No independent association between HSP70 gene polymorphism and IDDM.

A role for heat shock proteins (HSPs) in autoimmunity has recently been suggested by several authors. Autoantibodies against HSPs have been associated with such autoimmune diseases as systemic lupus erythematosus, polymyositis, and the NOD mouse model of diabetes. Moreover, genes for the major 70,000-M(r) HSP (HSP70) are located within the MHC. To investigate a potential association of an HSP70-2 gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed restriction-fragment-length polymorphism (RFLP) of this gene in 29 families with one or more member affected by IDDM. With the enzyme PstI, as reported previously, two HSP70-2 alleles of 8.5- and 9.0-kb were found. The 8.5-kb allele was found more frequently on diabetic haplotypes compared with control haplotypes (41 of 66 [62%] vs. 20 of 46 [43%], P = 0.03). This association was due to the conservation of alleles on extended haplotypes we previously reported to be associated with diabetes on initial analysis of families. Twenty-three of 26 diabetic DR3 haplotypes and 3 of 3 normal DR3 haplotypes and all instances of [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] had the 8.5-kb allele, whereas 0 of 9 normal DR2 haplotypes and 0 of 2 diabetic DR2 haplotypes had the 8.5-kb allele (P = 8 x 10(-7) DR3 vs. DR2 haplotypes). The alleles were equally distributed among DR4 haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental evaluation of the effects of zoledronic acid on regenerate bone formation and osteoporosis in mandibular distraction osteogenesis.

PURPOSE: The aim of this study was to evaluate the effects of systemically administered zoledronic acid (ZA) on the bone mineral density (BMD) and bone mineral content (BMC) at mandibular distraction sites in rabbits. MATERIALS AND METHODS: Eighteen New Zealand white rabbits were randomly divided into 2 groups. Bone lengthening was performed in the left portion of the mandible through distraction osteogenesis at a rate of 0.5 mm every 12 hours for 5 days. While the experimental group rabbits were administered intravenous 0.1 mg/kg ZA, control group rabbits were given only saline infusion during operation. All animals were sacrificed at the end of the consolidation period of 28 days. The mandibles of all animals were removed and both the anterior and posterior pin regions of the regenerate and regenerate region were evaluated by dual energy x-ray absorptiometry (DEXA). BMD and BMC data were statistically analyzed. RESULTS: Except for 1 rabbit from the experimental group that had an infection at the external pin region, all animals showed complete clinical healing. When the values in the group receiving ZA were compared with those of the control group, it was observed that the BMD values of the anterior pin region of regenerate, regenerate region, and posterior pin region increased by 23%, 20%, and 31%, respectively; and BMC values increased by 22%, 24%, and 32%, respectively. When data of these regions were compared, both BMD and BMC were found statistically different in all regions (P < .05). CONCLUSION: Results of this study showed that ZA had positive effects on new bone formation at and around the distraction gaps of the lengthened rabbit mandibles by distraction osteogenesis.     

Complotypes in Pemhigus vulgaris: Differences between Jewish and Non-Jewish patients

Haplotypes of alleles of the major histocompatibility complex (MHC) complement genes BF, C2, C4A, and C4B are inherited as single highly polymorphic genetic units called complotypes. There are about a dozen complotypes with frequencies above about 0.01 in Caucasians. In the blistering disease pemphigus vulgaris, the complotypes SC21 and SB45 were found to be markedly elevated in patients compared with general Caucasian controls. The SC21 increase was in Ashkenazi Jewish patients exclusively (relative RISK = 17 in that population), whereas SB45 was found solely in non-Jewish Caucasians (specific population relative RISK = 57). Although there are unusually high relative risks, it is most unlikely that these complotypes represent susceptibility genes for pemphigus vulgaris. Rather, it is probable that they mark extended major histocompatibility complex haplotypes with fixed DNA so that independent examples in the population have the same alleles. It is likely that it is the class II genes on these haplotypes that confer susceptibility     

Analysis of isolated cranial nerve manifestations in patients with cancer

The aim of this study was to assess the underlying causes of isolated cranial nerve (CN) manifestations in cancer patients. In a prospective study over a 16 month period, 20 of 242 patients presented with isolated CN manifestations, and were assessed for the following: primary site; CN symptoms and signs; length of time between primary diagnosis and neurological involvement; and survival following the neurological diagnosis. The most frequent primary site was determined as hematological malignancy (9/20). Thirteen of the 20 patients presented with single CN manifestations. Underlying causes of CN manifestations in 16 of the 20 patients were related to metastases. They included meningeal carcinomatosis (10/16), brain stem metastases (3/16), primary brain astrocytomas (1/16), and metastases out of the central nervous system (2/16). The remaining four patients' CN manifestations related to non-metastatic conditions. Although most of the isolated CN manifestations were due to systemic metastasis, in particular to the meninges, up to 20% were related to benign conditions.     

Prognostically significant heterogeneity of cytoplasmic islet cell antibodies in relatives of patients with type I diabetes.

