Apparent Host Research Articles

A Human Hematopoietic Environment and Autologous T-Cell Growth Support Proliferation of Chronic Lymphocytic Leukemia B Cells in Immune-Deficient Mice

B-cell type chronic lymphocytic leukemia (B-CLL), an incurable disease of unknown etiology, results from the clonal expansion of a CD5+CD19+ B lymphocyte. Progress into defining the cell of origin of the disease and identifying a stem cell reservoir has been impeded because of the lack of reproducible models for growing B-CLL cells in vitro and in vivo. To date, attempts to adoptively transfer B-CLL cells into immune deficient mice and achieve engraftment and growth are sub-optimal. At least one possible cause for this is the murine microenvironment's inability to support B-CLL survival and proliferation. We have attempted to overcome this barrier by creating a human hematopoietic microenvironment by reconstituting the tibiae of NOD/SCID/γcnull mice by intrabone (ib) injection of 1–3 × 105 CD34+ cord blood cells along with ~106 bone marrow-derived human mesenchymal stem cells (hMSCs). When human engraftment of 1–10% CD45+ cells was documented in the blood by immunofluorescence using flow cytometry, a total of 108 PBMCs from individual B-CLL patients were injected into the same bones. Before injection, B-CLL PBMCs were labeled with CFSE to permit distinction of leukemic B cells from normal B cells that might arise from the injected CD34+ cells. CFSE labeling also permitted tracking initial rounds of cell division in vivo. Every two weeks after B-CLL injection, peripheral blood from the mice was examined for the presence of cells bearing human CD45, CFSE, and various human lineage markers by flow cytometry. In the presence of a human hematopoietic microenvironment, CD5+CD19+ leukemic cells underwent at least 6 cell doublings, after which CFSE fluorescence was no longer detectable. Timing of B-CLL cell division varied among patients, occurring between 2 to 6 weeks after the injection of PBMC. In contrast, leukemic cells injected into mice that were not reconstituted by ib injection with hCD34+ cells and hMSCs or were reconstituted with only hMSCs failed to proliferate. Moreover the number of CFSE+CD5+CD19+ cells detected in the blood of mice with a human hematopoietic microenvironment far exceeded that in mice receiving only hMSC. Robust T-cell expansion occurred in several mice receiving CD34+ cells; in some instances T-cell growth was also found without hCD34+ cell injection, although in these cases it was usually less extensive. Based on genome-wide SNP analyses, the T cells were of B-CLL patient origin and not from hCD34+ cells. Furthermore, most of the mice with significant T-cell overexpansion died within 6 weeks of B-CLL cell injection from apparent graft vs. host disease. Therefore in subsequent experiments, we eliminated T cells by injecting an anti-CD3 antibody (OKT3); this treatment led to an inhibition of B-CLL cell proliferation. Moreover the percentage of CD38+ cells in the CFSE+CD5+CD19+ cell fraction was similar to that in the donor patient inoculum only in the mice in which T-cell-mediated B-CLL cell proliferation occurred. The percentage and intensity of CD38− expressing B-CLL cells was higher in the spleen and bone marrow (BM) of mice not treated with OKT3 antibody. Finally, the percentage of CFSE+CD5+CD19+ cells in the spleen far exceeded that in the blood, BM, liver and peritoneum, even when leukemic cells were no longer present in the blood and other organs; these findings suggest that the spleen is better at supporting B-CLL cell viability and proliferation than the other anatomic sites. These studies demonstrate conditions making adoptive xenogeneic transfer and clonal expansion of B-CLL cells into a mouse model possible. Factors conferring an advantage in this model include both a human hematopoietic environment and autologous T cell growth. Increased numbers of CD38+ B-CLL cells, similar to those in the patient, were only found when leukemic B cell division occurred. The optimal site for B-CLL cell growth was murine spleen. Since non-genetic factors promoting B-CLL expansion are not completely known, this model will be useful in discovering these as well as for studying the basic biology of this disease, such as if leukemic stem cells exist and also to conduct preclinical tests on possible therapeutics.

