PubMed Health⌕ Search

Biomedical subjects

R Kain

Publications and source records attributed to R Kain.

At least 19 recordsLinked to original sources
PubMed2005

Interdigitating dendritic cell sarcoma of the parotid gland.

Interdigitating dendritic cell sarcomas (IDCSs) are extremely uncommon tumours that arise predominantly in lymphoid tissue. We report a case of an IDCS arising in the parotid gland of a 73-year-old man. Clinically, a primary salivary gland tumour was suspected but fine needle aspiration cytology suggested a soft tissue tumour. A diagnosis of IDCS was made on histopathological examination of the resection specimen, with subsequent confirmation by electron microscopy. Given the extreme rarity of this tumour at this site, it is unlikely to be a common diagnostic problem, but the importance of multiple diagnostic modalities is emphasized. The findings of cytology, histology, immunohistochemistry and electron microscopy have not previously been described together in a single case report of this tumour.

Aged↗
PubMed2004

Cryopreservation of a whole ovary as a strategy for restoring ovarian function.

PURPOSE: To evaluate whether a total ovary can successfully be cryopreserved and thawed under maintenance of high proportions of structurally normal primordial follicles. METHODS: Porcine ovaries were explanted immediately after slaughtery. Ten ovaries were cooled to -196 degrees C using cryoprotective solution and a computer-controlled freezing technique. Five contralateral ovaries were fixed with formalin for histological examination, the five remaining ovaries were directly plunged in liquid nitrogen. After three weeks of storage, frozen ovaries were thawed and examined by light and electron microscopy. Viability was assessed by evaluation of intact primordial follicles with respect to cellular and intracellular structures. RESULTS: Histological viability of primordial follicles in computer-frozen ovaries was 84.4% (76.1-90.6%), as compared to non-frozen control samples (92-100%; mean 97.6%) and to ovaries plunged in liquid nitrogen without cryoprotection 21.1% (4.5-35.0%). CONCLUSIONS: Cryopreservation of whole ovaries may present a feasible way to maintain high numbers of viable primordial follicles in ovarian tissue retransplantation.

Animals↗
PubMed2000

The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization.

Eph receptor tyrosine kinases and their ephrin ligands have been implicated in embryonic vascular development and in in vivo models of angiogenesis. Eph proteins may also regulate tumor neovascularization, but this role has not been previously investigated. To screen for Eph proteins expressed in tumor blood vessels, we used tumor xenografts grown in nude mice from MDA-MB-435 human breast cancer cells or KS1767 human Kaposi's sarcoma cells. By immunohistochemistry, the ephrin-A1 ligand and one of its receptors, EphA2, were detected throughout tumor vasculature. Double-labeling with anti-CD34 antibodies demonstrated that both ephrin-A1 and EphA2 were expressed in xenograft endothelial cells and also tumor cells. Furthermore, EphA2 was tyrosine-phosphorylated in the xenograft tumors, indicating that it was activated, presumably by interacting with ephrin-A1. Ephrin-A1 and EphA2 were also detected in both the vasculature and tumor cells of surgically removed human cancers. In an in vitro angiogenesis model, a dominant negative form of EphA2 inhibited capillary tube-like formation by human umbilical vein endothelial cells (HUVECs), demonstrating a requirement for EphA receptor signaling. These data suggest that ephrin-A1 and EphA2 play a role in human cancers, at least in part by influencing tumor neovascularization. Eph proteins may represent promising new targets for antiangiogenic cancer treatments.

Animals↗
PubMed2000

Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis.

Phage that display a surface peptide with the NGR sequence motif home selectively to tumor vasculature in vivo. A drug coupled to an NGR peptide has more potent antitumor effects than the free drug [W. Arap et al., Science (Washington DC), 279: 377-380, 1998]. We show here that the receptor for the NGR peptides in tumor vasculature is aminopeptidase N (APN; also called CD13). NGR phage specifically bound to immunocaptured APN and to cells engineered to express APN on their surface. Antibodies against APN inhibited in vivo tumor homing by the NGR phage. Immunohistochemical staining showed that APN expression is up-regulated in endothelial cells within mouse and human tumors. In another tissue that undergoes angiogenesis, corpus luteum, blood vessels also expressed APN, but APN was not detected in blood vessels of various other normal tissues stained under the same conditions. APN antagonists specifically inhibited angiogenesis in chorioallantoic membranes and in the retina and suppressed tumor growth. Thus, APN is involved in angiogenesis and can serve as a target for delivering drugs into tumors and for inhibiting angiogenesis.

