Multiple sulphatase deficiency presenting at birth

A new case of multiple sulphatase deficiency with onset at birth is described. The patient had many dysmorphic features and hydrocephalus, similar to one other case with early onset described in the literature. The new patient differed from the other case in having chondrocalcificans congenita, heart abnormalities and an abnormal fold of tissue present between the laryngeal inlet and the oesophagus. Excessive mucopolysacchariduria was present and there was profound deficiency of all sulphatases examined in plasma, leucocytes and cultured skin fibroblasts.     

Role of carbohydrate in binding of IgG to the Fc receptor of neonatal rat enterocytes

Monoclonal IgG1, IgG2a, IgG2b and IgG2c were prepared from rat hybridoma cells treated with tunicamycin in order to inhibit N-linked glycosylation. The IgG produced by these cells was about 70% lower in carbohydrate content compared to IgG from equivalent untreated cells, but was similar to the corresponding normal IgG in terms of antigen binding. However, the ability of carbohydrate deficient (CHO-) IgG to bind in vitro to Fc receptor extracted from jejunum of neonatal rats was impaired in most cases and, in all but one case, the amount of CHO- IgG transported from gut lumen to blood in vivo was markedly reduced. No reduction in binding of normal IgG to extracted receptor was observed in the presence of various sugars. It is postulated that N-linked carbohydrate acts to stabilize the structure within the IgG molecule which is responsible for binding to this Fc receptor, possibly in the CH2 domain.     

Lesions in the liver and kidney ofDirofilaria immitis-infected dogs following treatment with ivermectin

Six dogs with spontaneous heartworm disease were injected with a single dose of ivermectin. After 48 h of treatment, microfilariae counts were reduced by 92%–98% of pretreatment counts. In pretreatment biopsies examined by light and electron microscopy, microfilariae were unaltered in the sinusoids of the liver and also in the glomerular capillaries and interstitial blood vessels of the kidney. However, there was irregular thickening and dense deposits in the basement membranes of glomerular capillaries, along with a modest increase in mesangial cells and matrix.In post-treatment liver biopsies examined by light microscopy, there were numerous granulomas in the sinusoids which contained degenerated microfilariae. In post-treatment kidney biopsies there was moderate thickening of glomerular basement membranes along with pronounced proliferation of mesangial cells and matrix. Glomerular capillaries were partially or completely occluded by degenerated microfilariae. In addition, there were interstitial granulomas in the kidney.It was observed with the aid of electron microscopy that highly vacuolated and degenerated microfilariate were incorporated into granulomas in the liver sinusoids of post-treatment biopsies. In post-treatment kidney biopsies glomerular capillaries were usually occluded by degenerated microfilariae. Basement membranes were thickened and contained dense deposits. Mesangial cells and matrix were extensively increased. Interstitial granulomas in the kidney contained dead microfilariae.     

Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications     

Rapid diagnosis of Brucella bacteremia by using the BACTEC 9240 system.

Almost 93% of 97 separate patient isolates of Brucella bloodstream infections were recovered within 5 days of incubation by using the BACTEC 9240 continuous-monitoring blood culturing system.     

Some properties of dendritic macrophages from peripheral lymph

Peripheral lymph was collected from the skin and liver of sheep, and from the intestine of rats. The dendritic macrophages contained in it were isolated by centrifuging the lymph over a layer of 'Nycodenz'. Similar cells were produced by culturing mononuclear cells from venous blood, but the yields were very small. The numbers of dendritic cells in the lymph from the legs of sheep increased five-fold after xylene had been applied to the skin. Dendritic macrophages displayed abundant class II histocompatibility antigens on their surfaces, as well as immunoglobulins. Although the latter were probably acquired passively, they remained present for several days on cells cultured in vitro. When in vitro, dendritic cells could be shown to phagocytose marker particles, such as latex beads, but their performance was unimpressive compared to macrophages from the peritoneal cavities of rats. In contrast, their ability to phagocytose rapidly T4 phage or influenza viruses unequivocal and striking.     

