Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet.

Although plasma cholesterol levels are not generally associated with Alzheimer disease (AD) incidence, in vitro studies have found that increased cellular cholesterol levels are associated with increases in -amyloid (A ) production, with a concomitant decrease in sAPPa, the secreted non amyloidogenic fragment of the amyloid precursor protein (APP). In two previous studies using a mouse model for AD-like pathology, non-physiological high-cholesterol diet has been shown to increase plasma and cerebral cholesterol levels, but have resulted in conflicting results on cerebral A levels. In the present study APPSWE male transgenic mice were fed either a chow diet or a physiological high-fat high-cholesterol Western-type diet until the mice reached 1 year of age. Mice fed the Western type diet, compared to the low-fat chow diet, had increased body weight, plasma and cerebral cholesterol levels, as well as a 50% increase in cerebral A levels. Cerebral levels of total APP were not altered while cerebral apoE levels were increased in the mice fed the Western-type diet, versus the chow-fed mice. These data demonstrate that chronic intake of a non-toxic high-cholesterol diet, which is similar to a human diet in fat and cholesterol content, was effective in increasing A levels and further suggests that dietary cholesterol and/or fat may be a risk factor for AD.

Brain region-specific up-regulation of mouse apolipoprotein E by pharmacological estrogen treatments.

Cerebral apolipoprotein E (apoE) has been implicated in neuronal protection and repair. Due to the variable levels and types of estrogen receptors within different brain regions, the effect of estrogen on apoE and the mechanism of this effect may vary within different regions. Ovariectomized female C57BL/6 mice were treated with pharmacological levels of 17 beta-estradiol or placebo for 5 days, resulting in supraphysiological plasma levels of estradiol in the treated mice. ApoE and glial fibrillary acidic protein (GFAP) levels were measured in the cortex, hippocampus and diencephalon. 17 beta-Estradiol up-regulated apoE but not GFAP in the cortex and diencephalon, whereas in the hippocampus, GFAP and apoE were equally up-regulated. Treatment of estrogen receptor (ER) alpha knockout mice with 17 beta-estradiol or treatment of C57BL/6 mice with 17 alpha-estradiol, a poor estrogen receptor agonist, specifically induced apoE in the cortex, but not in the diencephalon. These results indicate that 17 beta-estradiol effects on apoE are either directly or indirectly mediated by ER alpha in the diencephalon, while the effects in the cortex may be mediated by a non-classical mechanism or by ER beta. Measurement of mRNA levels in estrogen versus placebo-treated wild-type mice indicated that the effect of 17 beta-estradiol on apoE was not associated with changes in apoE mRNA levels.

Long-term study of gammopathies. Clinically benign cases showing transition to malignant plasmacytomas after long periods of observation.

Since 1968, our Clinical Chemistry laboratory has been performing protein electrophoresis on sera of patients with total protein levels of over 85.0 g/L and under 55.0 g/L. Monoclonal gammopathies were found in 534 cases. Immunoelectrophoresis was carried out using antisera to the heavy chains gamma, alpha, mu, delta, and epsilon, and to the light chains kappa and lambda. Urine from these patients was tested for Bence-Jones protein. Records and smears, when available, were examined for clinical or hematologic evidence of multiple myeloma and other lymphoid malignancies. Sixty-five percent of these 534 cases were referred to the laboratory with a provisional diagnosis of plasmacytoma but 35% were not clinically suspected. Twenty-two cases with gammopathy, but no clinical or hematologic symptoms of plasma cell dyscrasia, were selected and followed up. Eight of these patients (36%) had converted to malignancy by the end of ten years. These results show the value of screening for abnormal proteins and the need for a long-term follow-up in such patients, prior to diagnosis of plasma cell dyscrasia.

Nephronophthisis with massive proteinuria.

A 23-year-old male whose uncle died of nephronophthisis, and whose pathology is also discussed, presented with 5 g of protein in a 24-hour urine collection. Nephrogenic diabetes insipidus and salt wasting were present in addition to azotemia. Characterization of the proteinuria, including elevated alpha globulins by electrophoresis and markedly elevated urinary beta-microglobulins by radioimmunoassay (49.55 mg/L) indicated predominantly tubular proteinuria. A percutaneous renal biopsy showed normal glomeruli, interstitial inflammation and fibrosis, and tubular atrophy. Electron microscopy revealed notable alterations of the tubular basement membrane.

hPL deficiency with normal estriol levels in a normal pregnancy.

