Relationship between rate of glucose or propionate infusion and milk protein yield and concentration in dairy cows: A meta-regression.

Although postruminal glucose infusion into dairy cows has increased milk protein yield in some past experiments, the same trend has not been observed in others. A meta-regression of 64 sets of observations from 29 previously published glucose and propionate infusion studies in dairy cattle, treating study and experiment (study) as random effects, was performed to establish the general effects of glucose equivalent (GlcE) infusion rate on milk true protein (MTP) yield and content, if any, and to identify independent, fixed-effect variables that accounted for the changes in MTP yield and content that were observed. Candidate explanatory variables included rate and site of infusion, diet composition and intake, body weight and lactation stage of the cows, and the change in nutrient intake between GlcE and control treatments. Across all studies, according to a model containing only the random effects of study and experiment, GlcE infusion at an average of 954 g/d increased MTP yield by 26 g/d, on average, whereas mean MTP content was not affected. Backward stepwise elimination of potential explanatory variables from a full mixed model produced a final, reduced model for MTP yield that retained a positive, second-order quadratic effect of infusion rate of GlcE and a positive, linear effect of the change in crude protein intake (CPI) between GlcE treatment and control. This change in CPI due to GlcE infusion ranged from -0.546 to 0.173 kg/d in the dataset. The model fit indicated that when CPI was allowed to drop during GlcE infusion, the effect of GlcE on MTP yield was smaller than when CPI was maintained or increased, in a manifestation of the classic protein:energy interaction. The final reduced model for MTP content contained the same explanatory variables as for MTP yield, plus a negative effect of intravenous compared with gastrointestinal infusion. Overall, the meta-analysis revealed that both MTP yield, and content were positively related to GlcE infusion rate and to the change in CPI between glucose treatment and control.

Differential voluntary feed intake and whole transcriptome profiling in the hypothalamus of young sheep offered CP and phosphorus-deficient diets.

A reduction in voluntary feed intake is observed in ruminants consuming nutrient-deficient diets, such as those with a low CP or P content, and has been attributed to active metabolic regulation, rather than a physical constraint. The hypothalamus is the key integrator of feed intake regulation in mammals. The objectives of this experiment were to (1) establish a model of metabolic feed intake regulation in ruminants consuming diets of variable CP and P content, and (2) determine key biochemical pathways and influential points of regulation within the hypothalamus. Merino wethers [n = 40; 23.7 ± 1.4 kg liveweight (mean ± SD)] were fed one of five dietary treatments (n = 8/treatment) for 63 days in individual pens. The treatments included targeted combinations of high (H) and low (L) CP (110 and 55 g/kg DM) and high and low P (2.5 and 0.7 g/kg DM) with 9 MJ metabolisable energy (ME) per kg DM which were fed ad libitum (UMEI; unrestricted ME intake) resulting in four experimental diets (HCP-HP-UMEI, LCP-HP-UMEI, HCP-LP-UMEI and LCP-LP-UMEI). An additional nutritional treatment (HCP-HP-RMEI) restricted intake of the HCP-HP diet to an equivalent ME intake of wethers consuming the LCP-LP-UMEI treatment. Wethers offered the LCP-HP-UMEI, HCP-LP-UMEI and LCP-LP-UMEI treatments consumed 42, 32 and 49% less total DM (P ≤ 0.05), respectively than the HCP-HP-UMEI treatment, and this was not attributable to any physical limitation of the rumen. Plasma concentrations of urea nitrogen and inorganic phosphate indicated that these nutrient deficiencies were successfully established. To assess potential mechanisms, RNA-seq was conducted on samples from the arcuate nucleus (ARC), ventromedial hypothalamus and lateral hypothalamus of the wethers, yielding a total of 301, 8 and 148 differentially expressed genes across all pairwise comparisons, respectively. The expression of NPY, AGRP and CARTPT, known for their regulatory role in mammalian feed intake regulation, had a similar transcriptional response in the ARC of wethers consuming nutrient-deficient treatments and those consuming a ME-restricted treatment, despite these wethers expressing behaviours indicative of satiated and hungry states, respectively. In addition, genes involved with glycolysis (TPI1), the citric acid cycle (CS, OGDH, GLUD1, GOT1) and oxidative phosphorylation (COX5A, ATP5MC1, ATP5F1B, ATP5MC3) were downregulated in the ARC of wethers fed a nutrient deficient (LCP-LP-UMEI) relative to the non-deficient (HCP-HP-UMEI) treatment. In summary, a model for voluntary feed intake restriction was established to determine genome-wide molecular changes in the hypothalamus of young ruminants.

Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.

We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.

Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica.

Establishment of adherence by Entamoeba histolytica is mediated by a 170-kD Gal/GalNAc inhibitable lectin and is required for cytolysis and phagocytosis of mammalian target cells. We studied the biochemical mechanisms of the in vitro interaction between rat and human colonic mucins and axenic E. histolytica trophozoites. Crude mucus prevented amebic adherence to Chinese hamster ovary (CHO) cells by up to 70%. Purification of the colonic mucins by Sepharose 4B chromatography, nuclease digestion, and cesium chloride gradient centrifugation resulted in a 1,000-fold enrichment of the inhibitory mucins. Purified rat mucin inhibited amebic adherence to and cytolysis of homologous rat colonic epithelial cells. Oxidation and enzymatic cleavage of rat mucin Gal and GalNAc residues completely abrogated mucin inhibition of amebic adherence. The binding of rat 125I-mucin to amebae was galactose specific, saturable, reversible, and pH dependent. A monoclonal antibody specific for the 170-kD amebic Gal/GalNAc lectin completely inhibited the binding of rat 125I-mucin. Rat mucin bound to Affigel affinity purified the amebic lectin from conditioned medium. Colonic mucin glycoproteins act as an important host defense by binding to the parasite's adherence lectin, thus preventing amebic attachment to and cytolysis of host epithelial cells.

Extramedullary hematopoiesis. A cause of severe generalized lymphadenopathy in agnogenic myeloid metaplasia.

Although microscopic evidence of extramedullary hematopoiesis in lymph nodes is a frequent finding in autopsy studies of patients with agnogenic myeloid metaplasia, clinically significant lymphadenopathy is a rare occurrence. In this article we describe an unusual case of severe generalized lymphadenopathy and lymphedema secondary to extramedullary hematopoiesis in multiple lymph nodes. With the use of low-dose radiotherapy, both the lymphadenopathy and lymphedema resolved.

Avoiding the cost of males in obligately asexual Daphnia pulex (Leydig).

Asexual organisms are thought to gain an advantage by avoiding the cost of producing males. In the cladoceran Daphnia pulex (Leydig), male production is determined by the environment and is independent of the origin of the asexual obligate parthenogens from the sexual cyclical parthenogens. If there is a cost to producing males, successful obligate parthenogens should have reduced or eliminated male production. Field and laboratory observations showed that obligate parthenogens have much-reduced male production compared to cyclical parthenogens. Although the reduction or elimination of males in the obligate parthenogens suggests that the cost of males is avoided, the coexistence of sexual and asexual forms of D. pulex may be partially explained by cyclical parthenogens compensating for the cost of males by having greater fecundity. In addition, the absence of a mating constraint for the obligate parthenogens may favour an increased allocation to asexual diapausing eggs earlier in the season compared to the cyclical parthenogens which require mating with males to produce sexual diapausing eggs. No difference in the production of diapausing eggs was observed, probably because males were abundant in populations of cyclical parthenogens and do not appear to limit the production of sexual diapausing eggs. D. pulex is a useful system for determining the ecological consequences of abandoning sexual reproduction and explaining the coexistence of sexual and asexual forms of a species.

Immunophenotypic analysis of sinonasal non-Hodgkin's lymphomas.

A panel of paraffin effective antibodies recognizing B cells and T cells (LN-2, MB1, L26, MT1, UCHL1, kappa, lambda) was used to characterize the immunophenotypes of 26 sinonasal non-Hodgkin's lymphomas. Seventeen tumors were stage I, five were stage II, one was stage III, and three were stage IV. Nine lymphomas were classified morphologically as large cell, six were large cell immunoblastic, six were small cleaved cell, two were mixed small and large cell, two were small noncleaved cell, and one was lymphoblastic. None were follicular. Twenty-two lymphomas had a B cell immunophenotype, three were T cell neoplasms, and one was immunoreactive only for MT1. This predominance of sinonasal lymphomas with a B cell immunophenotype in patients residing in the United States contrasts with the almost exclusive occurrence of T cell sinonasal lymphomas in Chinese patients living in Hong Kong and Japanese patients residing in regions of Japan that are nonendemic for human T cell leukemia virus-1.

