Skin metastasis, an uncommon course of prostate carcinoma: a report of two cases.

Prostate cancer is one of the most common cancers among men worldwide and in the USA. Most prostate cancer progression either locally invades to seminal vesicles or metastasizes distally to bone. Skin is not a common site of metastasis for the majority of malignancies including prostate cancer. This paper reports two extremely rare cases of prostate carcinoma metastatic to the skin: a 74-year-old man previously treated with radiation for prostate cancer with cutaneous metastases to the shoulder and a 68-year-old man with prostate adenocarcinoma and cutaneous metastases to the groin. Both patients were diagnosed with skin punch biopsy and later confirmed with immunohistochemical staining for PSA and prostate specific acid phosphatase, specific for prostatic carcinoma. Although unusual, development of multiple skin lesions in patients with prostate adenocarcinoma should raise the flags of cutaneous metastases.

Regeneration, stem cells, and the evolution of tumor suppression.

All multicellular organisms have requirements for tumor suppression to regulate cellular proliferation during either embryonic development or adult life. However, different organisms have vastly different requirements. Adult tumor suppression is probably not crucial to organisms possessing both short life spans and largely postmitotic soma. In contrast, animals with lifelong tissue turnover or those capable of regenerating body parts lost to injury must possess evolutionarily selected mechanisms to control rates of cell proliferation such that tissue homeostasis can be maintained or restored after injury. We hypothesize that these biological differences may help to explain why the lists of tumor suppressor genes in humans and Drosophila are largely nonoverlapping. Here, we address this disparity by examining the tumor suppressor gene content of two outgroups to the vertebrates and flies/nematodes: the freshwater planarian and the single-celled choanoflagellate. Both of these organisms have recently had their genomes sequenced, giving us a first glimpse of which known tumor suppressor genes have been maintained during evolution. In addition, we attempt to resolve which genes may have had ancestral tumor suppressor function and which may have acquired this function de novo.

Spectral phase effects on nonlinear resonant photochemistry of 1,3-cyclohexadiene in solution.

We have investigated the ring opening of 1,3-cyclohexadiene to form 1,3,5-cis-hexatriene (Z-HT) using optical pulse shaping to enhance multiphoton excitation. A closed-loop learning algorithm was used to search for an optimal spectral phase function, with the effectiveness or fitness of each optical pulse assessed using the UV absorption spectrum. The learning algorithm was able to identify pulses that increased the formation of Z-HT by as much as a factor of 2 and to identify pulse shapes that decreased solvent fragmentation while leaving the formation of Z-HT essentially unaffected. The highest yields of Z-HT did not occur for the highest peak intensity laser pulses. Rather, negative quadratic phase was identified as an important control parameter in the formation of Z-HT.

Control of Raman lasing in the nonimpulsive regime.

We explore coherent control of stimulated Raman scattering in the nonimpulsive regime. Optical pulse shaping of the coherent pump field leads to control over the stimulated Raman output. A model of the control mechanism is investigated.

The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans.

The ability to discriminate between different chemical stimuli is crucial for food detection, spatial orientation and other adaptive behaviours in animals. In the nematode Caenorhabditis elegans, spatial orientation in gradients of soluble chemoattractants (chemotaxis) is controlled mainly by a single pair of chemosensory neurons. These two neurons, ASEL and ASER, are left-right homologues in terms of the disposition of their somata and processes, morphology of specialized sensory endings, synaptic partners and expression profile of many genes. However, recent gene-expression studies have revealed unexpected asymmetries between ASEL and ASER. ASEL expresses the putative receptor guanylyl cyclase genes gcy-6 and gcy-7, whereas ASER expresses gcy-5 (ref. 4). In addition, only ASEL expresses the homeobox gene lim-6, an orthologue of the human LMX1 subfamily of homeobox genes. Here we show, using laser ablation of neurons and whole-cell patch-clamp electrophysiology, that the asymmetries between ASEL and ASER extend to the functional level. ASEL is primarily sensitive to sodium, whereas ASER is primarily sensitive to chloride and potassium. Furthermore, we find that lim-6 is required for this functional asymmetry and for the ability to distinguish sodium from chloride. Thus, a homeobox gene increases the representational capacity of the nervous system by establishing asymmetric functions in a bilaterally symmetrical neuron pair.

