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A Palekar

Publications and source records attributed to A Palekar.

14 recordsLinked to original sources
PubMed2000

Effect of pantothenic acid on hippurate formation in sodium benzoate-treated HepG2 cells.

Inborn errors of urea synthesis result in hyperammonemia. Sodium benzoate (SB) therapy has been beneficial in the treatment of hyperammonemia. It conjugates with glycine to form hippurate, which is then excreted. SB has also been used to treat children with nonketotic hyperglycinemia (NKH), where glycine is removed, on conjugation, as hippurate. In mammalian liver mitochondria, SB is activated by an ATP-dependent reaction to its CoA ester, before conjugation with glycine. Pantothenic acid (PA) is the precursor of CoA. In this investigation, increasing the amounts of PA increased CoA levels in HepG2 cells. It also significantly increased formation of hippurate in SB-treated cells. These findings suggest a beneficial effect of PA on the SB therapy in children with NKH as well as hyperammonemia.

Cell Line↗
PubMed1989

Dukes' classification revisited. Findings from the National Surgical Adjuvant Breast and Bowel Projects (Protocol R-01).

The relative prognostic value of the Dukes, Astler, and Coller and TNM staging systems was evaluated for 745 pathologically evaluable patients with rectal cancer enrolled in protocol R-01 of the National Surgical Adjuvant Breast and Bowel Projects. All three methods were found to be highly interrelated. However, the magnitude and consistency of prognostic discrimination among stages was best exhibited by the Dukes' and TNM systems. Survival was comparable among patients with Astler and Coller A and B1 and TNM T1N0M0 and T2N0M0 lesions. Since neither method improved on the predictability noted in Dukes' A cases it is suggested that the use of confusing subscripts is unnecessary. On the other hand, striking prognostic discrimination was observed when Dukes' C cases were subdivided according to depth of tumor penetration as proposed by Astler and Coller and designated as C1 and C2. Multivariate analyses revealed this feature to be independent of number of nodal metastases (1-4 versus 5+ positive), their site (near or far from the growth), or degree of tumor differentiation. The site of nodal metastases appeared to be related to numbers of nodal metastases rather than site per se. Considerations of the findings indicate that the Dukes' staging method is the simplest and most consistent algorithm related to prognosis. The only modification that would enhance its value in this regard would be the subdivision of C cases according to the criteria of Astler and Coller rather than that proposed by Dukes himself.

Aged↗
PubMed1987

Expression of LewisX and sialylated LewisX antigens in human colorectal polyps.

The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.

Antibodies, Monoclonal↗
PubMed1986

Cancer-associated alterations of blood group antigen expression in human colorectal polyps.

Human colorectal carcinoma tissues may exhibit several patterns of altered blood group substance (BGS) expression: reappearance of A, B, H, or Lewisb antigens in distal colon; deletion of BGS in the proximal colon with or without precursor substance accumulation; and incompatible BGS expression in proximal or distal colon. The present study evaluated these cancer-associated alterations in colorectal polyps with different malignant potential. With respect to ABH antigens, hyperplastic polyps (HPs), considered to have no malignant potential, did not exhibit incompatibility and only a few cases demonstrated BGS reappearance or deletion. Adenomatous polyps (APs) however, frequently reexpressed ABH antigens or expressed incompatible BG-A or B in 27% of polyps; one specimen demonstrated BG-B deletion. Precursor expression was not found in HPs but was frequently observed in APs. Reappearance of ABH in distal polyps was significantly correlated with increasing grade of dysplasia, but was not significantly correlated with polyp size or histological type. With respect to Lewis antigen expression, Lewisb reappearance occurred in almost every distal polyp, and Lewisa-Lewisb coexpression was also quite common. Lea deletion was frequently noted, especially in HP, but the significance of this finding is unclear. This study indicates that several antigenic alterations that occur in colorectal cancer tissues also appear in premalignant polyps, and often in early stages of the neoplastic process. The observation that incompatible expression of BG-A or B occurs only in AP and cancer tissues (as well as mucosa adjacent to cancer) but not in fetal colonic mucosa, adult normal colonic mucosa, or HP, suggests that this may be a cancer-specific phenomenon.

ABO Blood-Group System↗
PubMed1986

Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues.

