Lower face asymmetry as a marker for developmental instability.

OBJECTIVES: Fluctuating asymmetries in the craniofacial skeleton have been shown to be predictive for mortality from degenerative diseases. We investigate whether lower face asymmetries are a potential marker for the developmental origins of health and disease. METHODS: The lower face of a representative sample of 6654 12- to 17-year old United States (US) adolescents (1966-1970, National Health Examination Survey III) was classified as asymmetric when the mandibular teeth occluded prognathically (forward) or retrognathically (backward) on one side of the face only. It was investigated whether these lower face asymmetries were directional (preferentially to the left or the right) or fluctuating (random left-right distribution) in the US population. RESULTS: Lower face asymmetries affected 1 in 4 of the US adolescents. Unilateral retrognathic dental occlusions were fluctuating asymmetries, had a US prevalence of 17.0% (95% confidence interval: 15.5-18.4) and were associated with race/ethnicity (P < .0001), not with handedness (P < .7607). Unilateral prognathic dental occlusions were directional asymmetries (P < .0001), had a US prevalence of 7.6% (95% confidence interval: 6.4-8.7) and were associated with large household size (P < .001) and handedness (P < .0223). Lower face asymmetries were not associated with distinct heritable traits such as color blindness. CONCLUSIONS: The findings suggest that lower face asymmetries are a marker for environmental stress and cerebral lateralization during early development.

Canine Nervous System Lymphoma Subtypes Display Characteristic Neuroanatomical Patterns.

Primary and secondary nervous system involvement occurs in 4% and 5%-12%, respectively, of all canine non-Hodgkin lymphomas. The recent new classification of canine malignant lymphomas, based on the human World Health Organization classification, has been endorsed with international acceptance. This histological and immunocytochemical classification provides a unique opportunity to study the histologic anatomic distribution patterns in the central and peripheral nervous system of these defined lymphoma subtypes. In this study, we studied a cohort of 37 dogs with lymphoma, which at necropsy had either primary (n = 1, 2.7%) or secondary (n = 36; 97.3%) neural involvement. These T- (n = 16; 43.2%) or B-cell (n = 21; 56.8%) lymphomas were further classified into 12 lymphoma subtypes, with predominant subtypes including peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), respectively. This systematic study identified 6 different anatomically based histologically defined patterns of lymphoma infiltration in the nervous system of dogs. Different and distinct combinations of anatomical patterns correlated with specific lymphoma subtypes. Lymphoma infiltration within the meningeal, perivascular, and periventricular compartments were characteristic of DLBCL, whereas peripheral nerve involvement was a frequent feature of PTCL. Similarly cell counts above 64 cells/µL in cerebrospinal samples correlated best with marked meningeal and periventricular lymphoma infiltration histologically. Prospective studies are needed in order to confirm the hypothesis that these combinations of histological neuroanatomic patterns reflect targeting of receptors specific for the lymphoma subtypes at these various sites.

Temporal and geographic clustering of polyomavirus-associated olfactory tumors in 10 free-ranging raccoons (Procyon lotor).

Reports of primary nervous system tumors in wild raccoons are extremely rare. Olfactory tumors were diagnosed postmortem in 9 free-ranging raccoons from 4 contiguous counties in California and 1 raccoon from Oregon within a 26-month period between 2010 and 2012. We describe the geographic and temporal features of these 10 cases, including the laboratory diagnostic investigations and the neuropathologic, immunohistochemical, and ultrastructural characteristics of these tumors in the affected animals. All 9 raccoons from California were found within a localized geographic region of the San Francisco Bay Area (within a 44.13-km radius). The tight temporal and geographic clustering and consistent anatomic location in the olfactory system of tumor types not previously described in raccoons (malignant peripheral nerve sheath tumors and undifferentiated sarcomas) strongly suggest either a common cause or a precipitating factor leading to induction or potentiation of neuro-oncogenesis and so prompted an extensive diagnostic investigation to explore possible oncogenic infectious and/or toxic causes. By a consensus polymerase chain reaction strategy, a novel, recently reported polyomavirus called raccoon polyomavirus was identified in all 10 tumors but not in the normal brain tissue from the affected animals, suggesting that the virus might play a role in neuro-oncogenesis. In addition, expression of the viral protein T antigen was detected in all tumors containing the viral sequences. We discuss the potential role of raccoon polyomavirus as an oncogenic virus.

Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.

Cerebral edema contributes significantly to morbidity and death associated with many common neurological disorders. However, current treatment options are limited to hyperosmolar agents and surgical decompression, therapies introduced more than 70 years ago. Here we show that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema caused by acute water intoxication. Brain tissue water content and swelling of pericapillary astrocytic foot processes in AQP4-deficient mice were significantly reduced. In another model of brain edema, focal ischemic stroke produced by middle cerebral artery occlusion, AQP4-deficient mice had improved neurological outcome. Cerebral edema, as measured by percentage of hemispheric enlargement at 24 h, was decreased by 35% in AQP4-deficient mice. These results implicate a key role for AQP4 in modulating brain water transport, and suggest that AQP4 inhibition may provide a new therapeutic option for reducing brain edema in a wide variety of cerebral disorders.

Ribosomal Protein Conferring Sensitivity to the Antibiotic Spectinomycin in Escherichia coli.

Reconstitution of 30S ribosomal particles from 16S ribosomal RNA and total proteins, or from core proteins and split proteins obtained from the ribosomes of strains of Escherichia coli sensitive to and resistant to spectinomycin, shows that the split protein fraction determines the response of polypeptide synthesis in virto to spectinomycin. Reconstitution of active particles in the presence of isolated split proteins allowed the identification of the single split protein responsible for spectinomycin sensitivity.

Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas.

Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

Mercury speciation analyses in HgCl(2)-contaminated soils and groundwater--implications for risk assessment and remediation strategies.

Since the 19th century, mercury(II)chloride (HgCl(2)) has been used on wood impregnation sites to prevent wooden poles from decay, leaving behind a legacy of highly contaminated soil/aquifer systems. Little is known about species transformation and mobility of HgCl(2) in contaminated soils and groundwater. At such a site the behaviour of HgCl(2) in soils and groundwater was investigated to assist in risk assessment and remediation. The soil is low in organic carbon and contains up to 11,000 mg Hg/kg. Mercury (Hg) concentrations in groundwater decrease from 230 to 0.5 microg/l within a distance of 1.3 km. Hg species transformations in soil and aqueous samples were analysed by means of solid-phase Hg pyrolysis and CV-AAS. In aqueous samples, Hg species were distinguished between ionic/reactive Hg and complex-bound Hg. Potential mobility of Hg in soils was studied through batch experiments. Most Hg in the soil is matrix-bound HgCl(2), whereas in the aquifer secondary formation to Hg(0) could be observed. Aqueous Hg speciation in groundwater and soil solutions shows that an average of 84% of soluble Hg exists as easily reducible, inorganic Hg species (mostly HgCl(2)). The proportion of complex-bound Hg increases with distance due to the transformation of inorganic HgCl(2). The frequent occurrence of Hg(0) in the aquifer suggests the formation and degassing of Hg(0), which is, in addition to dilution, an important process, lowering Hg concentrations in the groundwater. High percentage of mobile Hg (3-26%) and low seepage fluxes will result in continuous Hg release over centuries requiring long-term groundwater remediation. Results of soluble Hg speciation suggest that filtering materials should be adapted to ionic Hg species, e.g. specific resins or amalgamating metal alloys.

Choroid plexus tumors in 56 dogs (1985-2007).

