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Biomedical subjects

N Tanda

Publications and source records attributed to N Tanda.

17 recordsLinked to original sources
PubMed2000

Expression of apoptotic signaling proteins in leukoplakia and oral lichen planus: quantitative and topographical studies.

Although the pathogenesis of leukoplakia has been unclear, carcinogenic transformation is postulated to result from alterations of apoptotic signal transduction proteins in epithelial cells. The pathogenesis of oral lichen planus (OLP) has also been unclear, but apoptotic changes of the epithelial cells in OLP have been reported. In the present study, we used a histochemical approach to describe human keratinocyte-expression of several apoptotic signaling proteins in leukoplakia, in OLP, and in normal oral mucosa as a control. Mucosal biopsies from patients with leukoplakia (n=13), OLP (n=10), and normal oral mucosa (n=9) were frozen, sectioned and immunostained with monoclonal antibodies to wild-type (wt) tumor suppressive protein p53, cyclin-dependent kinase inhibitor p21WAF1/CIP1 and the oncoproteins MDM2, and Bcl-2. Apoptosis was assessed in all cases by the TUNEL method. MDM2 and Bcl-2 expression in keratinocytes were quantitatively greater in leukoplakia than in OLP. Wt-p53 and p21WAF1/CIP1 expression was quantitatively greater in keratinocytes in OLP than in leukoplakia. Keratinocyte maturation appeared histologically normal in OLP, even though wt-p53 and p21WAF1/CIP1 were expressed in these cells. Altered keratinocyte maturation was seen in leukoplakia lesions expressing MDM2 and Bcl-2. No significant difference for the number of apoptotic epithelial cells was observed between leukoplakia and OLP, in spite of the divergent outcomes of the apoptotic signaling proteins.

Adult↗
PubMed2000

Immunolocalizaiton of c-Myc and bcl-2 proto-oncogene products in gingival hyperplasia induced by nifedipine and phenytoin.

BACKGROUND: Hyperplastic gingival tissues show the histopathological characteristics of thick parakeratinized squamous epithelia with acanthosis and rete pegs elongated into the lamina propria. However, the pathogenic factors that contribute to the epithelial morphogenesis of this disease are obscure and remain to be studied. METHODS: We immunohistochemically examined the expression of both c-Myc and bcl-2 oncoprotein, which can exert influence on the epithelial morphogenesis and homeostasis, in 12 hyperplastic gingival tissues induced by nifedipine and phenytoin as well as 5 control tissues using avidin-biotin-peroxidase complex methods. RESULTS: Four specimens out of 5 nifedipine-induced and 5 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of c-Myc oncoprotein, whereas no significant immunostaining of c-Myc oncoprotein was found in 5 control tissues. The c-Myc oncoprotein-positive cells were observed to be localized in the basal and suprabasal cell layers of the hyperplastic gingival epithelia. Although all of the 12 hyperplastic gingival epithelia showed the distribution of bcl-2 oncoprotein in the basal and suprabasal layer cells, in 5 control epithelia the bcl-2 oncoprotein expression was slight and confined to the basal layer cells. CONCLUSIONS: The results of our present study indicate that the synergistic overexpression of c-Myc and bcl-2 oncoprotein may be related to the pathogenesis of gingival hyperplasia induced by nifedipine and phenytoin, especially to the morphogenesis of hyperplastic epithelia.

Adolescent↗
PubMed1999

Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin.

BACKGROUND: Although it has been thought that drug-induced gingival hyperplasia is not related to tumorigenesis, recent case reports have shown that squamous cell carcinomas may arise in gingival hyperplasia induced by cyclosporin and phenytoin. The possible implications between the pathogenesis of this disease and tumorigenesis have not been elucidated and remain to be studied. METHODS: We immunohistochemically examined the expression of tumor-related markers such as p53 protein and Ki-67 antigen in 11 hyperplastic gingival tissues induced by nifedipine and phenytoin, as well as 5 control tissues using an avidin-biotin-peroxidase complex method. RESULTS: Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of p53 protein in the nuclei of epithelial cells, while no expression of p53 protein was observed in the epithelia of the 5 non-hyperplastic control tissues. The immunoreactions against p53 protein showed sporadic distribution in the suprabasal layers of hyperplastic epithelia. The mean percentage of epithelial cells expressing Ki-67 antigen in the hyperplastic gingival tissues was more than 10% higher than that in the controls. The expression of Ki-67 antigen was suppressed in the typical rete pegs deeply elongated into lamina propria of hyperplastic gingival tissues. Intense immunostaining of Ki-67 antigen was found in fibroblasts of hyperplastic gingival tissues, while that of the control tissues was negligible. CONCLUSIONS: The expression of p53 protein in gingival hyperplasia suggests that the pathogenesis of this disease is involved with impaired DNA, while the growth arrest observed in the hyperplastic epithelia with typically elongated rete pegs as expressed with Ki-67 antigen may prevent the invasive expansion of epithelial cells undergoing DNA damage within gingival tissues and may consequently suppress tumorigenic progression.

