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1.
Rev Epidemiol Sante Publique ; 67(1): 43-49, 2019 Feb.
Article in French | MEDLINE | ID: mdl-30429062

ABSTRACT

BACKGROUND: Caregivers play an essential role in maintaining home care for elderly people with dementia. However, it is difficult for caregivers to target their own needs as well as those of the person with neurocognitive disorders they support on a daily basis. Identifying the needed resources can also be difficult. In order to better assist caregivers in identifying resources needed to support their role, this study aims to understand the factors that influence their help-seeking process. METHODS: This qualitative and descriptive study focuses on the point of view of the main people affected by this problem: caregivers. Eleven caregivers of elderly people with dementia living at home were recruited by convenience sampling. Semi-structured interviews were conducted, and the data were analyzed according to Mast's typology. RESULTS: The factors influencing caregivers help-seeking process were categorized into five themes: 1) service-related (e.g. wait times); 2) personal (e.g. feeling intrusive); 3) experiential (e.g. positive use of a service); 4) relational (e.g. rejection of the elder), and 5) informational (e.g. directed to the right service). CONCLUSION: Caregivers face many challenges in their help-seeking process and want to be more proactively accompanied in a way adapted to their changing needs.


Subject(s)
Caregivers/psychology , Help-Seeking Behavior , Home Care Services , Neurocognitive Disorders/therapy , Aged , Female , Humans , Male , Middle Aged , Qualitative Research , Social Support
2.
Int J Surg Case Rep ; 7C: 10-5, 2015.
Article in English | MEDLINE | ID: mdl-25574767

ABSTRACT

INTRODUCTION: Primary hyperparathyroidism is usually seen in females above the age of 50 years, with a prevalence of 21/1000,(1) whereas the incidence in patients aged 12-28 years is less than 5%.(2) A solitary adenoma is responsible for 80% of cases of primary hyperparathyroidism.(3) Primary hyperparathyroidism is most commonly asymptomatic.(4) The incidence of acute pancreatitis associated with hyperparathyroidism is less than 10%.(5,6) The incidence of hyperparathyroidism associated with a Brown tumour is less than 5%.(7) PRESENTATION OF CASE: A 19 year old female patient presented with recurrent acute pancreatitis and swelling over the mandible. Complete investigative workup revealed a solitary parathyroid adenoma causing hyperparathyroidism. Surgical exploration with excision of the parathyroid adenoma was performed, following which the patient recovered uneventfully. DISCUSSION: The patient was initially managed as a case of acute pancreatitis, and although not suspected initially, a high index of suspicion for hyperparathyroidism developed after a biopsy of the mandibular swelling showed the presence of osteoclastic giant cells indicating the possibility of a Brown tumour. Further investigations then revealed the presence of a solitary parathyroid adenoma with coexistent hyperparathyroidism which was then managed surgically. CONCLUSION: The young age of the patient, and her presentation with acute pancreatitis and a Brown tumour of the mandible make this an extremely rare presentation of parathyroid adenoma.

3.
Br J Cancer ; 110(3): 609-15, 2014 Feb 04.
Article in English | MEDLINE | ID: mdl-24366295

ABSTRACT

BACKGROUND: The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer. METHODS: Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed. RESULTS: A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1-2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases. CONCLUSIONS: Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.


Subject(s)
Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Lymphatic Metastasis/pathology , Pathology, Surgical , Adult , Aged , Biopsy , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Preoperative Care
4.
Obstet Gynecol Int ; 2012: 414086, 2012.
Article in English | MEDLINE | ID: mdl-22496699

ABSTRACT

A shift toward a disease-based therapy designed according to patterns of failure and likelihood of nodal involvement predicted by pathologic determinants has recently led to considering a selective approach to lymphadenectomy for endometrial cancer. Therefore, it became critical to examine reproducibility of diagnosing the key determinants of risk, on preoperative endometrial tissue samples as well as the concordance between preoperative and postresection specimens. Six gynaecologic pathologists assessed 105 consecutive endometrial biopsies originally reported as positive for endometrial cancer for cell type (endometrioid versus nonendometrioid), tumor grade (FIGO 3-tiered and 2-tiered), nuclear grade, and risk category (low risk defined as endometrioid histology, grade 1 + 2 and nuclear grade <3). Interrater agreement levels were substantial for identification of nonendometrioid histology (κ = 0.63; SE = 0.025), high tumor grade (κ = 0.64; SE = 0.025), and risk category (κ = 0.66; SE = 0.025). The overall agreement was fair for nuclear grade (κ = 0.21; SE = 0.025). There is agreement amongst pathologists in identifying high-risk pathologic determinants on endometrial cancer biopsies, and these highly correlate with postresection specimens. This is ascertainment prerequisite adaptation of the paradigm shift in surgical staging of patients with endometrial cancer.