Amino Acid Motifs↗
PubMed2000

Renal oncocytoma with prominent intracytoplasmic vacuoles of mitochondrial origin.

AIMS: We observed two oncocytomas with prominent intracytoplasmatic vacuoles. To investigate if this previously undescribed finding is a diagnostic feature and compatible with the diagnosis of oncocytoma, we characterized these vacuoles by electron microscopy and immunohistochemistry. METHODS AND RESULTS: The tumours were analysed by transmission electron microscopy. Immunohistochemistry was performed with antimitochondrial antibody, anti-Golgi-zone antibody, anti-lysozyme antibody and anti-human-trans-Golgi-network antibody. By electron microscopy, the vacuoles were found to be double-membrane-bounded, and some contained fragmented christae. Immunohistochemistry showed a positive reaction of the vacuoles with anti-mitochondrial antibody. Staining with anti-Golgi-zone antibody, anti-lysozyme antibody and anti-human-trans-Golgi-network antibody was negative. CONCLUSION: Both tumours are benign oncocytomas. The phenomena of cells with prominent intracytoplasmatic vacuoles is not inconsistent with the diagnosis of oncocytoma. The vacuoles are of mitochondrial origin and may develop, by balloon degeneration, as a mechanism of mitochondrial involution and elimination.

Adenoma, Oxyphilic↗
PubMed2000

The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis.

BACKGROUND: Recruitment of leukocytes during immune responses requires the coordinate expression of adhesion molecules in concert with chemokines and their receptors. The Duffy antigen receptor for chemokines (DARC) binds multiple chemokines and is expressed on postcapillary venules in the normal kidney. The chemokine receptor CCR5, which shares the ligand regulated upon activation, normal T-cell expressed and secreted (RANTES) with DARC, is expressed by infiltrating T cells in the renal interstitium. As DARC might be involved in the attraction of CCR5-positive cells, we studied the distribution of DARC and CCR5 in two forms of cell-mediated renal injury: renal allograft rejection and crescentic glomerulonephritis (cGN). METHODS: A total of 87 renal specimens, including 12 pretransplant biopsies, 47 transplant biopsies (Banff 1, N = 10; Banff 2, N = 19; and various other lesions N = 18), and 28 biopsies from patients with cGN, was analyzed. Immunohistochemistry for CCR5 and DARC was performed on serial sections of formalin-fixed and paraffin-embedded tissue. RESULTS: Compared with pretransplant biopsies, the mean number of DARC-positive interstitial venules was significantly increased during both transplant rejection and cGN. This was accompanied by an infiltration of CCR5-positive leukocytes. During transplant rejection, the number and distribution of CCR5-positive cells correlated with DARC-positive venules. Infiltrating CCR5-positive leukocytes were found mainly in the interstitium, often clustering around Bowman's capsules in biopsies from cGN. The number of glomerular CCR5 positive cells is low, but they are common in a subset of crescents. CONCLUSIONS: We hypothesize that the increased number of DARC-positive venules in areas of interstitial injury and the colocalization with CCR5-positive infiltrating leukocytes may indicate a role for endothelial DARC expression during leukocyte adhesion and interstitial infiltration.

Acute Disease↗
PubMed2000

Capillary haemangioma of the testis.

A case of testicular capillary haemangioma is reported and the importance of intraoperative examination of this very rare lesion emphasised. Capillary haemangioma of the testis can be similar to malignant testicular tumours on clinical presentation, as well as on ultrasonography and magnetic resonance imaging, and therefore should be included in the intraoperative differential diagnosis. Because of the benign nature of this lesion, conservative surgical treatment by means of tumour enucleation with preservation of the testis is possible, if intraoperative examination of frozen sections of representative tissue can be performed.

Adolescent↗
PubMed1999

Anti-cancer activity of targeted pro-apoptotic peptides.

We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. The pro-apoptotic domain was designed to be nontoxic outside cells, but toxic when internalized into targeted cells by the disruption of mitochondrial membranes. Although our prototypes contain only 21 and 26 residues, they were selectively toxic to angiogenic endothelial cells and showed anti-cancer activity in mice. This approach may yield new therapeutic agents.

