Updated and expanded study of polycythemia vera and other myeloproliferative neoplasms in the tri-county area.

INTRODUCTION: The results of a 2001-2005 polycythemia vera (PV) investigation in Eastern Pennsylvania revealed a disease cluster plus underreporting and false reporting to the Pennsylvania Cancer Registry (PCR). PURPOSE: The objectives of this study were 1) to assess PV reporting to the PCR in 2006-2009, 2) to determine whether a cancer cluster persisted, and 3) to determine whether other myeloproliferative neoplasms (MPNs), including essential thrombocytopenia (ET), were subject to similar reporting problems. METHODS: Cases were identified from: 1) PCR records from the Tri-County, 2) reviewing billing records at Tri-County hematologist/oncologist offices, and 3) self-identification. An expert panel of physicians reviewed medical records and determined "true," "false," or "indeterminate" cases reported to the PCR. The analyses were conducted to determine sensitivity and positive predictive value (PPV) of case reporting to the PCR, estimate cancer incidence rates, and evaluate the presence of cancer clusters. RESULTS: Of 290 cases identified, 90% were from the original PCR, 9% from billing records, and 1% from self-report. Fifty-five cases consented to participate, and medical records were obtained for 44. The expert panel determined that 45% were true cases, 32% were false cases, and 23% were indeterminate. PV had 100% (95% CI, 59-100) sensitivity, but only 47% PPV (95% CI, 20-70): ET had 78% (95% CI, 47-99) sensitivity and 100% PPV (95% CI, 59-100). Low participation and chart review rates led to rates with wide confidence intervals. We did not identify any PV cancer clusters, but we did identify a cluster of 9 ET cases in the Wilkes-Barre, Pennsylvania area. CONCLUSION: The current study was limited by the low response rate (22%) from MPN patients in the Tri-County area. This study identified 47% PPV for PV reporting and 100% PPV for ET.

Iron-binding characterization and polysaccharide production by Klebsiella oxytoca strain isolated from mine acid drainage.

AIMS: To investigate Klebsiella oxytoca strain BAS-10 growth on ferric citrate under anaerobic conditions for exopolysaccharide (EPS) production and localization on cell followed by the purification and the EPS determination of the iron-binding stability constant to EPS or biotechnological applications. METHODS AND RESULTS: Klebsiella oxytoca ferments ferric citrate under anaerobic conditions and produces a ferric hydrogel, whereas ferrous ions were formed in solution. During growth, cells precipitate and a hydrogel formation was observed: the organic material was constituted of an EPS bound to Fe(III) ions, this was found by chemical analyses of the iron species and transmission electron microscopy of the cell cultures. Iron binding to EPS was studied by cyclic voltammetric measurements, either directly on the hydrogel or in an aqueous solutions containing Fe(III)-citrate and purified Fe(III)-EPS. From the voltammetric data, the stability constant for the Fe(III)-EPS complex can be assumed to have values of approx. 10(12)-10(13). It was estimated that this is higher than for the Fe(III)-citrate complex. CONCLUSIONS: The production of Fe(III)-EPS under anaerobic conditions is a strategy for the strain to survive in mine drainages and other acidic conditions. This physiological feature can be used to produce large amounts of valuable Fe(III)-EPS, starting from a low cost substrate such as Fe(III)-citrate. SIGNIFICANT AND IMPACT OF THE STUDY: The data herein demonstrates that an interesting metal-binding molecule can be produced as a novel catalyst for a variety of potential applications and the EPS itself is a valuable source for rhamnose purification.

The analytical relations between particles and probe trajectories in atomic force microscope nanomanipulation.

Analytical expressions relating the trajectories of spherical nanoparticles pushed by an atomic force microscope tip to the scan pattern of the tip are derived. In the case of a raster scan path, the particles are deflected in a direction defined by the geometries of tip and particles and the spacing b between consecutive scan lines. In the case of a zigzag scan path, the particles are deflected in a range of directions around 90 degrees, also depending on the parameter b. Experimental results on gold nanoparticles manipulated on silicon surfaces in ambient conditions confirm the predictions of our model.

