Netrin-G2 and netrin-G2 ligand are both required for normal auditory responsiveness.

Mice in which netrin-G2 has been genetically inhibited do not startle to an acoustic stimulus, but otherwise perform normally through a behavioral test battery. Light microscopic examination of the inner ear showed no obvious structural abnormalities. Brainstem responses to acoustic stimuli (auditory brainstem responses, ABR) were also present, confirming the lack of any overarching defects in the inner ear or auditory nerve. Genetic inhibition of netrin-G2 ligand produced a nearly identical phenotype, that is, no startle with ABR present, and otherwise normal. This similarity confirms that these two proteins act in the same biological pathway. We have also determined that the affinity between the two proteins is strong, around 2.5 nM, similar to that observed between netrin-G1 and netrin-G1 ligand - 2.3 nM in our hands. The combination of equivalent phenotypes when genetically inhibited coupled with evidence of a strong biochemical interaction supports the notion of a receptor-ligand interaction between these two proteins in vivo. This interaction is critical for auditory synaptic responsiveness in the brain.

Exploratory studies of PM10 receptor and source profiling by GC/MS and principal component analysis of temporally and spatially resolved ambient samples.

For a recent exploratory study of particulate matter (PM) compositions, origins, and impacts in the El Paso/Juarez (Paso del Norte) airshed, the authors relied on solvent extraction (SX)-gas chromatography/mass spectrometry (GC/MS) procedures to characterize 24-hr quartz fiber (QF) filter samples obtained from nine spatially distributed high-volume (Hi-Vol) PM10 samplers as well as on thermal desorption (TD)-GC/MS methods to characterize 45 time-resolved (2-hr) filter samples obtained with modified 1-m3/hr PM10 samplers. Principal component analysis and related chemometric techniques were used for data reduction and data fusion as well as for multiway data correlation. A high degree of correspondence (R2 = 0.821) was found between the rapid TD-GC/MS method (which can be carried out on 2-hr filter slices containing only microgram amounts of sample) and conventional SX-GC/MS procedures. The four main source patterns of organic PM components observed in GC/MS profiles of both temporally and spatially resolved receptor samples obtained in the El Paso/Juarez border airshed during the study period are interpreted to represent (1) vehicular emissions plus resuspended urban dust; (2) biomass combustion; (3) native vegetation detritus and resuspended agricultural dust; and (4) waste burning. Moreover, principal component analysis of combined, variance-weighted, temporally resolved TD-GC/MS data and spatially resolved SX-GC/MS data was used to determine approximate source locations for specific PM components identified in time-resolved receptor sample profiles. The same approach can be used to determine approximate circadian concentration profiles of specific PM components identified in spatially resolved receptor sample profiles.

The deep-sea as a final global sink of semivolatile persistent organic pollutants? Part I: PCBs in surface and deep-sea dwelling fish of the north and south Atlantic and the Monterey Bay Canyon (California).

The understanding of the global environmental multiphase distribution of persistent organic pollutants (POPs) as a result of the physico-chemical properties of the respective compounds is well established. We have analysed the results of a vertical transport of POPs from upper water layers (0-200 m) to the deepwater region (> 800 m) in terms of the contamination of the biophase in both water layers. The contents of persistent organochlorine compounds like polychlorinated biphenyls (PCBs) in fish living in the upper water layers of the North Atlantic and the South Atlantic, and at the continental shelf of California (Marine Sanctuary Monterey Bay and its deep-sea Canyon) are compared to the levels in deep-sea or bottom dwelling fish within the same geographic area. The deep-sea biota show significantly higher burdens as compared to surface-living species of the same region. There are also indications for recycling processes of POPs--in this case the PCBs--in the biophase of the abyss as well. It can be concluded that the bio- and geo phase of the deep-sea may act similarly as the upper horizons of forest and grasslands on the continents as an ultimate global sink for POPs in the marine environment.

The deep-sea as a final global sink of semivolatile persistent organic pollutants? Part II: Organochlorine pesticides in surface and deep-sea dwelling fish of the north and south Atlantic and the Monterey Bay Canyon (California).

