Spectrum of autoantibodies against a dynamin-related protein, dymple

OBJECTIVE: To characterize the clinical features of patients with autoantibodies against dymple, a dynamin-related protein. METHODS: Serum samples from 281 patients with rheumatic diseases were examined. The characteristics of antidymple and antibody-reactive determinants were investigated by immunoblotting with the recombinant dymple antigen, including its deletion mutants, and by immunofluorescence studies with affinity-purified serum. RESULTS: Five serum samples (2%) were found to have antidymple. All of these patients were male, and 4 of them had interstitial pneumonitis. Their sera were considered to mainly recognize the N-terminus of dymple, which contains GTP-binding motifs. CONCLUSION: Dymple, which joins the cytoplasmic autoantigens, could be a marker for a newly recognized subset of connective tissue diseases.     

Immunological follow-up in children born to HIV-1 infected mothers.

From November 1985 to January 1990 we examined 156 children born to 154 HIV-1 seropositive mothers every 3 months. Eighty-seven infants were over 18 months by January 1990. Six of them met the CDC criteria of HIV-1 infection or died from AIDS; a transmission rate of 7%. Six of the children aged less than 18 months also met the CDC criteria of HIV-1 infection. These 12 infected children were compared with the 81 presumably unifected children. The perinatal findings were similar in both groups. Most of the HIV-1 infected babies showed early abnormalities in humoral and cellular immunity, hypergammaglobulinemia, low percentage of CD4 circulating lymphocytes and increased spontaneous in vitro immunoglobulin production. These changes were persistent in the HIV-1 infected children, but sporadic in those uninfected. Immunological abnormalities were frequently found before clinical symptoms appeared. We conclude that repeated immunological abnormalities in babies born to HIV-1 seropositive mothers are suggestive of HIV-1 infection.     

Remission following an elemental diet or prednisolone in Crohn's disease

The short- and long-term effects of an elemental diet in children with acute Crohn's disease were compared with those of prednisolone in historical controls. Clinical remission was induced in 25 of 30 and in 18 of 28 episodes treated for six weeks with an elemental diet and prednisolone. Patients with proximal disease had longer remission after treatment with an elemental diet (p < 0.05) than did patients with colonic disease after treatment with prednisolone (p < 0.01). Disease activity index score improved in both groups compared with the pretreatment scores (p < 0.05). However, the improvement in the elemental diet group was significantly better than in the prednisolone group (p < 0.001). Changes in linear growth were better after treatment with an elemental diet compared with steroids (p < 0.001). Serum albumin and haematocrit concentrations all improved significantly in the children treated with an elemental diet (p < 0.001) but not in those treated with steroids. Thus an elemental diet was better than prednisolone in proximal disease and confirmed improved growth and nutritional status.     

Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal–cervical ratio. Ovarian volume was also significantly increased in thelarche and thelarche variant. The fundal–cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Treatment for locally advanced esophageal carcinoma complicated by fistulas: Case report

Two cases of advanced esophageal carcinoma complicated by fistula formation, treated with esophageal prostheses followed by chemotherapy or concurrent chemoradiotherapy, are reported. Chemoradiotherapy may be indicated in esophageal carcinoma cases with fistulas if an excellent antitumor response is expected. However, the indication for prosthesis insertion should be limited due to the risk of perforation, which may be a lethal complication.     

Immediate food hypersensitivity reactions on the first known exposure to the food

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.     

Reverse geometrical selectivity in glucuronidation and sulfation of cis- and trans-4-hydroxytamoxifens by human liver UDP-glucuronosyltransferases and sulfotransferases

The phenolic active metabolites, cis-4-hydroxytamoxifen (cis-HO-TAM) and trans-4-hydroxytamoxifen (trans-HO-TAM), of the anti-breast-cancer drug, trans-tamoxifen (TAM), were geometrically selectively glucuronidated in the manner of cis>trans by microsomes and sulfated in the manner of trans>cis by cytosol from the liver of 10 human subjects (7 females and 3 males). There was a large individual difference in the microsomal glucuronidation of cis-HO-TAM, which correlated well with glucuronidation of 4-hydroxybiphenyl by human liver microsomes. However, there was only a slight correlation between the glucuronidation of cis-HO-TAM and trans-HO-TAM or 4-nitrophenol (NP). A small individual difference was observed for the human liver cytosolic sulfation of trans-HO-TAM, which correlated well with the sulfation of NP. Recombinant human UDP-glucuronosyltransferase (UGT)2B15 catalyzed the cis-selective glucuronidation of geometrical isomers of HO-TAM. UGTs1A1, 1A4, 1A9 and 2B7 had weak activity toward HO-TAMs with a much smaller cis-selectivity than did UGT2B15. UGTs1A3 and 1A6 had no detectable activity toward these substrates. Among the four known major sulfotransferases (SULTs) occurring in the human liver, SULT1A1 was strongly suggested to play the most important role in the hepatic cytosolic trans-selective sulfation of HO-TAM isomers. A good correlation was observed between the hepatic cytosolic sulfation of trans-HO-TAM and NP, a standard substrate for SULT1A1. SULT1E1 had slight activity toward the HO-TAMs. SULTs1A3 and 2A1 had no detectable activity toward HO-TAMs.     

Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients

The immune response against melanoma can be influenced by cytokines with potentially opposite effects on tumour cell growth, such as interleukin-10 (IL10), interleukin-6 (IL6) and interferon-gamma (IFNgamma). Our objective in this study was to investigate whether polymorphisms in the regulatory regions of IL10, IL6 and IFNgamma genes are associated with the development of primary cutaneous melanoma and/or the prognosis of this tumour. We studied genotypic variations at positions -1082, -819 and -592 in the IL10 promoter, -174 in the IL6 promoter and +874 in the IFNgamma intron 1 in 42 melanoma patients and 48 healthy controls. These two populations showed very similar genotypic frequencies for IL10, IL6 and IFNgamma gene polymorphisms. There was a significant increase in the prevalence of IL10 low expression genotypes, specially the ACC/ATA genotype, among patients with a poorer prognosis. In contrast, IL6 promoter and IFNgamma intron 1 gene polymorphisms did not correlate with melanoma prognosis. These data indicate that investigation of polymorphisms in the regulatory regions of IL10, IL6 and INFgamma genes does not seem to be useful for predicting the risk of development of primary cutaneous melanoma. However, IL10 low expression genotypes may be associated with a poorer outcome in melanoma patients.