Adolescent↗
PubMed1998

A novel evaluation system of metastatic potential of oral squamous cell carcinoma according to the histopathological and histochemical grading.

We established a new evaluation system for metastatic potential of oral squamous cell carcinoma (SCC), utilizing a combined examination of histopathological grades of the carcinomas based on cell differentiation and invasive mode according to Yamamoto's criteria, and the cellular expressions of CD44, E-cadherin (E-cad), heparan sulfate glycosaminoglycan (HS-GAG) and Phaseolus vulgaris leukoagglutinin (L-PHA)-binding oligosaccharides on the carcinomas. Histochemical patterns of expression of these markers were classified into positive (+2), weakly positive (+), and negative (-). The histopathological grades and the histochemical patterns of the SCC were estimated on a 0-2 point scale, i.e. point 2 for poorly differentiated, mode 4D, CD44++, E-cad-, HS-GAG++, or L-PHA++; point 1 for moderately differentiated, mode 4C, CD44+, E-cad+, HS-GAG+, or L-PHA+; and point 0 for well differentiated, mode 1, mode 2, mode 3, CD44-, E-cad++, HS-GAG-, or L-PHA-. As a result, incidence of metastasis in the cases with a total score of more than 6 (62.8%) was significantly higher than that with a total score of less than 5 (9.3%). This evaluation system will yield useful information concerning the prognosis of patients with oral SCC.

Biomarkers, Tumor↗
PubMed1998

IL-1 beta and IL-6 in mouse parotid acinar cells: characterization of synthesis, storage, and release.

Synthesis, storage, and secretion of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) and the anti-inflammatory cytokine IL-6 have not been established in normal exocrine gland secretory cells. Parotid glands and isolated acinar cells prepared from BALB/c mice were homogenized for RNA isolation and reverse transcription-polymerase chain reaction (RT-PCR). IL-1 beta and IL-6 enzyme-linked immunosorbent assays (ELISAs) were done on supernatants prepared from mouse parotid acinar cell (MPAC) preparations unstimulated or stimulated between 0 and 10 min with 10(-5) M norepinephrine at 37 degrees C. MPACs were fixed in paraformaldehyde, frozen sectioned for light and electron microscopy, and labeled with antibodies to IL-1 beta and IL-6. Mouse specific riboprobes to IL-1 and IL-6 were used for in situ hybridization. RT-PCR yielded the expected IL-1 (336-bp) and IL-6 (614-bp) mRNA products. By ELISA, stimulated MPACs showed a significant increase in IL-1 beta (P < 0.03) and IL-6 (P < 0.01) release into supernatants by 10 min that paralleled the time course of amylase release. In situ hybridization showed the presence of transcripts for IL-1 and IL-6 in glandular epithelial cells. Gold-labeled IL-1 beta and IL-6 were significantly higher (P < 0.01) in granules than in the nucleus and cytoplasm. This study shows that MPACs synthesize IL-1 beta and IL-6 and release these cytokines from their granules after alpha- and beta-adrenergic stimulation.

Amylases↗
PubMed1997

Expression of the JNK2-alpha1 gene in the developing chick brain.

We have isolated chicken JNK2-alpha1 encoding a c-Jun N-terminal kinase, and examined the expression during embryogenesis. The kinase domain sequence is well conserved between chicken and mammals, but carboxy-terminal sequence of JNK is divergent from subtype 1 and 2, possibly derived from alternative splicing. The JNK2-alpha1 gene is preferentially expressed in the neuroepithelium of developing brain at stages 16-26, and transcripts are not detectable in the other region including spinal cord. These results suggest that JNK2-alpha1 is involved in development of the central nervous system as a mediator of stress-activated protein kinase pathway conferring competence to the external stimuli such as growth factors.

Amino Acid Sequence↗
PubMed1997

Changes in glomerular epithelial cells induced by FGF2 and FGF2 neutralizing antibody in puromycin aminonucleoside nephropathy.