Intranasal tolerance and histopathologic effects of a novel synthetic interferon, rIFN-alpha Con1.

In a double-blind trial 119 adults were randomly assigned to receive daily sprays of placebo (N = 30) or rIFN-alpha Con1 3 MU (N = 29), 9 MU (N = 30), or 30 MU (N = 30) per day for 25 consecutive days. Fifty-nine subjects were removed from treatment because of abnormal nasal exams (N = 56) or irritative symptoms (N = 3). The fraction of drop-outs in the placebo group (30%) was significantly different (P less than 0.05) from that in the 3 MU (55%), 9 MU (57%), or 30 MU (67%) groups. Nasal mucosal biopsies collected 1-2 days after completing spray use detected moderate or marked lymphocytic infiltration in 10% of placebo (N = 10), 90% of 3 MU (N = 9), 85% of 9 MU (N = 13), and 70% of 30 MU (N = 10) subjects (P less than 0.05, placebo vs each rIFN-alpha Con1 group). All 3 dose levels of rIFN-alpha Con1 were associated with significant clinical and histopathologic signs of nasal irritation. The findings suggest that intranasal rIFN-alpha Con1 does not have a more favorable therapeutic index than rIFN-alpha 2 and that the risk of nasal irritation relates more closely to the anti-viral activity than the protein content of the rIFN-alpha administered.

Tolerance and nasal histopathologic effects of long-term, low-dose intranasal recombinant interferon alpha-2A (Roferon-A).

The dose-related tolerance and histopathologic effects of intranasal recombinant interferon alpha-2a (rIFN-alpha 2a) were determined in a blind study in which healthy subjects were randomized to receive sprays of interferon (IFN) (3 or 6 MU/day) or placebo for 28 days. Adverse nasal symptoms (bleeding, obstruction, irritation) tended to occur more often in the IFN 6 MU/day group. Blind analysis of biopsy samples collected before and after IFN treatment revealed that both IFN groups had significant histologic changes, most commonly an increased degree of lymphocytic infiltration in the subepithelium and underlying glandular zones. Changes developed in 61% of 18 recipients of IFN 6 MU/day, 37% of 19 recipients of IFN 3 MU/day, and 6% of 18 placebo recipients. Serum antibodies to rIFN-alpha 2a detectable by EIA were found in 4 recipients of IFN 3 MU/day and 2 recipients of IFN 6 MU/day, one-third of whom were positive by neutralization bioassay. The findings would predict that these rIFN-alpha 2a dosages would be associated with an excess of adverse side effects during long-term use in healthy adults.

Nonspecific esterase staining patterns in acute monocytic leukemia.

Staining patterns for nonspecific esterase (NSE) were analyzed retrospectively in 14 cases of acute monocytic leukemia (M5) using alpha-naphthyl acetate as substrate. An attempt was made to correlate variability in NSE activity with clinical findings. Two staining patterns were distinguished: (1) diffuse fine granular cytoplasmic staining, and (2) dense focal staining superimposed on a weak positive cytoplasmic background. The 14 cases were divided into two groups according to their different staining qualities: Group 1 (6) diffuse and Group 2 (8) focal. All six cases of Group 1 were typical hypercellular acute leukemias. Group 2 contained four cases of hypercellular acute leukemia and four cases of hypocellular acute leukemia. All the cases of hypocellular leukemia showed the pattern of focal NSE activity. No difference in the clinical presentation or course of the disease between Groups 1 and 2 was found.

Promyelocyte morphology. Differentiation of acute promyelocytic leukemia from benign myeloid proliferations.