5.
Acta Trop ; 116(2): 127-33, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20609356

ABSTRACT

We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 µg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 µg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 µg/ml. Flavone immobilized female adult worms at 31.2 µg/ml (MTT>80%) and microfilariae at 62.5 µg/ml. Rutin killed microfilariae at 125 µg/ml and inhibited MTT-reduction in female worms for >65% at 500 µg/ml. Naringin had adulticidal effects at 125 µg/ml while chrysin killed microfilariae at 250 µg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.


Subject(s)
Brugia malayi/drug effects , Filaricides/pharmacology , Flavanones/pharmacology , Flavonoids/pharmacology , Animals , Brugia malayi/isolation & purification , Coloring Agents , Disease Models, Animal , Elephantiasis, Filarial/drug therapy , Female , Flavanones/standards , Flavonoids/standards , Gerbillinae/parasitology , Hesperidin/pharmacology , Humans , Male , Murinae/parasitology , Rutin/pharmacology , Survival Analysis , Tetrazolium Salts , Thiazoles
6.
Pathol Res Pract ; 206(11): 776-81, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-20400232

ABSTRACT

Hydatidiform moles are gestational diseases with abnormal development of the villous trophoblast and characterized by an excess of paternal to maternal genetic material. Complete moles are usually diploid and androgenetic, and are thought to develop after the fertilization of an "empty ovum" by either a haploid spermatozoon or two spermatozoa. We report a case of a complete mole in which fluorescence in situ hybridization (FISH) incidentally disclosed trisomy 13. Microsatellite genotyping showed a single allele at each of the markers tested on the chorionic villi, and comparison with parental peripheral blood specimens revealed that the markers were all of paternal origin. These results confirmed the paternal origin of all three copies of chromosome 13, and the isodisomy for each chromosome was consistent with duplication of a monospermic fertilization event and subsequent non-disjunction. To the best of our knowledge, this is the only case of an androgenetic complete mole with trisomy 13 described in the scientific literature. We present a review of the literature and hypothesize that the trisomy 13 in our case likely resulted from non-disjunction of chromosome 13.


Subject(s)
Hydatidiform Mole/secondary , Uterine Neoplasms/pathology , Biomarkers, Tumor/metabolism , Chorionic Villi/metabolism , Chorionic Villi/pathology , Chromosome Disorders , Chromosomes, Human, Pair 13 , Combined Modality Therapy , Fathers , Female , Genotype , Humans , Hydatidiform Mole/genetics , Hydatidiform Mole/therapy , In Situ Hybridization, Fluorescence , Male , Microsatellite Repeats , Middle Aged , Pregnancy , Trisomy , Trisomy 13 Syndrome , Trophoblasts/metabolism , Trophoblasts/pathology , Uterine Neoplasms/genetics , Uterine Neoplasms/therapy
7.
Gynecol Oncol ; 116(1): 28-32, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19875161