Proximal and Distal Predictors of AIDS Risk Behaviors among Inner-city African American and European American Women

AIDS risk behavior and attitudes towards safer sex were studied in a sample of 666 African American and 626 European American women. Condom use, AIDS-related knowledge, risk perception, self-efficacy beliefs, attitudes and perceived partner attitudes, and an assertive coping style were analyzed with regard to mean differences and predictive power in both ethnic groups. Compared to European American women, African American women had less knowledge and lower self-efficacy beliefs towards safer sex behavior, but they perceived themselves to be at more risk and reported greater condom use. Further, ethnicity was found to moderate the effects of the psychological predictors on safer sex behavior. This moderator effect was tested using a structural equation modeling design. In both groups, risk perception was the strongest predictor of condom use. Among African American women, social-cognitive barriers (e.g. low self-efficacy beliefs, negative attitude towards condom use) worked as a second predictor and mediator of the effects of risk perception on condom use. In contrast, among European American women, social-cognitive factors had no effect on condom use. In general, prediction of safer sex behavior was stronger among African American women.     

The effects of butterbur on the histamine and allergen cutaneous response.

BACKGROUND: Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma. However, no data are available regarding its effects on the histamine and allergen cutaneous response. OBJECTIVE: To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses. METHODS: Atopic patients were randomized into a double-blind, double-dummy, crossover study to receive for 1 week butterbur, 50 mg twice daily (8 AM and 10 PM); fexofenadine, 180 mg once daily (10 PM), and placebo once daily (8 AM); montelukast, 10 mg once daily (10 PM), and placebo once daily (8 AM); or placebo twice daily (8 AM and 10 PM). Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine, allergen, and saline control at 10-minute intervals for 60 minutes. RESULTS: Twenty patients completed the study. The mean +/- SE histamine wheal and flare responses, respectively, were significantly attenuated (P < .05) by fexofenadine (9.4 +/- 1.8 mm2 and 13.5 +/- 3.2 mm2) compared with placebo (15.5 +/- 3.3 mm2 and 179.8 +/- 74.3 mm2) but not by butterbur (16.4 +/- 2.1 mm2 and 297.7 +/- 121.2 mm2) or montelukast (19 +/- 1.9 mm2 and 240.2 +/- 66.6 mm2). The allergen wheal and flare responses, respectively, were also significantly attenuated (P < .05) by fexofenadine (31.1 +/- 6.3 mm2 and 256.9 +/- 86.5 mm2) compared with placebo (65.4 +/- 15.2 mm2 and 1,014.5 +/- 250.0 mm2) but not by butterbur (50.4 +/- 9.2 mm2 and 1,110.3 +/- 256.1 mm2) or montelukast (58.8 +/- 9.1 mm2 and 1,463.6 +/- 295.6 mm2). CONCLUSIONS: Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo, whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation. This finding would suggest that butterbur may not be effective in allergic skin disease.     

COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia

The skeletal dysplasias are a clinically and genetically heterogeneous group of conditions affecting the development of the osseous skeleton and fall into the category of rare genetic diseases in which the diagnosis can be difficult for the nonexpert. Two such diseases are pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which result in varying degrees of short stature, joint pain and stiffness and often resulting in early onset osteoarthritis. PSACH and some forms of MED result from mutations in the cartilage oligomeric matrix protein (COMP) gene and to aid the clinical diagnosis and counselling of patients with a suspected diagnosis of PSACH or MED, we developed an efficient and accurate molecular diagnostic service for the COMP gene. In a 36-month period, 100 families were screened for a mutation in COMP and we identified disease-causing mutations in 78% of PSACH families and 36% of MED families. Furthermore, in several of these families, the identification of a disease-causing mutation provided information that was immediately used to direct reproductive decision-making.