BACKGROUND: Choroid plexus tumors (CPTs) comprise approximately 10% of all primary brain tumors in dogs. The clinical utility of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, or both in the presumptive diagnosis of CPTs has not been determined. OBJECTIVES: To report MRI and CSF findings in dogs with CPT and determine if there are distinguishing features that allow clinical discrimination between the tumor grades. ANIMALS: Fifty-six client-owned dogs with naturally occurring CPT. METHODS: Retrospective case series. The inclusion criterion was histologically confirmed CPT. Blinded review of cranial MRI and cisternal CSF analysis was performed. RESULTS: Thirty-six of 56 dogs had a choroid plexus carcinoma (CPC) and 20 had a choroid plexus papilloma (CPP). Golden Retrievers were overrepresented compared with the hospital population (frequency 3.7 times that expected, confidence interval 95%= 2.0-6.7, P< .0002). Median CSF protein concentration in CPCs (108 mg/dL, range 27-380 mg/dL) was significantly higher than in CPPs (34 mg/dL, range 32-80 mg/dL) (P= .002). Only dogs with CPCs had a CSF protein concentration >80 mg/dL. Cytological evidence of malignancy in CSF was seen in 7 of 15 CPCs. Only CPCs had evidence of intraventricular or subarachnoid metastases on MRI. CONCLUSIONS AND CLINICAL IMPORTANCE: MRI, CSF analysis or both can help to differentiate between CPPs and CPCs, and may provide valuable prognostic and pretreatment information.

Magnetic resonance imaging and histological classification of intracranial meningiomas in 112 dogs.

BACKGROUND: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. HYPOTHESIS: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. ANIMALS: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. METHODS: Retrospective observational study. RESULTS: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.

Transient cerebral ischemia. Association of apoptosis induction with hypoperfusion.

Apoptosis is thought to be important in the pathogenesis of cerebral ischemia. The mechanism of apoptosis induction remains unclear but several studies suggest that it is preferentially triggered by mild/moderate microcirculatory disturbances. We examined in cats whether induction of apoptosis after 2.5 h of unilateral middle cerebral artery occlusion plus 10 h of reperfusion is influenced by the degree of cerebral microcirculatory disturbance. Quantitative monitoring over time of the disturbances of cerebral microcirculation in ischemic brain areas and evaluation of cytotoxic edema associated with perfusion deficits was achieved by using two noninvasive magnetic resonance imaging techniques: (a) high-speed echo planar imaging combined with a bolus of magnetic susceptibility contrast agent; and (b) diffusion-weighted imaging. Apoptosis-positive cells were counted in anatomic areas with different severity of ischemic injury characterized by magnetic resonance imaging, triphenyltetrazolium chloride, and hemotoxylin and eosin staining. The number of apoptosis-positive cells was significantly higher in anatomic areas with severe perfusion deficits during occlusion and detectable histologic changes 10 h after reperfusion. In contrast, in areas where perfusion was reduced but maintained during occlusion there were no detectable histological changes and significantly fewer apoptosis-positive cells. A similar number of cells that undergo apoptosis were shown in regions with transient or prolonged subtotal perfusion deficits. These results suggest that the apoptotic process is induced in the ischemic core and contributes significantly in the degeneration of neurons associated with transient ischemia.

[Meningoradiculitis caused by herpes simplex virus type 2]. / Meningoradiculitis door herpes-simplexvirus type 2.

A 24-year-old immune-competent woman was admitted to hospital with a three-day history of fever and headache. On examination bilateral facial nerve palsy, lumbosacral radicular pain, reduced sacral sensibility and urinary retention were found. Open perianal lesions were suspect for genital herpes. The symptoms were compatible with a meningoradiculitis including a sacral polyradiculitis. On testing, cerebrospinal fluid was found to be abnormal with a lymphocytic cell reaction. Polymerase chain reaction (PCR) of cerebrospinal fluid and of the perianal lesions was positive for herpes simplex virus type 2 (HSV-2). An MRI scan showed colouration of part of the cauda equina. The patient was treated by intravenous injections of acyclovir 10 mg/kg t.i.d. for 21 days, after which she completely recovered. HSV-2 infection of the nervous system can cause lymphocytic, and sometimes recurrent meningitis as well as sacral polyradiculitis. It may also occur without any symptomatic genital herpes infection. A positive result from a PCR test of the cerebrospinal fluid confirms this diagnosis. Treatment with acyclovir should be started as soon as possible.

