The value of health libraries and librarians to the Irish health system.

Librarians working in the Irish health sector are under threat. This is a relatively young profession in comparison with international counterparts, with a low staffing base even at its peak. The public sector moratorium has led to professionally qualified librarians and library assistants not being replaced right across the health system. Librarians are employed in the HSE, voluntary sector, and university sectors. The value that this profession brings to healthcare has been documented in systematic reviews and literature in other countries. In Ireland this group is represented by the Health Science Libraries Group (HSLG), a section of the Library Association of Ireland. The HSLG commissioned research into the status of the profession as well as Irish health libraries. This resulted in the publication of the "SHeLLI Report" in 2011. Results of the report are outlined here and selected examples of value of librarians to healthcare are described.

Development of a reference material for analysing naturally occurring radioactive material from the steel industry.

Accurate measurement of naturally occurring radionuclides in blast furnace slag, a by-product of the steel industry, is required for compliance with building regulations where it is often used as an ingredient in cement. A matrix reference blast furnace slag material has been developed to support traceability in these measurements. Raw material provided by a commercial producer underwent stability and homogeneity testing, as well as characterisation of matrix constituents, to provide a final candidate reference material. The radionuclide content was then determined during a comparison exercise that included 23 laboratories from 14 countries. Participants determined the activity per unit mass for 226Ra, 232Th and 40K using a range of techniques. The consensus values obtained from the power-moderated mean of the reported participant results were used as indicative activity per unit mass values for the three radionuclides: A0(226Ra) = 106.3 (34) Bq·kg-1, A0(232Th) = 130.0 (48) Bq·kg-1 and A0(40K) = 161 (11) Bq·kg-1 (where the number in parentheses is the numerical value of the combined standard uncertainty referred to the corresponding last digits of the quoted result). This exercise helps to address the current shortage of NORM industry reference materials, putting in place infrastructure for production of further reference materials.

Mechanism of suppression of lipopolysaccharide-driven B cell differentiation by anti-mu antibodies. Evidence for a trans-acting repressor of transcription.

Bivalent anti-mu antibodies suppress LPS-driven B cell differentiation by inhibiting the coordinate activation of a family of differentiation-related genes, including those encoding the heavy, light, and J chains of IgM. We have shown that the presence of inhibitors of RNA or protein synthesis during a pulse with anti-mu can interfere with induction of suppression. We suggest that suppression is mediated by a trans-acting repressor protein with specificity for common motifs in regulatory regions of each of these genes.

Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to -chain.

Germfree BALB/c mice have been treated from birth with intraperitoneal injections of purified goat antibodies to mouse IgM. The treated mice, and controls which had received an equivalent amount of goat gamma-globulin, were sacrificed at 8 or 13 wk of age. Compared to controls, mice given anti-micro (a) had very few germinal centers in spleen and lymph node, (b) had decreased numbers of mature plasma cells synthesizing IgM and IgG1 in spleen, and virtual absence of IgA-synthesizing plasma cells in the gut, (c) had greatly diminished numbers of B lymphocytes bearing membrane-bound immunoglobulins of the IgM, IgG1, IgG2, and IgA classes in spleen, (d) had reduced synthesis of IgM, IgG2, and IgA by in vitro spleen cultures, and (e) had significant decreases in serum levels of IgM, IgG1, IgG2, and IgA. The treated animals failed to make antibodies to ferritin after hyperimmunization, and lacked natural antibodies to sheep erythrocytes. These results indicate that cells ultimately committed to synthesis of IgG1, IgG2, and IgA immunoglobulins are derived from cells which have expressed IgM determinants at an earlier stage of differentiation. They are consistent with a proposed two-stage model for plasma cell differentiation. The first stage is antigen independent, involves sequential activation of Cmicro, Cgamma, and Calpha genes by progeny of a single stem cell, and results in the formation of B lymphocytes bearing membrane-bound recognition antibodies of each class. The second, antigen-dependent, stage results in formation of mature plasmacytes and memory cells.

Pre-B and B cells in rabbits. Ontogeny and allelic exclusion of kappa light chain genes.