ABSTRACT

OBJECTIVE: To compare the incidence of pelvic lymph node metastases in early stage cervical cancer patients undergoing sentinel lymph node biopsy (SLN) to a matched cohort undergoing pelvic lymphadenectomy. METHODS: All patient data were entered prospectively into an ongoing cervical cancer database. Since April 2004, 87 patients with FIGO stage IA/B1 cervical cancer underwent SLN detection with identification of bilateral SLN. This cohort (cases) was compared to a matched group of patients who underwent complete pelvic lymphadenectomy (controls). The groups were matched 3:1 for tumour size (+/-5 mm), histology, depth of invasion (+/-2 mm), and presence of capillary lymphatic space invasion (CLS). Descriptive statistics were calculated for all variables of interest. The association between cases and controls and lymph node metastases was carried out using a conditional logistic regression analysis. RESULTS: 81 women in the SLN cohort were matched with 1 control, 72 cases with 2 controls, and 65 cases with 3 controls. Among cases, 14 (17%) had pelvic lymph nodes metastases vs. 15 (7%) in the controls (p=0.0059, odds ratio= 2.8, 95% CI=1.3-5.9). Among the 14 cases of SLN metastases, 11 were detected by frozen section and 3 were detected on final paraffin sectioning. All were detected by H and E stains. The size of the SLN metastases ranged from less than 1 mm to 8 mm. CONCLUSIONS: Sentinel lymph node biopsy in early cervical cancer is a more sensitive procedure in detecting pelvic lymph node metastases compared to complete lymphadenectomy.


Subject(s)
Lymph Nodes/pathology , Lymph Nodes/surgery , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Adult , Case-Control Studies , Cohort Studies , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Neoplasm Staging/standards , Sentinel Lymph Node Biopsy
8.
Gynecol Oncol ; 113(1): 42-6, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19174307

ABSTRACT

OBJECTIVE: To summarize our experience in the frozen section (FS) assessment of the trachelectomy surgical margin. METHODS: All surgeries from 1994 to 2007 were performed by one surgeon. The FS examination was consistently carried out by a group of gynecologic pathologists according to the protocol described in details in this article. Cases were retrieved from the pathology files and the slides were reviewed by two pathologists. RESULTS: 132 patients were identified with complete pathology records. They ranged from 17 to 46 years old (median 31). Surgeries were performed for clinical Stages 1A (n=39) and 1B (n=93) tumors (63 adenocarcinoma, 59 squamous cell carcinoma, 7 adenosquamous and 3 others). In 78 cases, no residual tumor was seen in the trachelectomy specimens as it was resected by the preceding LEEP or cone. The margin was reported as negative in 123, suspicious in 3 and positive in 6 cases. It was revised in 16 cases (6 positive, 2 suspicious and 8 negative but <5 mm). Final margin assessment agreed with the FS diagnosis in 130 (98.5%) and showed interpretational overcall in 2 cases (1.5%); only one of which resulted in a revised margin. No false negative intraoperative assessment was found. CONCLUSIONS: We describe our FS protocol and summarize our data. This protocol is reliable since none of the patients was under-treated.


Subject(s)
Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Adolescent , Adult , Female , Frozen Sections , Gynecologic Surgical Procedures/methods , Humans , Intraoperative Period/methods , Middle Aged , Neoplasm Staging , Young Adult
10.
Immunol Invest ; 17(1): 19-24, 1988 Mar.
Article in English | MEDLINE | ID: mdl-3391650

ABSTRACT

Patients with metastatic breast carcinoma (BCa) have defective peripheral blood lymphocyte (PBL) responsiveness to mitogenic and antigenic stimulation. In the following experiments, glycopeptides were isolated from the pronase digests of breast carcinoma tissue. After elution from Sephadex G-50, glycopeptides from BCa inhibited PBL responsiveness to mitogenic (PHA) stimulation. The glycopeptides contained blood group I-antigenic determinants. These experiments demonstrate the presence of blood group I-active peptides in breast carcinoma that suppress peripheral blood lymphocyte functions. Further studies are in progress.


Subject(s)
Blood Group Antigens/immunology , Breast Neoplasms/immunology , Glycopeptides/physiology , I Blood-Group System/immunology , Immunosuppressive Agents/isolation & purification , Humans , Immune Tolerance , In Vitro Techniques , Lymphocyte Activation , Lymphocytes/immunology
11.
Clin Immunol Immunopathol ; 45(2): 196-207, 1987 Nov.
Article in English | MEDLINE | ID: mdl-3665200

