Blood cholesterol and apolipoprotein B levels in relation to intakes of animal and plant proteins in US adults

Few studies have examined the association between specific sources of protein and blood lipids in a national sample of adults. We examined this relationship in a sample of adults 20 years and older who participated in phase 1 (1988-91) of the Third National Health and Nutrition Examination Survey, a representative sample of the United States non-institutionalized population. After excluding those participants who reported having been told they had high blood cholesterol concentrations, the final sample size was 6228. Mean intakes of different sources of proteins, as a percentage of total protein, were compared in quartiles of blood lipids. Intakes were adjusted for age, sex and race. Additional adjustments were made for other dietary variables, recall day, BMI, smoking, and income. We observed a lower percentage meat, fish and poultry (MFP) protein intake, including a lower percentage of beef and pork protein, among persons in the lowest quartile of serum total cholesterol and apolipoprotein B (ApoB) concentrations than among persons in the higher quartiles. The percentage of plant protein intake was higher in the lowest quartile than in the highest quartile of serum cholesterol. We also observed a higher percentage of fruit protein intake with lower serum cholesterol and ApoB concentrations. We conclude that in this cross-sectional sample, consumption of MFP proteins was consistently higher among persons with higher cholesterol concentrations while consumption of plant proteins was consistently higher among persons with lower cholesterol concentrations. Our findings support the importance of assessing intake of specific protein sources, especially in studies that address dietary intake in relation to blood lipids.     

Isolation of Malassezia furfur from a cat

During a survey of the occurrence of Malassezia species in the external ear canals of cats without otitis externa, Malassezia furfur was isolated. This is the first report of the isolation of M. furfur from cats.     

Correlation between changes in morphology, electrical properties, and angiotensin-converting enzyme activity in the failing heart.

Evidence is available that morphologic and electrophysiologic abnormalities are present in the failing heart. In the present work, the progressive changes in electrical properties and morphology of the failing heart of Syrian cardiomyopathic hamsters (TO2) were investigated at different stages of the pathological process, and the possible role of the renin-angiotensin system was studied. Cardiomyopathic hamsters 2 and 11 months of age were used. Age-matched normal hamsters (F1B) were utilized as controls. Measurements of membrane potential, conduction velocity and refractoriness were made with conventional intracellular electrodes connected to a high impedance DC amplifier. Serum and cardiac angiotensin-converting enzyme (ACE) activities were measured in controls and cardiomyopathic animals. The results indicated that interstitial fibrosis and calcification were present in the heart of 2-month old Syrian cardiomyopathic hamsters. Measurements of the resting potential performed in the isolated right ventricle of 2-month old Syrian cardiomyopathic hamsters indicated an average value of -66.7 +/- 0.96 mV (n = 25); in the controls of the same age was -78.5 +/- 1 mV (n = 25, P < 0.05); and in 11-month old cardiomyopathic hamsters was -67.8 +/- 0.83 mV (n = 10). The duration of the action potential measured at 50 and 90% of repolarization in 2-month old hamsters was well above the controls. The conduction velocity measured in the isolated right ventricle of 2-month old Syrian cardiomyopathic hamsters (44.2 +/- 1.6 cm/s, n = 12) was not different from the control (43.7 +/- 1.1 cm/s, n = 7, P > 0.05) but was significantly larger than that recorded from the ventricle of 11-month old animals (37.8 +/- 2.9 cm/s, n = 11, P < 0.05). ACE activity was 0.26 +/- 0.01 nmol/mg x min in the heart of controls at 2 months of age and did not change with age. Although in the 2-month old cardiomyopathic hamsters the enzyme activity (0.28 +/- 0.04 nmol/mg x min) was not different from the controls (P > 0.05), in myopathic animals at 11 months of age, the enzyme activity (0.56 +/- 0.027 nmol/mg x min) was greater than controls (P < 0.05). The ACE activity in plasma followed the same pattern. The conclusion from these experiments is, that some parameters like resting potential, action potential duration, and morphological abnormalities appeared quite early in the failing process. The decline in conduction velocity, however, appeared later on, concurrently with the activation of plasma and cardiac renin-angiotensin systems.     

