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A pony was vaccinated with recombinant OspA vaccine (rOspA) and then exposed 3 months later to Borrelia burgdorferi-infected ticks (Ixodes scapularis) collected in Westchester County, N.Y. At 2 weeks after tick exposure, the pony developed a high fever (105 degrees F). Buffy coat smears showed that 20% of neutrophils contained ehrlichial inclusion bodies (morulae). Flunixin Meglumine (1 g daily) was given for 2 days, and the body temperature returned to normal. PCR for ehrlichial DNA was performed on blood samples for 10 consecutive days beginning when the pony was first febrile. This pony was monitored for another 3.5 months but developed no further clinical signs. The 44-kDa immunodominant human granulocytic ehrlichiosis antigen gene was amplified by PCR and cloned into a pCR2.1 vector. DNA sequence analysis of this gene showed it was only 8 bp different (99% identity) from the results reported by others (J. W. Ijdo et al., Infect. Immun. 66:3264-3269, 1998). Western blot analysis, growth inhibition assays, and repeated attempts to isolate B. burgdorferi all demonstrated the pony was protected against B. burgdorferi infection. These results highlight the potential for ticks to harbor and transmit several pathogens simultaneously, which further complicates the diagnosis and vaccination of these emerging tick-borne diseases.

Objectives: Quality of life (QOL) data were used to evaluate the effects of self-administered intracavernosal injection of alprostadil for erectile dysfunction, when used for up to 18 months during a 13 country Phase III clinical trial., Methods: The Duke Health Profile was used to measure patients' physical and psychosocial QOL at baseline, 3, 6, 12 and 18 months. Changes from baseline were measured using paired t-tests, with additional analyses by cause of dysfunction, starting dosage, and prior treatment., Results: Patients displayed significant improvements in mental and social health and self-esteem at six months (P < 0.01, n = 570), with greater improvements at 12 and 18 months. Anxiety and depression measures also improved significantly at 12 and 18 months, as did the summary general health score. Worse pain scores were observed in the first year but not at 18 months. Those with a starting dosage of 10-20 micrograms, those with psychogenic causes of dysfunction, and those with no prior treatment for erectile dysfunction generally showed the greatest improvements., Conclusion: In this study, the clinical improvements in erectile function due to intracavernosal alprostadil therapy were complemented by QOL improvements, particularly in the mental health, of many patients.

The implementation of a rat hepatocyte model system and differential display-polymerase chain reaction resulted in the isolation of ZFP-37 as a peroxisome proliferator-responsive gene. In addition to being responsive to peroxisome proliferators, rat ZFP-37 (rZFP-37) mRNA accumulates rapidly after treating cells with several other hepatic tumor promoters, serum, and cycloheximide, indicating that this gene belongs to the immediate-early growth responsive gene family. Although rZFP-37 and mouse ZFP-37 (mZFP-37) are both members of the Krüppel-associated box and C2H2 zinc finger superfamily of proteins, there are several features that distinguish the two proteins. The primary protein sequences of rat and mouse ZFP-37 are highly conserved, especially within the region encoding the 12 C2H2 zinc finger motifs; however, a region believed to be involved in DNA binding in mZFP-37 is divergent in rZFP-37. Mouse ZFP-37 mRNA is expressed almost exclusively in testes and brain, whereas rZFP-37 mRNA is expressed in testes, brain, kidney, spleen, thymus, lung, and at low levels in liver. A major difference between regulation of ZFP-37 in the two species exists as rZFP-37 is induced, while mZFP-37 is repressed, in liver by the administration of the potent peroxisome proliferator Wy 14,643. Despite the fact that mZFP-37 is believed to be important in cell growth and differentiation in testes and brain, the pronounced differences in regulation of this gene in two closely related species preclude an extrapolation to rZFP-37's biological role. Nonetheless, the effects of tumor promoters and mitogens on its expression and the inclusion of rZFP-37 into the immediate-early growth gene families raise the possibility that this gene plays a role in hepatocyte proliferation and/or differentiation., (Copyright 1998 Academic Press.)