The understanding of the global environmental multiphase distribution of persistent organic pollutants (POPs) as a result of the physico-chemical properties of the respective compounds is well established. We have analysed the results of a vertical transport of POPs from surface water to deepwater in terms of the contamination of the biota living in the respective environmental compartments. Samples were taken from the North and the South Atlantic and from the uprising water region of the continental shelf of California (Marine Sanctuary Monterey Bay and its Canyon). The contents of persistent organochlorine pesticides (DDTs, chlordanes, toxaphenes, HCHs, and HCB) in surface-living fish are compared to those in deepwater fish of the same geographic area. The deepwater biota show significantly higher burdens as compared to surface-living species of the same region. There are also indications for recycling processes of POPs of the class of organochlorine pesticides in the biophase of the abyss as well. It can be concluded that the bio- and geophase of the deep-sea may act as an ultimate global sink for persistent semivolatile contaminants in the marine environment like the soil on the continents.

Multifunctional organic nitrates as constituents in European and US urban photo-smog.

Air samples of the atmospheric ground layer in the cities of Ulm in Germany, Las Vegas, Nevada, and Salt Lake City, Utah, in the US were analyzed for organic nitrates. The air samples were taken around noon in summer at sunny weather conditions. 43 (C6-C13) alkyl mononitrates, 24 (C3-C6) alkyl dinitrates, and 19 (C2-C6) hydroxy alkyl nitrates have been identified. The analytical protocol included high-volume-sampling, NP-HPLC group separation, high resolution capillary gas chromatography, and detection by the highly selective mass spectrometer detector (SIM mode, m/z = 46). The levels of the sum of 15 (C6-C10) alkyl mononitrates ranged from 2.9 to 11.0 parts per trillion (ppt(v)). The levels of the sum of 21 (C3-C6) alkyl dinitrates ranged from 2.3 to 10.5 ppt(v), and the levels of the sum of 7 (C2-C4) hydroxy alkyl nitrates ranged from 7.3 to 28 ppt(v), respectively, in the urban air samples. These results emphazise the contribution of the alkyl dinitrates and hydroxy alkyl nitrates besides the alkyl mononitrates to the budget of NO(Y) compounds. No major differences in levels and pattern of the organic nitrates are present in air of the German and the US cities.

Biomarkers of DNA damage in marine mammals.

Certain environmental contaminants found in marine mammals have been shown to cause DNA damage and cancer. The micronuclei (MN), sister chromatid exchange (SCE) and/or chromosome aberration (CA) assays were used to assess baseline (spontaneous) levels of DNA damage in blood lymphocytes of individuals of the relatively healthy and lightly contaminated Arctic beluga whale (Delphinapterus leucas), Sarasota Bay, FL, bottlenose dolphin (Tursiops truncatus) and Northwestern Atlantic grey (Halichoerus grypus) and harp (Phoca groenlandicus) seal populations. MN cell (MNC) frequencies ranged between 2 and 14/1000 binucleated (BN) cells and were statistically similar between species. In bottlenose dolphins, MNC frequency was correlated with age and was significantly higher in females than in males. No intraspecific variation in MNC frequency was found in beluga whales. Intraspecific variation was not tested in seals due to the small sample size. Frequencies of SCEs and total CAs, excluding gaps, ranged, respectively, between 1 and 15 SCE(s)/per cell and 4-6 CAs/100 cells in beluga whales. SCE and CA frequencies did not vary with age or sex in beluga whales. The MN, SCE and CA assays were found to be practical tools for the detection of DNA damage in marine mammals and could be used in the future to compare DNA damage between relatively lightly and highly contaminated populations.

A method for the determination of environmental contaminants in living marine mammals using microscale samples of blubber and blood.

As part of a study examining the possible effects of organochlorine compounds on juvenile northern elephant seals (Mirounga angustirostris), blubber and blood samples were taken from animals present on the Año Nuevo (California) rookery, and from animals admitted for rehabilitation at The Marine Mammal Center (Sausalito CA). Blubber samples were collected from immobilized seals. A pre-cleaned 6 mm K-medic biopsy punch was used to extract the blubber from a 1 cm incision near the hip, near the dorsal mid point. Blood samples were taken from the extradural vein; two mL of serum was analyzed for organochlorine compounds. Blubber samples (approximately 0.1g) were ground with Na2SO4 and extracted with 20 mL hexane:methylene chloride (1:1). Sera samples were extracted using commercially available disposable C18 columns. The extracts were separated on a micro-Florisil column, and analyzed by HRGC-ECD. Lipid determination in the serum was obtained by colorimetric analysis with 20 microliters samples. Results from the analysis of replicates and standard reference materials showed good recoveries, precision, and accuracy for both the blubber and blood methods.