Interfacial electrostatics of self-assembled monolayers of alkane thiolates on Au(111): work function modification and molecular level alignments.

We have isolated at T < 150 K a weakly adsorbed dimethyl disulfide (DMDS) layer on Au(111) and studied how the vibrational states, S core hole level shifts, valence band photoemission, and work function measurements evolve upon transforming this system into chemisorbed methylthiolate (MT) self-assembled monolayers (SAM) by heating above 200 K. By combining these observations with detailed theoretical electronic structure simulations, at the density functional level, we have been able to obtain a detailed picture of the electronic interactions at the interface between Au and adsorbed thiolates and disulfides. All of our measurements may be interpreted with a simple model where MT is bound to the Au surface with negligible charge transfer. Interfacial dipoles arising from Pauli repulsion between molecule and metal surface electrons are present for the weakly adsorbed DMDS layer but not for the chemisorbed species. Instead, for the chemisorbed species, interfacial dipoles are exclusively controlled by the molecular dipole, its interaction with the dipoles on neighboring molecules, and its orientation to the surface. The ramifications of these results for alignment of molecular levels and interfacial properties of this class of materials are discussed.

Metal work-function changes induced by organic adsorbates: a combined experimental and theoretical study.

The role of molecular dipole moment, charge transfer, and Pauli repulsion in determining the work-function change (Deltaphi) at organic-metal interfaces has been elucidated by a combined experimental and theoretical study of (CH(3)S)(2)/Au(111) and CH(3)S/Au(111). Comparison between experiment and theory allows us to determine the origin of the interface dipole layer for both phases. For CH(3)S/Au(111), Deltaphi can be ascribed almost entirely to the dipole moment of the CH(3)S layer. For (CH(3)S)(2)/Au(111), a Pauli repulsion mechanism occurs. The implications of these results on the interpretation of Deltaphi in the presence of strongly and weakly adsorbed molecules is discussed.

Study on the toxicity of phenolic and phenoxy herbicides using the submitochondrial particle assay.

A simple and rapid in vitro toxicological assay, utilizing submitochondrial particles (SMP), has been used to evaluate the toxic effects of fifteen herbicides belonging to the phenol and phenoxyalkanoic acid chemical classes. The SMP assay allows the quantitative evaluation of the toxicity of compounds with different mechanisms of action: uncouplers, inhibitors of the enzyme complexes involved in reverse electron transfer and in oxidative phosphorylation and chemicals that alter the membrane structure. The two groups of herbicides showed different levels of toxicity. For phenol derivatives, EC50 values ranged from 0.16 microM (ioxynil) to 6.7 microM (2,4-dinitrophenol), whereas for phenoxy herbicides EC50 values ranged from 21 microM (2,4,5-trichlorophenoxyacetic acid, 2,4,5-T) to 110 microM (4-chloro-2-methylphenoxyacetic acid, MCPA). On the average, the toxicity of phenolic compounds is greater than that of phenoxyalkanoic acids by two orders of magnitude. Quantitative structure-activity relationships (QSAR) were developed between EC50 values and various molecular descriptors. The results suggest the existence of different mechanisms of action for the two classes of compounds. The findings obtained for phenolic herbicides are consistent with a protonophoric uncoupling mechanism, whereas for phenoxy herbicides a non-specific mode of action at membrane level can be hypothesized.

Dizygotic twinning, cryptorchism, and seminoma in a sibship.

Cryptorchism was diagnosed in all 3 male members of 2 pairs of dizygotic twins in a sibship. Two of these brothers developed seminomas at age 31 and 33 years. Studies revealed a nephew with an atrophic testicle, but no additional instances of twinning, cryptorchism or testis cancer. Cryptorchism has been reported previously in 3 of 8 sets of twins with testis cancer, but rarely in familial testis cancer affecting other relatives. Hormonal factors may be involved in the association of twinning, cryptorchism and testis cancer in this family.