ABSTRACT

Tumor cells elaborate and release into the circulation a variety of glycoproteins. An enzyme-linked immunosorbent assay (ELISA) was developed to monitor carbohydrate structures secreted into the circulation. Among these antigens are the structures specific for the blood group I antigens, which are incompletely converted to ABH antigens on the membranes of tumor cells. The I antigens in the sera of 67 women with breast carcinoma (BCa), 58 with benign breast disease (BBD), and 47 controls were measured by the ELISA. In this assay, I antigen from ovarian cyst mucin was bound to the wells of polystyrene microtiter plates. The monoclonal human anti-I antibody (Hy) was added to the wells along with perchloric acid extracts of patient and control sera at five different dilutions. The anti-I binding to the solid-phase I antigen was determined after incubation steps with peroxidase-labeled anti-human IgM and substrate. The amount of sera extracts giving 50% inhibition of anti-I (Hy) binding was determined from the inhibition curves which were corrected by integrating the slope values into that of the standard curve obtained with extracts of normal sera. The I antigens were significantly higher in pathologic stage (PS) IV sera (P less than 0.001), and comparable in PS I, PS II, and PS III and BBD sera to those in control sera. The anti-I (Hy) binds strongly Gal 1,4 GlcNAc 1,6 Gal (alpha GalNAc); Gal 1,4 GlcNAc 1,6 (Gal 1,4 GlcNAc 1,3) Gal; and to a lesser extent Gal 1,4 GlcNAc 1,3 Gal 1,4 GlcNAc (0.06, 0.09, and 0.35 mM, giving 50% inhibition, respectively). It was concluded that similar or related structures may be expressed on the membrane of metastatic BCa cells.


Subject(s)
Antigens, Neoplasm/analysis , Blood Group Antigens/analysis , Breast Neoplasms/immunology , Enzyme-Linked Immunosorbent Assay , Fibrocystic Breast Disease/immunology , I Blood-Group System/analysis , Antibodies, Neoplasm/immunology , Female , Humans , Oligosaccharides/immunology , Ovarian Neoplasms/immunology
12.
Cancer Metastasis Rev ; 6(4): 541-57, 1987.
Article in English | MEDLINE | ID: mdl-3327632

ABSTRACT

Blood group-related oligosaccharides have been isolated from a limited number of carcinomas. The carcinoma-associated oligosaccharides show chain elongation, for example due to repeating Gal 1,4 GlcNAc 1,3 sequences, or a higher degree of branching, which permit increased sialylation and fucosylation. Abnormal carbohydrate structures have been demonstrated on tumor cell membranes by immunological techniques, which suggests deletion of ABH, accumulation of 'crypt' antigens such as I and T antigens, and abnormal expression of Lewis antigens. Changes in carcinoma-associated oligosaccharides can result from altered biosynthetic processing in the Golgi apparatus or the occurrence of abnormal tumor glycosyltransferase isoenzymes. Structural alterations of oligosaccharides on the tumor cell membrane are related to the regulation of tumor growth, cell-cell interaction, cell differentiation, and metastasis. Glycoproteins secreted by tumor cells into the circulation evoke cellular and humoral immunity and cause immune suppression by binding to cytotoxic T lymphocytes and lymphocyte subsets. The relationship of oligosaccharide structures to biologic function awaits elucidation.


Subject(s)
Blood Group Antigens , Neoplasms/metabolism , Oligosaccharides/metabolism , Animals , Blood Group Antigens/immunology , Cell Membrane/metabolism , Glycoproteins/blood , Glycosylation , Humans , Mucins/metabolism , Neoplasms/immunology , Neoplasms/pathology , Oligosaccharides/physiology , Structure-Activity Relationship , Transferases/metabolism
13.
Mol Immunol ; 23(2): 217-20, 1986 Feb.
Article in English | MEDLINE | ID: mdl-3517622

ABSTRACT

In previous work we found that a monoclonal cold hemagglutinin from patient Hy strongly bound antigens contained in stage IV breast cancer sera. To infer the chemical structure of the antigens expressed in the cancer sera, we studied the specificity of the antibody (Hy). The antibody (Hy) had I specificity, based on agglutination scores with adult and cord red blood cells. The binding of the antibody to synthetic and milk oligosaccharides was determined using a solid phase enzyme immunoassay (EIA). The anti-I antibody (Hy) strongly bound LacNAc0-Me, LacNAc1----6Gal, LacNAc1----6 (LacNAc1----3)Gal, LacNAc-1----6 alpha GalNAc, LacNAc1----3LacNAc, and LacNAc, 0.05, 0.06, 0.09, 0.22, 0.35 and 0.75 mM giving 50% inhibition, respectively. The anti-I antibody (Hy), similar to the anti-I antibody (Ma), strongly bound LacNAc1----6Gal, but it differed from the anti-I antibody (Ma) in its cross-reactivity with the i sequence. The anti-I antibody (Hy) showed similar reactivities as the hybridoma monoclonal antibodies M18 and M39 with LacNAc1----6Gal and with the i-active sequence. The EIA procedure is a useful alternative to either radioimmunoassay or immunoprecipitation method in the study of anti-I,i specificities.