Keck Spectroscopy of ROSAT Ultraluminous X-Ray Source Candidates

ABSTRACTWe present results of optical follow-up observations of ultraluminous X-ray source (ULX) candidates. A published ROSAT catalog of 87 ULX candidates named 19 of these as having optical counterparts in Digitized Sky Survey (DSS) images. Using Keck optical spectroscopy, we classify 16 ULX candidates in this subset as well as one other ULX candidate from the catalog with a counterpart in the DSS. This is one of the largest sets of optical identifications of such objects thus far. Fifteen are background active galactic nuclei (AGNs); two are foreground stars in our Galaxy. These findings are consistent with background and foreground object expectations, as derived from log N - log S relations. The logarithmic X-ray to optical flux ratios of these objects are also typical of background and foreground objects. Finally, we discuss the nature of ULX candidates outside the optical extent of their apparent host galaxies.

Morphological variation in different populations of Aceria anthocoptes (Acari: Eriophyoidea) associated with the Canada thistle, Cirsium arvense, in Serbia

The russet mite, Aceria anthocoptes (Nal.), is the only eriophyid that has been recorded on Canada thistle, Cirsium arvense (L.) Scop. It has been noted in several European countries and recently in the USA. With its apparent host specificity and because of the damage it causes to its host plant, A. anthocoptes is being studied as a potential candidate for classical biological control. The aim of the present study was to examine quantitative morphological traits in four populations of A. anthocoptes living on two infraspecific host plant taxa (C. arvense var. arvense and C. arvense var. vestitum) in two geographically separate areas of Serbia in order to test the hypothesis of absence of the possible host plant impact on mite morphology. MANOVA analysis revealed significant differences between populations from different localities in Serbia. Populations of A. anthocoptes inhabiting two thistle varieties in the vicinity of Belgrade differed significantly from mites inhabiting the same two host varieties in the vicinity of the town of Ivanjica. Canonical discriminant analysis showed that the trait which best discriminates the populations of A. anthocoptes is the number of dorsal annuli. It was not possible to ascribe morphological differences to the impact of the host plant.

An Antibody Delivery System for Regulated Expression of Therapeutic Levels of Monoclonal Antibodies In Vivo

Monoclonal antibody (mAb) delivery by gene transfer in vivo may be an attractive alternative to current mAb therapies for applications that require long-term therapy. This article describes a transfer system that allows inducible high-level expression of unmodified mAbs in vivo. A recombinant adeno-associated viral (rAAV) vector is used that comprises an expression cassette consisting of a dimerizer-regulated promoter that drives expression of the antibody heavy and light chains linked by a 2A self-processing peptide and a furin cleavage site. Following intravenous injection of the rAAV vector, serum mAb levels >1 mg/ml were attained by administration of the inducer, rapamycin. Antibody expression could be rapidly shut off by discontinuing treatment with rapamycin. By optimizing the furin cleavage sequence, this system generated native antibody in vivo, decreasing the likelihood of a host immune response to foreign sequences. In summary, this optimized mAb expression system allows regulated high-level expression of native full-length mAbs in vivo and may offer a new opportunity for delivery of therapeutic mAbs in the clinic.

An Antibody Delivery System for Regulated Expression of Therapeutic Levels of Monoclonal Antibodies In Vivo

An Antibody Delivery System for Regulated Expression of Therapeutic Levels of Monoclonal Antibodies In Vivo

Favorable long-term outcome of nephrotic syndrome after allogeneic hematopoietic stem cell transplantation