Pre-B cells in developing rabbits were identified by immunofluorescence as cells containing small amounts of cytoplasmic IgM (cIgM) but lacking surface immunoglobulin (sIg). During ontogeny the first pre-B cells appeared in fetal liver at 23 days gestation, 2 days before the appearance of sIgM+ B lymphocytes. Pre-B cells were relatively frequent in fetal and adult bone marrow, but were not found in other tissues except rarely in fetal spleen. Allelic exclusion is apparently established at this early stage of development, because individual pre-B cells and B lymphocytes from heterozygous rabbits expressed only one of the alternative alleles in amounts sufficient for detection. Development of isotype diversity among rabbit B lymphocytes followed the general pattern seen in mouse and man. sIgM+ cells were detected before birth. Expression of sIgG was detected in neonatal rabbits on cells which were also sIgM+ but in older animals most sIgG+ cells lacked sIgM. Cells bearing sIgA were not found until 5-6 days of age, and had no other isotype on their surface.

Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.

Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin-induced immunoglobulin suppression in vitro. Possible implications for B-cell tolerance to self.

Purified goat antibodies against mouse mu-chains and rabbit antibodies against mouse Ig determinants, and their Fab fragments, inhibited the development of IgM-bearing B cells in explant cultures of 14-day mouse fetal liver, and caused the disappearance of cell surface IgM in explant and dissociated cell cultures of more developed lymphoid tissues. While treatment of cultures of fetal or newborn liver, or adult bone marrow, with low concentrations (less than or equal to 10 mug/ml) of anti-Ig for less than or equal to 24 h caused the complete, but reversible, disappearance (modulation) of cell surface IgM, treatment for greater than or less than 48 h produced irreversible IgM suppression. In contrast, anti-Ig-induced suppression of cell surface IgM in cultures of adult spleen or lymph nodes required much higher concentrations of antibody (greater than or equal to 100 mug/ml) and was always reversible. These differences between immature and mature IgM-bearing cells could not be related to differences in the amount of surface IgM on the cells. The remarkable sensitivity of newly formed B cells to IgM modulation and irreversible IgM suppression when ligands bind to their Ig receptors, may have important implications for B-cell tolerance to self antigens.

Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice.

We used immunofluorescence to examine the developmental relationship of Ia and IgD on B cells. Pre-B cells in fetal liver did not express Ia. Only very few surface IgM-positive (sIgM+) B cells in fetal spleen were found to be Ia+ and were weakly stained for Ia. After birth there was a linear increase in the proportion of sIgM+ spleen cells which expressed Ia, reaching 95% by 9 days. Adult bone marrow also contains a sizeable proportion of sIgM+ Ia- cells. Unstimulated cells from fetal or newborn liver and spleen expressed Ia at the same rate in culture. Anti-Ia antisera suppressed the LPS-induced differentiation of IgM and IgG plasma cells in cultures of neonatal lymphocytes. Ia was also detected on IgM and IgG plasma cells in vitro suggesting that lipopolysaccharide (LPS)-stimulated B cells by may express Ia antigens, induced by LPS, or appearing as part of normal differentiation. IgD did not appear on sIgM+ cells until 3 days of age and then rose slowly to reach adult levels later than Ia antigens.

Buckling without Bending: A New Paradigm in Morphogenesis.

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out of phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2D morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluidlike film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential." Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bioinspired applications, and address how our model is and is not unique to the developing nervous system.

Differentiation capacity of cultured B lymphocytes from immunodeficient patients.

Peripheral blood lymphocytes from 27 healthy individuals and from 18 patients with a diverse spectrum of defects in humoral immunity were examined for their capacity to undergo terminal differentiation in vitro. Pokeweed mitogen induced cells from normal persons to synthesize and secrete IgM. IgG, and IgA as detected by Immunofluorescence and incorporation of [(14)C]amino acids, Lymphocytes from three boys with X-linked agammaglobulinemia were stimulated to proliferate, but did not synthesize immunoglobulin. Lymphocyte cultures from three of four patients having agammaglobulinemia with B lymphocytes produced different immunoglobulin classes in ratios similar to the in vivo distribution of classes of B lymphocytes, Lymphocytes from a dysgammaglobulinemic boy deficient in serum IgG and IgA, but who had normal numbers of IgM-, IgG-, and IgA-bearing B lymphocytes, could not be stimulated by pokeweed mitogen to make IgG and IgA. Synthesis and secretion of IgA, as well as IgM and IgG, was detected in cell cultures from each of 10 patients with isolated IgA deficiency. The results suggest that deficiencies in immunoglobulin synthesis may reflect either (a) failure to develop B lymphocytes, (b) arrested development of B lymphocytes due to intrinsic metabolic abnormalities, or (c) disturbance of factors extrinsic to the B lymphocyte which are essential for normal induction of plasma cell maturation.