Familial carcinoma of ureters and other genitourinary organs.

We report on a woman, her mother and her mother's cousin who had papillary transitional cell carcinoma of the ureter associated with other cancers of the genitourinary tract. Neoplasms in these family members may be due to interactions between host susceptibility factors and exposure to environmental carcinogens. Studies of peripheral blood karyotype and urine mutagenic activity yielded normal results.

Familial renal carcinoma.

Renal carcinoma developed in two or more members of nine families. Multiple generations were affected in five kindreds, and siblings in four. The median age at cancer diagnosis was a decade earlier than usual, and individual patients had bilateral or multifocal lesions; these are features of hereditary forms of diverse cancers. No patient had von Hippel-Lindau disease or other predisposing genetic syndromes. Karyotypes of the peripheral blood of nine persons showed no instance of a 3;8 chromosome translocation as recently reported in association with renal carcinoma in ten members of one family. The findings show that familial renal cancer is more common than previously reported in the literature.

Heterogeneous response to X-ray and ultraviolet light irradiations of cultured skin fibroblasts in two families with Gardner's Syndrome.

A heterogeneous response to X-ray and far UV (254 nm) light irradiations was found in cultured skin fibroblast lines from 2 separate families with Gardner's syndrome. When compared to 2 normal control cultures and cultures from 2 patients with nonfamilial colon cancer, cultures from 4 clinically affected members of family 1 showed increased sensitivity to the lethal effects of both X-ray and UV light irradiations. These cells also showed a delayed pattern of X-ray potentially lethal damage repair (PLDR) and absent UV PLDR. In contrast, cultures from 3 members of family 2 (2 of whom were clinically affected) showed a normal response of survival and PLDR to both X-ray and UV light irradiations. Thus increased sensitivity of cultured skin fibroblasts to X-ray and UV light irradiations was not a consistent in vitro finding in patients with Gardner's syndrome. However, in families with Gardner's syndrome who demonstrate in vitro radiosensitivity, additional studies are needed to assess the usefulness of these techniques in detecting affected individuals prior to the development of colon carcinoma and other manifestations.

Acute myelocytic leukemia in two brothers with polyposis coli and carcinoma of the colon.

Two brothers developed multiple adenomatous polyps of the colon and colonic adenocarcinoma, the classic features of familial polyposis coli. Both also developed acute myelocytic leukemia. This constellation of neoplasms is distinct from other genetic syndromes that feature polyposis coli. The parents of the brothers are first cousins, suggesting autosomal recessive inheritance of these multiple neoplasms. Autosomal dominant of X-linked transmission is also possible and should be evaluated in other affected families.

The surgical management of hereditary multifocal renal carcinoma.

A family was described recently in which renal carcinoma developed in 10 members in 3 consecutive generations. The cancer tended to develop in patients at an early age, and to occur in both kidneys and at multiple sites more frequently than in nonfamilial renal cancer. The finding of a balanced reciprocal translocation between chromosomes 3 and 8 in affected family members suggest that an inherited genetic defect predisposes to the development of this cancer in middle-aged patients and offers a marker for screening individuals at risk. We herein discuss the surgical management of 4 family members, the proband and 3 relatives, who were discovered on screening to have bilateral, multifocal renal cancer. Certain compromises in the principles of radical tumor surgery have proved effective in these 4 patients. Partial nephrectomy has resulted in total extirpation of the bilateral tumors with survivals of 2 to 4 years without need for chronic dialysis. The sequential order of surgical procedures is important since partial nephrectomy of the least affected side first allows a total nephrectomy on the more affected side to be done later, when necessary, without transient renal failure.

Acute leukemia and preleukemia in eight males in a family: an X-linked disorder?

Eight males in a family died of acute leukemia or a potentially preleukemic blood disease. Three patients were descendants of a man through his first wife, and the other five through his second wife. The pattern of disease in the family suggests X-linked inheritance through the two wives, although other mechanisms cannot be excluded. No detectable action of environmental leukemogens was observed in this family disorder.