrosine kinase and protein kinase C-dependent pathway.

The intracellular signaling pathways responsible for tumor necrosis factor (TNF)-alpha stimulation of lymphocyte adhesion to brain microvascular endothelial cells (BMEC) were studied using inhibitors of protein kinase C (bisindolylmaleimide HCl, H-7, or staurosporine), or protein tyrosine kinase (genistein). Each of these blocked the ability of BMEC to respond to TNF-alpha. In contrast, BMEC treated with H-89, an inhibitor of protein kinase A, or the adenylate cyclase inhibitor, dideoxyadenosine, responded normally to TNF-alpha. Forskolin, an adenylate cyclase agonist, significantly increased lymphocyte adhesion to BMEC. These data indicate that intracellular signaling by TNF-alpha in BMEC is mediated through a protein kinase C and tyrosine kinase dependent pathway.

Differential regulation of tissue-specific lymph node high endothelial venule cell adhesion molecules by tumour necrosis factor and transforming growth factor-beta 1.

Lymphocytes migrate from blood into lymph nodes (LN) of rats specifically at segments of venules lined by high endothelium (HEV). We have previously shown that pretreatment of LN HEV cells with pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), augments their adhesiveness for thoracic duct lymphocytes (TDL). Here we report that a mouse monoclonal antibody, 3C10, recognized tissue-specific endothelial determinants on rat LN HEV cells and blocked their adhesiveness for TDL and EL-4J cells transfected with rat L-selectin. In contrast, 3C10 antibody did not inhibit lymphocyte attachment to Peyer's patch (PP) frozen sections or cultured PP HEV cells. The antibody immunoprecipitated from LN HEV cells two proteins with apparent molecular weights of 90,000 and 50,000. The expression of 3C10 antigen on LN HEV cells was increased by incubation with TNF-alpha or IFN-gamma. Furthermore, pretreatment of cytokine-stimulated LN HEV cells with 3C10 antibody blocked TDL binding in a dose-dependent manner. In contrast, 3C10 antigen expression on LN HEV cells was significantly decreased following incubation of cells with transforming growth factor-beta 1 (TGF-beta 1). In addition, TGF-beta 1 also abrogated the adhesiveness of LN HEV cells stimulated with TNF-alpha, IFN-gamma or both cytokines. Together, these data suggest that endothelial determinants recognized by the 3C10 antibody are tissue-specific ligands for lymphocyte adhesion and cytokines such as TNF-alpha and TGF-beta differentially regulate their expression and function.

Transforming growth factor-beta receptor binding and function are decreased in psoriatic dermal endothelium.

T lymphocyte adhere to dermal microvascular endothelial cells (DMEC.) as the first step in their emigration from the blood vasculature into diseased skin. Earlier studies have shown that the adhesiveness of cultured DMEC. from normal skin for lymphocytes can be blocked by transforming growth factor-beta1 (TGF-beta1). In contrast, TGF-beta1 has no effect on the adhesive properties of DMEC from psoriatic plaques, and this response is attenuated by the addition of interleukin-4 (IL-4). In the present study, we show that both TGF-beta1 and TGF-beta2, and to a lesser extent TGF-beta3 isoforms block the ability of normal but not psoriatic DMEC to bind lymphocytes. Pretreatment with TGF-beta1 selectively inhibited the tumor necrosis factor-alpha(TNF-alpha)-stimulated expression of E-selecting on normal DMEC but had no psoriatic DMEC. Scatchard analysis revealed both low- and high-affinity receptors on normal DMEC. The baseline number of high-affinity TGF-beta receptors was significantly reduced on psoriatic DMEC, whereas IL-4 treatment of DMEC altered the binding affinity but not the number of receptors. The protein and mRNA transcripts of type I and type II TGF-beta receptor genes were detectable in psoriatic DMEC. A reduction in the autophosphorylation the TGF-beta type II receptor protein, a constitutively active serine/threonine kinase, however, was detected in psoriatic DMEC. These in vitro finding suggest that reduction of TGF-beta receptor expression and function may contribute to lymphocyte infiltration into psoriatic plaques in vivo by allowing dermal microvascular endothelium to escape form the negative regulation by TGF-beta.

The intracellular signaling pathways involved in MCP-1-stimulated T cell migration across microvascular endothelium.

