PubMed Health⌕ Search

Biomedical subjects

H Kamma

Publications and source records attributed to H Kamma.

At least 19 recordsLinked to original sources
PubMed2005

MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.

Adenocarcinoma↗
PubMed2004

Production of CA125 by human lung cancer cell lines.

CA125, which until recently was considered an ovary specific tumor marker, is elevated in the serum of patients with many pathological conditions, including lung cancer. In order to investigate the production of CA125 by human lung cancer cell lines, cell culture and immunochemical staining were performed in three cell lines. Our results showed the cell surface expression of CA125 in both adenocarcinoma and large cell carcinoma cell lines and the production of CA125 in culture medium. This is considered as evidence for in vitro production of CA125 by human lung cancer, and suggests that CA125 elevation is not only the result of ovarian cancer but may be due to other pathological conditions, including lung cancer.

Biomarkers, Tumor↗
PubMed2003

hnRNP B1 expression in benign and malignant lung disease.

Evidence is accumulating to suggest that hnRNP B1 expression may be a useful tool in the early diagnosis of lung cancer. This study examined the immunohistochemical expression of hnRNP B1 in archived sections of resected lung cancers and compared the patterns of expression with those seen in similar archived sections of non-neoplastic lung. Particular attention was paid to the expression of hnRNP B1 in the benign bronchial cells in both cases, to establish if overexpression of this protein in respiratory epithelial cells is specific for malignancy. Nineteen cases of different types of non-small cell carcinoma were examined (eight squamous cell, six adenocarcinomas, two carcinosarcomas, two undifferentiated large cell carcinomas, and one mucoepidermoid carcinoma) and compared with sections from 16 open lung biopsies (three cases of cryptogenic fibrosing alveolitis, two cases of sarcoidosis, two cases of organizing pneumonia, and one case each of tuberculosis, extrinsic allergic alveolitis, non-specific interstitial pneumonitis, pneumocystis pneumonia, aspergilloma, respiratory bronchiolitis-interstitial lung disease, mineral dust disease, Sjögren's syndrome and systemic sclerosis vascular variant). All the tumours showed positive staining, with the vast majority, 16/19 (84%), showing strong diffuse nuclear staining. The background cells of these cases showed positive staining in alveolar macrophages, lymph node germinal centres, bronchial mucous glands, and bronchial epithelial cells. No significant difference was seen in the percentage of positive bronchial epithelial cells in bronchi adjacent to the tumour compared with the resection margins. In the benign lung cases, positive bronchial epithelial cells were seen in a small percentage, 3/16 (18%), of cases, but the majority of cases showed no or very focal staining. The levels of expression between benign epithelial cells of malignant cases, compared with benign, showed a significant difference when the staining was assessed in percentage of positive nuclei (p = 0.001, Fisher's exact test). The results confirm that hnRNP B1 is widely expressed in a range of lung carcinomas; that expression is seen in benign bronchial epithelial cells and inflammatory cells; and that expression in background bronchial epithelial cells appears to be higher in malignant than in benign lung disease. It is feasible that this biomarker may be of use in the detection of early lung cancer, provided that levels of expression can be accurately quantified.

Adenocarcinoma↗
PubMed2003

HnRNP A2/B1 proteins in nontumorous alveolar cells.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1, had been reported to detect preclinical lung cancer for early detection. In order to examine whether the expression of the protein is specific for lung cancer, we investigated the expression of the protein in human nonmalignant alveolar cells. Human airway cells obtained by bronchoalveolar lavage (BAL) were analyzed by immunostaining and Western blotting using monoclonal antibodies 4G8 (specifically reacts to A2) and 2B2 (specific to B1). In alveolar cells obtained by BAL, hnRNP A2/B1 proteins were localized primarily in the nucleus, excluding the nucleolus, although the expression of A2 protein was weaker than that of B1 protein. Staining pattern of these cells was similar to those observed in cancer cells. Western blotting with 4G8 and 2B2 demonstrated expression of A2 and B1 proteins in the airway cells. HnRNP A2/B1 proteins were apparently expressed in nonmalignant alveolar cells as well as cancer cells, although the expression in alveolar cells was weaker than that of cancer cells. More quantitative determination of A2/B1 is required to elucidate their significance in early lung cancer detection.