Amino Acid Sequence↗
PubMed1999

[Ovarian tissue banking--primary results].

Lifelong hormone replacement therapy and infertility often follow oncological therapy in young women due to a dramatic reduction of the primordial follicle reserve. Reimplantation and function of frozen ovarian tissue slices were successfully demonstrated in animal models, but the durability is limited. Cryopreservation of a whole ovary could reestablish an almost normal ovarian function. Experiments with porcine ovaries showed histological viability. Cryopreservation and retransplantation of sheep ovaries should demonstrate success by hormonal response and pregnancy.

Animals↗
PubMed1998

Molecular cloning and expression of a novel human trans-Golgi network glycoprotein, TGN51, that contains multiple tyrosine-containing motifs.

Previously, it has been shown that glycoproteins with approximately 130-kDa molecular mass react with antisera from patients with renal vasculitis (Kain, R., Matsui, K., Exner, M., Binder, S., Schaffner, G., Sommer, E. M., and Kerjaschki, D. (1995) J. Exp. Med. 181, 585-597). To search for a molecule that reacts with the antibodies, we screened a lambdagt11 human placental cDNA library. Two of the isolated clones were found to encode a putative counterpart of the rodent trans-Golgi network (TGN) glycoprotein 38, hTGN46, which has the tyrosine containing motif YQRL shared by mouse and rat TGN38. Moreover, reverse transcription-polymerase chain reaction analysis of hTGN46 transcripts and genomic analysis of a cDNA deposited as an expressed sequence tag in dbEST Data Base revealed that additional cDNAs exist that are produced by alternate usage of 3'-splice sites of intron III. Alternative splicing results in frame shifts and leads to novel larger translation products with one (for hTGN48) or two (for hTGN51) additional tyrosine-containing motifs. hTGN51 expressed in Chinese hamster ovary cells were localized to the trans-Golgi network, overlapping with beta-1,4-galactosyltransferase even after mutating the tyrosine-containing motif common to hTGN46. In contrast, mutated hTGN48 and hTGN46 are no longer retrieved to the TGN. These results strongly suggest that hTGN51 may have a unique function compared with hTGN46 or hTGN48 in shuttling between the cell surface and the TGN.

Amino Acid Sequence↗
PubMed1997

Altered Golgi localization of core 2 beta-1,6-N-acetylglucosaminyltransferase leads to decreased synthesis of branched O-glycans.

Mucin type O-glycans with core 2 branches are distinct from nonbranched O-glycans, and the amount of core 2 branched O-glycans changes dramatically during T cell differentiation. This oligosaccharide is synthesized only when core 2 beta-1, 6-N-acetylglucosaminyltransferase (C2GnT) is present, and the expression of this glycosyltransferase is highly regulated. To understand how O-glycan synthesis is regulated by the orderly appearance of glycosyltransferases that form core 2 branched O-glycans, the subcellular localization of C2GnT was determined by using antibodies generated that are specific to C2GnT. The studies using confocal light microscopy demonstrated that C2GnT was localized mainly in cis to medial-cisternae of the Golgi. We then converted C2GnT to a trans-Golgi enzyme by replacing its Golgi retention signal with that of alpha-2,6-sialyltransferase, which resides in trans-Golgi. Chinese hamster ovary cells expressing wild type C2GnT and the chimeric C2GnT were then subjected to oligosaccharide analysis. The results obtained clearly indicate that the conversion of C2GnT into a trans-Golgi enzyme resulted in a substantial decrease of core 2 branched oligosaccharides. These results, taken together, strongly suggest that the predominance of core 2 branched oligosaccharides in those cells expressing C2GnT is due to the fact that C2GnT is located earlier in the Golgi than alpha-2,3-sialyltransferase that competes with C2GnT for the common substrate. Furthermore, alteration of Golgi localization renders the chimeric C2GnT much less efficient in synthesizing core 2 branched oligosaccharides, indicating the critical role of orderly subcellular localization of glycosyltransferases.

Animals↗
PubMed1997

[Microscopic polyangiitis with eosinophilia--an overlap syndrome or separate disease entity? A case report and review of the literature].

