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Biomedical subjects

J Pawade

Publications and source records attributed to J Pawade.

16 recordsLinked to original sources

Expression of RND proteins in human myometrium.

RHO GTPases are key regulators of the actin cytoskeleton and stress fiber formation. In the human uterus, activated RHOA forms a complex with RHO-associated protein kinase (ROCK) which inhibits myosin light chain phosphatase (PPP1R12A), causing a calcium-independent increase in myosin light chain phosphorylation and tension (Ca2+ sensitization). Recently discovered small GTP binding RND proteins can inhibit RHOA and ROCK interaction to reduce calcium sensitization. Very little is known about the expression of RND proteins in the human uterus. We tested the hypothesis that the uterine quiescence observed during gestation is mediated by an increase in RND protein expression inhibiting RHOA-ROCK-mediated PPP1R12A phosphorylation. Immunohistochemistry and immunoblotting were used to determine RHOA and RND protein expression and localization in nonpregnant, pregnant nonlaboring, and laboring patients at term and patients in spontaneous preterm labor. Changes in protein expression estimated by densitometry between different patient groups were measured. A significant increase of RND2 and RND3 protein expression was observed in pregnant relative to nonpregnant myometrium associated with a loss of PPP1R12A phosphorylation. RND transfected myometrial cells demonstrated a dramatic loss of stress fiber formation and a "rounding" phenotype. RND upregulation in pregnancy may inhibit RHOA-ROCK-mediated increase in calcium sensitization to facilitate the uterine quiescence observed during gestation.

Adult↗

The potential role of serology in diagnosing chronic lymphogranuloma venereum (LGV): a case of LGV mimicking Crohn's disease.

We present the case of a 26 year old HIV positive homosexual man who was managed for suspected Crohn's disease for over 1 year before lymphogranuloma venereum (LGV) was clinically diagnosed. He had presented with constipation, secondary to acute haemorrhagic proctitis, and subsequently had two chlamydia negative rectal smears, using direct fluorescent antibody (DFA) Chlamydia trachomatis staining. Positive chlamydial serology guided retrospective testing of an early rectal biopsy, which was found to have C trachomatis by polymerase chain reaction (Roche Cobas) and identified as LGV serovar L2 by the Sexually Transmitted Bacteria Reference Laboratory (STBRL), Health Protection Agency (HPA), Colindale, London. Chlamydial serology may have a role in identifying late stage LGV infection. Although no standardised test currently exists, consideration should be given to evaluating the role of chlamydial serology in establishing a diagnosis of LGV.

Adult↗

TNFalpha polymorphism frequencies in HPV-associated cervical dysplasia.

OBJECTIVES: Persistent high-risk HPV infection of the uterine cervix is associated with CIN and cervical carcinoma. Women with a reduced pro-inflammatory response to HPV are likely to be susceptible to viral persistence, and therefore, potentially more vulnerable to cervical neoplasia. In this study, we investigate whether nucleotide sequence polymorphisms in the TNFalpha (TNFSF2) gene (which can modify gene transcription up to 9-fold) might influence susceptibility to, or evolution of, CIN. METHODS: Induced heteroduplex analysis was used to identify polymorphisms at positions TNFalpha -308 and -238 in women with normal cervical cytology and with cervical disease. Patients with low-grade disease were HPV typed using general primer GP5+/6+ PCR/EIA and reverse line blotting, and were reassessed for disease status at 6 and 24 months. RESULTS: CIN patients as a group had a significantly higher frequency of TNFalpha -308 low-secretor genotypes (GG) compared to controls, and this effect was most pronounced in the CIN1 group (P = 0.01 and P = 0.004, respectively). TNFalpha polymorphism frequencies at position -238 were similar for patients and controls. Neither polymorphism was associated with the presence of HPV infection at recruitment or disease outcome at 6 or 24 months. CONCLUSIONS: These findings support the hypothesis that susceptibility to CIN is influenced by TNFalpha -308 polymorphism.

Female↗

Idiopathic hypereosinophilic syndrome associated with cutaneous infarction and deep venous thrombosis.

We report a case of idiopathic hypereosinophilic syndrome (HES) presenting with cutaneous infarction and subsequent extensive deep vein thrombosis. The eosinophilia improved dramatically with systemic corticosteroid therapy. A variety of skin disorders have been associated with HES, although there are no previous reports of HES associated with cutaneous infarction. HES is a rare disorder characterized by a sustained overproduction of eosinophils and multisystem disease. The aetiology of the eosinophilia remains uncertain but clonal populations of abnormal T-cells producing interleukin 5 may be implicated.

Adult↗

Primary pleural lymphomas.

Two patients are presented with primary low grade pleural B cell lymphomas with no history of a pyothorax.

Asbestos↗

Cutaneous presentation of steroid responsive blastoid natural killer cell lymphoma.

CD56+ lymphomas derived from natural killer (NK) cell lineage are rarely encountered in Western populations and their clinical and pathological features have not been fully defined. The majority of reported cases are lymphomas of the nasal cavity, which are most commonly seen in Asia. A subtype of CD56+ lymphoma has recently been described (blastoid NK-cell lymphoma) which characteristically presents in older patients with cutaneous infiltrates and disease at other nodal and extranodal sites. We describe a case that correlates well with the clinicopathological features of blastoid NK-cell lymphoma. An unusual feature in our patient was that the cutaneous features of the lymphoma showed complete resolution shortly following commencement of oral steroid therapy.