The development of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HS-CT) is a rare complication with few long-term outcome data. Clinical course and long-term outcome of three adult patients and one child with NS after HSCT (total number of transplants n = 533) are presented. The median age at onset of NS was 35 years (range 15 - 56), occurring at a median of 17 months (range 11 - 21) after HSCT. Discontinuation of cyclosporine A (CSA) prior to onset of NS was a consistent feature and occurred a median of 6 months (range 2 - 10 months) prior to the development of NS. The histopathological lesion was membranous nephropathy (n = 3) and membranoproliferative glomerulonephritis Type 1 (n = 1). History of acute or concomitant clinically apparent chronic graft versus host disease (GVHD) was present in all cases except the pediatric patient who had abundant DR-activated cytotoxic T cells without evidence of viral reactivation. Long-term immunosuppression for 11 - 36 months with steroids (n = 1), combined steroids and CSA (n = 2) or CSA alone in steroid-refractory NS (n = 1) resulted in sustained remission of the NS in all patients (12 months - 8 years off immunosuppression). NS after HSCT seems to be etiologically related to subclinical or overt chronic GVHD, which flares up after discontinuation of CSA. However, resumption of immunosuppression can reverse NS as well as GVHD and induce favorable sustained long-term remission.

PARASITES OF THE STOUT RAZOR CLAM TAGELUS PLEBEIUS (PSAMMOBIIDAE) FROM THE SOUTHWESTERN ATLANTIC OCEAN

This work describes the parasites and their respective pathologies in the stout razor clam, Tagelus plebeius (Lightfoot, 1786) (Psammobiidae) from Argentinean coasts. It represents the first report about a histopathological survey for these species in the Southwestern Atlantic. Specimens of T. plebeius were collected at Mar Chiquita coastal lagoon (37°46′S, 57°27′W) (n = 104 dissected under stereomicroscope, n = 28 histologically sectioned and microscopically examined) and from the mouth of the Quequén Salado River (38°56′S, 60°33′W) (n = 14 dissected under stereomicroscope). Tagelus plebeius was found housing two ciliate species without apparent host reaction and acting as first intermediate host for two digenetic trematode species of the families Fellodistomidae and Gymnophallidae, by hosting sporocysts (mainly in gonad and digestive gland that results in the replacement of host tissues) and as second intermediate host by housing a gymnophallid metacercaria. Likewise, T. plebeius was found parasitized by a larval spirurinae nematode encapsulated by hemocytes. The finding of two ciliate species, the gymnophallid cercaria and metacercaria, and the larval nematode represents the first record for the host. The Southwestern Atlantic populations of this clam seem to be devoid of serious pathogens in the study area.

Have we detected the most luminous ULX so far?

abstract We report the XMM–Newton detection of a moderately bright X-ray source (F0.5−7∼ 8.2 × 10−14 erg cm−2 s−1) superimposed on the outer arms of the inactive spiral galaxy MCG–03-34-63 (z= 0.0213). It is clearly offset from the nucleus (by about 19 arcsec) but well within the D25 ellipse of the galaxy, just along its bar axis. The field has also been observed with the Hubble Space Telescope (HST), enabling us to compute a lower limit of >94 on the X-ray-to-optical flux ratio which, together with the X-ray spectrum of the source, argues against a background active galactic nucleus. On the other hand, the detection of excess X-ray absorption and the lack of a bright optical counterpart argue against foreground contamination. Short time-scale variability is observed, ruling out the hypothesis of a particularly powerful supernova. If it is associated with the apparent host galaxy, the source is the most powerful ultraluminous X-ray source detected so far, with a peak luminosity of ∼1.35 × 1041 erg s−1 in the 0.5–7 keV band. If confirmed by future multi-wavelength observations, the inferred bolometric luminosity (∼3 × 1041 erg s−1) requires a rather extreme beaming factor (larger than 115) to accommodate accretion on to a stellar-mass black hole of 20 M⊙ and the source could instead represent one of the best intermediate-mass black hole candidate so far. If beaming is excluded, the Eddington limit implies a mass of >2300 M⊙ for the accreting compact object.