Tumor proliferative activity and response to first-line chemotherapy in advanced breast carcinoma

Summary The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( 25% of stained cells) or high (> 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3–58).Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analy-sis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.Presented in part at the Annual Meeting of the American Society of Clinical Oncology, May 14–17, 1994, Dallas, TX, USA     

SIALYL-Tn ANTIGEN DISTRIBUTION IN HELICOBACTER PYLORI CHRONIC GASTRITIS IN CHILDREN: AN IMMUNOHISTOCHEMICAL STUDY

Sialyl-Tn antigen (STn) is a mucin-type carbohydrate normally present in goblet cells of small and large bowel. STn expression has been demonstrated to occur in complete and incomplete intestinal metaplasia as well as in many carcinomas but in no normal gastric cell. The aim of our present study was to evaluate the distribution of STn in Helicobacter pylori chronic gastritis (HpCG) of pediatric patients. Eighteen gastric biopsies from 15 children (mean age: 11.5 years) with HpCG, 9 gastric biopsies from 9 children without H. pylori infection, and 1 heterotopic gastric mucosa in Meckel's diverticulum were immunostained using the anti-STn antibody STn1 (18/18), NCL-MUC-1 (7/18), and NCL-MUC-2 (18/18) antibodies. Also, sulfated mucosubstances were investigated with the Alcian Blue-Periodic Acid Schiff (AB-PAS), pH 1.0 stain. Although with different intensity (weak in 5/18, moderate 9/18, and intense 4/18) all cases with HpCG exhibited STn immunoreactivity. The expression of STn was found to be located mainly to the supranuclear region of the epithelial cells at the foveolae and glandular necks, with occasional cells showing diffuse cytoplasmic staining. When reactivity was intense, it was for the most part found in the cells at the neck of the glands. The mucus out of the luminal border above the positive cells was usually also stained. MUC-1 was negative (2/7) or weakly positive (5/7) in a few surface mucous cells. MUC-2 was negative (16/18) or occasionally detected in some foveolar and surface cells (2/18). AB-PAS pH 1.0 revealed the presence of sulfomucins in the cytoplasm of isolated cells of gastric pits and glands of most cases (11/15). None of these findings was observed in the control group. We conclude that STn can be identified in gastric cells of pediatric patients with HpCG and that this does not correlate with other mucosubtances markers. Thefindings could indicate that minimal intestinal metaplasia takes place in children with HpCG.     

Identification and characterization of a T-helper peptide from carcinoembryonic antigen.

PURPOSE: The purpose of this research was to identify promiscuous T-helper cell determinants (THd) from carcinoembryonic antigen (CEA) to be used to prime T-cell help for cancer therapy. CEA was selected because this antigen is expressed in an important variety of carcinomas. EXPERIMENTAL DESIGN: Potential promiscuous THd from CEA were predicted using available computer algorithms. Predicted peptides were synthesized and tested in binding experiments to different HLA-DR molecules. Binder peptides were then used to prime T-cell responses both in vitro and in vivo. RESULTS: Twenty 15-mer peptides from CEA were predicted to bind to different HLA-DR molecules. The promiscuous character of these peptides was demonstrated in binding experiments. Fifteen of 20 peptides tested were able to bind to HLA-DR4, but only CEA (625-639) was shown to be presented after processing of recombinant CEA. CEA (625-639) was also found to be presented by HLA-DR53. Moreover, immunization of HLA-DR4 transgenic mice with CEA (625-639) in conjunction with class I epitope OVA (257-264), induced a CTL response specific of OVA (257-264). CONCLUSIONS: CEA (625-639) might be a relevant promiscuous THd peptide for cancer therapy.     

Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells.

PURPOSE: ZD1839 is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that has shown clinical activity against EGFR-expressing tumors. Our aim was to explore the effects of ZD1839 in breast cancer cell lines expressing different levels of EGFR and the closely related HER2 receptor. EXPERIMENTAL DESIGN: We studied the growth-inhibitory effects of ZD1839 in a series of breast carcinoma cell lines. In HER2-overexpressing BT-474 breast cancer cells, we studied the effects of ZD1839 on cell growth and heterodimerization of receptors under basal and ligand-stimulated conditions. RESULTS: ZD1839 was an equally potent inhibitor of growth in breast cancer cells expressing high levels of EGFR and HER2. In BT-474 breast cancer cells, ZD1839 abolished EGF- and heregulin-induced activation of ErbB receptors and downstream signaling molecules. Because ZD1839 does not inhibit the HER2 tyrosine kinase in vitro, and because heregulin is a ligand that activates HER2 by binding to HER3 and HER4 but does not bind to the EGFR, our findings suggested that ZD1839 interfered with HER2 function in intact cells. Searching for mechanisms, we report that ZD1839 induces the formation of inactive unphosphorylated EGFR/HER2 and EGFR/HER3 heterodimers. Furthermore, ZD1839 completely abolishes basal and heregulin-induced formation of active phosphorylated HER2/HER3 heterodimers. CONCLUSIONS: ZD1839 inhibits the growth of HER2-overexpressing breast cancer cells, possibly by sequestration of HER2 and HER3 receptors in an inactive heterodimer configuration with the EGFR. Our findings suggest that there is a strong rationale to conduct clinical trials of ZD1839 in patients with HER2-overexpressing breast tumors.