Bone marrow aspirates from patients with acute agranulocytosis or a marked left shift in myeloid maturation can mimic acute leukemia, particularly acute hypergranular promyelocytic leukemia. Bone marrow aspirates from 16 cases of apparent acute promyelocytic leukemia, 4 cases of acute agranulocytosis, and 1 case of a marked myeloid left shift were studied for the presence or absence of differentiating features. Normal or reactive promyelocytes were characterized by prominent paranuclear clear Golgi zones, whereas promyelocytes from true leukemic cases all had heavy azurophilic granules dispersed diffusely throughout the cytoplasm. Prominent Golgi zones in promyelocytes were associated only with benign myeloid conditions and were not observed in acute promyelocytic leukemia. The presence of prominent clear Golgi zones in promyelocytes is an important feature assisting in the distinction between leukemic and benign promyelocytes.

Platelet vacuoles in acute megakaryoblastic leukemia.

The case of a 53-year-old man with acute megakaryoblastic leukemia (M7) was studied. At time of diagnosis, the platelet count was 980 X 10(9)/L and abnormal platelet vacuoles were present. The vacuoles were periodic acid-Schiff (PAS) positive. Electron microscopic examination showed large aggregates of glycogen. Findings of qualitative platelet function studies were abnormal. The authors' study and review of the literature indicates that thrombocytosis with large platelet vacuoles accompanying a blast cell population suggests a diagnosis of M7 and indicates the need for appropriate confirmatory studies.

Non-Hodgkin's lymphomas of the sinonasal region: histologic subtypes and their clinicopathologic features.

The authors describe 11 patients with non-Hodgkin's lymphoma arising in the nasal cavity or paranasal sinuses. Seven were men and four were women. The median age of the women was 76 years; the median age of the men was 45 years. The most common presenting symptoms were nasal obstruction and unilateral facial swelling. The most frequent sites of disease were maxillary antrum (ten cases), nasal cavity (eight cases), and ethmoid sinus (seven cases). Eight patients had involvement of multiple sinuses. Six patients were clinical stage I E, two were II E, one was stage III E, and two were stage IV. Histologic subtypes included diffuse small cleaved cell (1 case), diffuse large cell (4 cases), and diffuse large cell immunoblastic (6 cases). Three patients having immunoblastic lymphoma had longstanding sinusitis, rhinitis, and allergies. Overall, 55% of patients died of disease. Three of four patients with the diffuse large cell subtype were free of tumor (mean follow-up 50 months). Five of six patients having immunoblastic lymphoma died of disease from 1 to 13 months following diagnosis (mean 6.4 months).

Salivary duct carcinoma: an analysis of four cases with review of literature.

Salivary duct carcinoma (SDC) is a histologically distinctive neoplasm of the parotid gland. The criteria for the diagnosis of SDC are circumscribed epithelial nests having a papillary, cribriform, and/or solid architecture coupled with central necrosis. The infiltrating cancer can be papillary, resembling the intraductal component or have a nonspecific, undifferentiated pattern. The authors are presenting four cases and compare them with 11 other acceptable cases from the literature. The neoplasm occurs beyond the age of 50 (median 63 years) and has a dismal prognosis with nearly two-thirds of the patients developing distant metastases. All surviving patients have been treated with combined parotidectomy and radiotherapy.

Megakaryocytic leukemia; identification utilizing anti-factor VIII immunoperoxidase.

Coagulation Factor VIII is produced by endothelial cells and megakaryocytes. Antibody directed against Factor VIII or its associated antigens has been shown to be a sensitive marker for both normal and neoplastic endothelial cells. Its use to identify neoplastic megakaryocytes has not been described. We used immunoperoxidase localization of Factor VIII to identify megakaryocytes and immature megakaryocytic precursors in a case of megakaryocytic leukemia.

Immunoglobulin gene rearrangement in abnormal lymph node hyperplasia.

The histologic designation "abnormal lymphoid hyperplasia" is applied to lymph nodes demonstrating varying degrees of architectural effacement and/or cytologic atypia. Although some of these cases may be suggestive of non-Hodgkin's lymphoma, a definitive diagnosis is not possible despite careful morphologic and immunophenotypic studies. Because the demonstration of immunoglobulin and T-cell receptor gene rearrangements by Southern blot analysis provides a sensitive marker of lineage and clonality in lymphoid malignant conditions, the frequency with which such gene rearrangements could be identified in abnormal hyperplasia and their significance were studied. DNA samples from lymph node biopsy samples of 11 patients with abnormal lymphoid hyperplasia were analyzed for rearrangements of immunoglobulin and T-cell receptor genes by Southern blot hybridization. Six of these patients had monoclonal B-cell populations identified by immunoglobulin gene rearrangements; all were found subsequently to have non-Hodgkin's lymphoma by repeated biopsy from 8 days to 46 months later. Two patients with negative Southern blot studies also developed lymphoma, one a T-cell non-Hodgkin's lymphoma and one a cutaneous B-cell non-Hodgkin's lymphoma. Three patients without detectable gene rearrangements showed no evidence of malignant lymphoma at 36-, 45-, and 60-month follow-up evaluations. Southern blot analysis thus identified monoclonal B-cell lymphoid populations in a subset of patients with abnormal lymphoid hyperplasia; the presence of clonal immunoglobulin gene rearrangement predicted progression to overt non-Hodgkin's lymphoma.

Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians.

Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR-based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) TaqI B (P = .029) and the GABAA-beta2 subunit C1412T (P = .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2 TaqI A, or the GABAA alpha1(A15G), alpha6(T1519C), and gamma2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P = .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-beta2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.

UDP-sugar hydrolase isozymes in Salmonella enterica and Escherichia coli: silent alleles of ushA in related strains of group I Salmonella isolates, and of ushB in wild-type and K12 strains of E. coli, indicate recent and early silencing events, respectively.

Escherichia coli contains a single periplasmic UDP-glucose hydrolase (5'-nucleotidase) encoded by ushA. Salmonella enterica, serotype Typhimurium, also contains a single UDP-glucose hydrolase but, in contrast to E. coli, it is membrane-bound and is encoded by the non-homologous ushB gene; Salmonella enterica (Typhimurium) also contains a silent allele of the ushA gene (ushA0). In this report, we show that nearly all natural isolates of Salmonella contain both UDP-sugar hydrolases, i.e. they are UshA+ UshB+. The only exceptions are all from sub-group I (S. gallinarum, S. pullorum, and most Typhimurium strains), are UshA- UshB+, and several have been shown to contain an ushA0 allele. These data, together with the fact that these latter strains are closely related genetically, strongly suggests a recent silencing mutation(s). We also report the presence in E. coli K-12, and in natural isolates of E. coli, of a DNA sequence which is homologous to the ushB gene of Salmonella; since E. coli does not contain UshB activity, we tentatively refer to this sequence as ushB0. Since all E. coli strains investigated are UshB-, we conclude that the silencing mutation(s) occurred relatively early following the divergence of Escherichia coli and Salmonella from a common ancestor that was ushA+ ushB+.

Gamma heavy chain disease: report of a case associated with trisomy of chromosome 7.

A case of gamma heavy chain disease is reported in a 52-year-old white male who presented with fever and generalized lymphadenopathy. A lymph node biopsy showed malignant lymphoma. A partial transient response was obtained with cyclophosphamide, vincristine, prednisone, and doxorubicin. He died 3 months after diagnosis from disease progression and infectious complications. Chromosome analysis of cells from an involved lymph node showed the presence of trisomy 7. Chromosome abnormalities have been reported in three of ten previously published cases of gamma heavy chain disease. Trisomy of chromosome #7 has not previously been reported.

Primary gastric lymphoma. Problems in staging and management.

A retrospective review of 28 patients with primary gastric lymphoma was performed to determine the optimal treatment modality. The presenting signs and symptoms resembled peptic ulcer disease or gastric carcinomas. The majority of the lymphomas were of the diffuse histiocytic subtype. There was a 75 percent resectability rate in those patients operated on. Palliative resection produced a 5 year duration of survival of 28 percent and curative resection, 43 percent. Eighteen patients underwent a subtotal gastrectomy, and a total of 10 patients presented with stage I disease. The longest median duration of survival at last follow-up was 32 months for patients with stage IB disease compared with a median duration of survival of 8 months for those with stage III disease. Adjuvant radiotherapy and chemotherapy may improve survival after a curative resection is performed if there is serosal penetration or nodal involvement.