Adult↗
PubMed2003

Imbalance between apoptosis and telomerase activity in myelodysplastic syndromes: possible role in ineffective hemopoiesis.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats. The hnRNP B1 is a marker for early cancer. The aim of our study was to clarify the relationships between prognosis and apoptosis, telomerase activity (TA) and hnRNP expression in the bone marrow. The subjects were 51 patients with MDS, including patients with refractory anemia (RA) (n = 32), refractory anemia with ringed sideroblasts (RARS) (n = 1), refractory anemia with excess blasts (RAEB) (n = 7), refractory anemia with excess blasts in transformation (RAEB-t) (n = 8) and chronic myelomonocytic leukemia (CMMoL) (n = 3). We also studied 6 cases with acute myelogenous leukemia (AML) arising from MDS (AML-MDS) and 10 control subjects. Bone marrow biopsies were stained immunohistochemically for caspase-3 (marker of apoptotic activity) and human telomerase reverse transcriptase (hTERT), and hnRNP B1. Fatal pancytopenia was the cause of death in 19 of the 51 patients. The caspase-3 positive cell rate was higher in MDS (16.3%) than in controls (4.4%) and AML-MDS (0.5%). The percentage of hnRNP B1-positive cells was higher in MDS (15.3%) and AML-MDS (56.3%) than in controls (5.6%). In MDS, hnRNP B1 levels were higher in RAEB and RAEB-t subtypes than in RA and RARS. The percentage of hTERT-positive cells was higher in AML-MDS (50.0%) than in controls (20.2%) and MDS (23.6%). Our findings suggest that activation of apoptosis occurs in MDS in the absence of hTERT expression, implicating high apoptosis in the absence of high TA with ineffective hematopoiesis. Poor prognosis correlated with higher caspase-3 and lower hTERT rates. In MDS, hnRNP B1 activity may be associated with leukemic transformation.

Adolescent↗
PubMed2001

Characterization of hnRNP A2 and B1 using monoclonal antibodies: intracellular distribution and metabolism through cell cycle.

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 are nuclear RNA binding proteins involved in pre-RNA processing. The alternative splicing of the second mini exon of A2/B1 gene produces A2 and less abundant B1. It has been reported that patients with autoimmune diseases frequently have blood autoantibody valence for A2/B1, and recently that the overexpression, especially of B1, is useful for detecting cancers in early stage. Three anti-A2/B1 monoclonal antibodies were developed using recombinant A2 protein and synthesized peptides around the second splicing site. Three antibodies could separately recognize A2 and B1, and their specificity made them useful in the study of the biochemical and functional properties of A2 and B1. These antibodies have demonstrated differences between A2 and B1 in the intracellular distribution and in the metabolism through cell cycle. They are valuable reagents to clarify the clinical significance of A2/B1 in autoimmune diseases and cancers.

Amino Acid Sequence↗
PubMed2001

Interaction of hnRNP A2/B1 isoforms with telomeric ssDNA and the in vitro function.

Overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, especially of B1 has been reported as a useful marker to detect cancers in early stage, although the biological reason is not clear. A2/B1 proteins were previously reported to bind telomeric DNA repeats. Alternative splicing of A2/B1 gene produces abundant A2, less abundant B1, and testis-specific minor isoforms B0a and B0b. In this study, B1 and B0b that have the N-terminal 12 amino acid insertion were suggested to have higher affinities to telomeric single-stranded DNA (ssDNA) than A2 and B0a. Kinetic analyses using purified B1 and B0b indicated that they interact dynamically with a single array of telomeric repeats. Furthermore, functional assays demonstrated that B1 and B0b bind with telomeric repeats in a tandem fashion and protect them from a nuclease and promote telomerase activity. A2/B1 proteins, especially B1 and B0b, may function as telomeric ssDNA-binding proteins in cancer and reproductive cells.