Purpose: Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pHe) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can be enhanced by using acidified dosing solutions. We evaluated (a) the effect of pHe on MMC activity in patient bladder tumors in vitro, and (b) the pH dependency of MMC activity in 2-dimensional monolayer and 3-dimensional multilayer cultures of human bladder RT4 tumor cells., Methods: Patient bladder tumors were maintained as 3-dimensional histocultures. RT4 cells were harvested and maintained as monolayer cultures or as 3-dimensional cell pellets on a collagen gel matrix. The cell pellets were 300-450 cell layers and 4,000-5,000 microns in diameter. Tumors or cells were incubated for 2 hr with MMC-containing media at pHe of 5, 6, and 7.4. The drug effect was measured by the inhibition of DNA precursor (thymidine) incorporation. The stability of MMC as a function of pHe was determined. About 24% of MMC was degraded following 2 hr exposure at pHe 5 and < or = 2% at pHe 6 and 7.4., Results: The drug concentrations required to inhibit thymidine incorporation by 50% (IC50) were corrected for the degraded MMC at acidic pHe. The results showed no pH-dependent MMC activity in human patient bladder tumors nor in RT4 multilayer cultures; the IC50 values were about 10 micrograms/ml at all three pHe. In contrast, the monolayer RT4 cultures showed a pH-dependent MMC cytotoxicity; the IC50 were 0.1, 0.8 and 1.2 micrograms/ ml at pHe 5, 6 and 7.4, respectively (p < 0.05). Pre-incubation of multilayered RT4 cultures in acidic pH medium for 8 hr enhanced the MMC activity; the IC50 was reduced by about 5 fold at pHe about 3 fold at pHe 6. Similar pH-dependent MMC activity was found when multilayers were pre-treated for 1 hr with 0.5 microgram/ml nigericin, a proton ionophore known to cause the intracellular pH (pHi) to equilibrate with pHe., Conclusions: These data suggest that the difference in the pH dependency of MMC activity in the monolayer and multilayer systems was due to the different experimental conditions. The time lag for pHi to equilibrate with pHe in the multilayer systems and the instability of MMC at low pHe imply that the efficacy of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing solution.

Purpose: This study compared the sensitivity of rat prostate MAT-LyLu primary and lymph node metastatic tumors to taxol., Methods: Tumors were established by subcutaneous implantation of tumor cells in a hind leg (primary site) of male Copenhagen rats. Lymph node metastases were used for serial transplantation. Eleven pairs of primary and metastatic tumors between the sixth and twentieth generations were harvested and maintained as 3-dimensional histocultures. The effects of taxol (24 hr treatment at 1 nM to 10 microM) were measured by the appearance of apoptotic cells, and by the inhibition of DNA precursor (thymidine) incorporation. To determine the basis of differential sensitivity of primary and metastatic tumors to the DNA inhibition, we examined the expression of multidrug resistance pglycoprotein (Pgp) and the accumulation of 3H-taxol after 24 hr exposure and the retention after a 48 hr washout period., Results: The fraction of apoptotic cells increased linearly with the logarithm of taxol concentration to a maximal value of 25%; the concentration-response curves for primary and metastatic tumors were superimposable. Taxol produced a sigmoidal, concentration-dependent inhibition of thymidine incorporation; the maximal inhibition of approximately 40% was reached at 0.1 and 1 microM for primary and metastatic tumors, respectively. Within the primary or metastatic subgroups, the IC30 (drug concentration that produced a 30% inhibition of DNA synthesis) among consecutive generations varied by < 5 fold, but the primary tumor consistently showed a lower IC30 than the daughter or the parent metastatic tumor (mean, 20-fold; median, 15-fold; range, 6- to 56-fold). The finding that the lower drug sensitivity in metastatic tumors was not exhibited in its daughter primary tumor but was regained in its daughter metastatic tumors suggests that the chemoresistant phenotype is maintained only in lymph nodes and not in the primary site. There were no differences in the Pgp status (neither tumor expressed Pgp), accumulation and retention of taxol in primary and metastatic tumors., Conclusions: Taxol induced apoptosis and inhibited DNA synthesis in the rat MAT-LyLu primary and lymph node metastatic tumors. The apoptotic effect was not different among the two tumors, whereas the primary tumor was more sensitive to the inhibition of DNA synthesis. The differential sensitivity of the two tumors to the DNA effect is not associated with a difference in Pgp expression, drug accumulation nor drug retention, and appears to be associated with changes that are linked to lymph node metastasis.