The adherence and transmigration of T cells through microvascular endothelium is an essential step for recruitment into inflammatory lesions, although the factors that stimulate the directional migration of T cells have not been fully characterized. In the present study we investigated the capacity of chemokines to induce migration of T cells across dermal microvascular endothelial cell monolayer. The results showed that recombinant MCP-1 significantly induced transendothelial migration of both resting and activated T cells. Maximal induction of migration was observed at a concentration of 10 ng/ml and a 3- to 4-hr incubation period. In contrast, the chemokines IL-8, RANTES, and MIP-1 alpha failed to stimulate T cell migration at doses as high as 100 ng/ml. In studies designed to investigate the intracellular signaling pathways mediating the MCP-1 effect, the results showed that MCP-1 at doses ranging from 10 to 100 ng/ml did not cause an increase in intracellular calcium ions in T cells, even though this chemokine induced rapid calcium mobilization in monocytes. Furthermore, pretreatment of T cells with either bisindolymaleimide HCl, a specific inhibitor of protein kinase C, or genistein, a protein tyrosine kinase inhibitor, significantly decreased the MCP-1-induced transmigration in a dose-dependent manner. In contrast, T cells pretreated with the protein kinase A-specific inhibitor H89 responded normally to MCP-1 stimulation. Finally, T cell transmigration was inhibited by antibodies against CD11a, thereby confirming the importance of beta 2-integrin in the transmigration process.

UVB therapy decreases the adhesive interaction between peripheral blood mononuclear cells and dermal microvascular endothelium, and regulates the differential expression of CD54, VCAM-1, and E-selectin in psoriatic plaques.

A dermal lymphocytic infiltrate is a characteristic feature of psoriasis, and may be involved in the pathogenesis of the disease. We have previously shown that specialized dermal microvascular endothelial cells (DMEC) in psoriatic lesions promote the selective adherence of the CD4 CD45Ro helper T-cell subset. In this study, we examined the adhesive interaction between peripheral blood mononuclear cells and psoriatic DMEC in patients treated with ultraviolet B light (UVB), and correlated the results with the expression and function of endothelial adhesion molecules on DMEC. Seven psoriatic patients were exposed to one MED of UVB daily for 14 days, and the binding properties of their peripheral blood mononuclear cells (PBMC), and tissue specimens taken from their lesions on days 0, 2, 3, 6, 8, 11 and 14 of UVB treatment, were studied. The ability of psoriatic PBMC to adhere to non-irradiated control or UVB-treated psoriatic plaques was reduced by 70% after treatment with 2-3 MED, and complete inhibition was obtained after 8-11 MED. In contrast, exposure of psoriatic plaques to 2-3 MED had no effect on the capacity of DMEC to support normal PBMC binding, which was only reduced after 8-11 MED. In addition, psoriatic plaques which were shielded from direct UVB exposure also showed decreased PBMC binding, suggesting a systemic effect of UVB treatment. Immunoperoxidase staining revealed that CD54 (ICAM-1) and E-selectin were strongly expressed on dermal vessels in untreated psoriatic plaques. Treatment of patients with 6-8 MED significantly decreased CD54 and E-selectin expression. In contrast, VCAM-1 expression on untreated plaques was weaker than that of CD54 and E-selectin, but was markedly induced following UVB treatment. In functional blocking studies, preincubation of tissue from untreated psoriatic plaques with anti-E-selectin antibody, but not antibodies against CD54 and VCAM-1, significantly inhibited the ability to bind normal PBMC. These observations suggest that UVB treatment interferes with the adhesive properties of both psoriatic PBMC and endothelial cells, and differentially regulates the expression of endothelial adhesion molecules. The study also provided direct evidence for the involvement of E-selectin in the adhesion of circulating lymphocytes to psoriatic endothelial cells.

Evidence of post-transcriptional regulation of L-selectin gene expression in rat lymphoid cells.