Systemic vasculitides are potentially life-threatening diseases. Early and appropriate diagnosis based on case history, clinico-pathological features, and laboratory parameters, such as the presence of anti-neutrophil cytoplasmic antibodies (ANCA), is crucial for starting appropriate and, often, life-saving therapeutic measures. We report a 50-year-old female patient who presented with fever, arthralgias and hemoptysis. Skin signs included disseminated hemorrhagic pustules, ulcerations of oral and genital mucosa, subcutaneous nodules on arms and legs, and a pyoderma gangrenosum-like lesion on the right leg. Laboratory investigations revealed a peripheral eosinophilia and a positive cANCA titer. Histopathologic analysis of various biopsy specimens showed a granulomatous vasculitis in the subcutis, a nongranulomatous vasculitis with massive eosinophil infiltration in the lungs, and a segmental, necrotizing glomerulonephritis in the kidneys. Differential diagnosis included Wegener's granulomatosis, microscopic polyangiitis (MPA) and Churg-Strauss syndrome. MPA was diagnosed based on clinical and histopathological criteria. An interesting feature of this case was marked peripheral and tissue eosinophilia. Therapy consisted of cyclophosphamide and methylprednisolone. The patient went into a long-lasting clinical remission one month after starting therapy.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

A novel variant of lysosomal acid lipase in cholesteryl ester storage disease associated with mild phenotype and improvement on lovastatin.

Cholesterol ester storage disease (CESD) is a rare congenital disorder of lipid metabolism, with mutation of the lysosomal acid lipase gene, causing chronic liver disease, usually before adolescence. We here describe three adult siblings with CESD diagnosed by light microscopic demonstration of excessive lysosomal storage of lipids with accumulation of foamy cells in liver biopsies and by a decrease in acid lipase activity (2-3% of controls). One patient (male, 46a) had extensive liver fibrosis, another (female, 58a) had cirrhosis of the liver. The third patient had died from variceal haemorrhage (female, 56a). Using sequence analysis of RT-PCR products of LAL mRNA, the patients were identified as compound heterozygotes for a G-->A substitution at position -1 of the exon 8 splice donor site and a point mutation at the second allele, resulting in a His108-->Pro shift. In two patients, therapy with lovastatin was initiated, which led to normalisation of serum cholesterol and triglyceride levels. After 12 months, liver biopsy demonstrated a significant decrease in vacuolisation of hepatocytes, with fewer and smaller droplets. Semi-automated computer-assisted image analysis of electron microscopic sections demonstrated a decrease in the hepatocellular lysosomal area from 20.5+/-7.1% to 11.7+/-6.5% (p<0.05) and 41.7+/-5.1% to 33.4+/-4.4% (p<0.01). We conclude that in two siblings with a novel LAL variant and mild phenotype of CESD, lovastatin decreased both serum lipid concentrations and hepatocellular lysosomal content.

Anticholesteremic Agents↗
PubMed1995

A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells.

Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a different, structurally related 130-kD membrane protein on the cell surface of renal microvascular endothelial cells are autoantigenic targets for ANCA in patients with active NCGN.

Amino Acid Sequence↗
PubMed1994

[Ultrasound-guided fine-needle biopsy with an automatic full-incision system: the initial experiences and comparison with a conventional biopsy gun].

The purpose of this study was to evaluate the efficacy of a new automatic biopsy device (Autovac, Angiomed, Karlsruhe, Germany) in ultrasound (US) guided biopsies of focal abdominal lesions. 50 consecutive patients with focal abdominal lesions underwent US guided biopsies. In the first 24 patients, needle passes were performed with the Autovac system (outer diameter 0.95 mm) as well as with the Biopty gun (outer diameter 0.9 mm) (Bard Covington, USA). The size and the quality of the histologic and the cytologic material obtained by both systems were evaluated by histopathologists blinded to the system used. Autovac yielded significantly more material (defined as the area of the obtained tissue cores) and a significantly higher quality score than did the Biopty system. 96% of the histologic specimen and 100% of the cytologic smears obtained with Autovac were diagnostic, compared to 70 and 81% with Biopty, respectively. With the exception of a short-time elevation of the blood pressure in one patient, no complications occurred. The results indicate an advantage of the automatic full-cut type system Autovac over the tru-cut type Biopty gun in US-guided biopsies of focal abdominal lesions.

Abdomen↗