Food Safety: Human Health Hazard from Antimicrobial‐Resistant Enterococci in Animals and Food

The use of antimicrobial agents in the modern farm industry has created a reservoir of resistant bacteria in food animals. Foods of animal origin are often contaminated with enterococci that are likely to contribute resistance genes, virulence factors, or other properties to enterococci IN humans. The potential hazard to human health from antimicrobial-resistant enterococci in animals is questioned by some scientists because of evidence of host specificity of enterococci. Similarly, the occurrences of specific nosocomial clones of enterococci in hospitals have lead to the misconception that antimicrobial-resistant animal enterococci should be disregarded as a human health hazard. On the basis of review of the literature, we find that neither the results provided by molecular typing that classify enterococci as host-specific organisms nor the occurrence of specific nosocomial clones of enterococci provide reasons to change the current view that antimicrobial-resistant enterococci from animals pose a threat to human health. On the contrary, antimicrobial resistance genes appear to spread freely between enterococci from different reservoirs, irrespective of their apparent host association.

Functional defect of natural immune system in an apparent immunocompetent patient with pulmonary cryptococcosis

We report a case of pulmonary cryptococcosis in a 21-year-old Italian female smoker with no apparent immune disorder. In this study we demonstrated that: (i) patient's neutrophils and monocytes manifested a significant reduction of killing activity against Cryptococcus neoformans as well as Candida albicans; (ii) the suppression was more pronounced in monocytes than in neutrophils; (iii) neutrophils and monocytes showed a significant impairment of TNF-alpha, IL-1beta, and nitric oxide production. These results suggest that the apparent immunocompetent host with pulmonary cryptococcosis could have specific defects in natural immune system mechanisms.

Pharmacokinetics, pharmacodynamics, and hepatitis C viral kinetics during antiviral therapy: The null responder

Our aim was to study the effect of ribavirin on viral kinetics and to study the early patterns of response to antiviral therapy of hepatitis C and their correlation with interferon pharmacokinetics and pharmacodynamics. We conducted a randomized, controlled trial of peginterferon alfa-2a with or without ribavirin in interferon naïve patients with HCV genotype 1. HCV RNA levels were measured at frequent intervals during treatment together with serum levels of peginterferon alfa-2a and 2'5'oligoadenylate synthetase (OAS). Of 29 patients treated, 14 had a complete response at day 29 while 15 had a null response (less than 1 log decline in HCV RNA). There were no significant differences between complete and null responders with regard to gender, age, race, body mass index, HCV subtype, baseline HCV RNA levels, serum aminotransferase activities, stage of fibrosis, peak OAS, or interferon levels. Mean serum IFN levels at day 29 and OAS levels at day 3 were no different between complete and null responders (15,525 vs. 30,768 pg/ml and 2,044 vs. 2,323 pM/hr, respectively, P = n.s.). Addition of ribavirin to pegylated IFN did not significantly affect day 29 IFN levels or Day 3 OAS levels. In conclusion, null responders to either peginterferon alone or in combination with ribavirin have little or no decrease in serum HCV RNA early in therapy and rarely go on to achieve sustained virologic response and have no apparent host differences than complete responders, suggesting that interferon resistance in these patients may be virally rather than host-determined.

Diversity and assemblage structure of phytophagous Hemiptera along a latitudinal gradient: predicting the potential impacts of climate change

