Congenital disorder of glycosylation type 1a: three siblings with a mild neurological phenotype.

We report 3 siblings (1 male and 2 female) recently diagnosed with congenital disorder of glycosylation type Ia (CDG-Ia) in their mid-20s. They experience mild mental retardation but manage to function independently in society. Their professions are library assistant, professional artistic painter and secretarial work. All three siblings have cerebellar hypoplasia and ataxia, but are able to ambulate easily. Two of the siblings have required strabismus surgical repairs. All have antithrombin III deficiency, osteoporosis, and mild dysmorphic features. Hypergonadotrophic hypogonadism was a feature of the two female siblings. A type 1 sialotransferrin pattern and phosphomannomutase (PMM) deficiency have been demonstrated. They are compound heterozygotes for R141H and L32R mutations in the PMM2 gene. While there is clinical heterogeneity in CDG-Ia, we believe that our patients are among the mildest of intellectually affected CDG-Ia patients reported to date.     

Water-borne stimuli released by predatory crabs and damaged prey induce more predator-resistant shells in a marine gastropod

Individuals of the morphologically variable, rocky intertidal gastropod Thais (or Nucella) lamellosa developed larger apertural teeth when held in the presence of the predatory crab Cancer productus than when held in its absence, regardless of whether snails were fed or not. In addition, among fed snails larger apertural teeth were produced in the presence of crabs fed conspecific snails than in the presence of crabs fed frozen fish. Because all snails were held in containers through which water flowed from physically separated aquaria holding the crabs, these results indicate that water-soluble chemical cues released by this predatory crab and by damaged conspecifics induced T. lamellosa to improve the defense effectiveness of their shells. Finally, when allowed access to food, snails exposed to these stimuli ate fewer barnacles and grew less than those in the controls.     

Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis

Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 × 10⁻⁴v 1.4 × 10⁻⁴, Mann-Whitney U, P < .02). The level in CD (4.0 × 10⁻⁴) was similar to FAR Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAR This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition.     

Ulcerating rheumatoid nodule of the vulva.

A case of an ulcerating rheumatoid nodule of the vulva in a 76 year old woman with rheumatoid arthritis complicated by Felty's syndrome is reported. The patient presented with a mass in the vulval region. On clinical examination, she had an ulcerated mass associated with inguinal lymphadenopathy. These findings resulted in a clinical diagnosis of invasive carcinoma of the vulva and an excision biopsy was carried out. On microscopic examination, the lesion showed the characteristic features of a rheumatoid nodule with ulceration of overlying epidermis. Adjacent vessels showed inflammation and fibrinoid necrosis of their walls suggestive of a vasculitis. Awareness of the possibility of ulceration in rheumatoid nodules may facilitate diagnosis and avert unduly aggressive treatment.     

Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin- releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.      

Monoclonal antibody analysis of serotype-restricted and unrestricted bluetongue viral antigenic determinants

Twenty-one monoclonal antibodies that react with bluetongue virus (BTV) and have restricted or unrestricted serotype specificities were identified in culture supernatants of hybridomas derived from lymphocytes of mice immunized with BTV serotype 17. Hybridomas were screened and antibody specificities characterized in a solid-phase radioimmunoassay and by immunoprecipitation with radiolabeled, BTV 17-infected cell lysates. Three general serotype specificities were demonstrated by 13 antibodies that precipitated structural viral protein 9 (VP 9). One antibody precipitated VP 7, a 48,000 dalton nonstructural protein, and reacted in radioimmunoassay with 20 BTV serotypes and Epizootic Hemorrhagic Disease of Deer Virus serotype 1 (EHDV 1), EHDV 2, and Ibaraki virus, but not with uninfected cells. One serotype-specific antibody neutralized infectivity, inhibited hemagglutination by BTV 17, and precipitated VP 2 and VP 3. A second antibody, with restricted serotype specificity, precipitated VP 2 and VP 8. These results confirm those of others (Huismans and Erasmus, Onderstepoort J. Vet. Res. 48, 51-58, 1981) that BTV serotype-specific and neutralizing epitopes are associated with VP 2.