High Globulin Research Articles

Use of metabolic profiles in dairy cattle in tropical and subtropical countries on smallholder dairy farms

Metabolic profile testing has generally been used as part of a multidisciplinary approach for dairy herds in temperate climates. Our goal was to evaluate the effectiveness of the technique for identifying constraints on productivity in small herds in environments less favorable for milk production. Metabolites tested were chosen for stability in the sample after collection of blood, ease of analysis and practical knowledge of the meaning of the results. Blood levels of five different metabolites in low-producing dairy cows belonging to smallholders in tropical and subtropical environments were measured. The study involved 13 projects with 80 cows in each, carried out in six Latin American, six Asian, and one southern European countries. Data were also collected on feeding, body condition score (BCS) and weight change, parasitism, and reproduction. In Chile, Mexico, Paraguay, Philippines, Uruguay, and Venezuela, globulin levels were high in >17% of cows sampled on each occasion. Globulin levels were also high in Turkey and Vietnam on one or more occasions. In Paraguay, 49% of cows had high globulin levels at two to three months after calving. These results suggest that inflammatory disease was present to a potentially important degree, although this was not always investigated and not always taken into account. In all countries except Mexico and Venezuela, high β-hydroxybutyrate (BHB) levels before calving in many cows highlighted the presence of condition loss in late pregnancy, an important potential constraint on productivity and fertility. Fewer cows showed high BHB levels in lactation, whereas change in BCS and weight was more sensitive for measuring negative energy balance. Urea concentrations were low in only small numbers of cows suggesting that dietary protein shortages were not common. Albumin values were low mainly in cows where globulin values were high and, hence, did not generally provide additional information. The exception was in China where pregnant yaks over winter had high BHB and low albumin values, suggesting that they were seriously underfed. This observation stimulated a successful nutritional intervention in the following winter. Inorganic phosphate values were within the reference range in most countries a majority of the time suggesting, contrary to expectation, that this mineral was not commonly a constraint. The use of metabolic profile testing proved valuable in drawing attention to important potential constraints on productivity in dairy cows in tropical and subtropical environments and in confirming those which were not.

Febrile morbidity in severe and critical ovarian hyperstimulation syndrome: a multicentre study.

The objective of this study was to define the incidence of febrile morbidity and its causes in severe and critical ovarian hyperstimulation syndrome (OHSS). For this purpose, we reviewed the medical records of all OHSS patients hospitalized in 16 out of 19 tertiary medical centres in Israel between January 1987 and December 1996. Febrile morbidity was defined as at least one episode of temperature rise above 38 degrees C lasting > or =24 h. A total of 2902 patients (3305 hospitalizations) with OHSS was identified, of whom 196 had severe, and 13 critical, OHSS. Among the 209 patients investigated the incidence of febrile morbidity was 82.3%, of which 20.5% was attributed to urinary tract infection, 3.8% to pneumonia, 3.3% to upper respiratory tract infection, 2.0% to intravenous line phlebitis, 1.0% to cellulitis at an abdominal puncture site, 1.0% to postoperative wound infections and 0.5 % to gluteal abscess at the site of progesterone injection. Non-typical organisms were frequently isolated, such as Pseudomonas, Proteus, Klebsiella and Enterobacter species. No infectious aetiology was found in 105 patients (50.2%). Hypoglobulinaemia was recorded in most patients, while ascitic and pleural fluids aspirated from these patients contained high globulin concentrations. We conclude that infection-related febrile morbidity in severe and critical OHSS is high, and may be attributed to some degree of immunodeficiency associated with loss of plasma globulins to the third space. However, non-infection-related febrile morbidity is even higher and may be attributed to endogenous pyrogenic mechanisms.