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

We examined the genetic basis for adenosine deaminase (ADA) deficiency in seven patients with late/delayed onset of immunodeficiency, an underdiagnosed and relatively unstudied condition. Deoxyadenosine-mediated metabolic abnormalities were less severe than in the usual, early-onset disorder. Six patients were compound heterozygotes; 7 of 10 mutations found were novel, including one deletion (delta 1019-1020), three missense (Arg156 > His, Arg101 > Leu, Val177 > Met), and three splicing defects (IVS 5, 5'ss T+6 > A; IVS 10, 5'ss G+1 > A; IVS 10, 3'ss G-34 > A). Four of the mutations generated stop signals at codons 131, 321, 334, and 348; transcripts of all but the last, due to delta 1019-1020, were severely reduced. delta 1019-1020 (like delta 955-959, found in one patient and apparently recurrent) is at a short deletional hot spot. Arg156 > His, the product of which had detectable activity, was found in three patients whose second alleles were unlikely to yield active ADA. The oldest patient diagnosed was homozygous for a single base change in intron 10, which activates a cryptic splice acceptor, resulting in a protein with 100 extra amino acids. We speculate that this "macro ADA," as well as the Arg156 > His, Arg101 > Leu, Ser291 > Leu, and delta 1019-1020 products, may contribute to mild phenotype. Tissue-specific variation in splicing efficiency may also ameliorate disease severity in patients with splicing mutations.

Hyper IgM syndrome associated with defective CD40-mediated B cell activation.

Recent studies show that most patients with X-linked hyper IgM syndrome have defects in the gene for CD40 ligand. We evaluated 17 unrelated males suspected of having X-linked hyper IgM syndrome. Activated T cells from 13 of the 17 patients failed to bind a soluble CD40 construct. In these patients, the sequence of CD40 ligand demonstrated mutations. By contrast, T cells from the remaining four patients exhibited normal binding to the CD40 construct. Sequencing of the cDNA for CD40 ligand from these patients did not show mutations. The possibility that hyper IgM syndrome in these four patients was due to abnormalities in the B cell response to CD40-mediated signals was examined. Peripheral blood lymphocytes were stimulated with anti-CD40 alone, IL4 alone or anti-CD40 plus IL4. In comparison with B cells from controls or patients with hyper IgM syndrome and mutant CD40 ligand, B cells from the patients with hyper IgM syndrome and normal CD40 ligand were defective in their ability to secrete IgE (P < 0.02) or express activation markers, CD25 and CD23 (P < 0.02) in response to stimulation with anti-CD40. The failure of these B cells to respond to CD40-mediated activation could not be attributed to a generalized deficiency in B cell activation because IL4 induced normal up-regulation of CD23 and CD25 expression. These findings indicate that hyper IgM syndrome may result from defects in expression of CD40 ligand by activated T cells or defects in CD40-mediated signal transduction in B cells.

Zinc pyrithione in alcohol-based products for skin antisepsis: persistence of antimicrobial effects.

Alcohol-based products for skin antisepsis have a long history of safety and efficacy in the United States and abroad. However, alcohol alone lacks the required antimicrobial persistence to provide for the sustained periods of skin antisepsis desired in the clinical environment. Therefore, alcohol-based products must have a preservative agent such as iodine/iodophor compounds, chlorhexidine gluconate, or zinc pyrithione, to extend its antimicrobial effects. Iodine, iodophors, and chlorhexidine gluconate are well-characterized antimicrobials and preservatives. The thrust of our effort was to examine the characteristics of the lesser-known zinc pyrithione and to evaluate its utility as a preservative in the formulation of alcohol-based products for skin antisepsis. This work includes a literature review of current zinc pyrithione applications in drugs and cosmetics, a safety and toxicity evaluation, consideration of the proposed mechanisms of antimicrobial action, in vitro and in vivo efficacy data, and a discussion of the mechanisms that confer the desired antimicrobial persistence. In addition, alcohol-based, zinc pyrithione-preserved, commercially available products of skin antisepsis are compared with other commercially available antimicrobials used for skin antisepsis and with additional alcohol-based products with different preservatives. The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.