Subject(s)
Antibodies, Monoclonal/immunology , Antibody Specificity , Blood Group Antigens/immunology , Hemagglutinins/immunology , I Blood-Group System/immunology , Binding, Competitive , Hemagglutination , Humans , Immunoenzyme Techniques , Oligosaccharides/metabolism
14.
J Biol Chem ; 261(4): 1599-608, 1986 Feb 05.
Article in English | MEDLINE | ID: mdl-3003076

ABSTRACT

A combination of reverse phase and normal phase high pressure liquid chromatography has been used to separate the reduced oligosaccharides produced by alkaline borohydride degradation of a blood group A ovarian cyst mucin glycoproteins. Fourteen compounds, ranging in size from a monosaccharide to a decasaccharide, have been isolated preparatively using a Zorbax C-18 reverse phase column eluted with water and a MicroPak AX-5 normal phase column eluted with aqueous acetonitrile. The purity of the products and their structures were determined from the fully assigned high field proton NMR spectra. The resonances of exchangeable amide protons, observed by the Redfield selective pulse sequence in H2O, were assigned by decoupling to the resonances of H2 of the 2-acetamido sugars. Nuclear Overhauser effects were used to establish the relationship of the anomeric protons and those of the aglycone. In exception to earlier proposals that nuclear Overhauser effect on irradiation of the anomeric proton should always be observed at the proton attached to the aglycone carbon, we find that for the linkage of GalNAcp(1----3)Gal, nuclear Overhauser effect on irradiation of the alpha-anomeric proton resonance is observed not at H3 but at H4 of galactose. A combination of NMR methods and enzymatic degradation was employed to determine the structures of 13 different oligosaccharides of which seven have not previously been reported. These oligosaccharides, which terminate with beta-Gal, alpha-Fuc, beta-GlcNAc, and alpha-GalNAc, account for 75% of the total glycoprotein carbohydrate, the remainder being isolated as a mixture of glycopeptides and a high molecular weight polysaccharide whose NMR spectrum implies a simple repeating subunit structure closely related to that of the oligosaccharides.


Subject(s)
Adenocarcinoma, Mucinous/analysis , Blood Group Antigens/analysis , Mucins/analysis , Neoplasm Proteins/analysis , Ovarian Neoplasms/analysis , Sugar Alcohols/analysis , Carbohydrate Sequence , Chromatography, High Pressure Liquid , Female , Humans , Magnetic Resonance Spectroscopy
15.
Exp Cell Biol ; 54(5-6): 319-32, 1986.
Article in English | MEDLINE | ID: mdl-2433170

ABSTRACT

When incubated in preconditioned medium, i.e. spent media from the hepatocellular carcinoma (PLC/PRF/5) cell cultures, human embryonic liver (HEL) cells differentiate and acquire oncologic phenotypes. This is caused by transcriptional alterations in fetal gene expression. This occurs when hepatocytes are proliferating rapidly and secreting alpha fetoprotein (AFP), and later when the quiescent state is reached with secretion of albumin (ALB). The present studies examined the parameters signaling oncologic transformation during liver cell differentiation in the conditioned medium. mRNAs coding for AFP, ALB and HBsAg were isolated from HEL, adult liver cells (ADLC) and from PLC/PRF/5 cells, respectively. cDNA molecules complementary to these polysomal mRNA molecules were constructed and labeled with 32P. These tracers were used to quantitate changes in cellular mRNA X AFP, mRNA X ALB and mRNA X HBsAg directly by DNA molecular hybridization during HEL cells cultivation in the preconditioned medium. Under these conditions, the changes in cellular mRNA X HBsAg and mRNA X AFP correlated with an increased tumorigenicity in athymic Nu/Nu mice, membrane galactosyltransferase and phospho-tyrosine kinase activities.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Transformation, Neoplastic , Liver Neoplasms/pathology , Liver/embryology , RNA, Messenger/biosynthesis , Albumins/genetics , Cell Differentiation , Cell Division , Cell Line , Culture Media , DNA/biosynthesis , Hepatitis B Surface Antigens/genetics , Humans , Liver/metabolism , Liver/pathology , Protein Biosynthesis , RNA, Messenger/analysis , alpha-Fetoproteins/genetics
16.
J Chromatogr ; 328: 259-69, 1985 Jun 28.
Article in English | MEDLINE | ID: mdl-3839799