Sample cleanup by solid-phase extraction for the ultratrace determination of polychlorinated dibenzo-p-dioxins and dibenzofurans in biological samples.

A sample cleanup method for the isolation of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) by solid-phase extraction is described. A C18 bonded silica cartridge is used for the initial extraction and enrichment of the analytes. Subsequent cleanup is achieved with a dual-cartridge arrangement consisting of a bonded benzenesulfonic acid cartridge in series with a silica cartridge. A Florisil cartridge is employed for the final cleanup step. Sample preparation procedures used for blood plasma and animal tissues are described. The precision and accuracy of the method is validated by determining recoveries of 2,3,7,8-substituted PCDD and PCDF congeners spiked at various levels in blood plasma and in animal tissues. The effectiveness of the cleanup method is shown by the analysis of wild bird eggs which are highly contaminated with a variety of pesticides and polychlorinated biphenyls. The application of this cleanup method to human plasma containing PCDDs/PCDFs at parts-per-quadrillion levels and results of analyses by high-resolution mass spectrometry and low-resolution mass spectrometry are presented. The validity of this method is demonstrated by the comparable results obtained from this method and from other established methods.

Organochlorines, including chlordane compounds and their metabolites, in peregrine-falcon, prairie-falcon, and clapper-rail eggs from the USA.

Four compounds present in technical chlordane (trans- and cis-nonachlor, and tentatively MC-2 and MC-5) and three metabolites of chlordane (heptachlor epoxide, oxychlordane, and U-4) were identified by GC/MS in peregrine-falcon (Falco peregrinus anatum) eggs. Levels of Heptachlor epoxide, oxychlordane, trans- and cis-chlordane, trans- and cis-nonachlor, MC-2, and MC-5 were quantified by GC/ECD in peregrine-falcon eggs from the US east coast, Colorado, and California; and in prairie-falcon (Falco mexicanus) and light-footed-clapper-rail (Rallus longirostris levipes) eggs from California. The eggs were collected between 1986 and 1989. Oxychlordane, heptachlor epoxide, trans- and cis-nonachlor, MC-2, and MC-5 were detected in every egg analyzed. Heptachlor, trans-, and cis-chlordane were either not detected, or present at low levels in the eggs. The highest Sigmachlordane levels were found in the East Coast peregrine-falcon eggs at a geometric mean (geom. mean) concentrations of 1800 microg/kg (ppb); the lowest levels of Sigmachlordane were found in the prairie-falcon eggs at a concentration of 120 microg/kg (geom. mean). Of the technical chlordane compounds measured, MC-2 bioaccumulated to the greatest degree. SigmaDDT levels in the falcons ranged from 11 000 microg/kg (geom. mean) in the Colorado samples to 8800 microg/kg (geom. mean) in the East Coast and California peregrines. SigmaDDT levels in the rail eggs were 3000 microg/kg (geom. mean). The highest SigmaPCB levels were found in the East Coast peregrine-falcon eggs at a concentration of 14 000 microg/kg (geom. mean); the lowest levels of SigmaPCB were found in the prairie-falcon eggs at a concentration of 350 microg/kg (geom. mean).

Colon and rectal carcinoma. Forty years and 1400 cases.

One thousand four hundred cases of colorectal carcinoma were treated primarily at the Wake Forest University Medical Center between 1945 and 1985. The surgical approach was constant in all patients without obvious stage IV disease: wide resection, including at least the primary-level and intermediate-level lymph nodes. There were 812 women and 588 men in the series. Sixty-eight per cent of the 1400 cancers occurred in the rectosigmoid, but only 53 per cent of the last 300 cases were in this region. Initial staging showed 560 cases (40%) of local disease, 504 cases (36%) of regional disease, and 336 cases (24%) of distant disease. Cecal, ascending, hepatic, and transverse lesions were most often associated with stage IV disease. Among the 1115 patients with long-term follow-up, 44 per cent with stage I disease, 37 per cent with stage II disease, 24 per cent with stage III disease, and 6 per cent with stage IV disease had survived for 5 years or longer. There were no differences when 5-year survival was correlated with site. This review provided no evidence that wide resection leads to increased long-term survival.