A unique water optional health care personnel handwash provides antimicrobial persistence and residual effects while decreasing the need for additional products.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) has published guidelines for hand hygiene practices, recommending a handwash regimen that alternates between waterless alcohol products and antimicrobial or nonantimicrobial soap and water. The advent of an alcohol-based product that can be used with or without water (ie, water optional) to decontaminate the hands while providing immediacy of kill and antimicrobial persistence could reduce the confusion associated with handwash guidelines. Such a product has been developed, is alcohol-based (61%), and zinc pyrithione (ZPT) preserved (61% alcohol-ZPT) and has proven to be fully compliant with the Food and Drug Administration (FDA) and CDC guidelines. METHODS: FDA-required testing of the 61% alcohol-ZPT product for the health care personnel handwash indication was performed as outlined in the Tentative Final Monograph (TFM) for Health-Care Antiseptic Drug Products, employing waterless and water-aided product applications. It was next assessed for antimicrobial persistence and residual effects by comparing it, in separate waterless and water-aided applications, with commonly available handwashes containing various antimicrobials in a 5-day study employing 49 subjects, in which samples were collected immediately and at 4 hours and 8 hours postapplication. The skin conditioning properties of this formulation were investigated via appropriate methods. RESULTS: The 61% alcohol-ZPT product easily produced >3.0 log 10 reduction in the indicator strain ( Serratia marcescens ) following the first wash, exceeding the 2.0 log 10 FDA requirement. This level of performance was maintained through the tenth wash, surpassing the 3.0 log 10 FDA requirement for the handwash indication. For the assessment of persistence and residual effect in the waterless mode, the water-optional, 61% alcohol-ZPT product consistently produced log 10 reductions of nearly 3.5 or greater at every point over the entire study period. In the water-aided configuration, similar results were obtained as log 10 reductions of 2.5 were observed. The formulation is nonirritating, actually contributing to hand skin condition. CONCLUSIONS: The 61% alcohol-ZPT product exceeds all FDA criteria for the health care personnel handwash indication and is a significant advancement in the concept of skin antisepsis. It represents a single product suitable for use in all hand hygiene settings, demonstrating improved antimicrobial persistence and residual effects. The 61% alcohol-ZPT formulation contributes positively to overall hand conditioning, and a previously reported study has documented it to be virucidal for several DNA and RNA viruses.

Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway.

Tumor angiogenesis is essential for tumor growth and metastasis and is dependent on key angiogenic factors. Angiogenin (ANG), a 14.2-kDa polypeptide member of the RNase A superfamily, is an angiogenic protein that has been reported to be upregulated and associated with poor prognosis in some human cancers. The mechanisms through which aberrant ANG levels promote specific steps in tumor progression are unknown. Here, we show that ANG expression in human tissues is strongly correlated with an invasive cancer phenotype. We also show that ANG induces cellular survival, proliferation, endothelial tube formation and xenograft angiogenesis and growth. Novel mechanistic investigations revealed that ANG expression stimulated matrix metallopeptidase-2 (MMP2) expression through the phosphorylation of ERK1/2. Targeting ANG in vivo with N65828, a small-molecule inhibitor of the ribonucleolytic activity of human ANG, resulted in the diminution of xenograft tumoral growth through the inhibition of angiogenesis. Our findings support an unrecognized interplay between ANG, ERK1/2 and MMP2 that can impact tumor growth and progression. The targeting of ANG and associated factors could provide a novel strategy to inhibit tumor establishment and growth.

Tritiated imipramine binding. A peripheral marker for serotonin in Parkinson's disease.

