Hyperplastic pacinian corpuscles: an uncommonly encountered lesion of the hand

The occurrence of hyperplastic pacinian corpuscles in the hand is rare, with only 13 cases reported in the literature. We describe such a case in a 70-year-old male who had worked as a locksmith for many years. A grape-like cluster of firm, rice-sized nodules was discovered in the subcutaneous tissue of the finger following a glass-induced injury. Histopathological findings revealed pacinian corpuscles to be increased in size and number. Individual corpuscles consisted of a central nerve fiber surrounded by 35 to 60 concentric lamellae (normal controls from other specimens: 13–15 lamellae). The external corpuscular diameter ranged from 1.8 to 3.2 mm (normal controls from other specimens: 1.6 mm). Immunohistochemistry showed positive staining with Leu 7 antibody and anti-glial fibrillary acidic protein in the small nerves situated in the vicinity of the pacinian corpuscles, but not in the corpuscles themselves. The lesion reported here clearly differed from both neurofibroma with occasional pacinian differentiation and the so-called pacinian neurofibroma. There was no evidence of neurofibromatosis.     

Identification of a parathyroid hormone in the fish Fugu rubripes.

A PTH gene has been isolated from the fish Fugu rubripes. The encoded protein of 80 amino acid has the lowest homology with any of the PTH family members. Fugu PTH(1-34) had 5-fold lower potency than human PTH(1-34) in a mammalian cell system. INTRODUCTION: Parathyroid hormone (PTH) is the major hypercalcemic hormone in higher vertebrates. Fish lack parathyroid glands, but there have numerous attempts to identify and isolate PTH from fish. MATERIALS AND METHODS: Polymerase chain reaction (PCR) was performed with primers based on preliminary data from the Joint Genome Institute database. PCR amplification was performed on genomic DNA isolated from Fugu rubripes. PCR products were purified and DNA was sequenced. All sequence was confirmed from more than one independently amplified PCR product. Multiple sequence alignments were carried out, and the percentage of identities and similarities were calculated. An unrooted phylogenetic tree, using all the known PTH and PTH-related protein (PTHrP) amino acid sequences, was determined. Synthetic peptides were tested in a biological assay that measured cyclic adenosine 3',5'-monophosphate formation in UMR106.1 cells. Rabbit polyclonal antisera specific for N-terminal human PTHrP and one rabbit polyclonal antiserum specific for N terminus hPTH were used to test the cross-reactivity with fPTH(1-34) in immunoblots.     

Validating the self-reported fertility status of rural Malawian women.

This study uses data from a population-based survey to examine the fertility schedules of 704 women in a rural district of Malawi. The main objective is to assess self-reported fecundity status as a measure of fertility impairment. Life tables are used to examine the timing and tempo of births for women reporting difficulty getting pregnant as compared to women with no reported fecundity difficulties. Results of the analysis indicate that women with self-reported fecundity difficulties are older at each birth and have longer median birth intervals than do women with no reported difficulties. Cox proportional hazards models show that the report of a difficulty getting pregnant is significantly associated with at least a 30% lower likelihood of a first, second, or third birth. The relationships are not modified when accounting for demographic characteristics, previous sexual behaviors, or STI status.     

A performance curve for assessing change in Percentage of Consonants Correct Revised (PCC-R).

PURPOSE: Interpreting the rapidly changing speech skills of young children recovering from neurological injury is difficult because developmental expectations are generally available only at relatively lengthy intervals (e.g., 6 or 12 months). In this research note, the authors describe the process of generating a Percentage of Consonants Correct-Revised (PCC-R; L. D. Shriberg, D. Austin, B. A. Lewis, J. L. McSweeny, & D. L. Wilson, 1997a) performance curve and illustrate some of its applications for assessing change in performance over time. METHOD: The authors compiled mean PCC-R scores from 16 samples of typically developing children (18-172 months) and used curve fitting to test more than 11,000 statistical models of monthly growth in PCC-R. They selected a parsimonious and developmentally plausible model with R(2) = .9839 (p < .0005) and used it to generate the PCC-R, standard deviation, and standard error expected at each monthly age. RESULTS: The PCC-R performance curve distinguished among 65 children (37-57 months of age) diagnosed independently with normal or disordered speech with a high degree of success. More important, the PCC-R performance curve can be used to identify the points at which children (18-172 months) recovering from neurological injury achieve normal-range consonant production. CONCLUSION: The curve-fitting approach holds promise as a means of interpreting temporal variations in speech production at a finer grain than existing normative data currently allow.     