Evaluating medical treatment of impotence.

The nocturnal penile tumescence study, bulbocavernosus reflex latency time, and ultrasonic blood flow studies have made possible a more objective determination of the success or failure of various means used to treat impotence. A group of 60 patients with a history of impotence and flat nocturnal penile tumescence readings were selected for evaluation. Thirty were diabetic and 30 had idiopathic impotence. These patients were treated with a vasodilator, told to stop smoking for six weeks, or both. The results indicate that greater than one third of the patients were able to have intercourse and show NPT activity after treatment. Our study indicates that there is a select group of diabetics, as well as patients with idiopathic impotence, who may respond to medical management.

Vascular factor in erectile failure among diabetics.

Clinical, sexual, and laboratory evaluations were made on 47 impotent diabetics. All patients were given a Doppler PAPS examination and a neurologic assessment of the penis (BCRL and/or CMG). Nerve conductivity tests of the legs were also administered to most patients. The groups were classified as to whether they were insulin or noninsulin dependent. Abnormalities of penile arterial flow were detected in 95.7 per cent of all the patients. Penile arterial occlusions without associated penile neuropathies occurred in 61.7 per cent. Penile neuropathies were found in 34 per cent, and all were associated with varying degrees of penile arterial obstruction. Diabetics who were dependent on insulin showed a high frequency of vascular pathologies and a 12 to 15 per cent higher rate of penile neuropathies than the group not dependent on insulin. Our study suggests that obstruction of penile arteries is the primary factor in erectile dysfunction of diabetics. Those impotent diabetics without any overt penile nerve damage might be good candidates for revascularization procedures.

Red cell surface antigen and its relationship to survival of patients with transitional cell carcinoma of the bladder.

We studied 73 patients with transitional cell carcinoma of the bladder seen from 1967 to 1973. The red cell antigen test was done in a controlled blind study to determine if tumor behavior can be predicted by this test. Our results do not substantiate the findings of other investigators who have reported excellent correlation. We did not find statistical evidence that loss of antigen could be equated to a poor prognosis. We noted that patients in group O gave the weakest reaction and that this test had to be done in a modified fashion in tumors from these patients. It also was noted that as individuals age they tend to lose the red cell antigen. There is no doubt that this test, as reported in the literature, is a great advance in the study of bladder cancer. Further refinement in technique and more data are needed to substantiate its accuracy in predicting the behavior of bladder cancer.

Hypercalcemic crisis secondary to a functioning parathyroid cyst.

A case of hypercalcemic crisis secondary to a large functioning parathyroid cyst is presented. Because none of the theories about the origin of parathyroid cysts are well substantiated or accepted, these cysts should be referred to simply as parathyroid cysts, functional or nonfunctional.

Carcinoma of the parathyroid.

We report on eight cases of parathyroid carcinoma seen at the Bowman Gray School of Medicine, Winston-Salem, NC, since 1969. Diagnosis of a parathyroid disorder was made on the basis of elevated serum calcium levels and associated disorders such as renal calculi, peptic ulcer disease, pancreatitis, and demineralization of bone. Six of the involved glands were on the left side. In seven patients, the disease was localized to the gland or adjacent structures; one patient had cervical lymph node invasion. Except for the last patient, in whom radical neck dissection and wide excision was done, local excision with adequate margins was the only procedure done. The patient with metastases died of his disease four years later. One patient died of myocardial infarction two years later, but had been normocalcemic in the interval between operation and death, and one patient is hypercalcemic and has had two local recurrences within a 3 1/2 year period. The other five patients are alive and well. The routine use of automated serum level determinations of all hospitalized patients has led to early detection of this malignancy, while it is still a stage I lesion in many instances. On the basis of this material, we conclude that radical neck dissection can no longer be advocated as a routine measure in the treatment of parathyroid carcinoma.

A study of 48 cases of incidental carcinoma of the prostate followed 10 years or longer.

We reviewed 48 cases of incidental carcinoma treated conservatively. Patients with poorly differentiated, multiple foci or with well differentiated, multiple foci had a poor prognosis, whereas those with well differentiated, few foci (1 to 3) had a good prognosis. We believe that patients with multiple foci (poorly or well differentiated) should be treated aggressively, either by radical prostatectomy or radiotherapy. However, we recommend conservative treatment for patients with well differentiated, few foci.