ABSTRACTAims The aims were (1) to assess the species richness and structure of phytophagous Hemiptera communities along a latitudinal gradient, (2) to identify the importance of rare species in structuring these patterns, and (3) to hypothesize about how phytophagous Hemiptera communities may respond to future climate change.Location East coast of Australia.Methods Four latitudes within the 1150 km coastal distribution of Acacia falcata were selected. The insect assemblage on the host plant Acacia falcata was sampled seasonally over two years. Congeneric plant species were also sampled at the sites.Results Ninety‐eight species of phytophagous Hemiptera were collected from A. falcata. Total species richness was significantly lower at the most temperate latitude compared to the three more tropical latitudes. We classified species into four climate change response groups depending on their latitudinal range and apparent host specificity. Pairwise comparisons between groups showed that the cosmopolitan, generalist feeders and specialists had a similar community structure to each other, but the climate generalists had a significantly different structure. Fifty‐seven species were identified as rare. Most of these rare species were phloem hoppers and their removal from the dataset led to changes in the proportional representation of all guilds in two groups: the specialist and generalist feeders.Main conclusions We found no directional increase in phytophagous Hemiptera species richness. This indicates that, at least in the short term, species richness patterns of these communities may be similar to that found today. As the climate continues to change, however, we might expect some increases in species richness at the more temperate latitudes as species migrate in response to shifting climate zones. In the longer term, more substantial changes in community composition will be expected because the rare species, which comprise a large fraction of these communities, will be vulnerable to both direct climatic changes, and indirect effects via changes to their host's distribution.

Salmonella Epidemiology and Pathogenesis in Food-Producing Animals.

This review reviews the pathogenesis of different phases of Salmonella infections. The nature of Salmonella infections in several domesticated animal species is described to highlight differences in the epidemiology and pathogenesis of salmonellosis in different hosts. The biology of Salmonella serovar host specificity is discussed in the context of our current understanding of the molecular basis of pathogenesis and the potential impact of different virulence determinants on Salmonella natural history. The ability to colonize the intestine, as evidenced by the shedding of relatively large numbers of bacteria in the feces over a long period, is shared unequally by Salmonella serovars. Studies probing the molecular basis of Salmonella intestinal colonization have been carried out by screening random transposon mutant banks of serovar Typhimurium in a range of avian and mammalian species. It is becoming increasingly clear that Salmonella pathogenicity island 2 (SPI2) is a major virulence factor during infection of food-producing animals, including cattle and poultry. The prevalence of Salmonella serovars in domestic fowl varies in different countries and with time. Although chickens are the natural hosts of serovars Gallinarum and Pullorum, natural outbreaks caused by these serovars in turkeys, guinea fowl, and other avian species have been described. There are two possible explanations to account for the apparent host specificity of certain Salmonella serovars. Environmental factors may increase exposure of particular animal species to certain serovars. Alternatively, there are genetic differences between these serovars, which allow them to survive and/or grow in specific niches only found within ruminants or pigs.

Occurrence of Perkinsus olseni (Protozoa: Apicomplexa) and other parasites in the venerid commercial clam Pitar rostrata from Uruguay, southwestern Atlantic coast

A study was conducted into the health status of natural populations of the venerid clam Pitar rostrata from Uruguay. Perkinsus sp. was detected in 22% of the clams. Severe hemocytic infiltration was detected in the tissues parasitized by this protozoan parasite. The sequencing of the ITS-5.8S gene cluster of the parasite confirmed that it belonged to the Perkinsus olseni species. Rickettsia or Chlamidia-like organisms were also found, with a prevalence of 11%, although without apparent host reaction; an unidentified species of Coccidia was found in the nephridia of 78% of the clams, with the intensity of infection ranging from moderate to high. A gregarine, Nematopsis-like organism was observed mainly in the epithelial cells of the intestine, without host response and with a prevalence of 56%. Of the metazoan parasites, trematodes were found in 11% of the individuals analyzed.

New human and mouse microRNA genes found by homology search

Conservation of microRNAs (miRNAs) among species suggests that they bear conserved biological functions. However, sequencing of new miRNAs has not always been accompanied by a search for orthologues in other species. I report herein the results of a systematic search for interspecies orthologues of miRNA precursors, leading to the identification of 35 human and 45 mouse new putative miRNA genes. MicroRNA tracks were written to visualize miRNAs in human and mouse genomes on the UCSC Genome Browser. Based on their localization, miRNA precursors can be excised either from introns or exons of mRNAs. When intronic miRNAs are antisense to the apparent host gene, they appear to originate from ill-characterized antisense transcription units. Exonic miRNAs are, in general, nonprotein-coding, poorly conserved genes in sense orientation. In three cases, the excision of an miRNA from a protein-coding mRNA might lead to the degradation of the rest of the transcript. Moreover, three new examples of miRNAs fully complementary to an mRNA are reported. Among these, miR135a might control the stability and/or translation of an alternative form of the glycerate kinase mRNA by RNA interference. I also discuss the presence of human miRNAs in introns of paralogous genes and in miRNA clusters.