Alternative Splicing↗
PubMed2001

Persistent fifth aortic arch associated with type A aortic arch interruption. Histological study and morphogenesis.

A male infant, having a persistent fifth aortic arch and interruption of the aorta distal to the left subclavian artery, underwent successful surgical treatment. A histological study of the excised segment of the aorta showed that the ductal tissue extended to the junction between the fifth arch and the descending aorta with consequent narrowing in the corresponding region. The ductal tissue, however, did not contribute to occlusion in the fourth aortic arch. The morphogenesis of this combination of aortic arch anomalies was also discussed.

Aorta, Thoracic↗
PubMed2001

Non-invasive lobular carcinoma within a fibroadenoma, a preoperatively diagnosed case.

Breast cancer within a fibroadenoma is rare and usually diagnosed postoperatively from pathological specimens. This paper reports a 54-year-old female with non-invasive carcinoma within a fibroadenoma, diagnosed preoperatively. She underwent a medical examination and mastopathy was suspected. On physical examination a mass 2 cm in diameter was palpated in the left breast. Ultrasonography showed a mass with smooth margins and uniform internal echoes, but cytology showed malignancy. Mammography showed a round mass with distinct margins and no calcification. As fibroadenoma, diagnosed by ultrasonography and mammography, and breast cancer, diagnosed by cytology, were not consistent results several core biopsies were performed. Needle biopsy showed proliferation of atypical epithelial cells; breast cancer within a fibroadenoma was diagnosed. MRI showed a circular mass with distinct, smooth margins and in a dynamic study, the mass showed irregular staining and the presence of early staining. Left lumpectomy and dissection of the left axillary lymph nodes was performed. Histological examination showed non-invasive lobular carcinoma occurring within a fibroadenoma.

Biopsy, Needle↗
PubMed2001

Topographical analysis of p53 expression and DNA ploidy in early bronchial squamous cell carcinoma and preneoplastic lesions.

The significance of p53 mutations and DNA aneuploidy in carcinoma cells has been investigated on the basis of a multi-step development theory of carcinogenesis. It has, however, not been determined whether these alterations can be used as diagnostic markers for the early detection of bronchial squamous cell carcinoma (BSqCC). To address this problem, we topographically investigated p53 alterations and DNA aneuploidy in 24 X-ray-negative, early BSqCC patients with various preneoplastic lesions and in 25 non-carcinoma patients with preneoplastic lesions. Bronchial lesions (n=88) were morphologically classified as hyperplasia (HP, n=5), squamous metaplasia (SM, n=23), low-grade dysplasia (LGD, n=14), high-grade dysplasia (HGD, n=11), intraepithelial carcinoma including 'carcinoma in situ' (CIS) (IEC, n=15), and microinvasive carcinoma (MIC, n=20). Immunohistochemistry for the p53 protein and image cytometry for DNA ploidy detection were performed in serial sections of each lesion. Overexpression of p53 protein was detected in 36, 73, and 65% of the HGD, IEC, and MIC lesions, respectively. Aneuploid DNA profiles were found only in carcinoma lesions, 33% in IEC and 85% in MIC. The topographical analysis revealed two types of early BSqCCs, one with adjacent preneoplastic lesions (sequential type, n=8) and another without such lesions (de novo type, n=16). The p53 protein was frequently overexpressed in both types (sequential type, 79%; de novo type, 62%). In the sequential type, however, the p53 protein was overexpressed in HGD lesions that were directly adjacent to p53-overexpressing carcinoma lesions without exception. The present topographical study suggests that p53 mutations play an important role in the carcinogenesis of BSqCC and that p53-overexpressing HGD lesions in sequential types should be regarded as 'truly' preneoplastic lesions that actually develop into carcinomas. In addition, our study demonstrated that DNA aneuploidy might occur at times after p53 alteration with increasing frequency, as invasive growth begins. Such combination analysis of p53 immunohistochemistry and nuclear DNA ploidy in routine histology may contribute to estimates of malignant potential in preneoplastic and intraepithelial squamous lesions and provide additional information for early detection of BSqCC.