ABSTRACT

The branched hexasaccharide whose trivial name is lacto-N-hexaose (LNH) as well as a mono- and a difuco-derivative were isolated from human breast milk of a Lewis a positive donor by high-performance liquid chromatography (HPLC). Reversed-phase HPLC on C18 columns which have been used previously in our laboratory for successful separations of the smaller milk oligosaccharides were not effective in this system. However, normal-phase HPLC on an amino-bonded silica column (Varian AX-5) gave both analytical and preparative separations. The identity of the LNH core structure was verified both by HPLC and by NMR spectroscopy of the fucosidase digestion products of the fucosylated oligosaccharides. LNH was identified by NMR spectroscopy of the reduced and acetylated derivative whose high field spectrum has been previously reported. The positions of fucosylation of beta-GlcNAc residues were determined by the characteristic chemical shifts of the resonances assigned to alpha-fucose H1 and H5. The assignment of many of the resonances to sugar ring protons was possible using difference decoupling methods. The observation of nuclear Overhauser effects between the anomeric protons and the aglycone protons of adjacent residues confirmed the assignment of the glycosidic linkages.


Subject(s)
Milk, Human/analysis , Oligosaccharides/analysis , Chromatography, High Pressure Liquid , Female , Humans , Hydrolysis , Magnetic Resonance Spectroscopy , alpha-L-Fucosidase
17.
Biochim Biophys Acta ; 802(1): 29-40, 1984 Nov 06.
Article in English | MEDLINE | ID: mdl-6487655

ABSTRACT

Normal-phase high-pressure liquid chromatography (HPLC) on amino-bonded silica with elution by aqueous acetonitrile is shown to be an especially suitable complement to reverse-phase HPLC on octadecyl silica for the fractionation of oligosaccharide alditols produced by alkaline borohydride degradation of mucin glycoproteins. The former technique separates well on the basis of molecular size, while the latter method shows selectivity for stereoisomers. Stereoisomeric pairs of tetra-, penta- and hexasaccharide alditols show relative retention times ranging from 3 to 12, resulting in excellent preparative separations in reverse-phase chromatography. From a single ovarian cyst glycoprotein, H and Lewis b active, 13 oligosaccharides, representing essentially the entire carbohydrate content, have been isolated. The structures of 12 of the oligosaccharides have been determined by 1H-NMR spectroscopy. For those oligosaccharides which have been isolated from other sources and whose NMR spectra have been previously reported, unambiguous structural identification follows directly. Structures of oligosaccharides differing by only one or two residues from those whose NMR spectra are known may be deduced by a simple algorithm utilizing chemical shift analogies.


Subject(s)
Mucins/analysis , Oligosaccharides/analysis , Ovarian Cysts/analysis , Sugar Alcohols/analysis , Chromatography, High Pressure Liquid , Female , Humans , Magnetic Resonance Spectroscopy
18.
Biochim Biophys Acta ; 798(2): 283-90, 1984 Apr 10.
Article in English | MEDLINE | ID: mdl-6712992