Species diversity and structure of phytophagous beetle assemblages along a latitudinal gradient: predicting the potential impacts of climate change

Abstract. 1. Assemblages of phytophagous beetles on Acacia were examined along a 1150 km latitudinal gradient in eastern Australia to investigate the potential effects of climate change on insect communities. The latitudinal gradient was used as a surrogate for differences in temperature. Several possible confounding variables were held constant by selecting comparable sites and emphasising a single host‐plant species.2. Total species richness increased towards the tropics, but there were no significant differences among latitudes for average species density, species richness, Fisher's α, or average Chao‐1 index.3. Beetles sampled along the gradient were classified into four climate change response groups, depending on their latitudinal range and apparent host specificity: cosmopolitan species, generalist feeders, climate generalists, and specialists. These four groups might respond differently to shifting climate zones. Cosmopolitan species (22% of community, found at more than one latitude and on more than one host plant) may be resilient to climate change. Generalist feeders (16%, found only at one latitude but found on more than one Acacia species) may well feed on several species but will have to move with their climatic envelope. Climate generalists (6%, found only on Acacia falcata but found at more than one latitude) may be constrained by the host species' ability to either cope with the changing climate or move with it. Finally, specialists (55%, found only on A. falcata and at only one latitude) may be forced to move poleward concurrently with their host species, or go extinct.4. The analyses indicate that community structure may be fairly resilient to temperature change. The displacement or local extinction of species, especially the species that are found at only one latitude and on only one host plant, however, may lead to significant changes in community composition.

Description of Brachylecithum mackoi n. sp. (Digenea: Dicrocoeliidae) from the European hedgehog, Erinaceus europaeus (Insectivora: Erinaceidae).

A new hepatic dicrocoeliid species, Brachylecithum mackoi n. sp. (Digenea, Dicrocoeliidae), is described from the European hedgehog, Erinaceus europaeus (L.) (Insectivora, Erinaceidae). An infected host was found in the Mediterranean island of Elba (Italy), and more than 60 individuals were isolated from the biliary ducts. The holotype and 55 paratypes were examined. Brachylecithum mackoi n. sp. differs from congeneric species found in mammal hosts by having well-developed lappets in the ventral sucker, a sloping uterus between anterior testis and acetabulum, no overlap between vitellaria, and metrical features in the body size, sucker diameters, cirrus sac, and size of eggs. The only other Brachylecithum species of erinaceids in Europe and Africa, Brachylecithum aetechini Dollfus, 1951, differs from the new species in the above-mentioned morphological characters, greater dimensions of the body, and oral sucker, pharynx, cirrus sac, and egg dimensions. The presence of B. mackoi n. sp. in Elba Island is discussed in the light of apparent host specificity of erinaceid dicrocoeliids and geographical distribution of Palearctic and Ethiopian Erinaceidae.

Mechanical characteristics of the bone–graft–cement interface after impaction allografting