Aneuploidy↗
PubMed2000

Immunohistochemical study of the hnRNP A2 and B1 in the rat forebrain.

Immunohistochemical techniques were employed to examine the distribution of RNA-binding proteins A2 and B1 in the rat forebrain. Intense A2 and B1 immunolabeling were observed in the nucleoplasm of the neurons in the cerebral cortices, hippocampal formation, olfactory regions, caudate-putamen as well as the supraoptic nucleus of hypothalamus. In contrast, within the bed nucleus of the stria terminalis, as well as the medial and lateral habenular nucleus of thalamus, immunoreactivity for both proteins was weak. Within the globus pallidus and thalamic nucleus immunoreactivity for A2 was hardly detectable despite of intense B1 immunolabeling, while within the endopiriform nucleus and lateral and basolateral nucleus of amygdala intensity of B1 immunolabeling was relatively weak compared to A2. Our study suggests that the distribution of A2 and B1 are not constant throughout the forebrain and this diversity may reflect the post-transcriptional regulation of cell-specific gene expression of neuronal cells.

Animals↗
PubMed2000

Testis- and developmental stage-specific expression of hnRNP A2/B1 splicing isoforms, B0a/b.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) A2 and B1 are abundant nuclear proteins that bind to nascent RNAs synthesized by RNA polymerase II. Previously we had found that the splicing isoforms hnRNP B0a/b, from which the ninth exon of the A2/B1 gene is excluded, are abundantly expressed in testis. We postulated that B0a/b are testis-specific isoforms, and investigated the expression of A2/B1 and B0a/b in rat tissues and in postnatal development of rat testes using RNase protection assay, immunoblotting, and immunohistochemistry. We found that hnRNP B0a/b mRNAs are expressed in several tissues but that the testis alone expresses B0a/b proteins. A sequential study using neonatal rat testes demonstrated that B0a/b mRNAs are produced after 17 days of age, but not translated until 4 weeks of age when round spermatids appear in addition to spermatogonia and spermatocytes. Immunohistochemically, hnRNP A2/B1 isoforms are expressed during spermatogenesis from spermatogonia through round spermatids, whereas the expression of A1 is restricted to spermatogonia. This expression pattern in the rat testis is maintained from birth through adulthood. These results suggest that the expression of the hnRNP A2/B1 gene is partly regulated by a testis-specific post-transcriptional mechanism, and that the products of the A2/B1 gene, especially hnRNP B0a/b, are involved in spermatogenesis.

Animals↗
PubMed2000

Molecular characterization of a mouse heterogeneous nuclear ribonucleoprotein D-like protein JKTBP and its tissue-specific expression.

The human DNA- and RNA-binding protein JKTBP is a new member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that are involved in mRNA biogenesis. We cloned and characterized a mouse homolog and studied its expression in mouse tissues. The cDNA encoded a 301-residue polypeptide. There is only a single amino acid difference between the mouse and human sequences. Northern blotting indicated ubiquitous but varied expressions of approximately 1.4 and 2.8kb mRNAs in various tissues. Immunoblotting indicated that the amounts of protein of about 38kDa were higher in the brain and testis than in other tissues. An additional protein of about 53kDa was found in the brain and testis. Germ cell-deficient W/W(v) mutant mice and aged mice had the reduced amounts of JKTBP in the testes. Immunohistochemical staining indicated cell type-specific expression of JKTBP in tissues: neurons and spermatocytes displayed strong signal intensities. The signals were confined to the nucleus. The amount of 38kDa JKTBP was estimated to be approximately 1.3x10(7) molecules per HL-60 cell. These results indicate that JKTBP is an abundant, highly conserved nuclear protein.

Animals↗
PubMed2000

Late recurrence of small-cell lung cancer: a case report.