Aged↗

B-cell (CD79a+) lymphoma affecting the tarsal joint synovia in a sheep.

A lymphoma affecting the synovia was identified in both tarsal joints of an aged sheep. With a panel of cross-reactive antibodies specific for lambda and kappa immunoglobulin light chain, MHC class II, CD3, CD79a and the Ki-67 antigen, the neoplasm was classified as a B-cell lymphoma with uniform expression of surface membrane CD79a. This would seem to be the first report of a lymphoma affecting the synovia in a domestic animal, and the first use of the CD79a reagent on ovine tissue.

Animals↗

Low-grade B-cell lymphomas of the splenic marginal zone: a clinicopathological and immunohistochemical study of 14 cases.

We have studied 14 cases of low-grade, splenic marginal zone, B-cell non-Hodgkin's lymphoma. The clinical presentation in all cases was with splenomegaly and, in 10 cases, circulating neoplastic lymphoid cells in the peripheral blood with involvement of bone marrow. In all cases the splenic white pulp was hyperplastic with expansion of marginal zones and varying degrees of infiltration of germinal centres by neoplastic cells. The cells were a mixture of medium sized lymphocytes with moderate amounts of cytoplasm and finely dispersed nuclear chromatin, together with occasional blast cells with small nucleoli. Satellite red pulp aggregates of tumour cells centred on small epithelioid cell clusters were seen in all cases. These appear to be a characteristic and diagnostically important feature of splenic marginal zone lymphoma. The tumour cells expressed CD20, CD45RA, bcl-2 and the antigens detected by MB2. All cases expressed IgM with light chain restriction. In addition, IgD was expressed in four cases. The follicular dendritic cell network was disrupted in those follicles which were infiltrated by tumour cells. A network of stromal myoid cells, at the periphery of the marginal zone, identified by expression of alpha-smooth muscle actin, was preserved. Alpha-smooth muscle actin positive dendritic cells were also seen within and around satellite tumour nodules in the red pulp.

Aged↗

Primary lymphoma of the ampulla of Vater.

A 57-year-old woman was investigated for obstructive jaundice with endoscopic retrograde cholangiopancreaticography that showed a tumor at the ampulla of Vater. A Whipple's procedure was performed. A protuberant tumor was present at the ampulla of Vater in the background of multiple mucosal polyps in the duodenum. Light microscopy revealed a diffuse non-Hodgkin's lymphoma with centrocytelike cells forming lymphoepithelial lesions and infiltrating the sphincter of Oddi. The duodenal polyps were hyperplastic lymphoid follicles with reactive germinal centers. Immunohistochemical staining characterized the tumor as a B-cell neoplasm with IgA heavy-chain and lambda light-chain restrictions. Complete remission of the disease occurred after surgery. The clinical, histologic, and immunohistochemical features of this lymphoma are suggestive of histogenetic derivation from mucosal-associated tissue.

Ampulla of Vater↗

Cystic hamartoma of the renal pelvis.

We describe three hitherto undocumented cases of renal lesion in the adult age group that share a similar site and histological features. They are three adult women, with a short clinical history of pain and an abdominal mass. A partial or complete nephrectomy resulted in clinical cure. All cases showed an intrarenal multicystic mass situated adjacent to the pelvicalyceal system. These vaguely circumscribed lesions had no true capsule and blended in with the adjacent renal parenchyma. The histological appearance was distinctive and characterised by disorderly biphasic proliferation of epithelial and mesenchymal elements. The epithelial component consisted of tubules and cysts lined by cuboidal and columnar epithelium showing focal oncocytic changes. The stroma was cellular and predominantly fibroblastic with scattered bundles of smooth muscle cells. Despite extensive sampling, blastemal cells were not identified. The tubular epithelium was positive for CAM 5.2, epithelial membrane antigen, carcinoembryonic staining, and vimentin immunostaining. The stroma stained positively for vimentin and smooth muscle bundles for alpa smooth muscle actin and desmin. The cytological appearances of these lesions were benign. We propose that these are benign hamartomatous lesions arising as a result of faulty focal embryogenesis. They are distinct from well recognised lesions such as multilocular cysts, partially differentiated nephroblastomas, mesoblastic nephromas, and nephrogenic adenofibromas.

Adult↗

Lymphomas of mucosa-associated lymphoid tissue arising in the urinary bladder.

The clinical, histological and immunohistochemical findings in five primary lymphomas of the urinary bladder are reported. One patient had both lymphoma and transitional cell carcinoma of the bladder. All of the lymphomas showed histological features of mucosa-associated lymphoid tissue (MALT) lymphomas with centrocyte-like cells in all cases. One patient with pre-existing cystitis glandularis showed lymphoepithelial lesions. Biopsies from four patients contained reactive germinal centres and, in two of these, there was follicular colonization by tumour cells. In three patients, repeat biopsies, over several years, showing the changes of MALT lymphoma, were diagnosed as cystitis. We suggest that a large proportion of primary lymphomas of the bladder are lymphomas of MALT and that the characteristic morphological and immunohistochemical features of these tumours should be sought in biopsies containing large numbers of lymphoid cells.

Adult↗