Hypertension in patients presenting with stroke.

Hypertension is a major risk factor for stroke disease. There is now some international agreement on what constitutes hypertension, and at what level of blood pressure treatment is required. Large randomised controlled trials demonstrate the benefit of reducing blood pressure for the primary and secondary prevention of stroke disease. Studies have also demonstrated the benefit of particular classes of antihypertensive agents in certain patient groups. Research is beginning to elucidate the problems of hypertension in the acute phase of ischaemic stroke and the therapeutic strategies that may be helpful. Given the significant impact of stroke disease on all health services, it remains an important priority to determine the best management of hypertension in stroke.

Recruitment of a hedgehog regulatory circuit in butterfly eyespot evolution.

The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes in development, but the nature of these changes is largely unknown. In butterflies, eyespots have evolved as new pattern elements that develop from special organizers called foci. Formation of these foci is associated with novel expression patterns of the Hedgehog signaling protein, its receptor Patched, the transcription factor Cubitus interruptus, and the engrailed target gene that break the conserved compartmental restrictions on this regulatory circuit in insect wings. Redeployment of preexisting regulatory circuits may be a general mechanism underlying the evolution of novelties.

Differential development and characterization of rapid acute neuronal tolerance to the depressant effects of ethanol on cerebellar Purkinje neurons of low-alcohol-sensitive and high-alcohol-sensitive rats.

Rapid acute neuronal tolerance (RANT) to the depressant effects of ethanol (EtOH) is a desensitization of EtOH-induced depression of neuronal firing that develops over the first 5 to 7 min of EtOH exposure. This phenomenon has been hypothesized to play a role in acute behavioral insensitivity to EtOH and is expressed by cerebellar Purkinje neurons in animals selectively bred for insensitivity to EtOH-induced ataxia, such as low-alcohol-sensitive (LAS) rats and short-sleep mice. Purkinje neurons of animals bred for high sensitivity to EtOH-induced behavioral ataxia, such as high-alcohol-sensitive (HAS) rats and long-sleep mice, only infrequently express such acute tolerance to EtOH-induced depression of neuronal activity. However, because higher EtOH doses are required to depress Purkinje neuron activity in LAS rats than in HAS rats, it was not known whether the higher EtOH doses that depress LAS neurons would also induce RANT to EtOH in HAS rats, which were generally not exposed to such high EtOH doses in previous studies. Furthermore, the conditions for development and maintenance of RANT to EtOH had not been characterized. We found that RANT to EtOH-induced depression of cerebellar neurons principally developed within 5 min of EtOH application and recovered within 20 min of the last EtOH exposure and that neurons in HAS rats did not develop acute tolerance to the higher EtOH doses that were effective in LAS rats. We conclude that this rapid tolerance contributes to the acute EtOH sensitivity difference between LAS and HAS rats.

Early recognition of cutaneous melanoma.

Criteria for the early recognition of malignant melanoma include appreciation of variegation in color and irregularity of lesion border and pigment pattern. Application of these criteria should result in the diagnosis of cutaneous melanoma in its premetastatic surgically curable phase.

Acute copper intoxication. Pathophysiology and therapy with a case report.

We report a case of cupric sulfate intoxication in a child who had a serum copper level of 1,650 mug/100 ml. His course was accompanied by hemolytic anemia and renal tubular damage. We review the pathophysiology of copper metabolism and intoxication. We also review modes of therapy, with specific reference to the initial approach, using dimercaprol (BAL) and edetic acid rather than penicillamine.