Impaction allografting is an attractive procedure for the treatment of failed total hip replacements. The graft–cement–host bone interface after impaction allografting has not been characterized, although it is a potential site of subsidence for this type of revision total hip reconstruction. In six human cadaveric femurs, the cancellous bone was removed proximally and local diaphyseal lytic defects were simulated. After the impaction grafting procedure, the specimens were sectioned in 6 mm transverse sections and push-out tests were performed. From the adjacent sections the percentage cement contact of the PMMA cement with the endosteal bone surface was determined. The host bone interface mechanical properties varied significantly along the femur largely due to different interface morphologies. The apparent host bone interface shear strength was highest around the lesser trochanter and lowest around the tip of the stem. A significant positive correlation was found between the percentage cement contact and the apparent host bone interface shear strength ( r 2=0.52). The sections failed in 69% of the cases through a pure host bone interface failure without cement or allograft failure, 19% failed with local cement failure, and 12% with a local allograft failure. The apparent host bone interface strength was on average 89% lower than values reported for primary total hip replacements and were similar to cemented revisions proximally and lower distally. This study showed that cement penetration to the endosteal surface enhanced the host bone–graft interface.

Toward an Understanding of the Progenitors of Gamma‐Ray Bursts

The various possibilities for the progenitors of gamma-ray bursts (GRBs) manifest in differing observable properties. Through deep spectroscopic and high-resolution imaging observations of some GRB hosts, I demonstrate that well-localized long-duration GRBs are connected with otherwise normal star-forming galaxies at moderate redshifts of order unity. I test various progenitor scenarios by examining the offset distribution of GRBs about their apparent hosts, making extensive use of ground-based optical data from Keck and Palomar and space-based imaging from the Hubble Space Telescope. The offset distribution appears to be inconsistent with the coalescing neutron star binary hypothesis but statistically consistent with a population of progenitors that closely traces the ultra-violet light of galaxies. This is naturally explained by bursts which originate from the collapse of massive stars. This claim is further supported by the unambiguous detections of emission ''bumps'' which can be explained as supernovae that occur at approximately the same time as the associated GRB; if true, GRB 980326 and GRB 011121 provide strong observational evidence connecting cosmological GRBs to high-redshift supernovae and implicate massive stars as the progenitors of some long-duration GRBs. Interestingly, most alternative models of these bumps require wind-stratified circumburst media; this too, implicates massive stars. In addition to this work, I also constructed the Jacobs Camera (JCAM), a dual-beam optical camera for the Palomar 200-inch Telescope designed to follow-up rapid GRB localizations (abridged).

The Apparent Host Galaxy of PKS 1413+135: [ITAL]Hubble Space Telescope[/ITAL], [ITAL]ASCA[/ITAL], and Very Long Baseline Array Observations

PKS 1413+135 (z = 0.24671) is one of very few radio-loud active galactic nuclei (AGNs) with an apparent spiral host galaxy. Previous authors have attributed its nearly exponential infrared cutoff to heavy absorption but have been unable to place tight limits on the absorber or its location in the optical galaxy. In addition, doubts remain about the relationship of the AGN to the optical galaxy given the observed lack of reemitted radiation. We present new Hubble Space Telescope (HST), ASCA, and Very Long Baseline Array observations, which throw significant new light on these issues. The HST observations reveal that the active nucleus of PKS 1413+135 has an extremely red color, (V-H) = 6.9 mag, requiring both a spectral turnover at a few microns because of synchrotron aging and an absorbing region the size of a giant molecular cloud. Combining constraints from the HST and ASCA data, we derive an intrinsic column NH = 4.6 × 1022 cm-2 and covering fraction f = 0.12. The spin temperature of the molecular absorption lines found by previous authors suggests that the cloud is located in the disk of the optical galaxy, making our sight line rather unlikely (P ~ 2 × 10-4). The properties of this region appear typical of large giant molecular clouds in our own Galaxy. The H I absorber appears centered 25 mas away from the nucleus, while the X-ray and nearly all of the molecular absorbers must cover the nucleus, implying a rather complicated geometry and cloud structure, in particular requiring a molecular core along our line of sight to the nucleus. Interestingly, the HST/NICMOS data require the AGN to be decentered relative to the optical galaxy by 13 ± 4 mas. This could be interpreted as suggestive of an AGN location far in the background compared with the optical galaxy, but it can also be explained by obscuration and/or nuclear structure, which is more consistent with the observed lack of multiple images.