Respiratory syncytial virus infection in pediatric patients

Respiratory syncytial virus (RSV) infection is the major cause of childhood lower respiratory illness worldwide. This article summarizes the characteristics of the virus and the humoral response; the epidemiology of RSV and prevention of its spread through handwashing and cleaning of fomites; and recent information on morbidity in the hospitalized child and risk factors for complicated hospitalization. Specific antiviral treatments (ribavirin and high titer RSV immune globulin) seem to be of marginal benefit. Nonspecific treatments such as bronchodilators, steroids, and antibiotics are widely used, but support for their use is limited. The ineffectiveness of treatment modalities emphasizes the importance of implementing preventive measures. These include avoiding certain exposures (eg, caregiver smoking), early discontinuation of breast-feeding, and crowds, where possible. Prevention of infection with RSV immune globulin and vaccination also are discussed.

Legumin proteins from seeds of Phaseolus vulgaris L.

Summary Legumin proteins have been partially purified from seeds of the common or french Bean (Phaseolus vulgaris L.). Characteristic of legumins, these are high molecular weight globulin proteins consisting of disulphide-linked α- and β-subunits. The N-terminal sequences of both α- and β-subunits of one of the legumin proteins were determined by automated protein sequencing. The legumin sequence exhibits close similarity to the legumin sequences of other crop plants in the legume family and particularly to soybean legumin. While the β-subunits show only a single polypeptide size class of∼21 kDa the α-subunits show a range of sizes from 55 kDa down to 35 kDa. This paper provides the first unequivocal proof of the presence of this class of globulin in Phaseolus vulgaris.

Autoimmune Hepatitis

Autoimmune hepatitis is a chronic necroinflammatory liver disorder of unknown cause associated with circulating autoantibodies and a high serum globulin level. Since the first descriptions of the disorder in the 1950s, it has been known by a variety of terms, most commonly “autoimmune chronic active hepatitis,” but in 1992 the International Autoimmune Hepatitis Group recommended the term “autoimmune hepatitis” as the most appropriate and least redundant for this disease.1 It is important to distinguish autoimmune hepatitis from other forms of liver disease because a high percentage of cases respond to antiinflammatory and immunosuppressive treatment. Early diagnosis with appropriate management can . . .

PROSPECTIVE DEVELOPMENT OF A CARDIAC SCORING SYSTEM TO PREDICT THE SEVERITY AND OUTCOME OF CONGENITAL HEART DISEASE (CHD). 211

There is a pressing need for a simple and reproducible cardiac scoring system (CSS) to predict the severity of CHD. We have previously developed a CSS based on the published risk of common congenital cardiac defects. Components of the CSS are scored as follows: cyanosis (0-room air saturation>85%, 1-saturation 2/3 systemic), and heart failure (0-none, 1-controlled with medication, 2-uncontrolled). The total score ranges from 0-6. To assess the usefulness of the CSS, 416 children with all types of CHD(age < 48 months) enrolled in a prospective trial of high titer RSV immune globulin to prevent RSV illness were scored on entry. Patients were enrolled over a three year period at 17 centers and were followed for 8 months(December through August) in the year they were entered. Score at entry: 0(n=25), 1(n=121), 2(n=141), 3(n=92), 4(n=28), 5(n=7), not scored (n=2) was assessed against other measures of morbidity and mortality. This CSS predicted hospitalization, need for cardiac surgery, and mortality in a large population of children with multiple forms of CHD. We propose that this CSS is able to predict both morbidity and mortality in children with simple and complex CHD.Table