A 67-year-old man was admitted with small-cell lung cancer (SCLC). The patient was given four courses of platinum-containing chemotherapy followed by chest irradiation, and good partial response (PR) was obtained. The patient did well for 4 years, until he sought treatment for a painful subcutaneous tumor. Chest computed tomography scan revealed the mass extending from the tumor in lung parenchyma with osteolytic lesion of the third rib bone. Pathologic examination of the subcutaneous lesion revealed SCLC. The patient was given two courses of the same combination chemotherapy administered as initial therapy. Regression of the mass was observed, and the response was evaluated as a good PR. How to approach late recurrence of SCLC is discussed.

Aged↗
PubMed2000

Expression of hnRNP A2/B1 proteins in human cancer cell lines.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is recently reported informative as a marker of lung cancer for early detection. To examine whether the expression of the proteins is specific for lung cancer, immunological analyses were performed both in lung and non-lung cancer cell lines. In immunostaining and Western blotting, the expression of A2/B1 was observed not only in the lung cancer cells but also in non-lung cancer cells. The expression of hnRNP A2/B1 is not specific for lung cancer and quantitative determination of A2/B1 is required to elucidate their significance in carcinogenesis.

Heterogeneous-Nuclear Ribonucleoprotein Group A-B↗
PubMed1999

Molecular characterization of the hnRNP A2/B1 proteins: tissue-specific expression and novel isoforms.

hnRNP A2/B1 proteins are among the most abundant pre-mRNA-binding proteins of vertebrates and structurally similar to hnRNP A1. We have produced two specific monoclonal antibodies against A2 and B1 and studied their molecular characteristics and in vivo expression in rat tissues. Immunoprecipitation demonstrated that the hnRNP A2/B1 complexes contain many snRNP (small nuclear ribonucleoprotein) proteins, consistent with their role in pre-mRNA splicing. RNA polymerase II inhibition causes nucleocytoplasmic shuttling of A2 and B1. In most tissues, they are localized in the nucleus; however, in the squamous epithelium of the skin and esophagus A2 is also distributed in the cytoplasm. The relative amounts of A2 and B1 are not constant among different tissues. In the adrenal, only A2 is extremely abundant in the medulla but not in the cortex. In the testis the expression of A2 and B1 are observed through spermatogenesis, and different from A1 which is stringently repressed in spermatocytes. We also found and cloned a novel testis-specific isoform of A2/B1, namely hnRNP B0. The difference of expression of A2, B1, and A1 provides new information on their in vivo roles. The diversity of A/B group hnRNP proteins may have important effects on the posttranscriptional regulation of cell-specific gene expression.

Amino Acid Sequence↗
PubMed1999

Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer.

Small cell lung cancer (SCLC) is characteristically not associated with tumour-infiltrating lymphocytes. Since SCLC has been reported to show marked reduction of class I HLA, the reduced expression has been considered a means of escaping anti-cancer immunity. However, HLA-DR expressed in cancer cells is now known to contribute to anti-cancer immunity. To clarify the difference in HLA-DR expression between SCLC and non-small cell lung cancer (NSCLC), and the mechanism, the expression and the cis- and trans-acting factors involved were investigated. HLA-DR was not immunohistochemically detected in any SCLC and could not be induced by interferon gamma (IFN-gamma) in any SCLC cell line, whereas HLA-DR was expressed to varying degrees and was easily induced in NSCLC. SCLC cell lines lacked class II transactivator (CIITA) even after IFN-gamma induction, whereas NSCLC cell lines expressed CIITA. The other class II HLA-specific transcription factors were expressed and genomic DNA of HLA-DR, including the promoter, was conserved well both in SCLC and in NSCLC cell lines. CIITA transfection improved the expression of HLA-DR in SCLC. In conclusion, the lack of CIITA results in severe deficiency of HLA-DR expression in SCLC. Since CIITA has also been reported to induce class I HLA, CIITA transfection might make it possible to establish effective anti-cancer immunotherapy against SCLC through the up-regulation of class I and class II HLA.

Blotting, Northern↗