In the present study, two series of experiments were done with PAN nephropathy rats given fibroblast growth factor 2 (FGF2) or FGF2 neutralizing antibodies. In the first series of experiments, a dose of 10 micrograms of FGF2 (FGF2 group), 40 micrograms of an FGF2 neutralizing antibody (Anti-FGF2 group) or an equal volume of physiological saline (Control group) was administered for four days after PAN injection. Urinary protein increased more in the FGF2 group than in the other two groups. PCNA (+) glomerular cells were found in decreasing order in groups FGF2, Control and Anti-FGF2. Most of the PCNA (+) cells were podocytes and epithelial cells of Bowman's capsule. Staining for desmin, a marker of podocyte injury, was significantly reduced in the Anti-FGF2 group. Glomerular adhesive lesions were found in decreasing order in groups FGF2, Control and Anti-FGF2. The second series of experiments was designed to study the effects of FGF2 neutralizing antibody (40 micrograms for 5 days after PAN injection, in MoAb group) on severely damaged podocytes caused by repeated (two courses) injections in the PAN nephropathy rats. The results were the same as those in series 1. An increase in urinary protein excretion was observed in both groups, but on the 40th day, the level of proteinuria in the MoAb group decreased abruptly. It was observed that the MoAb group had few adhesive glomeruli compared to the IgG group (administration of mouse IgG) and the PCNA (+) epithelial cells of Bowman's capsule were also few. It was supposed that FGF2 would promote the formation of adhesive lesions by stimulating the proliferation of podocytes and epithelial cells of Bowman's capsule. Additionally, FGF2 itself was thought to impair podocytes because of the increasing desmin score and proteinuria.

Animals↗
PubMed1997

Immunocytochemical localization of chymase to cytoplasmic vesicles after rat peritoneal mast cell stimulation by compound 48/80.

The subcellular events responsible for release of mediators by mast cells may help to clarify roles for mast cells in health and disease. In this study we show that the granule-associated protease chymase is also within cytoplasmic vesicles in appropriately stimulated rat peritoneal mast cells. Rat peritoneal mast cells were recovered before or 1-10 sec after exposure to the secretogogue compound 48/80 (10 micrograms/ml) and then were examined by radioimmunoassay to quantify histamine release or were processed, using routine methods for postembedding immunoelectron microscopy, to identify the subcellular localization of chymase. In comparison to unstimulated cells, compound 48/80 stimulated cells in two independent experiments showed an increase (15%, 28%) in the surface area of the cell and a decrease (12%, 6%) in the surface area of the total granule compartment before degranulation channel formation. These global cellular changes occurred in a background of transient but significant (p < 0.01) increases in the area and number of chymase-immunoreactive vesicles per microns2 cytoplasm. These changes were detectable at 5 or 7 sec after stimulation with compound 48/80 but returned to near prestimulation levels by 9 or 10 sec after addition of compound 48/80 (total cumulative histamine release was 28% by 8 sec and 47% by 14 sec). These observations suggest that vesicles participate in the early stages of regulated secretion of chymase from rat peritoneal mast cells.

Animals↗
PubMed1996

Expression of Phaseolus vulgaris leukoagglutinin-binding oligosaccharides in oral squamous cell carcinoma: possible association with the metastatic potential.

The expression of -GlcNAc beta 1-6Man-(beta 1-6) branched oligosaccharides in carcinoma cells has been considered to influence their metastatic potentials. In the present paper, the lectin histochemistry of oral squamous cell carcinomas obtained in biopsy from 34 patients with Phaseolus vulgaris leukoagglutinin (L-PHA), which potentially binds to N-glycosidic carbohydrates with beta 1-6 linked lactosamin antennae, was studied in order to analyze the relationship between their staining patterns and metastases. The L-PHA-binding oligosaccharides of the carcinomas were expressed on the cell surface in the following patterns: (i) all cells were positive for the staining ('positive'); (ii) some cells were positive but the rest of the carcinoma cells were negative ('weakly positive'); and (iii) all were negative ('negative'). Statistical analysis revealed that the incidence of the metastasis to regional lymph nodes in the 'positive' cases was significantly higher than that in the 'negative' cases. Moreover, the number of the CD14 positive cells including macrophages in the stroma adjacent to the carcinomas in the 'positive' cases was less than that in the 'negative' or 'weakly positive' cases. The expression of L-PHA-binding oligosaccharides in oral squamous cell carcinoma may be responsible for their metastatic potential to regional lymph nodes, possibly including their ability to escape macrophage recognition.

Carcinoma, Squamous Cell↗
PubMed1996

BMP signaling during bone pattern determination in the developing limb.

To examine the role of BMP signaling during limb pattern formation, we isolated chicken cDNAs encoding type I (BRK-1 and BRK-2) and type II (BRK-3) receptors for bone morphogenetic proteins. BRK-2 and BRK-3, which constitute dual-affinity signaling receptor complexes for BMPs, are co-expressed in condensing precartilaginous cells, while BRK-1 is weakly expressed in the limb mesenchyme. BRK-3 is also expressed in the apical ectodermal ridge and interdigital limb mesenchyme. BRK-2 is intensely expressed in the posterior-distal region of the limb bud. During digit duplication by implanting Sonic hedgehog-producing cells, BRK-2 expression is induced anteriorly in the new digit forming region as observed for BMP-2 and BMP-7 expression in the limb bud. Dominant-negative effects on BMP signaling were obtained by over-expressing kinase domain-deficient forms of the receptors. Chondrogenesis of limb mesenchymal cells is markedly inhibited by dominant-negative BRK-2 and BRK-3, but not by BRK-1. Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant-negative forms of BRK-2 and BRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.

Amino Acid Sequence↗
PubMed1995

A chicken Wnt gene, Wnt-11, is involved in dermal development.

We have isolated a new member of the Wnt gene family, Wnt-11, from chick embryo cDNA library and examined the expression pattern during embryogenesis by in situ hybridization. The Wnt-11 gene encodes Cys-rich secretory protein distantly related to Wnt-1 through Wnt-8 from the mouse and Xenopus. Expression of the Wnt-11 gene became evident at stage 14 in the dorsolateral region of somites and gradually restricted to the dermatome at stage 19 and later. In contrast to the other Wnt genes, Wnt-11 was not expressed in the neuroepithelium throughout stages 14-26. At stage 24 and later, Wnt-11 was expressed in the subectodermal mesenchyme of the limb and feather buds. The unique expression pattern of Wnt-11 in the paraxial mesoderm and dermatome suggests that Wnt-11 may play an important role in dermal development.

Amino Acid Sequence↗
PubMed1995

Expression of the hepatocyte growth factor gene during chick limb development.

It has been shown that mirror-image duplications of the zeugopodia and digits are formed when MRC-5 fibroblasts producing hepatocyte growth factor (HGF) are applied to the anterior region of the chick limb bud (Yonei et al. [1993] Dev. Biol. 160:246-253). To evaluate the role of HGF in limb development, we observed the expression pattern of the HGF gene using in situ hybridization. The HGF gene was expressed in the mesoderm of the limb bud and in the central core region of mandibular arch and maxillary processes at stages 17 to 24. When both wing and leg buds begin to extend distally, the HGF gene is expressed in the mesenchymal cells, but not in the ectodermal cells and somites. Concomitant with establishment of the apical ectodermal ridge, distal mesenchymal cells of the limb bud express the HGF gene intensely with a gradient higher in the distal region. The HGF expression is later confined to the ventral and subapical mesenchyme of the limb bud, although no signal is detectable in the apical and non-ridge ectoderm. However, signal for the c-met proto-oncogene encoding the HGF receptor is not detectable in the limb bud at stages 17 to 24. These results suggest that HGF produced in the limb mesoderm may be involved in initial induction and maintenance of the apical ectoderm during limb development.

Animals↗
PubMed1995

Cloning and characterization of Wnt-4 and Wnt-11 cDNAs from chick embryo.

We have isolated two members of the Wnt gene family, Wnt-4 and Wnt-11, from chick embryo cDNA library, and determined the entire coding sequences. The Wnt-4 and Wnt-11 genes encode secretory proteins composed of 351 and 354 amino acids, respectively, both having 24 Cys residues conserved among other Wnt family members. Alignment of the deduced amino acid sequences reveals that chicken Wnt-4 and Wnt-11 are most similar to Xenopus Wnt-4 and mouse Wnt-11; respectively. Northern blot analysis indicates the Wnt-4 expression at 1.5 kilobase and the Wnt-11 expression at 2.0 kilobase in the chick embryo.

Amino Acid Sequence↗
PubMed1994

Regional expression of the Cwnt-4 gene in developing chick central nervous system in relationship to the diencephalic neuromere D2 and a dorsal domain of the spinal cord.

Members of the Wnt gene family code for cysteine-rich, secreted proteins, which are differentially expressed in the developing brain and possibly act as an intercellular signaling molecule. A Wnt gene, e.g., Wnt-1 is known to be essential for specification of the midbrain cell fate. Since other members of the Wnt genes are likely to be also involved in development of the brain, we searched chick Wnt members expressing in specific domains of the brain. We found several novel Wnt members expressing specifically in the central nervous system of chick embryos. One of the genes was intensely expressed in a segment of the diencephalon at stages 14 and 20 and in a dorsal region of the spinal cord at stage 20. Although the expression patterns differ from those of mouse or Xenopus Wnt-4, the gene is highly homologous to the mouse or frog Wnt-4. Thus, we designated the gene as Cwnt-4 (chick Wnt-4). Our results suggested that Cwnt-4 is involved in segmentation of the forebrain into the neuromere D2 and in differentiation of the dorsal region of the spinal cord.

Amino Acid Sequence↗
PubMed1988

Sialolithiasis of a Blandin's gland duct.

A case of sialolithiasis in a Blandin's gland duct is reported. Although minor salivary glands calculi are not uncommon, Blandin's glands are rare sites of occurrence. In this case, a calculus without decalcification is reported. Not only clinico-pathological features but also electron probe micro analyzer plus energy dispersive X-ray spectroscopy studies are presented. These studies reveal that phosphorus is contained in only the basophilic part of the calculus and sulphur in both the basophilic and the eosinophilic parts.

Adult↗