Abnormal balance in the angiopoietin-tie2 system in human brain arteriovenous malformations.

Brain arteriovenous malformations (BAVMs) are congenital vascular lesions that often present as cerebral hemorrhage in young adults. The variable nature of the clinical course, especially with respect to spontaneous hemorrhage, recurrence, growth, and regression, suggests that BAVMs are lesions with active angiogenesis and vascular remodeling. We examined mRNA and protein expression of angiopoietin 1 (Ang1) and Ang2 by semiquantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, and Western blot in BAVMs and control brains obtained from temporal lobectomy for medically intractable seizures. Although Ang1 mRNA levels were similar in BAVMs and controls, Ang1 protein levels were 30% lower in BAVMs than in controls. Ang2 mRNA levels were 40% higher and Ang2 protein levels were 8-fold higher in BAVMs than in controls. In situ hybridization showed that the Ang2 mRNA was localized to the perivascular area in BAVMs. This abnormal balance in the Ang-Tie2 system may, in part, explain the aberrant vascular phenotype in BAVMs.

Mitigation of azinphos-methyl in a vegetated stream: comparison of runoff- and spray-drift.

The effectiveness of aquatic macrophytes in reducing runoff- and spray-drift-induced azinphos-methyl (AZP) input was compared in a vegetated stream. Water, sediment and plant samples were taken at increasing distances from a point of input during a spray-drift event and two runoff (10 and 22 mm/day) events. Peak concentrations of AZP decreased significantly (R2=0.99; p<0.0001; n=5) from 0.24 microg/l to 0.11 microg/l during the 10mm runoff event. No reduction took place during the 22 mm event. AZP concentrations were reduced by 90% following spray-drift input, with peak concentrations decreasing significantly (R2=0.93; p=0.0084; n=5) from 4.3 microg/l to 1.7 microg/l with increasing distance from the point of input. Plant samples taken after the spray-drift event showed increased AZP concentrations in comparison to before the event indicating sorption of the pesticide to the macrophytes. Although peak concentrations of AZP were as effectively mitigated during the 10mm runoff event as during the spray-drift event, predictive modelling revealed that maximum concentrations expected during a worst-case scenario 10mm runoff event (0 days after application) are an order of magnitude lower than what can be expected for a worst-case spray-drift and 22 mm runoff event, suggesting that spray-drift-derived pesticide concentrations are more effectively mitigated than those of runoff.

Genetic subgroups of anaplastic astrocytomas correlate with patient age and survival.

Astrocytomas are brain tumors with variable responses to radiation and chemotherapy. Tumor grade and patient age are important prognostic factors but do not account for the variability in clinical outcome. We hypothesized that genetic subgroups play a role in the outcome of grade III astrocytomas and studied 80 grade III astrocytomas by comparative genomic hybridization. Some chromosomal aberrations (+7p/q, -9p, -10q, -13q, +19q) were related to aberrations that are frequent in grade IV astrocytoma, whereas others (+10p, -11q, +11p, -Xq) were more frequent in grade III astrocytoma. +7p, +19 and -4q were more frequent in tumors from older patients while -11p was more frequent in tumors from younger patients. Finally, gains of 7p and 7q were associated with shorter patient survival, independent of age. Our results indicate that genetic events underlie the well-known effects of age on survival in grade III astrocytoma and demonstrate the importance of molecular classification in astrocytic tumors.

Phenotypic characteristics of adolescents with concave and convex facial profiles - The National Health Examination Survey.

It has been suggested that facial traits are informative on the inherited susceptibility to tuberculosis and obesity, two current global health issues. Our aim was to compare the phenotypic characteristics of adolescents with dental markers for a concave (n=420), a convex (n=978), and a straight (n=3542) facial profile in a nationally representative sample of United States adolescents. The results show that adolescents with a concave facial profile, when compared to a straight facial profile, had an increased waist-to-height ratio (Δ, 1.1 [95% CI 0.5-1.7], p<0.003) and an increased acne prevalence (OR, 1.5 [95% CI 1.2-1.9], p<0.001). Adolescents with a convex facial profile, when compared to a straight facial profile, had an increased prevalence of tuberculosis (OR, 4.3 [95% CI 1.4-13.1], p<0.02), increased ectomorphy (Δ, 0.3 [95% CI 0.2-0.4], p<0.0001), increased left-handedness (OR, 1.4 [95% CI 1.1-1.7], p<0.007), increased color-blindness (OR, 1.7 [95% CI 1.3-2.3], p<0.004), and rhesus ee phenotype (OR, 1.3 [95% CI 1.1-1.5], p<0.008). Adolescents with a concave facial profile, when compared to a convex profile, had increased mesomorphy (Δ, 1.3 [95% CI 1.1-1.5], p<0.0001), increased endomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), lower ectomorphy (Δ, 0.5 [95% CI 0.4-0.6], p<0.0001), and lower vocabulary test scores (Δ, 2.3 [95% CI 0.8-3.8], p<0.008). It is concluded that population-based survey data confirm that distinct facial features are associated with distinct somatotypes and distinct disease susceptibilities.

Expression and intracellular processing of chimeric and mutant CFTR molecules.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride channel comprising two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs) and a unique regulatory (R) domain. The most frequent cystic fibrosis (CF) mutation, a deletion of Phe508 in NBD1, results in the retention of the DeltaF508 CFTR in the endoplasmic reticulum, as do many other natural or constructed mutations located within the first NBD. In order to further define the role of NBD1 in CFTR folding and to determine whether the higher frequency of mutations in NBD1 with respect to NBD2 results from its position in the molecule or is related to its primary sequence, we constructed and expressed chimeric CFTRs wherein NBD domains were either exchanged or deleted. Synthesis, maturation and activity of the chimeras were assessed by Western blotting and iodide efflux assay after transient or stable expression in COS-1 or CHO cells respectively. The data showed that deletion of NBD1 prevented transport of CFTR to the cytoplasmic membrane whereas deletion of NBD2 did not impair this process but resulted in an inactive chloride channel. On the other hand, substituting or inverting NBDs in the CFTR molecule impaired its processing. In addition, while the NBD1 R555K mutation is known to partially correct the processing of CFTR DeltaF508 and to increase activity of both wild-type and DeltaF508 individual channels, it showed no positive effect when introduced into the double NBD1 chimera. Taken together, these observations suggest that the proper folding process of CFTR results from complex interactions between NBDs and their surrounding domains (MSDs and/or R domain).

Chromosomal abnormalities in glioblastoma multiforme by comparative genomic hybridization: correlation with radiation treatment outcome.

Glioblastoma multiforme (GM) is the most common and most malignant astrocytoma in adults. After surgery, radiation therapy extends patient survival; however, in vivo response to radiation therapy is variable. The purpose of this investigation was to determine whether the cytogenetic abnormalities of GM differ according to patient response to radiation therapy. Radiation response was defined by either progression [radiation-resistant (RR)] or resolution [radiation-sensitive (RS)] of tumor at the first postradiation radiographic imaging evaluation. Twenty RR and 10 RS frozen tissue specimens were subjected to cytogenetic analysis by comparative genomic hybridization. RS and RR specimens had different cytogenetic aberrations that mapped predominantly to chromosomes 7, 9, 10, 13, and 19. Relative gain of 7 occurred in 70% of the RR and 30% of the RS cases and was the most significant difference involving a single change between the two groups (P = 0.06). RR and RS specimens also differed in their patterns of simultaneous cytogenetic aberrations. A simultaneous gain of chromosomes 7 and 19 was found in 30% of the RR cases but was absent in the RS group. Concurrent loss of 9p23-24 and 13q14 regions was absent in the RS cohort but occurred in 30% of the RR series. This latter cytogenetic pattern was also associated with older age. Amplifications were more common in the RR series, but the difference did not reach statistical significance. The data suggest that GM with different in vivo responses to radiation therapy also differ cytogenetically.