Early investigations of lymphocyte migration in the rat operationally identified a lymphocyte membrane protein, designated 'A.11', which mediates lymphocyte adherence to lymph node (LN) high endothelial venules (HEV). To determine the primary structure of A.11 and examine its expression in lymphoid cells, we constructed an expression phage cDNA library of rat thoracic duct lymphocytes (TDL) and performed screening by immunoselection (utilizing an anti-A.11 polyclonal antiserum) as well as by hybridization selection. We have isolated a approximately 1.6 kb clone, RS-2, and sequencing revealed that it encodes rat L-selectin. The clone contains the complete coding sequence, a 105-bp 5' untranslated region and a 359-bp 3' untranslated region. Transfection of RS-2 cDNA into 70Z/3 cells conferred binding to HEV concomitant with expression of A.11, providing direct evidence that A.11 is rat L-selectin. Metabolic radiolabelling studies revealed that thymocytes synthesize markedly less L-selectin than do TDL or LN lymphocytes. However, Northern blot studies using RS-2 as a probe indicate that thymocytes possess more L-selectin RNA than does TDL. Together, these data provide evidence that post-transcriptional events contribute to regulation of L-selectin expression in thymocytes.

In vitro adhesive interactions between rat lymphocytes and lacrimal gland acinar epithelium. Phenotype of adherent lymphocytes and involvement of adhesion molecules.

The selective interaction of trafficking lymphocytes with glandular epithelial cells is thought to link the lacrimal gland (LG) to the mucosal immune network. An in vitro binding assay was used to determine the phenotype of adherent cell populations and to study the involvement of lymphocyte adhesion molecules in the adherence process. Enriched B cell populations showed greater binding to LG epithelium than did enriched T cell populations. Direct phenotyping of adherent lymphocytes demonstrated that B lymphocytes (particularly IgA+ and IgG+ cells) were the predominant participants in LG binding. In vitro binding to LG acinar epithelium was inhibited by mAb with specificity for rat lymph node and Peyer's patch homing receptors and, to a lesser degree, by anti-VLA-4 and LFA-1 but not by anti-CD44 or Thy-1. In addition, the presence of rat lymph node and Peyer's patch homing receptors on endogenous LG lymphocytes was demonstrated by flow cytometry. These data show that B cells are the predominant population adhering to LG epithelium and suggest that lymphocyte homing receptors mediate the adherence process. These findings indicate that selective interactions between lymphocytes and the glandular epithelium contribute to the presence of IgA-producing cells in the LG.

Transforming growth factor-beta differentially regulates the adhesiveness of normal and psoriatic dermal microvascular endothelial cells for peripheral blood mononuclear cells.

Lymphocytes adhere to dermal microvascular endothelial cells (DMEC) as the first step in their migration from the bloodstream into diseased skin. Psoriasis is characterized by an intense T-lymphocytic infiltrate in the dermis, which may be a consequence of the abnormal regulation of endothelial adhesiveness by cytokines released locally. In the present study, we investigated the effects of tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), IL-4, and transforming growth factor-beta 1 (TGF-beta) on the adhesiveness of DMEC isolated from psoriatic plaques or normal skin for human peripheral blood mononuclear cells (PBMC). The results showed that DMEC from both normal and psoriatic skin retain the capacity to adhere to 51Cr-labeled PBMC. Pretreatment of DMEC from normal skin with human recombinant IL-1 or TNF alone or in combination for 8 h significantly (p less than 0.01) enhanced their capacity to adhere to human PBMC. Similarly, treatment of normal DMEC with IL-4 also increased endothelial adhesiveness, although this cytokine required an incubation period of 24 h. In parallel studies, DMEC from psoriatic plaques were found to respond to the stimulatory effects of TNF, IL-1, and IL-4 in similar dose- and time-dependent manner. In contrast, although pretreatment of normal DMEC with TGF-beta (0.1 to 0.25 ng/ml) for 6 to 12 h significantly reduced (p less than 0.01) both the unstimulated and IL-1- and TNF-stimulated endothelial adhesiveness for normal PBMC, TGF-beta had no effect on the binding of unstimulated or cytokine-stimulated psoriatic DMEC to PBMC, even at concentrations as high as 2 ng/ml and incubation period of 36 h. These results suggest that cytokines stimulate the adhesiveness of DMEC through distinct pathways and provide evidence that TGF-beta may play an important regulatory role in the control of lymphocyte extravasation into normal skin. The altered responsiveness of psoriatic DMEC to TGF-beta may contribute to the intense dermal lymphocytic infiltrates in psoriasis.