ABSTRACT

Oligosaccharides were cleaved by base-borohydride from an I, H and Lea active ovarian cyst glycoprotein and purified by Bio-Gel P-6 and paper chromatography. The structures of five oligosaccharides, determined by compositional analyses, quantitative periodate oxidation, chronic acid oxidation, methylation analyses and enzymatic degradations, were as follows: oligosaccharide I, beta DGal1----3DGalNAc-ol; II, beta DGal1----4 beta DGlcNAc1----6(beta DGal1----3)DGalNAc-ol; III, alpha LFuc1----2 beta DGal1----4 beta DGlcNAc1----6(beta DGal1----3)DGalNAc-ol; IV, beta DGal1----3(alpha LFuc1----4)beta DGlcNAc1----3beta DGal1----4 beta DGlcNAc1----6(beta DGal1----3)DGal1NAcol; and V, beta DGal1----3(alpha LFuc1----4)beta DGlcNAc1----3 beta DGal1----4 beta DGlcNAc1----6[beta DGal1----3(alpha LFuc1----4)beta DGlcNAc1----3 beta DGal1----3 beta DGal1----3]DGalNAc-ol. Of the oligosaccharides 60% had a molecular size of a decasaccharide or smaller, the tetra- and pentasaccharides II and III predominating. Oligosaccharides I through IV have been previously isolated from several glycoproteins by other laboratories; the decasaccharide, V, is a new structure.


Subject(s)
ABO Blood-Group System , Blood Group Antigens , Lewis Blood Group Antigens , Oligosaccharides/isolation & purification , Ovarian Cysts/metabolism , Carbohydrate Conformation , Carbohydrate Sequence , Female , Glycoproteins/isolation & purification , Humans , I Blood-Group System
19.
Vox Sang ; 46(2): 75-9, 1984.
Article in English | MEDLINE | ID: mdl-6702145

ABSTRACT

The ABO group, Lewis type and secretor status were determined in 546 normal individuals (241 male, 305 female). Their serum was tested at 4 degrees C for agglutination of group O red blood cells; the antibody was presumed to be auto-anti-I; the results were expressed as a score. Among non-A female donors, the score was higher for secretors than nonsecretors (p less than 0.05). Among non-A secretors of both sexes, female donors had a higher score than male donors (p less than 0.05). These results suggest that the level of anti-I in the serum of normal individuals may be affected by the donor's ABO group, secretor status and sex.


Subject(s)
ABO Blood-Group System/genetics , Agglutinins/immunology , Saliva/immunology , Sex Characteristics , ABO Blood-Group System/immunology , Adolescent , Adult , Blood Grouping and Crossmatching , Cryoglobulins , Female , Hemagglutination Tests , Humans , I Blood-Group System/genetics , I Blood-Group System/immunology , Lewis Blood Group Antigens/genetics , Male
20.
Breast Cancer Res Treat ; 4(2): 105-8, 1984.
Article in English | MEDLINE | ID: mdl-6331553

ABSTRACT

Breast carcinoma (BCa) cells produce I antigen or I antigen-like substances that may influence serum anti-I. We determined cold hemagglutinins in 170 BCa patients, 97 women with benign breast disease, and 37 female controls of comparable ages to the patients. The results were expressed as an anti-I score. Serum IgM was measured by radial immunodiffusion. The data for the BCa patients were analyzed by pathologic stage (PS) and histologic category. The anti-I score for PS III (28.1 +/- 13.0; mean +/- S.D.) was higher (p less than 0.02), and that for PS IV (11.4 +/- 7.4) lower (p less than 0.02) than the control value (17.7 +/- 10.2). IgM concentrations of the BCa patients as a group or by PS were similar to those of the controls. The mean anti-I scores were higher in mucinous (31.1 +/- 14.9, p less than 0.001) and apocrine BCa (28.6 +/- 16.2, p less than 0.02) compared to the control value. IgM concentrations were elevated in mucinous (218.1 +/- 85.8 mg/dl, p less than 0.01) and apocrine BCa (241.9 +/- 99.0, p less than 0.005) compared to the control value (157.1 +/- 66.9). The results suggest an association of anti-I scores and PS of BCa and suggest an antigenic difference of mucinous and apocrine from infiltrative ductal BCa.


Subject(s)
Agglutinins/analysis , Antibodies, Neoplasm/analysis , Breast Neoplasms/immunology , Immunoglobulin M/analysis , Adenocarcinoma/immunology , Adenocarcinoma, Mucinous/immunology , Adult , Aged , Carcinoma, Intraductal, Noninfiltrating/immunology , Cryoglobulins , Female , Humans , Middle Aged
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