The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are more specific for colon cancer tissues than are simple, monofucosyl LeX antigens. The present investigation compared the expression of simple and extended LeY antigens in a variety of malignant and nonmalignant human colonic tissues to gain insight into the normal distribution and cancer-associated expression of these antigens. Monoclonal antibody AH-6, which recognizes the LeY epitope irrespective of its carrier carbohydrate chain, stained the majority of specimens regardless of malignant potential or location within the colon. In contrast, CC-1 and CC-2 monoclonal antibodies, which recognize extended LeY structures, and KH-1, which is specific to trifucosyl LeY, preferentially stained malignant colonic tissues and rarely stained normal colonic mucosae. Mucosa immediately adjacent to cancer usually stained with AH-6 but not with KH-1, CC-1, or CC-2. Extended or trifucosyl LeY antigen expression was limited exclusively to premalignant (adenomatous) polyps and was invariably absent from nonpremalignant (hyperplastic) polyps. Moreover, among adenomatous polyps, extended LeY antigen expression tended to correlate with three parameters of malignant potential: larger polyp size; villous histology, and severe dysplasia. AH-6 failed to distinguish between hyperplastic and adenomatous polyps. In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments. We conclude that in human colon, the LeY hapten is an oncodevelopmental cancer-associated antigen and extended LeY antigens are highly specific markers for malignancy and premalignancy.

Antibodies, Monoclonal↗
PubMed1986

Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues.

Biochemical studies have revealed that some normal cells express the LeX trisaccharide Gal beta 1----4(Fuc alpha 1----3)GlcNAc either on short-chain fucolipids or as a single immunodeterminant on glycolipid oligosaccharide side chains. Cancer cells, including those from colonic adenocarcinomas, express this antigen on longer type 2 blood group side chains as difucosylated or trifucosylated fucolipids. Moreover, sialylated forms of difucosylated LeX also accumulate in colon cancer but not in normal colonic mucosa. In the present study, six monoclonal antibodies which selectively recognize the various LeX-related antigens were used for immunohistochemical examination of these antigens in serial sections of human colonic tissue. All of these antigens were oncodevelopmental in human colon. Monoclonal antibodies anti-SSEA-1 and AH8-183, directed against short-chain, monofucosylated LeX, were unable to discriminate well between normal and malignant colonic tissue. However, the other four antibodies were much better at distinguishing cancer from normal tissue. FH6 was the most specific in that no normal tissues bound this antibody. However, FH6 failed to stain poorly differentiated cancers and some colloid-type carcinomas. FH4, which was also highly specific, stained almost all cancers, regardless of the degree of differentiation. FH4 primarily stained cancer cell cytoplasm, whereas the sialylated antigen defined by FH6 predominantly stained cell membranes. Differences were noted between the expression of LeX-related antigens in autopsied normal mucosa compared to mucosa of benign colonic diseases. Monoclonal antibodies recognizing long-chain polyfucosylated and sialylated LeX-related antigens appear to be useful tools for detection of colon cancer.

Antibodies, Monoclonal↗
PubMed1986

Comparison of T-antigen expression in normal, premalignant, and malignant human colonic tissue using lectin and antibody immunohistochemistry.

The Thomsen-Friedenreich antigen has been implicated as a cancer-associated antigen in some human organs including the colon. Most previous studies of Thomsen-Friedenreich antigen expression in the colon used peanut agglutinin (PNA) to identify the immunodeterminant in tissues. However, evidence from other organs suggests that anti-T antibodies have specificities which differ from those of peanut lectin. To elucidate the nature of the T-immunodeterminant in colonic mucosa, we compared staining by PNA to that of a polyclonal (PAb) and monoclonal (MAb) anti-T antibody. PNA demonstrated the best sensitivity (91%) in cancer tissues but the lowest specificity (68%) in normal mucosa. Staining with MAb was only 76% sensitive but 100% specific. Sensitivity and specificity of PAb were intermediate between PNA and MAb. MAb stained fewer adenomatous polyps than either PNA or PAb, but staining appeared to correlate with premalignant features of the polyps. PNA-binding sites were more prevalent than either PAb or MAb in hyperplastic polyps. Cell cytoplasm was stained by both antibodies more often than by PNA. The majority of fetal colonic specimens stained with all three reagents suggesting that Thomsen-Friedenreich antigen may be an oncodevelopmental antigen in human colon. Differences in staining patterns in some tissues may be due to different antigenic specificities among PNA, PAb, and MAb.

Adenoma↗
PubMed1985

Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue.

In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved.