This study was conducted to demonstrate that Na+ played a role in the paracellular transport of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (Pz-peptide), a hydrophilic proline-containing pentapeptide, across the rabbit colonic mucosa and Caco-2 cell monolayers. Over the 1 to 5 mM concentration range, Pz-peptide transport was 25 to 180 times greater from the mucosal-to-serosal than from the opposite direction. This asymmetry in transport was consistent with the ability of Pz-peptide to lower the transepithelial electrical resistance of Caco-2 cell monolayers only from the mucosal side. Blockade of Na+ access to the apically located amiloride-sensitive Na+ channel in the lower intestinal segments by mucosal 10 microM amiloride, serosal 100 microM ouabain or removal of Na+ ions in the mucosal fluid dramatically reduced Pz-peptide transport to 5% of the control. Moreover, Pz-peptide transport across Caco-2 cell monolayers could be titrated against mucosal Na+ concentration. There was a small mucosal-to-serosal solvent drag effect induced by transepithelial Na+ flux stimulated by Pz-peptide in the colon, contributing in part to enhanced paracellular solute transport. Overall, the above findings are consistent with a scenario whereby Pz-peptide stimulates transepithelial Na+ flux across the colonic segments at the level of the amiloride-sensitive Na+ channel, thereby triggering yet to be identified intracellular biochemical changes that ultimately result in tight junctional opening and enhanced paracellular solute transport.

Four paper-and-pencil spatial tests, measuring two- and three-dimesional spatial visualization and spatial orientation, were administered to 2508 Caucasian high-school students. Sibling correlations and within-sex score distributions were examined for the influence of a major sex-linked gene. Sex-linked influences were most clear on the test of two-dimensional visualization and on an average of the standard scores on all the tests. For those tests best fitting the genetic model, estimates of the frequency of the recessive gene (contributing to good performance) we-re near 0.45. There was evidence of incomplete dominance in females. Environmental or non-sex-linked genetic factors influenced spatial performance but did not systematically improve performance with age.

Monochromatic light was provided by a continuous wave Argon ion laser. We chose to study the in vitro effects of light at 457.9, 465.8, 476.5, 488.0, 501.7, and 514.5 nm as representative of a reasonably evenly spaced sampling across the blue-green spectrum. The in vivo experiments were conducted at 457.9, 476.5, 488.0, and 514.5 nm. In vitro light at 488.0 nm appeared to be more effective than the others studied. After 24 h of irradiance, the in vivo decline in serum bilirubin concentration produced by light at 488.0 nm was one-and-one-half, two, and four times as effective as light at 457.9, 476.5 and 514.5 nm, respectively. By 48 h of exposure, the declines produced by light at 457.9 nm and 488.0 nm are significantly superior to that at 476.5 nm and 514.5 nm, but they do not differ from one another.

Advantages of pressure scanning over other methods of tuning the wavelength of dye lasers are discussed. The construction of a pressure scanned high resolution dye laser is described. The laser has a scan range of more than 40 cm(-1) in its intermediate resolution mode, an improvement on the order of a hundredfold over previous methods of tuning. Preliminary tests have indicated a scan range of 4 cm(-1) in the high resolution mode. As a demonstration of its applicability and versatility, the laser was used to xesolve the ground state splitting of the chromium isotopes in ruby.

The hypothesis that sex differences in field independence and mental arithmetic can be accounted for by sex differences in spatial ability was supported for a group of 46 female and 35 male undergraduates. Sex-typing does not appear to be strongly related to spatial ability for either sex. There is a possibility of the existence of a field-independence trait independent of spatial ability, particularly among females; however, if such a trait does exist there do not appear to be significant sex differences with respect to it. Factor analysis indicates that tests of spatial ability, field independence, and mental arithmetic emerge together in a spatial ability factor. Sex differences in the factor structure of nine measures, most of which typically display sex differences (spatial ability, field independence, mental arithmetic, vocabulary, verbal and nonverbal creativity, femininity, and achievement motivation) were largely the result of differences with respect to a spatial factor.

Three cases of a bony canal have been found in 100 adult cranial bases on the lower half of the clival surface. The possible content, nature and significance of this canal are discussed and the term 'inferior median clival canal' assigned to this variety.

The electrokinetic behavior of red cell membrane vesicles of normal (ROV) and inverted (IOV) sidedness has been characterized using the laser Doppler technique of electrophoretic light scattering (ELS). At neutral pH ROV have a (approx. 25%) higher electrophoretic mobility than IOV and the two peaks can be resolved in the ELS spectrum to provide a quantitative estimate of the IOV/ROV ratio which is consistent with the ratio determined by assay of the activity of acetylcholinesterase. The ROV peak coincides with the mobility of fresh red blood cells and of resealed ghosts. Neuraminidase treatment reduces the ROV mobility by a factor of 2.6, while the IOV peak is reduced only slightly (less than 5%). Treatment with trypsin results in a single narrow ELS peak at about 60% of the mobility of ROV. Treatment of IOV with phospholipase C leaves the electrophoretic mobility unaltered, whereas treatment with phospholipase D increases their mode mobility by 22%. The mobility titration curve of IOV from pH 2 to pH 10 reveals three distinct inflection points which may be assigned to chemical groups on the cytoplasmic surface of the red cell membrane.