71 P - Immune profile in chronic lymphocytic leukemia

Immune profile in 29 cases with chronic lymphocytic leukemia (CLL) and I case with Richter's Syndrome was evaluated and compared with other prognostic parameters including disease stage, organomegaly, hematocrit, WBC count, platelet, bone marrow Involvement pattern, serum albumin and globulin profile and response to therapy. Monoclonal antibody panel included CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11b, CD13, CD14, CD19, CD20, CD22, CD23 and CD33. Surface antigenic expressions were as follows: CD2; in 5 of 16 cases (31%), CD3; in 2 of 23 cases (9%), CD4; in 2 of l6 cases (13%), CD5; in 24 of 27 cases (89%), CD7; in 11 of 26 cases (42%), CD8; in 1 of 17 cases (6%), CDl0; in 1 of 24 cases (4%-who was the case of Richter's Syndrome), CD11b; in none of the 11 cases, CD13; in 10 of 19 cases (53%) CD14; in none of 12 cases, CD19; in 27 of 29 cases (93%), CD20; in 5 of 15 cases (33%), CD22; in 5 of 8 cases (63%) and CD33; in 1 of 15 cases (6%). Between surface antigenic expressions, CD2 and CD7 expressions were associated with higher frequency of CD5 negativity as compared cases not expressing these antigens. When compared antigenic expressions and with other parometers, it bas been found that: CD2 expressions were associated wilh lower WBC Count, lower incidence of thrombocytopenia and splonemegaly and higher globulin value and higher incidence of thrombocytopenia and advanced stage disease. CD4 expression was associated with poorer response to therapy CD7 was associated with higher incidence of hepatomegaly, CD8 was associated with lower Hct value. CDl3 expression was associated with higher WBC count and more advanced stage disease. CD19 was associated with low risk of hepatomegaly, CD20 was assosiated with low risk of lymphadenopathy. CD22 was associated with lower incidence of hepatomegaly and well response to therapy.

High dose intravenous immune globulins and plasma exchange in Guillain-Barré Syndrome

We report the effects of treatment with plasma-exchange (PE) and intravenous immune globulins (IVIg) in 36 out of 50 patients with Guillain-Barré syndrome (GBS) recruited by an incidence study in the Emilia-Romagna region of Italy. Comparison of the patients treated with PE and IVIg showed no significant differences in terms of effectiveness in improving the clinical course of GBS: at one month, respectively 11.1% and 25% had recovered, and 55.5% and 58.3% had improved by at least one grade. These results are in agreement with those of the Dutch GBS trial. No relapses were observed in either group. Moreover, our results showed no difference in clinical outcome at 1 and 3 months between the patients receiving only one therapy and those receiving two; a second cycle of therapy did not seem to improve the clinical course of the disease significantly. We conclude that PE and IVIg are both safe and effective therapies for GBS.

Endemic goiter in the Jos Plateau region of northern Nigeria.

This study is an endemic goiter survey of 3476 school children in 13 Local Government Councils (LGCs) and 1004 subjects in a whole community of one LGC, Plateau State, Northern Nigeria, to determine the prevalence of goiter as well as to identify some of the etiological agents involved. Results of the survey showed that the disease is highly endemic in the area with prevalence varying in places from 1 to 23% of these subjects. Females showed a markedly higher prevalence of goiter. Analysis of 729 urine samples indicated that iodine excretion ranged from 3.5 to 1.3 microgram/dl (32-154 microgram/g creatinine) and was similar to that in iodine deficient areas in the world, but no relation was observed between the prevalence of goiter and urinary iodine. Urinary thiocyanate levels were less than 0.5 mg/dl, suggesting that the role of the thiocyanate as a goitrogen is not important in the region. Thyroid hormone parameters in village subjects with goiter were similar to those in goiter endemia except serum thyroxine (T4). An interesting result found in village subjects was very high serum thyroxine binding globulin, which leads to an increase in serum T4. This study indicated that Northern Nigeria is an area of endemic goiter. Although some areas in Plateau State are iodine deficient zones, we could not conclude that the etiology of endemic goiter in this area is associated with iodine deficiency. There may be an interplay of multiple factors of etiological importance.