ABO Blood-Group System↗
PubMed1983

Glutamine metabolism in bone.

Evidence is provided for the utilization of glutamine by calvaria and compact bone of rat. Glutamine was actively transported into calvaria, principally by sodium-dependent mechanisms; its uptake was significantly inhibited by neutral amino acids (alanine, proline, serine, asparagine) and glutamine analogs (L-glutamate-gamma-hydroxamate, albizziin). Glutamine was degraded to ammonia and glutamate by phosphate-dependent glutaminase, a mitochondrial enzyme present in both calvaria and compact bone. The enzyme exhibited an apparent Kmgln of 2.35 mM, a KactPO4 of 25 mM, and a broad pH optimum (7.5-9.5). It was inactivated by incubation of intact calvaria or bone homogenates with the glutamine analogs 6-diazo-5-oxo-L-norleucine (DON) and a 2-amino-4-oxo-5-chloropentanoic acid (chloroketone). Such treatment also severely inhibited (greater than 95%) both ammonia and 14CO2 formation from [U-14C]glutamine. Glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities were measured in bone. Amino-oxyacetate, an aminotransferase inhibitor, inhibited 14CO2 formation from [U-14C]glutamine. The data indicate that glutamine can serve as a precursor of ammonia, glutamate, other amino acids (alanine, aspartate, ornithine, proline) and carbon dioxide in bone and that phosphate-dependent glutaminase, transaminases, and citric acid cycle activity contribute to the observed metabolism.

Amino Acids↗
PubMed1978

Naloxone and intestinal motility.

It was supposed that the inhibition of intestinal peristalsis seen in animals and humans after abdominal surgery might be related to the release of endorphins, endogenous opiate receptor agonists, caused by the surgical stress and pain. However, naloxone, a potent morphine and endorphin antagonist, failed to block this peristaltic inhibition in rats, which leaves the mechanism of this inhibition, and thus the function of intestinal endorphins, still very much in doubt.

Animals↗
PubMed1978

The histopathology of mammographic patterns.

No significant correlation between the types of histologic alteration and various mammographic densities as described by Wolfe was found in specimen mammograms from 50 patients with cancer of the breast and a similar number with fibrocystic disease except for a greater incidence of fibrous mazoplasia in the "highest-risk" densities designated DY. This information is inconsistent with prevailing views that relate such risk for the development of mammary cancer to proliferative fibrocystic disease, vis-à-vis epithelial rather than stromal proliferation. This observation does not necessarily mitigate claims of risk attendant with various mammographic patterns, but indicates the need for further evaluation of this stromal alteration as a discriminant in this regard.

Breast Diseases↗
PubMedDate not supplied

Characterization of zona glomerulosa function in patients with classic and non-classic forms of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

The function of the adrenal zona glomerulosa was studied in 18 patients with 11-hydroxylase deficiency confirmed by elevated plasma levels of 11-deoxycortisol. Patients were divided into two groups. Group I (4 males, 7 females; aged 1.2-2.8 yrs) had symptoms at birth or shortly after (classic form), and Group II (4 males, 3 females; aged 7.3-20.1 yrs) had their first clinical manifestation during childhood (non-classic form). To study zona glomerulosa function, patients were given dexamethasone p.o. 2 mg/m2/day x6 days, thus suppressing the zona fasciculata. Six hours after the last dose of dexamethasone, the zona glomerulosa was stimulated by i.v. administration of furosemide 1.0 mg/kg as a single dose. Blood was drawn 2 h later. In the untreated state, all patients had striking elevation of ACTH (Group I: 1,070 +/- 380 pg/ml; Group II: 764 +/- 180 pg/ml), 11-deoxycortisol (Group I: 63,000 +/- 22,000 ng/dl; Group II: 17,200 +/- 5,200 ng/dl) and deoxycorticosterone (Group I: 1,100 +/- 67 ng/dl; Group II: 499 +/- 27 ng%) while plasma renin activity (< 0.5 ng/ml/h in both groups) and aldosterone (Group I: 3.0 +/- 1.8 ng/dl; Group II: 2.3 +/- 1.8 ng/dl) were markedly suppressed. After the administration of furosemide 4 patients in Group I were unable to increase aldosterone (2.8 +/- 0.9 ng/dl) secretion in spite of marked elevation of plasma renin activity (28 +/- 7 ng/ml/h), suggesting an impairment of 11-hydroxylase in the zona glomerulosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