The third published case of human placental lactogen (hPL) deficiency in a normal pregnancy is reported. The results of the 3 cases are discussed. In all cases, estriol levels were normal and hPL levels were either unmeasurable or below 1 microgram/ml. The placenta showed no obvious abnormalities. Growth hormone and prolactin determinations did not contribute to the understanding of the deficiency; neither did the glucose levels in the maternal blood. All 3 infants were male.

Yersinia enterocolitica: biochemical, serological, and gas-liquid chromatographic characterization of rhamnose-, raffinose-, melibiose-, and citrate-utilizing strains.

Thirteen atypical Yersinia enterocolitica isolates, all fermenting rhamnose, raffinose, and melibiose and utilizing sodium citrate within 24 to 48 h at 22 degrees C (Y.e.rh+), were examined biochemically-serologically, and by gas-liquid chromatography. These data, as well as cultural, biochemical, and antibiotic susceptibility data gathered from two previous studies involving (i) these same atypical Y.e.rh+ isolates, (ii) Y. enterocolitica serotypes O:1 through O:15 (rhamnose, raffinose, and citrate negative [Y.e.rh-]), (iii) Y. enterocolitica serotype O:16 (rhamnose positive but raffinose and citrate negative), and (iv) Yersinia pseudotuberculosis serogroups I through V were statistically compared. Both preand postabsorption agglutination studies demonstrated the serological distinctiveness of Y.e.rh+ from Y.e.rh- and Y. pseudotuberculosis. At the same time, three immunological groups among the 13 Y.e.rh+ strains were seen; 8 corresponded to Y. enterocolitica serotype O:17; 1 to Y. enterocolitica serotype O:16; and the remaining four were nontypable in antisera against known Y. enterocolitica antigen types. Each of the three Yersinia groups tested chromatographically produced acetic and lactic acids. Both Y.e.rh- and Y.e.rh+ formed propionic acid, but only Y.e.rh+ produced detectable amounts of succinic acid. Based on 49 variables, statistical analysis of the three Yersinia groups studied placed each of the Y.e.rh+ strains in a homogeneous group separate from both Y.e.rh- and Y. pseudotuberculosis. These data, coupled with deoxyribonucleic acid homology studies of Brenner and co-workers (D. J. Brenner, A. G. Steigerwalt, D. F. Falcao, R. E. Weaver, and G. R. Fanning, Int. J. Syst. Bacteriol. 26:180-194, 1976), support the distinctiveness of Y.e.rh+ from typical Y. enterocolitica and Y. pseudotuberculosis.

Unusual Yersinia enterocolitica isolates not associated with mesenteric lymphadenitis.

Thirteen Yersinia enterocolitica were recovered from a variety of clinical sources. Of these, only one was associated with mesenteric lymphadenitis and belonged to serotype 8. The 12 remaining strains were isolated from nonmesenteric sources and belonged to serotype 17. All strains exhibited the main characteristics of Y. enterocolitica which differentiated them from other Enterobacteriaceae, i.e., motility at 22 C but not at 37 C, positive urease and ornithine decarboxylase activities, and negative phenylalanine deaminase. These 12 strains differed, however, from other Y. enterocolitica previously described in the United States in that they fermented rhamnose and raffinose at 22 C, and failed to grow on Salmonella-Shigella and Hektoen-Enteric agars.

Characteristics of a bacteriocin derived from Streptococcus faecalis var. zymogenes antagonistic to Diplococcus peumoniae.

A bacteriocin-producing strain of Streptococcus faecalis var. zymogenes (E-1) was isolated from clinical material (conjunctiva). The active substance differed from bacteriocins described by other investigators primarily in its spectrum of antibacterial activity, especially by its marked inhibition of Diplococcus pneumoniae. The E-1 bacteriocin also inhibited nonhemolytic strains of enterococci as well as one-third of the Viridans group of streptococcal strains investigated. The degree of inhibition, however, as indicated by the size of the zones against the latter organisms, was significantly reduced. No activity was detected against any of the strains belonging to the following groups of bacteria: hemolytic enterococci, beta-hemolytic streptococci, nonhemolytic streptococci, staphylococci, and various gram-negative species. Similarly, three strains each of Bacillus cereus and Listeria monocytogenes and one strain of Erysipelothrix insidiosa were not inhibited. The bacteriocin was able to diffuse through bacterial membranes as well as cellulose dialyzer tubing. It was inactivated by heating to 80 C for 20 min but resisted inactivation by either trypsin or chloroform.

Association of mucoid encapsulated Moraxella duplex var. nonliquefaciens with chronic bronchitis.

The recovery of two strains of highly mucoid encapsulated Moraxella duplex var. nonliquefaciens from the sputum of two patients suffering from chronic bronchitis is described. The biochemical, morphological, and pathogenic characteristics of this microorganism are discussed.