High continuing pregnancy rates after in vitro fertilization-embryo transfer using medium supplemented with a plasma protein fraction containing α- and β-globulins

To evaluate both the laboratory and clinical outcomes after IVF-ET using culture media supplemented with a plasma protein fraction (PPF, Plasmatein; Alpha Therapeutics, Los Angeles, CA) containing albumin and significant amounts of alpha- and beta-globulins. One-year clinical trial of a PPF with high globulin content as a medium supplement during IVF, embryo growth, and ET. Fertility Center of San Antonio, a private, office-based center for assisted reproduction. Ninety-eight couples, with women ranging in age from 26 to 46 years, undergoing 103 ovum retrievals for IVF-ET as treatment for infertility because of tubal factor, endometriosis, anovulation, uterine or cervical factor, male factor, and unexplained causes. Fertilization rate, zygote cleavage rate, clinical pregnancy rate (PR), continuing PRs, and implantation rates. Supplementation with PPF in insemination, growth and transfer medium resulted in a clinical PR of 41.5% per transfer with continuing PRs of 35.2% per retrieval, 37.2% per patient, and 38.7% per transfer. A PPF containing significant amounts of alpha- and beta-globulins can serve as an effective protein supplement to IVF medium, with outcomes manifested as high continuing PRs. These data indicate a potential role for glycoprotein components of serum in supporting healthy embryo growth in vitro, although the mechanism may relate more to the general physicochemical properties of this fraction than to the actions of a specific component.

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Pharmaceutically prepared IgG, pooled from sera of over 2,000 normal individuals, contained both monomeric and dimeric IgG. Each type of IgG bound 125I-labeled interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. Increased binding to IgG was observed if 125I-IL-1 beta was denatured by heating to 39 degrees C. However, the binding of both nondenatured and denatured 125I-IL-1 beta was not inhibited by unlabeled IL-1 beta. In contrast, binding of 125I-IL-1 alpha, 125I-IL-6, and 125I-TNF alpha was inhibited by the corresponding unlabeled cytokine. Papain-digestion of IgG abolished binding of 125I-TNF alpha but failed to influence the displaceable binding of 125I-IL-1 alpha and 125I-IL-6. 125I-TNF alpha was a mixture of trimeric and monomeric forms, the latter being the predominant form at lower concentrations. The apparent saturability of 125I-TNF alpha was explained by a higher nonspecific binding of monomeric than of trimeric 125I-TNF alpha to IgG. The amounts of cytokine antibodies in IgG preparations would contribute approximately 2 micrograms anti-IL-1 alpha IgG and 1 microgram anti-IL-6 IgG per kg body wt during high dose immune globulin therapy. In conclusion, pharmaceutical preparations of human IgG contain specific and neutralizing, high affinity antibodies against IL-1 alpha and IL-6, but not against TNF alpha or IL-1 beta. There are significant methodological pitfalls that hamper detection of IgG autoantibodies against cytokines.

Clinical aspects of hepatitis B virus infection

Adults with a healthy immune system who are exposed to hepatitis B virus (HBV) usually suffer from a mild acute infection. The likelihood of chronicity is only 5%, but climbs as high as 90% in newborns and n the immunocompromised. Acute HBV infection can cause fulminant liver failure (case fatality rate of 80%). People with chronic infection tend to have no symptoms, normal liver enzymes, and normal or almost normal liver histology, making diagnosis difficult. Active viral replication occurs in most people with active liver disease. People with persistent active replication are at higher risk of death from liver disease or hepatocellular carcinoma (HCC) than those with inactive disease. HBV transmission occurs via sexual intercourse or blood or needle contact. In the US, iv drug use is the major risk factor for HBV infection in adults. Prevention of HBV infection is through patient education and vaccination. Some people advocate universal HBV vaccination because it is often difficult to vaccinate high risk populations and to identify risk factors. Universal vaccination is not cost effective in low risk areas, however, e.g., the US and Europe. Treatment for chronic HBV infection is limited. Response to interferon therapy depends on low HBV DNA levels, high transaminase levels, and a history of acute hepatitis. Short- and longterm response rates tend to be low, however ( 40% short term and much lower for longterm). Experimental drugs are thymosin and nucleoside analogues. Standard treatment for patients with end-stage chronic liver disease or fulminant hepatic failure is liver transplantation. High dose immune globulin is the best means to delay and prevent recurrent HBV infection in transplantation patients. Some problems with management of chronic HBV are prevention of HCC and recurrent HBV after transplantation. Variant viruses are mutations of the precore or of a surface gene. HIV/AIDS is often associated with HBV and hepatitis delta virus infection.

