Renal proliferative and phenotypic changes in rats with two-kidney, one-clip Goldblatt hypertension

Previous research in this laboratory has shown that preweaning and postweaning juvenile meadow voles, Microtus pennsylvanicus, can acquire a spatial task, the Morris water-maze task. The present study examined the influence of age of juvenile acquisition ("before weaning" (BW; Day 10 and 15 after birth) and "after weaning" (AW; Day 20 and 25 after birth)) of a spatial task on subsequent re-acquisition of the same hidden-platform spatial water-maze task. This study also compared sex differences and litter sex-ratio effects on reacquisition performance. Fifteen litters of adults were re-tested in the same water maze 6 weeks after being initially tested as juveniles. All analyses were conducted using a covariate that removed the group differences in the original task performance. Adult voles from female-biased litters, that had previously learned the task at an older juvenile age (AW), reacquired the same task faster than adults that had previously learned the task at a younger juvenile age (BW). In the adult BW group there was also a significant litter sex-ratio effect such that voles born into a female-biased litter re-acquired the task more slowly than did voles born into a male-biased litter. There were no significant sex or litter sex-ratio effects on spatial learning in the AW group. These results show that adult meadow voles can require a spatial task more quickly if they initially learned the task at an older juvenile age, suggestive of a period of infantile amnesia. In addition, these results indicate that the litter sex-ratio can affect adult spatial performance, suggesting that the relative amount of androgens in utero may influence the development of sexually-dimorphic spatial ability in adulthood.     

Simulation of the S2 state multiline electron paramagnetic resonance signal of photosystem II: a multifrequency approach

The S2 state electron paramagnetic resonance (EPR) multiline signal of Photosystem II has been simulated at Q-band (35 Ghz), X-band (9 GHz) and S-band (4 GHz) frequencies. The model used for the simulation assumes that the signal arises from an essentially magnetically isolated MnIII-MnIV dimer, with a ground state electronic spin ST = 1/2. The spectra are generated from exact numerical solution of a general spin Hamiltonian containing anisotropic hyperfine and quadrupolar interactions at both Mn nuclei. The features that distinguish the multiline from the EPR spectra of model manganese dimer complexes (additional width of the spectrum (195 mT), additional peaks (22), internal "superhyperfine" structure) are plausibly explained assuming an unusual ligand geometry at both Mn nuclei, giving rise to normally forbidden transitions from quadrupole interactions as well as hyperfine anisotropy. The fitted parameters indicate that the hyperfine and quadrupole interactions arise from Mn ions in low symmetry environments, corresponding approximately to the removal of one ligand from an octahedral geometry in both cases. For a quadrupole interaction of the magnitude indicated here to be present, the MnIII ion must be 5-coordinate and the MnIV 5-coordinate or possibly have a sixth, weakly bound ligand. The hyperfine parameters indicate a quasi-axial anisotropy at MnIII, which while consistent with Jahn-Teller distortion as expected for a d4 ion, corresponds here to the unpaired spin being in the ligand deficient, z direction of the molecular reference axis. The fitted parameters for MnIV are very unusual, showing a high degree of anisotropy not expected in a d3 ion. This degree of anisotropy could be qualitatively accounted for by a histidine ligand providing pi backbonding into the metal dxy orbital, together with a weakly bound or absent ligand in the x direction.     

Gingival recession and exposure of barrier membrane: effect on guided tissue regeneration of Class II furcation defects

The purpose of the present study was to evaluate the effect of barrier membrane exposure on the success of guided tissue regeneration in Class II furcation defects. Twenty-six subjects with mandibular Class II furcation defects received initial periodontal therapy followed by guided tissue regeneration surgery. The membrane was placed and the flaps were repositioned so that the membrane was totally submerged. Membranes were removed 4 to 6 weeks later, at which time the extent of their exposure was recorded. An overall improvement in all clinical parameters was observed for all subjects 1 year after surgery. Half of the patients had experienced no membrane exposure, while the other 13 subjects had experienced mild to pronounced exposure; both groups showed similar improvement in all clinical and surgical parameters. In light of the comparable results obtained in exposed sites, and the anatomic difficulties sometimes encountered in covering a membrane completely, in some of these cases the membrane may be left only partially submerged. This approach will allow for tighter occlusal "seal" of the tooth-membrane interface and preservation of the keratinized gingiva.     