A sapphire disk is used as a variable birefringent beam splitter for the linearly polarized pump beam in an oscillator-amplifier dye laser system. Rotation of the disk varies the extent of retardation. The induced elliptical polarization results in a variable back surface reflectance between approximately 0.02-0.15 for the green spectral region. Reflectances are measured on two disks with different thicknesses and compared with an approximate model describing the reflectance as a function of angle of rotation of the disk.

We have employed a purely optical method to measure spin-lattice relaxation in the lower excited (4)S(3/2) state of Er(3+) in LaF(3) at helium temperatures. Above 3 K the relaxation is dominated by an Orbach process through the upper (4)S(3/2) state. Below 3 K the relaxation is caused by some residual mechanism that obscures the Kramers-Van Vleck direct process. By relating the Orbach relaxation measurements to the homogeneous broadening of the upper (4)S(3/2) level, we determine values of the transition rates between the upper and lower (4)S(3/2) states.

A tunable jet-stream dye laser pumped by a cavity-dumped argon laser has been synchronized to a photoelastic modulator to measure magnetic circular dichroism. Gated signal amplification takes advantage of the laser's pulsed operation to detect weak dichroic signals. Comparative data show that the dye laser and gated amplification give a SNR better than that obtained with the previously used lamp, monochromator, and lockin detector. Other applications of the dye laser and gated amplification are discussed.

The paper-and-pencil spatial performance of right- and left-handed high school students was compared separately for 1236 males and 1241 females. Handedness differences in favor of right-handed subjects were found among males only. Analysis of data for a subgroup of 555 subjects indicated that handedness and sex-linked genetic effects acted independently and additively on spatial performance.

Under the light microscope, large and small types of spinal ganglion cells can be seen in the mouse. Among those of the small type bipolar cells are observed. By electron microscopy, the cells of the large type have a low electron density and those of the small type a high electron density. Bipolar cells continue to be observed among the latter. The cells of the spinal ganglia contain different cellular apparatus in enormous quantity. There are four kinds of lysosomes in the GERL, i.e. the coated vesicles, dense bodies, multivesicular bodies and autophagic vacuoles.

In sixty normal adult livers the retrohepatic segment of the inferior vena cava was found mostly to assume a curve to the left (75.00%). This segment has a length of 7.1 cm and is totally encircled by liver substance in 6.67% of cases. Altogether 492 ostia venae hepaticae were studied, averaging 8.2 per liver and classified as large, medium and small. The large ostia are divided into superior (SLO) and inferior (ILO) openings. The SLO are found opening into the upper end of the hepatic segment of the inferior vena cava, frequently with part of the venous walls exposed outside the liver. The ILO and medium ostia are present in 95% of the livers, appearing mainly on the lower quarter of the right half of the wall of the retrohepatic segment of the inferior vena cava as well as on the left anterior wall of that segment. The ILO may serve as the exit for several hepatic veins and they may be multiple. Their significance in respect of liver surgery is discussed.

Comparative studies were carried out under light, fluorescence- and electron-microscopic observations between young, adult and aged groups of albino rats with the following results: the neuronal packing density of locus ceruleus decreases with advanced age. In addition to the senescent loss of nerve cells, the surviving ones showed some shrinkage of perikarya and reduction or loss of Nissl substance. Some of them presented pyknosis, chromatolysis and loss of RNA in cytoplasm. Glial cells proliferated around the degenerating cells. Senescent cells showed an increase of heterochromatin and decrease of euchromatin. Changes in cytoplasmic organelles included the decrease of ribosomes, alterations in mitochondria and increase of lipofuscins. These senescent changes were thought to affect the absorption of nutrition, message exchange, protein synthesis, supply of energy and transport of materials by the nerve cells.

A periodontal survey applying CPITN was carried out in almost 500 male and female factory workers, 35-44 yr of age, in Shanghai, P.R. China. Calculus and shallow pockets were most frequent. Deep pockets of 6 mm and over were seldom found. The mean number of missing teeth was only 2.7 (out of 32). Problems associated with third molars seem to provide the largest immediate oral health problem.