Recent epidemiologic studies on nutrition and cataract in India, Italy and the United States.

Three independent case-control studies with similar methodologies were conducted in India, the United States and Italy to investigate risk factors by cataract type. Their common objectives were to evaluate risk factors for each cataract type, giving priority to nutritional factors, and to determine whether risk factors differed among cataract types. Data included self-reporting of food frequencies and various biochemical determinations. A higher body mass index was the only nutritional factor found by more than one study to be associated with cataract, being less frequent in cases than in controls. Blood nutritional status from one study showed that a high antioxidant index decreased risk for at least one cataract type, high glucose-6-phosphate dehydrogenase values increased risk for at least one cataract type, a high albumin globulin ratio decreased risk for mixed cataract, and high iron levels decreased risk for cortical cataract. Only one of the three studies found that a high nutritional status, high dietary antioxidant index, and use of multiple vitamin supplements decreased risk for cataract. Findings from these studies suggest socioeconomic and nutritional components to cataract risk, although not consistently across studies or cataract types. Differences between studies may be due to differences in populations and/or data collection methods. Because reducing cataract risk would have major implications for a large segment of the population, clinical trials seem appropriate to confirm and evaluate the potentially modifiable risk factors suggested by these studies.

Cytomegalovirus pneumonitis and bone marrow transplantation: identification of a specific high risk group.

To study the association between cytomegalovirus (CMV) excretion and interstitial pneumonitis in allogeneic bone marrow transplant (BMT) recipients, with reference to donor and recipient CMV antibody response. The incidence of CMV excretion was prospectively studied in 62 allogeneic bone marrow transplantations performed on adults and children. All recipients received CMV seronegative blood products. Prophylaxis with high dose acyclovir and CMV immune globulin was given to high risk patients (donor or recipient, or both, CMV seropositive). CMV excretion was detected in eight of 26 (31%) high risk patients but in only one of 36 low risk patients (donor and recipient both CMV seronegative). Five of the eight (63%) excretors in the high risk category developed CMV, of whom four (80%) belonged to the seropositive recipient/seronegative donor group, and included the three CMV seropositive recipients whose CMV complement fixation antibody titres were 64 or greater before transplantation. These findings suggest that there is a subgroup of patients at especially high risk of developing CMV.

Storage protein changes during zygotic embryogenesis in interior spruce.

The major storage proteins isolated from protein bodies of embryo tissues of interior spruce Picea glauca (Moench) Voss/Picea engelmanii Parry had apparent molecular weights of 41, 35, 33, 24 and 22 kD. Minor proteins of 30 and 27.5 kD were also observed. Based on their solubility characteristics, the 41 kD protein was identified as a water and buffer-soluble albumin, and the 35, 33, 24 and 22 kD proteins were characterized as buffer-insoluble, high salt-soluble globulins. Two-dimensional electrophoresis revealed each protein was composed of several isoelectric variants. Developmentally specific accumulation of storage proteins was observed during embryogenesis. The 41 kD protein only accumulated during the later stages of cotyledon maturation, whereas the other storage proteins began to accumulate during the early stages of embryo development. All storage proteins showed major accumulations during cotyledon maturation.

Hepatitis C virus antibodies in chronic active hepatitis: pathogenetic factor or false-positive result?

An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus (HCV) was used to test 143 serum samples from 53 patients with autoimmune chronic active hepatitis (AI-CAH). Optical density (OD) values in the assay correlated closely with serum globulin ( r=0·8846, p<<0·0005) and IgG ( r=0·6281, p<0·0005) concentrations but not with immunosuppressant therapy. OD values were positive in 20 (65%) of 31 with active disease and in only 1 (5%) of 22 in remission (p<0·0005). The association between positive results and active disease and high serum globulin levels was confirmed by serial studies in 6 of the patients. In contrast, none of 31 patients with primary biliary cirrhosis and only 2 of 24 with non-hepatic disorders associated with high IgG concentrations were positive, and these controls showed no correlation between OD values and serum globulins or IgG. The findings suggest that serum from Al-CAH patients may contain a component that gives false-positive results in the assay.