Stability and distribution of orally administered epidermal growth factor in neonatal pigs

Stability and distribution of orally administered epidermal growth factor (EGF) were examined in newborn and 5-day-old pigs. Forty-five minutes after oral administration of iodine-125 labeled EGF, 60 and 50% of the radioactivity administered were recovered from the internal organs in newborn and 5-day-old pigs, respectively. In both age groups, over 95% of the recovered radioactivity was found in the gastrointestinal tract, of which 78-86% was found in the luminal contents with the remaining found in the gastrointestinal wall. Within the gastrointestinal tract, 65-71% of radioactivity was found in the stomach, 27-30% in the proximal and mid small intestine and 3-4% was found in the distal part of the small intestine. There were no significant differences in the overall distribution of orally administered radioactivity between two age groups. Based on liquid chromatography and trichloroacetic acid precipitation, a substantial amount of EGF recovered from the luminal contents (63-86%) and the gastrointestinal wall (42-81%) remained "intact". The receptor binding ability of the EGF recovered from the gastric contents was 96-102% comparable to the native EGF tracer. The receptor binding ability remained high (40-58%) in the proximal small intestinal lumen and it decreased to 15% in the distal small intestinal lumen in newborn pigs. In 5-day-old pigs, EGF recovered from the small intestinal contents had 5 to 24% receptor binding ability when compared with native EGF tracer. The receptor binding ability of the EGF recovered from all other organs was below 5% with an exception of the gastric wall, from which recovered EGF retained 9 to 26% receptor binding ability. These results indicate that most of orally ingested EGF remained in the gastrointestinal tract in neonatal pigs 45 min after oral ingestion, and significant amount of the ingested EGF remained biologically active. It suggests that milk-borne EGF can survive in the gastrointestinal tract and may play a role in regulating gut development in neonatal animals.     

Epidemiology of infection with Epstein-Barr virus types 1 and 2: lessons from the study of a T-cell-immunocompromised hemophilic cohort

In apparent contrast to earlier work on Epstein-Barr virus (EBV) carriage in the general Caucasian population, in vitro virus isolations from human immunodeficiency virus (HIV)-positive male homosexual cohorts have shown frequent examples of multiple EBV infection and an overall prevalence of type 2 EBV strains exceeding 30%. Here we ask to what extent these findings might hold true in another T-cell-immunocompromised cohort, HIV-positive hemophilic patients. Resident EBV strains were rescued within lymphoblastoid cell lines derived from the blood and throat washings of 39 such individuals, using the same in vitro protocols of virus isolation as for the homosexual cohort. A mean of 19 independent cell lines was made per patient, and in each case the resident virus was characterized by PCR-based viral genomic analysis and by immunoblotting to reveal the viral "EBNAprint." By these criteria a significant proportion (14 of 39) of the hemophilic cohort carried more than one EBV strain, suggesting that T-cell impairment does indeed sensitize virus carriers to reinfection with new strains of exogenously transmitted virus. However, the overall incidence of type 2 EBV infection was 10%, which is close to that observed in the earlier work with healthy carriers and substantially lower than that seen in HIV-positive homosexuals. We infer that type 2 EBV is relatively rare in the general Caucasian population but has become endemic in the homosexual community.     

Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma

This report describes the clinicopathologic and immunohistochemical features of 14 cases of epithelioid trophoblastic tumor (ETT), a distinctive but rare gestational trophoblastic tumor. The patients with this neoplasm were in the reproductive age group and presented with abnormal vaginal bleeding. Although diagnosis was usually associated with a gestational event, the latter was sometimes remote. Two of the 14 patients presented with extrauterine ETT without evidence of prior gestational trophoblastic disease in the uterus. Serum human chorionic gonadotropin levels were elevated in eight of nine patients in whom this information was available. In the uterus, ETT presented as a discrete, hemorrhagic, solid and cystic lesion that was located either in the fundus, lower uterine segment, or endocervix. Microscopically, the tumor was composed of a relatively uniform population of mononucleate intermediate trophoblastic cells forming nests and solid masses. The cells resemble the trophoblastic cells in the chorion laeve, and we have therefore designated them "chorionic-type intermediate trophoblast." Typically, islands of trophoblastic cells were surrounded by extensive necrosis and were associated with a hyaline-like matrix creating a "geographic" pattern that is quite characteristic of this lesion. The mean mitotic count was two mitoses per 10 high-power fields, and the average Ki-67 nuclear labeling index was 18%. Immunohistochemically, all cases were diffusely positive for inhibin-alpha, cytokeratin (AE1/AE3), epithelial membrane antigen, E-cadherin, prolyl 4-hydroxylase, and epidermal growth factor receptor but were only focally immunoreactive for human placental lactogen, human chorionic gonadotropin, PlAP, and Mel-CAM. The monomorphic growth pattern of ETT resembles placental site trophoblastic tumor to a much greater degree than choriocarcinoma which is characterized by a dimorphic population of trophoblast. In contrast to placental site trophoblastic tumor, the cells of ETT are smaller and display less nuclear pleomorphism. In addition, ETT grows in a nodular fashion compared with the infiltrative pattern of placental site trophoblastic tumor. In some of the cases, the trophoblastic cells in ETT replaced the endocervical surface epithelium, giving the appearance that the tumor was derived from the cervix. Moreover, because the associated hyaline-like material in ETT resembles keratin, the tumor can be misinterpreted as a keratinizing squamous cell carcinoma of the cervix. Ten patients underwent total hysterectomy and two had an endometrial curettage only. The two patients who presented with extrauterine ETT underwent small bowel resection and lung resection. Two of 12 patients with ETT in the uterus developed metastasis in the lungs and bone. One of these patients is alive with disease at 43 months and one patient was lost to follow-up after 2 months. One of the two patients who had extrauterine disease died of widespread tumor 36 months after diagnosis. The remainder of the patients are alive and well from 1 to 120 months. In summary, ETT is a rare trophoblastic tumor that simulates carcinoma and can behave in a malignant fashion. It appears to be less aggressive than choriocarcinoma, more closely resembling the behavior of placental site trophoblastic tumor. Based on the morphologic and immunohistochemical features, it appears that ETT develops from neoplastic transformation of chorionic-type intermediate trophoblast.     

Treatment of pulmonary hypertension with inhaled nitric oxide during hepatic transplantation in an adolescent: reversibility of pulmonary hypertension after transplantation

Accusations of rape or sexual harassment are currently very high-profile in the military. This article discusses rape allegations in the military legal system from a psychiatric perspective. The original definition of "rape trauma syndrome" and subsequent psychiatric thinking about the diagnosis are briefly outlined. Common reactions seen in military victims in this era are described. A prototypical military case is presented. An adequate evaluation of an alleged victim is outlined. Credentials and preparation of an expert witness are also briefly discussed, with cautions about the use of expert testimony in cases of alleged sexual assault and rape trauma syndrome.     

Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation

Normal human diploid fibroblasts have a finite replicative lifespan in vitro, which has been postulated to be a cellular manifestation of aging in vivo. Several studies have shown an inverse relationship between donor age and fibroblast culture replicative lifespan; however, in all cases, the correlation was weak, and, with few exceptions, the health status of the donors was unknown. We have determined the replicative lifespans of 124 skin fibroblast cell lines established from donors of different ages as part of the Baltimore Longitudinal Study of Aging. All of the donors were medically examined and were declared "healthy," according to Baltimore Longitudinal Study of Aging protocols, at the time the biopsies were taken. Both long- and short-lived cell lines were observed in all age groups, but no significant correlation between the proliferative potential of the cell lines and donor age was found. A comparison of multiple cell lines established from the same donors at different ages also failed to reveal any significant trends between proliferative potential and donor age. The rate of [3H]thymidine incorporation and the initial rates of growth during the first few subcultivations were examined in a subset of cell lines and were found to be significantly greater in fetal lines than in postnatal lines. Cell lines established from adults did not vary significantly either in initial growth rate or in [3H]thymidine incorporation. These results clearly indicate that, if health status and biopsy conditions are controlled, the replicative lifespan of fibroblasts in culture does not correlate with donor age.     

Home use of a functional electrical stimulation system for standing and mobility in adolescents with spinal cord injury

OBJECTIVE: Functional electrical stimulation (FES) is a technology that may allow some patients with spinal cord injury (SCI) to integrate standing and upright mobility with wheelchair mobility. The purpose of this study was to document the patterns of home and community use of a FES system for standing and mobility. DESIGN: A telephone questionnaire was administered every 1 to 4 weeks for a minimum of 1 year. An interview was given at the end of the study to probe the motivators and barriers to home use. SETTING: Training for use of the FES system was performed in an inpatient pediatric rehabilitation setting. Data collection began after the subjects were discharged to home. PARTICIPANTS: Five adolescents with complete, thoracic-level SCI. INTERVENTION: Subjects participated in a program of FES exercise followed by training in basic mobility skills such as standing transfers, maneuvering, level ambulation, one-handed and reaching activities, and stair ascent/descent. MAIN OUTCOME MEASURE: The frequency with which the FES system was used at home and the activities for which it was utilized were documented. Motivators and barriers to FES home use were examined. RESULTS: Subjects donned the FES system on the average once every 3 to 4 days. Between 51% and 84% of the times donned, the system was used for exercise. The remaining times it was used for standing activities, most commonly reaching, one-handed tasks, and standing for exercise. "Motivators" included being able to do things that would otherwise be difficult, perceiving a healthful benefit or a sense of well-being from standing and exercise, and feeling an obligation to stand as a participant in a research study. "Barriers" to FES use included not finding time to use the system, having difficulty seeing opportunities to stand, and being reluctant to wear the FES system all day.     

PAK-104P, a pyridine analogue, reverses paclitaxel and doxorubicin resistance in cell lines and nude mice bearing xenografts that overexpress the multidrug resistance protein

For ethical decision-making near the end of life, autonomy is the moral North Star. At the same time, for some treatments, the burdens so clearly outweigh benefits that physicians may make a judgment not to offer the treatment. This is often clearer in surgery. A person with colon cancer and metastases may not insist on resection of the metastases. For some reason, some treatments have escaped these logical constraints. Attempted resuscitation of a dying patient is a good example. The circumstances in which a physician may make choices on behalf of a competent, terminally-ill patient without consent, and even without notification, are hotly debated, but data suggest that physicians do so frequently. Patients who lack capacity present even more difficult challenges. Advance directives, when available, can be extremely helpful, but even with them difficult problems can remain. If advance directives have not been established, family and close friends are an obvious source of guidance. Their legal role varies in different jurisdictions; in practice, they are crucial in bedside decision-making. Guardianship and alternatives to it remain a poor last resort. Euthanasia is a very difficult problem. We believe it is semantically misleading to lump under the term "passive euthanasia" those circumstances where potentially life-sustaining treatment is withheld or withdrawn. The tension between patient autonomy and medical common sense remains unresolved within the "futility" controversy. The authors believe it serves no purpose to discuss carefully with dying patients propositions that are nonsense. At the same time, physicians must not confuse decisions about quality of life with judgements about treatment effectiveness. We believe that what many, although not all, dying patients want are physicians with intelligent compassion who can take care of them through the dying process.