A significant proportion of relatives of patients with insulin-dependent (type I) diabetes with high titers of cytoplasmic islet cell autoantibodies (ICAs) do not progress to overt diabetes with up to 8 yr of follow-up. This may reflect that follow-up of such relatives has not been long enough to observe diabetes, that despite expression of identical ICAs, some relatives will not progress to diabetes; or that there is heterogeneity in what is identified as ICA. We identified a subset of ICA that was restricted in its species (not reacting with mouse islets) and cell-type reactivity within islets (beta-cell specific). Only one of eight relatives whose sera had the restricted pattern of reactivity progressed to overt diabetes, and on sequential evaluation, all but the one relative who progressed to diabetes have maintained normal first-phase insulin secretion to intravenous glucose. In contrast, by life-table analysis, 70% of relatives expressing nonrestricted ICA became diabetic within 5 yr of follow-up (1 of 8 vs. 16 of 25 diabetic at last follow-up, P less than 0.02). Moreover, preliminary data suggest a significant association of the human leukocyte antigen DQB1*0602 allele of DR2 haplotypes with the restricted ICA pattern (4 of 5 DQB1*0602 restricted vs. 0 nonrestricted ICA, P = 0.006). We propose that expression of a genetically determined restricted ICA pattern confers a markedly lower risk for progression to diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of total pericystectomy in hepatic hydatidosis

Between 1977 and 1995, 495 patients were operated on for hepatic hydatidosis. Total pericystectomy was performed in 26 patients (closed technique in 21 and open technique in 5). Twenty-one patients had single cysts and 5 had two cysts. The median cyst diameter was 8cm (range; 3–20cm). The requirements for total pericystectomy were: (1) the cyst(s) should be located away from the hepatic veins, large bile ducts, or major branches of the portal vein and hepatic artery and (2) the patient should be fit to undergo a major operation. There was no procedure-related morbidity. One patient developed a biliary fistula that closed after endoscopic sphincterotomy. The median hospital stay was 7 days (range; 3–22 days). The median follow up was 24 months (range; 9–114 months). There was disease recurrence in a non-adjacent segment in 1 patient at 4 years. Pericystectomy is a potentially dangerous operation, but it avoids problems with cavity management and has low rates of biliary fistula, spillage, and recurrence. Its success stems primarily from careful patient selection.     

Genetic screening: triumphs, problems, and controversies.

As genetic screening becomes more widespread, it becomes increasingly important to analyze the manifold implications of genetic screening programs. This paper characterizes the various types of programs and discusses some of the scientific, ethical, social, and economic issues that arise in evaluating any genetic screening program. Two examples of successful programs, newborn screening for phenylketonuria and carrier detection for Tay-Sachs disease, are presented. We then discuss three other screening programs that have not yet been fully implemented but which have already engendered a great deal of controversy: mass screening for heterozygosity for cystic fibrosis, DNA fingerprinting in the criminal justice system, and genetic screening in the workplace.     

The effect of intra-arterial papaverine on ECoG activity in the ketamine anesthetized rat

The opium alkaloid papaverine (PPV) causes vasodilatation of the cerebral arteries through direct action on smooth muscle that reduces the constriction of smooth muscle. Intra-arterial papaverine (IAP) has been used widely to increase the regional cerebral blood flow in order to reverse the cerebral vasospasm that occurs during endovascular procedures. IAP-induced seizures have been reported, although PPV has anticonvulsive effects. This study determined the effects of IAP on electrocorticography (ECoG) in the ketamine anesthetized rats. We used 24 Sprague–Dawley male rats weighing 200–250 g. The animals were divided randomly into four groups: three treatment groups (groups 1–3) and a control (group 4). Groups 1, 2, and 3 were given 1, 7, and 14 mg/kg IAP, respectively. The ECoG was compared across groups. Our results indicated that IAP did not cause seizures and that it decreased the frequency of ketamine-induced epileptiform activity in the 14 mg/kg group.     

Practical Approach to Data Collection in a European Dialysis Network

Collection of Dialysis Treatment Data and Patient-Related Information in a Single Dialysis UnitState—of—the—art dialysis machines are capable ofautomatically collecting huge volumes of dialysis treatmentdata(blood and dialysate flow rates,venous and arterialpressures, ultrafiltration rate, ultrafiltration volume,transmembrane pressure,conductivity,etc.)and dis—playing the information on the monitor screen.Commer—     

A glucose transport protein expressed predominately in insulin-responsive tissues.

Using low-stringency hybridization to the rat brain glucose transporter (GT), a 2489-base-pair cDNA clone was isolated from a rat soleus lambda gt10 cDNA library. It encodes a 509-amino acid protein whose sequence and predicted membrane structure is very similar to those of the rat brain and liver GTs. The muscle GT-like protein is 65% identical in amino acid sequence to the rat brain GT and 52% identical to the rat liver GT; the major differences are in the NH2- and COOH-terminal hydrophilic segments. This GT-like mRNA is expressed predominately in tissues where glucose transport is sensitive to insulin, including striated muscle, cardiac muscle, and adipose tissue; low-level expression is also detected in smooth muscle and kidney mRNA. This GT-like cDNA is the fourth member of the mammalian GT-related gene family identified to date. We propose that it encodes an insulin-sensitive GT.