Clinical and laboratory findings in cats infected with feline immunodeficiency virus

Thirty-two cats referred to the Feline Studies Centre between June 1987 and October 1988, and 14 in-contact cats, were found to be infected with feline immunodeficiency virus. Most of the 46 cats were non-pedigree and free ranging; 27 were male (19 neutered) and 19 were female (18 neutered). Their ages ranged from one to 17 years and the average age was 5.8 years. The most common clinical signs were lethargy, inappetence, weight loss, pyrexia and lymphadenopathy; most cases had multiple abnormalities. Other common signs were gingivitis, diarrhoea, rhinitis and ocular discharge. Eight cats had neoplasia. The commonest haematological abnormalities were anaemia, neutropenia, lymphopenia and monocytosis. Eight cats had lymphocytosis; seven of these were in a single house-hold. Several cats had high serum globulin levels and half of those tested had high IgG levels. Seven cats had no detectable antibody to feline immunodeficiency virus even though the virus was cultured from the peripheral blood lymphocytes. During follow-up for up to 60 weeks one cat died and 23 were destroyed on humane grounds.

In vitro and in vivo Characterization of Avian Reoviruses. II. Clinical Evaluation of Chickens Infected with Two Avian Reovirus Pathotypes

The effect of two avian reovirus isolates (2408 and 1733) on digestion and nutrient metabolism in infected chickens was assessed by an in vitro absorption assay and clinical blood chemistry analysis. Birds of various ages were inoculated orally and intratracheally with reovirus and sampled periodically for the respective assays. Transitory malabsorption was observed in the duodenum of birds infected with reovirus 2408. Conversely, increased absorption was detected in the ileum of these same birds. Clinical blood chemistry analyses of birds infected with both isolates revealed that severely affected birds had abnormally elevated plasma total protein, plasma albumin, and calcium levels. Decreases were found in percent bone ash and, due to abnormally high globulin levels, in albumin:globulin (A:G) ratios. A significant (P less than 0.05) correlation between body weights and total protein, albumin, A:G ratio, and bone ash was found in infected birds. The most pronounced metabolic and physiologic changes occurred in the severely affected birds, and, in general, pathogenicity of the isolates was reflected by the degree of metabolic change.

Marked Elevation and Cyclic Variation of Corticosteroid-Binding Globulin: An Inherited Abnormality?*

Unexplained high serum corticosteroid-binding globulin (CBG) concentrations [mean values, 78.8 and 55.7 mg/L; normal women, 38.8 +/- 3.8 (+/- SD) mg/L] were found repeatedly in two apparently healthy sisters who were not pregnant or taking exogenous estrogens. One had substantial variations in serum CBG and sex hormone-binding globulin concentrations during the menstrual cycle, which paralleled the normal cyclic changes in serum estradiol. The other woman was postmenopausal and had a high serum CBG concentration despite of low serum estradiol levels. We conclude those women have an inherited abnormality in CBG production.

Synergism of chronic alcoholism and hepatitis B infection in liver disease

One hundred and fifty-seven patients with alcoholic liver disease were studied. Hepatitis B surface antigen (HBsAg) was positive in 20.4% of the patients. Those who were positive for the HBsAg presented at an earlier age, had a lower albumin level, a higher globulin level, a more prolonged prothrombin time, were more likely to have features of cirrhosis in the liver biopsy, and were probably more likely to suffer from hepatic encephalopathy in the follow-up compared with those negative for HBsAg. The mortality of subjects was low both on admission and during follow-up. It is concluded that chronic alcoholism and hepatitis B virus infection act synergistically in producing more severe liver damage and causing cirrhosis at a younger age compared with chronic alcoholism alone. One possible reason for the low mortality of the patients might have been their relatively good nutritional status.