Conservation of the chromatophore pigment response

Toxicant sensing technology has evolved to include biological sensors, such as cell‐based biosensors, which rely on viable cells to convey a measurable physiological signal. Chromatophores are a class of pigment cells that have been investigated as cell‐based biosensors. We report the characterization of Oncorhynchus tshawytscha melanophores and describe the melanophore pigment response to neurotransmitters in terms of pigment area occupied. Compared with the previously described model, Betta splendens erythrophores, O. tshawytscha melanophores responded similarly, indicating that pigment responses are biologically conserved between these two species. Additionally, melanophores responded to mercuric chloride and sodium arsenite, similar to B. splendens erythrophores, suggesting that melanophores can be used as detectors for environmental toxicants. This report highlights the potential of O. tshawytscha melanophores to be used as cell‐based biosensors to address environmental toxicity, and warrants a continued investigation to strengthen this technology and its applications.     

Chloride current activated by cyclic AMP and parathyroid hormone in rat osteoblasts

In primary cultures of rat osteoblasts, studied with the whole-cell configuration of the patch-clamp technique, 8-bromo-cyclic AMP (8BrcAMP) forskolin (FS) and 1–34 parathyroid hormone (PTH) were shown to activate a Cl conductance. This conductance shows a pronounced outward rectification, even with symmetrical Cl concentrations. It is blocked partially and reversibly by 4,4-diisothiocyanatostilbene 2,2-disulfonic acid (DIDS) or diphenylcarboxylate (DPC). The blockade induced by DIDS is time-and voltage-dependent. The Cl responses to FS and PTH develop slowly, after a delay of several seconds and are very slowly reversible. These responses were observed only in a fraction of the cells tested and their detection was favoured by cell dialysis. This Cl current should be taken into account for studying possible modulations of the voltage-gated Ca currents of osteoblasts. It is suggested that its physiological role may be related to the well-known morphological changes induced by PTH in osteoblasts. The cyclic AMP-sensitivity, the outward rectification and the sensitivity to dialysis of this Cl current are reminiscent of the properties of the cystic fibrosis-sensitive Cl channels of epithelial cells.     

Effect of dipyridamole on fluorodeoxyuridine cytotoxicity in vitro and in cancer patients

Summary Dipyridamole (DP) has previously been studied both in vitro and in vivo in combination with various antimetabolites, including methotrexate and 5-fluorouracil (5FU). We evaluated in vitro and clinically the effects of adding DP to fluorodeoxyuridine (FUDR) in colorectal cancer. Using a human colony-forming assay, we observed that 0.05 M DP increased the cytotoxicity of FUDR by a median of 33.5-fold vs 1.5-fold for 5FU against human colon-cancer cell lines. The mechanism of the DP-enhanced antitumor activity of FUDR is not completely understood but appears to be related to a profound inhibition by DP of thymidine accumulation in and FUDR efflux from colon-cancer cell lines. On the basis of these in vitro results, 28 patients with metastatic colon cancer were entered in a clinical trial of monthly courses of 0.1 mg/kg FUDR daily for 14 days and 75 mg oral DP 5 times daily for 14 days starting on the 3rd day of continuous i.v. FUDR infusion. The pharmacokinetics of DP was studied in three patients; the results showed that 98% of total serum DP was protein-bound and that free DP levels were significantly lower than the concentrations necessary for the expected in vitro DP/FUDR modulation. Treatment was well tolerated, with only 12 patients developing mild to moderate toxicity. Of 27 evaluable patients, 4 achieved a partial response that lasted 2, 3, 5, and 6+ months. This relatively low response rate (15%), which is similar to that achieved with FUDR alone, may be explained by the low steady-state plasma concentrations of free DP achieved in our patients. Other means of DP administration, such as i.v., i.a., and i.p. injection, may be required to achieve free DP concentrations necessary for successful biochemical modulation of FUDR in patients.Supported in part by grants CA17094, CA23074, and CA39629 from the National Institutes of Health, Bethesda, Md 20205, and a grant from the Arizona Chronic Disease Commission. HSG is a recipient of an American Cancer Society Career Development Award     

Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients

Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in copper overload in various tissues and cells. The aim was to assess both the phenotype in Brazilian WD patients and the corresponding ATP7B genotype. Sixty subjects belonging to 46 pedigrees diagnosed as WD were included in this study. Direct sequencing of all 21 exons within ATP7B and their flanking introns was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained. We identified twenty-five mutations, twelve of them reported for the first time. The c.3402delC mutation had the highest allelic frequency (30.8%), followed by the c.2123T>C (p.L708P) (16.7%). Exons 8 and 15 were the site of 62.5% of the mutations. The common European mutation c.3207C>A (p.H1069Q) was not present at all. Phenotype varied greatly among individuals with the same ATP7B genotype. Our data confirm the heterogeneity of ATP7B genotype in Brazilian WD patients. The mutational spectrum is compatible with the Brazilian history of Mediterranean immigration; however, new mutations, and different frequencies and phenotype associated with the previously known mutations characterize this population. Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD.