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This paper presents numerical analyses of one-dimensional heat transfer in layered saturated soil with effective porosity and under a periodic temperature boundary condition using the numerical model HT1. The model characterizes the soil layer using separate columns to represent solid matrix and mobile pore fluid components, and a series-parallel approach to model soil thermal conductivity. Numerical simulations are presented to illustrate the effect of fluid velocity, thermal retardation factor, thermal conductivity of solid particles, effective porosity and layer heterogeneity. Numerical results indicate that increasing downward fluid velocity and decreasing retardation factor can increase the distance that temperature oscillations from the surface can propagate into the layer. In addition, decreasing fluid velocity, increasing retardation factor, and increasing thermal conductivity of solid particles can decrease the temperature oscillation amplitude in the soil. Temperature profiles also indicate the significance of soil effective porosity and multiple soil layers on heat transfer behavior.

We examined the chemical reactions influencing dissolved concentrations, speciation, and transport of naturally occurring arsenic (As) in a shallow, sand and gravel aquifer with distinct geochemical zones resulting from land disposal of dilute sewage effluent. The principal geochemical zones were: (1) the uncontaminated zone above the sewage plume [350 μM dissolved oxygen (DO), pH 5.9]; (2) the suboxic zone (5 μM DO, pH 6.2, elevated concentrations of sewage-derived phosphate and nitrate); and (3) the anoxic zone [dissolved iron(II) 100–300 μM, pH 6.5–6.9, elevated concentrations of sewage-derived phosphate]. Sediments are comprised of greater than 90% quartz but the surfaces of quartz and other mineral grains are coated with nanometer-size iron (Fe) and aluminum (Al) oxides and/or silicates, which control the adsorption properties of the sediments. Uncontaminated groundwater with added phosphate (620 μM) was pumped into the uncontaminated zone while samples were collected 0.3 m above the injection point. Concentrations of As(V) increased from below detection (0.005 μM) to a maximum of 0.07 μM during breakthrough of phosphate at the sampling port; As(III) concentrations remained below detection. These results are consistent with the hypothesis that naturally occurring As(V) adsorbed to constituents of the coatings on grain surfaces was desorbed by phosphate in the injected groundwater. Also consistent with this hypothesis, vertical profiles of groundwater chemistry measured prior to the tracer test showed that dissolved As(V) concentrations increased along with dissolved phosphate from below detection in the uncontaminated zone to approximately 0.07 and 70 μM, respectively, in the suboxic zone. Concentrations of As(III) were below detection in both zones. The anoxic zone had approximately 0.07 μM As(V) but also had As(III) concentrations of 0.07–0.14 μM, suggesting that release of As bound to sediment grains occurred by desorption by phosphate, reductive dissolution of Fe oxides, and reduction of As(V) to As(III), which adsorbs only weakly to the Fe-oxide-depleted material in the coatings. Results of reductive extractions of the sediments suggest that As associated with the coatings was relatively uniformly distributed at approximately 1 nmol/g of sediment (equivalent to 0.075 ppm As) and comprised 20%-50% of the total As in the sediments, determined from oxidative extractions. Quartz sand aquifers provide high-quality drinking water but can become contaminated when naturally occurring arsenic bound to Fe and Al oxides or silicates on sediment surfaces is released by desorption and dissolution of Fe oxides in response to changing chemical conditions.

Effective symptom management is a critical component of cancer treatment. Computational tools that predict the course and severity of these symptoms have the potential to assist oncology clinicians to personalize the patient's treatment regimen more efficiently and provide more aggressive and timely interventions. Three common and inter-related symptoms in cancer patients are depression, anxiety, and sleep disturbance. In this paper, we elaborate on the efficiency of Support Vector Regression (SVR) and Non-linear Canonical Correlation Analysis by Neural Networks (n-CCA) to predict the severity of the aforementioned symptoms between two different time points during a cycle of chemotherapy (CTX). Our results demonstrate that these two methods produced equivalent results for all three symptoms. These types of predictive models can be used to identify high risk patients, educate patients about their symptom experience, and improve the timing of pre-emptive and personalized symptom management interventions., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Social scientists need practical methods for harnessing large, publicly available datasets that inform the social context of aging. We describe our development of a semi-automated text coding method and use a content analysis of Alzheimer's disease (AD) and dementia portrayal on Twitter to demonstrate its use. The approach improves feasibility of examining large publicly available datasets., Method: Machine learning techniques modeled stigmatization expressed in 31,150 AD-related tweets collected via Twitter's search API based on 9 AD-related keywords. Two researchers manually coded 311 random tweets on 6 dimensions. This input from 1% of the dataset was used to train a classifier against the tweet text and code the remaining 99% of the dataset., Results: Our automated process identified that 21.13% of the AD-related tweets used AD-related keywords to perpetuate public stigma, which could impact stereotypes and negative expectations for individuals with the disease and increase "excess disability"., Discussion: This technique could be applied to questions in social gerontology related to how social media outlets reflect and shape attitudes bearing on other developmental outcomes. Recommendations for the collection and analysis of large Twitter datasets are discussed., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients., Methods and Analysis: A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes)., Ethics and Dissemination: Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts., Trial Registration Number: NCT02356081., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are stigmatizing illnesses characterized by cognitive difficulties, post-exertional malaise, unrefreshing sleep, and other symptoms. Patients are often incapacitated and stigmatized as having a psychological disorder. The Chronic Fatigue Attitudes Test (CAT) assesses stigmatizing views toward individuals with Chronic Fatigue Syndrome, however, there is little research examining factors that may account for variation in stigmatizing attitudes toward this group. We examined CAT scores among college age research volunteers (N = 90), hypothesizing that exposure to information about ME and CFS as a result of volunteering on a ME and CFS-related research project would be associated with less stigmatizing attitudes compared to volunteers on unrelated projects. Findings indicated that ME and CFS research volunteers expressed less stigmatizing attitudes. Educational efforts aiming to disseminate accurate information about ME and CFS may mitigate stigma and the experience of stigma among individuals with ME and CFS., Competing Interests: Conflict of Interest There are no conflicts of interest to report.

There is a growing range of treatment options for anal intraepithelial neoplasia (AIN). In HIV-positive patients, sustained treatment is often required to achieve clearance. The treatments considered are topically applied fluorouracil, imiquimod, cidofovir and trichloroacetic acid, the potential treatments of topical lopinavir and photodynamic therapy with aminolevulenic acid, and the surgical methods of electrosurgery, infrared coagulation and laser. Destructive treatment methods, possibly including TCA, are more effective than self applied topical treatments. Combining or alternating different treatments should be considered.

Objective: To determine whether imiquimod was more effective than placebo for the treatment of high-grade anal canal intraepithelial neoplasia (HG-ACIN)., Design: Double-blind, randomized placebo-controlled clinical trial., Methods: Sixty-four HIV-positive patients were randomized to self-application of imiquimod cream or matched placebo into the anal canal three times a week for 4 months. Response was assessed by cytology, high-resolution anoscopy and biopsy 2 months after therapy. All patients who failed to resolve were offered treatment with open-label imiquimod for a further 4 months., Results: Fifty-three patients completed the study, of which 28 patients were on active drug and 25 patients on placebo. In the imiquimod group, four patients resolved and eight patients downgraded to low-grade squamous intraepithelial lesion (LSIL) with a median follow-up of 33 months. In the placebo group, one patient resolved. Imiquimod was significantly associated with a positive outcome (P = 0.003). Only one patient discontinued owing to side effects. Twenty-one patients entered a second open-label phase of treatment. Five of these patients cleared their anal canal intraepithelial neoplasia (ACIN) and four patients downgraded to LSIL. The overall mean duration of follow-up was 36 months. During this extended follow-up period, 61% have exhibited sustained absence of high-grade squamous intraepithelial lesion (HSIL)., Conclusion: This study demonstrates the effectiveness of imiquimod for the treatment of ACIN, and the benefit of prolonged or repeated treatments. This form of therapy is likely to be especially valuable for patients with widespread multifocal ACIN who are otherwise difficult to treat, and should be considered as an adjunct to ablative therapy.

Readily prepared imidazole-based boronium ions form stable, hydrophobic, room-temperature ionic liquids (RTIL) with unique electronic and spectroscopic characteristics.

Background: Previous studies have reached differing conclusions about the utility of anal cytology as a screening tool for anal intraepithelial neoplasia (AIN). There is a need also to establish whether HPV typing offers a useful adjunct to screening., Methods: We analysed data from 99 consecutive homosexual/bisexual male patients (89 HIV-1 positive) who underwent high resolution anoscopy. Follow up visits for these patients were also included, giving a total of 160 anoscopic procedures. Comparison was made between results of anal cytology using the sampling method of Palefsky, and histological findings of biopsies taken from abnormal areas seen on high resolution anoscopic examination of the anal canal. Swabs taken concurrently with the cytology were analysed for the presence of human papillomavirus (HPV) DNA and compared with the cytological and histological findings., Results: The sensitivity of the cytology was 83%, and the specificity 38% when compared with histology. At screening of 34 asymptomatic men, 83% had anal cytological dysplasia and 78% had AIN. There were no significant differences in the prevalence of hrHPV genotypes between different cytological or histological grades of abnormalities., Conclusion: Anal cytology by the Palefsky method is simple to undertake, has a sensitivity and specificity comparable with cervical cytology, and can therefore be used as the basis of a pilot screening project in centres with large cohorts of HIV positive homosexual men who have a high risk of developing anal carcinoma. HPV genotyping is not a useful adjunct to cytological screening.

The monetary and personal costs to society of human papillomavirus (HPV) infection are enormous. In order to make a comparison of different treatment methods we reviewed the entire literature on HPV treatment from January 1966 to December 2003 using MEDLINE, with particular reference to published meta-analyses, randomized controlled and comparative studies. Patient-applied therapies offer patients the possibility of convenient and, on the whole, pain-free treatment. Podofilox (podophyllotoxin) and salicylic acid for genital and extragenital warts, respectively, have the additional advantage of being the most cost-effective treatments and, on this basis, they are to be commended as appropriate first-line agents. The second-line treatment of choice for common warts is cryotherapy. For recalcitrant common warts possible options include inosine pranobex with cryotherapy or electrosurgery, imiquimod with paring and occlusion, intralesional bleomycin, or diphencyprone. Alternative first-line and second-line treatments for genital warts would be either some form of surgical removal or imiquimod. The first option may be the cheapest but this has to be balanced against a degree of post-operative morbidity. Limited data from comparative studies do not show any clear difference in efficacy between cryotherapy, trichloroacetic acid, scissor excision, electrosurgery, and laser surgery in the treatment of genital warts, and the cost effectiveness of these therapies is probably similar to that of imiquimod. Cryotherapy and trichloroacetic acid are relatively expensive and inconvenient for patients and should be reserved as third-line treatments with certain exceptions, such as cryotherapy for meatal warts. The duration of treatment is significantly related to the number of warts present, the area covered by the warts, and the length of time the warts have been present. For recalcitrant anogenital warts third-line treatment options that show promise include surgery in combination with imiquimod or cidofovir cream. For squamous intraepithelial lesions that cannot easily be excised or physically ablated current treatment options include imiquimod and fluorouracil cream. The latter is an inexpensive option but causes the greatest morbidity. It is hoped that cidofovir may be added to this list if it becomes commercially available, and that protective and therapeutic HPV vaccines will transform the management of HPV in the future.

The anions of the sweeteners saccharin and acesulfame form ionic liquids when paired with a variety of organic cations.

Patients were recruited for hypnotherapy from a clinic for patients with frequently recurrent genital herpes simplex virus (rgHSV). Psychological and immunological parameters were measured 6 weeks prior to hypnotherapy and 6 weeks afterwards, during which time each patient kept a diary of symptoms of rgHSV. Following hypnotherapy there was a significant overall reduction in the number of reported episodes of rgHSV, accompanied by an increase in the numbers of CD3 and CD8 lymphocytes, which may represent a non specific effect of hypnosis. The improvers showed significant rises in natural killer (NK) cell counts, HSV specific lymphokine activated killer (LAK) activity, and reduced levels of anxiety when compared to non-improvers. NK cell numbers and HSV specific LAK activity may therefore be important in the reduction in rgHSV following hypnotherapy.

A narrow time window centered around the terminal mitosis of their precursors has been recognized to be critical for the determination and/or realization of the developmental fate of a variety of neuronal phenotypes. In contrast, individual cell lineages in the cerebellum get separated early during embryonic development, and at least precursors for granule neurons have been found to be specified while still proliferating. We utilized primary dissociated cultures to address the issue of whether the faithful development of cerebellar granule cells and basket/stellate cells is dependent on their mitotic history and on the completion of a fixed number of cell cycles. Neuroblasts derived from embryonic cerebellar anlagen and transferred into primary dissociated cultures stopped proliferating as assessed by a loss of expression of the cell proliferation marker, Ki-67, and a failure to incorporate 5-bromo-2'-deoxyuridine. Although these cells had been forced to leave the proliferating cell pool prematurely, they developed into granule neurons or basket/stellate cells as judged by their distinct pattern of expression of specific molecular markers and the acquisition of a typical morphology. This included the cell intrinsic capacity of granule neurons to position their afferent synapses specifically to their dendrites. Thus, the competence of cerebellar interneurons to differentiate appropriately is independent of the precise timing of their final mitosis; however, their sensitivity towards extrinsic developmental signals appears to vary in a cell cycle-dependent manner, as suggested by the failure to survive of those cells that were in S-phase at the time of cultivation.

Mossy fiber boutons are the sites of synaptic signalling between hippocampal granule and pyramidal neurons. We studied the formation and localization of these terminals during development of prenatal hippocampal neurons in primary culture. Using the synaptic vesicle membrane proteins synaptophysin and synaptoporin as markers we observed that both proteins were mainly localized in perikarya and processes of fetal hippocampal neurons during the first days in vitro (DIV). Following DIV 6 synaptophysin was present in small terminals. After DIV 20 in addition large terminals immunoreactive for synaptophysin and synaptoporin were found, which were identified by electron microscopy as mossy fiber boutons impinging on pyramidal neuron dendrites. Synaptic vesicles and endosomes in the mossy fiber boutons were labeled when incubated with exogenous horseradish peroxidase, indicating that they were competent for exo-endocytosis. Taken together, our data show that hippocampal granule neurons grown in dissociated primary cultures form mossy fiber boutons containing synaptophysin and synaptoporin at pyramidal cell dendrites. Since the composition and the characteristic morphology of mossy fiber boutons formed in vitro is the same as observed in vivo we conclude that their development follows an intrinsic program.

The effects of three forms of test feedback and text anxiety on test performance were examined within the context of a self-paced, criterion-based course in educational psychology. 73 undergraduate students completed seven units of work and were evaluated by computer-administered unit tests. Students were randomly assigned to one of three test feedback forms: (1) item-by-item knowledge of responses, (2) answer-until-correct, and (3) delayed feedback. Students received their assigned feedback during the first two units, after which they were allowed to choose. Test anxiety was measured prior to testing on Sarason's Test Anxiety Scale and during testing on an item administered by the computer program. Students who reported high test anxiety on the Test Anxiety Scale experienced more anxiety during testing than students reporting low test anxiety. Anxiety during testing was not related to type of feedback, and the two variables were not related to course performance on the second unit. Data collected at the conclusion of the semester indicated that students who reported higher test anxiety required more attempts to pass unit tests than those reporting lower test anxiety. Given a choice, students preferred answer-until-correct feedback. This preference was not related to Test Anxiety Scale scores. Anxiety during testing was not related to being allowed to choose forms of feedback.

The expression and subcellular location of glutamate receptor subunits 2&3 was investigated in the developing postnatal cerebellum. Immunoblotting revealed that glutamate receptor subunits 2/3 is expressed in an identical pattern of immunoreactive bands of approximately 108 kDa from postnatal day zero to adult animals. Light microscopy showed that within the cerebellar cortex, GluR 2/3 immunoreactivity was essentially confined to Purkinje neurons. Strong immunostaining could be observed at postnatal days 1-3 within Purkinje cell bodies and primary dendrites. With ongoing development, the cell body and an increasingly elaborate dendritic tree was outlined by immunoreaction product. In adult animals, staining of Purkinje cell dendrites was patchy, and staining intensity of the cell body, in particular, was greatly reduced. Ultrastructural analysis revealed that during early postnatal development, immunoreaction product was localized to the cell membrane, but was not confined to postsynaptic densities. From the second postnatal week, glutamate receptor subunits 2/3 immunoreactivity was largely restricted to postsynaptic densities. These observations reveal a developmentally regulated refinement of the subcellular distribution of defining subunits of the AMPA-type glutamate receptor. The presence of membrane bond receptors prior to the formation of synapses also provides a rationale for the known transmitter-mediated modulation of Purkinje cell dendritogenesis.

This study was designed to test a proposed dose modification for intravenous milrinone in congestive heart failure patients (CHF, NYHA I-II) with either moderate or severe renal impairment. All the patients were administered an intravenous loading dose of drug at 50 micrograms kg-1 over 10 min. This was followed by an 18 h maintenance infusion of milrinone at 0.45 or 0.35 micrograms kg-1 min-1 for the moderate (chromium-EDTA clearance of 31-75 mL min-1, n = 10) and severe renally impaired subjects (chromium-EDTA of clearance 10-30 mL min-1, n = 11), respectively. Plasma and urine samples were collected for up to 34 h and analysed for parent drug by validated HPLC methods. The mean (+/- s.d.) steady-state plasma concentrations of milrinone were within the therapeutic range (100-300 ng mL-1) for both groups, with values of 239 +/- 71 ng mL-1 and 269 +/- 32 ng mL-1 for the moderate and severe patients, respectively. No statistical differences were observed between the steady-state values for the two groups. With the exception of two patients per group, individual steady-state levels were also within the therapeutic range. Those outside the nominal range showed steady-state levels, ranging between 308 and 353 ng mL-1, that were not associated with any serious adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

The closely related synaptic vesicle membrane proteins synaptophysin and synaptoporin are abundant in the hippocampal formation of the adult rat. But the prenatal hippocampal formation contains only synaptophysin, which is first detected at embryonic day 17 (E17) in perikarya and axons of the pyramidal neurons. At E21 synaptophysin immunoreactivity extends into the apical dendrites of these cells and in newly formed terminals contacting these dendrites. The transient presence of synaptophysin in axons and dendrites suggests a functional involvement of synaptophysin in fibre outgrowth of developing pyramidal neurons. Synaptoporin expression parallels the formation of dentate granule cell synaptic contacts with pyramidal neurons: the amount of hippocampal synaptoporin, determined in immunoblots and by synaptoporin immunostaining of developing mossy fibre terminals; increases during the first postnatal week. Moreover, in the adult, synaptoporin is found exclusively in the mossy fibre terminals present in the hilar region of the dentate gyrus and the regio inferior of the cornu ammonis. In contrast, synaptophysin is present in all synaptic fields of the hippocampal formation, including the mossy fibre terminals, where it colocalizes with synaptoporin in the same boutons. Our data indicate that granule neuron terminals differ from all other terminals of the hippocampal formation by the presence of both synaptoporin and synaptophysin. This difference, observed in the earliest synaptic contacts in the postnatal hippocampus and persisting into adult life, suggests distinct functions of synaptoporin in these nerve terminals.

We have evaluated the disposition of milrinone in seven patients with low cardiac output after elective cardiac surgery involving cardiopulmonary bypass. Patients received a loading dose of milrinone 50 micrograms kg-1 given over 10 min followed immediately by an infusion of 0.5 microgram kg-1 min-1, continued for a minimum of 5 h. Plasma concentrations of milrinone were measured at designated intervals during the infusion and for 6 h after its termination, by high pressure liquid chromatography. Concentrations greater than 100 ng ml-1 were produced in all patients within 2 min of starting the loading dose and were maintained for the duration of the infusion. Volume of distribution, clearance and terminal half-life were similar to those found in patients with chronic cardiac failure.

1-(2-Chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), a water-soluble nitrosourea, differs from 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) by the placement of the cytotoxic group on C-1 of glucose. Its biological and biochemical properties are compared with those of chlorozotocin. At a 10% lethal dose (10 mg/kg i.p.), GANU demonstrates minimal myelosuppression. This dose failed to depress normal bone marrow DNA synthesis, in contrast to a 96% inhibition in L1210 DNA synthesis. In L1210 cell suspension, equimolar doses of GANU and chlorozotocin produced equivalent degrees of inhibition in DNA synthesis. GANU has significant L1210 activity in BALB/c X DBA/2 F1 mice treated on Day 2 of tumor growth. A 117% increased life-span and 15% 45-day survivors are atained with 15 mg/kg i.p., a 50% lethal dose. However, in concurrent studies using randomly selected littermate groups of mice, GANU proved less active than chlorozotocin which produced a 306% increased life-span (15 mg/kg i.p.). GANU and chlorozotocin have similar in vitro alkylating activity but the in vitro carbamoylating activity of GANU is sevenfold that of chlorozotocin. On a molar basis, the lethal toxicity of GANU is twice that of chlorozotocin. The significant carbamoylating activity of GANU may contribute to its greater toxicity and therefore limit the mumoles of alkylating agent that can be administered to the tumor. These structure-activity studies further confirm that the addition of a glucose carrier to a cytotoxic nitrosourea moiety can selectively reduce bone marrow toxicity while retaining antitumor activity.

The lethal and bone marrow toxicity and antitumor activity of the cis- and trans-2-hydroxylated metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) have been correlated with their relative in vitro alkylating and carbamoylating activities. Both the isomers have considerably greater alkylating activity and shorter chemical half-lives than the parent compound and on a molar basis have greater antitumor activity against i.p. L1210 leukemia. However, in terms of molar doses resulting in the death of 10% of normal mice, the cis- and trans-2 isomers were 2- and 3-fold more toxic than was CCNU in normal mice. In comparing the antitumor activity produced by a maximum nonlethal dose for each compound, we found that the trans isomer had activity identical to that of CCNU (413 and 410% increased life span compared to control), and the cis isomer had considerably less (152%). Like chlorozotocin, both isomers possess low carbamoylating activity and increased water solubility, two features that have been considered possible contributors to the bone marrow-sparing character of chlorozotocin. However, in the murine model the human bone marrow colony formation (CFU-C) assay neither hydroxylated metabolite of CCNU was associated with reduced myelotoxicity.

The basement membrane zone (BMZ) of human skin is a complex structure which contains several well-defined components including bullous pemphigoid antigen, laminin, type IV collagen, and proteoglycan. Characterization of additional basement membrane (BM) constituents has been limited by their relative inaccessibility, insolubility, and low tissue concentration. We have produced a murine monoclonal antibody that has enabled us to define a unique constituent of the BMZ of human stratified squamous epithelia. The monoclonal antibody (KF-1) was raised by standard techniques using suction blister-derived trypsinized human epidermal cells as the antigen. Indirect immunofluorescence and immunoperoxidase staining of human and rhesus monkey tissues with KF-1 produced linear BMZ staining of stratified squamous epithelia. Glandular and vascular BMs were not stained. Immunoelectron microscopic studies of normal human skin and esophagus showed specific binding of KF-1 to the lamina densa of the BMZ, a localization identical to that of type IV collagen. However, unlike type IV collagen, which is not species specific and is found in all BMs, the antigen defined by KF-1 is collagenase-resistant and is specific for primate stratified squamous epithelia. These findings confirm the existence of regional variation in BM composition, and demonstrate for the first time that the lamina densa of stratified squamous epithelial BMs contains a constituent other than type IV collagen.

Basic principles of production of monoclonal antibodies are discussed in this paper. In order to illustrate the usefulness of such production, studies of a new monoclonal antibody designated KF-2 which defines a unique cell-surface antigen found exclusively in the stratum spinosum of man and lower primates are recounted.