Cephalometric analysis and long-term outcomes of orthognathic surgical treatment for obstructive sleep apnoea.

The aim of this study was to describe skeletal and posterior airway changes after orthodontic treatment and surgical jaw advancement, and to evaluate whether there is a correlation between increasing advancement and a long-term reduction in obstructive sleep apnoea (OSA). Lateral cephalograms and polysomnography (apnoea-hypopnoea index, AHI) were collected from patients treated with bilateral sagittal split osteotomy (BSSO) or maxillomandibular advancement (MMA) in combination with orthodontics. Patients completed a questionnaire and the Epworth Sleepiness Scale (ESS) to assess long-term outcomes. Descriptive statistics for cephalometric measurements and linear regression were performed to find estimates of the final OSA (AHI and ESS) as a function of mandibular advancement. Forty-three patients with surgical advancement of the maxilla (5.2mm) and mandible (8.3mm) had a 4-mm increase in posterior airway. Thirty-three patients completed the long-term survey (6.3±2.6 years after treatment); 91% reported a reduction of OSA and were pleased with their facial appearance. The maxillomandibular and posterior airway increased. There was no evidence of a linear relationship between greater amounts of mandibular advancement and improvement of OSA. Patients with less than 10mm advancement had successful objective short-term and subjective long-term OSA reduction.

HIV-1 infectivity and host range modification by cathepsin D present in human vaginal secretions.

OBJECTIVE: To investigate HIV-1 infectivity in the natural environment of vaginal secretions. DESIGN: Vaginal wash samples collected from 14 healthy women were incubated in vitro with various HIV-1 strains for 10 min at 37 degrees C and then assayed for infectivity on primary lymphocyte cultures, or on CEM cells, or on CD4- ME180 cells derived from vaginal epithelium. METHODS: HIV-1 infectivity was measured by early virus growth in the various host cells tested using a quantitative p24 assay and by the Karber procedure. RESULTS: Preincubation of HIV-1(IIIB) with vaginal wash samples or 2 microg/ml cathepsin D increased the ability of the virus to grow in lymphocyte cultures. The vaginal wash effect was abolished by 5 microg/ml pepstatin A, an inhibitor of aspartyl proteases. Presence of precursor and mature forms of cathepsin D in vaginal wash was demonstrated after passage through a pepstatin A-agarose column. Median tissue culture infective doses of HIV-1(IIIB) and HIV-1(JRFL) strains were increased 14.4-fold and 18-fold, respectively, after preincubation in vaginal wash sample, and were increased by pretreatment with 2 microg/ml cathepsin D. When CD4 receptors of CEMss cells were blocked by OKT4a monoclonal antibody, the cells lost susceptibility to HIV-1 (IIIB), but supported the growth of virus pretreated with vaginal wash sample or cathepsin D. These treated viruses were able to initiate infection of CD4-ME180 epithelial cells, which were not receptive to untreated virus. ME180 cells were shown to possess the messenger of CXC-chemokine receptor-4. CONCLUSIONS: Vaginal secretions may help HIV-1 transmission to women by increasing infectivity for CD4+ cells and allowing entrance into some CD4-epithelial cells.

Bone resorption assessed by immunoassay of urinary cross-linked collagen peptides in patients with osteogenesis imperfecta.

Urinary excretion of type I collagen cross-linked N-telopeptides was studied in 52 children and adolescents with osteogenesis imperfecta (OI) and found to be above the 75th percentile of controls in 44 of the patients. OI patients suffering from fractures during the preceding 6 months had significantly higher values (p < 0.05). In contrast, patients with better motor performance tended to have lower values (p = 0.059). The concentration of urinary type I collagen cross-linked N-telopeptides was positively correlated with urinary calcium excretion (p < 0.05), which was found to be elevated in 20 of the patients. Our results show that during childhood and adolescence in OI not only the synthesis but also the turnover of mature cross-linked type I collagen is disturbed and provide evidence that bone resorption rates are elevated.