Tritiated imipramine binding in platelets has been used to evaluate serotonin activity in depression in previous studies. This article examined this marker as a possible measure of central nervous system serotonergic activity for depression in patients with Parkinson's disease (PD). The number of binding sites was significantly lower in depressed patients with PD than in a healthy control group. Patients with PD who were not depressed had lower values than the comparison group, but this difference was not significant. We also found a significant correlation between the receptor site values in platelets and cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (r = .59), but this was independent of a diagnosis of depression. Receptor site values were examined to identify appropriate cutoff scores to predict depression in the group of patients with PD. A maximum sensitivity of 50% was achieved with a specificity of 64%. Our results strongly support a generalized alteration in serotonin metabolism in depressed patients with PD, but tritiated imipramine binding in platelets is not a useful diagnostic tool for depression.

Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease.

Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug.

A clinicopathological comparison of community-based and clinic-based cohorts of patients with dementia.

OBJECTIVES: To compare the sensitivity and specificity of the clinical diagnosis of Alzheimer disease, the distribution of pathological causes, and the demographic and clinical characteristics of 2 different groups of patients with dementia. DESIGN: Retrospective clinicopathological study. SETTING: A memory disorder clinic in a university hospital and a multiethnic community. PATIENTS: Sixty-three patients from a memory disorder clinic and 26 patients from a large community-based study who underwent autopsy after clinical evaluation. MAIN OUTCOME MEASURES: Differential distribution of clinical and pathological findings, with clinicopathological correlations. RESULTS: Clinic patients were younger at diagnosis, more educated, and more likely to be white. Of the 63 clinic patients we evaluated, 29 (46%) had a pathological diagnosis of definite AD, 15 (24%) had a diagnosis of mixed AD, and 19 (30%) had a diagnosis of another type of dementia. The pathological diagnoses in the community patients were distributed as follows: 6 (23%) had definite AD, 6 (23%) had mixed AD, 6 (23%) had cerebrovascular disease, and 8 (31%) had another type of dementia. The difference in distribution of pathological diagnoses between these 2 groups was only significant for cerebrovascular diseases. For patients seen at the clinic, the sensitivity of the clinical diagnosis of AD was 98% and the specificity was 84%; for the community group, the sensitivity was 92% and the specificity was 79%. CONCLUSIONS: The difference in sensitivity and specificity of clinical diagnosis was not statistically significant between the groups of clinic patients and community patients. Dementia associated with cerebrovascular disease was more prevalent in the community sample. This difference may be attributable to clinical and demographic differences between the 2 groups.

Apparent cytomegalovirus epithelial keratitis in a cardiac transplant recipient.

A 44-year-old immunosuppressed man developed initial symptoms of intermittent irritation of the left eye three months after cardiac transplantation. Symptoms increased, with decreased vision, photophobia, and lacrimation. Slit lamp examination showed slightly raised, swollen, grayish epithelium in a broad multibranching dendritic pattern associated with fine and medium punctate epithelial erosions that stained slightly with fluorescein. Histopathologic study of the corneal epithelial scraping demonstrated swollen epithelial cells with intranuclear and intracytoplasmic viral inclusions. Viral cultures manifested a cytopathic pattern characteristic of cytomegalovirus 14 days after inoculation on human embryonic lung cells (MRC-5). Pretransplantation cytomegalovirus IgM and IgG serologic titers were negative (less than 1:16 for IgG, no IgM noted) until the onset of symptoms. Subsequently, IgM titers rose against cytomegalovirus consistent with concurrent infection.

Neural control of ectopic filiform spines in adult tongue.

The tongue surface directly above a fungiform taste bud is flat, thinly keratinized, and free of filiform spines. We examined fungiform papillae in serial sections of rat and gerbil tongues after unilateral transection of the chorda-lingual nerve had caused many fungiform taste buds to degenerate. Such empty fungiform papillae often formed a solitary keratinized outgrowth that closely resembled the spine of an ordinary filiform papilla. By six months an ectopic spine was found on 61% of empty fungiform papillae, but never on fungiform papillae that contained a taste bud. Experimental innervation of the tongue reduced the incidence of ectopic filiform spines in proportion to the cross-sectional area of the trigeminal nerve branches tested (the mylohyoid nerve, the lingual nerve, lingual + mylohyoid or lingual + auriculotemporal nerves). The chorda tympani nerve was 60 times more effective than trigeminal nerves in preventing ectopic filiform spines. We suggest that positive and negative trophic actions are normal characteristics of taste axons, for they promote the formation of taste buds and prevent the expression of ectopic filiform spines. By preventing the outgrowth of ectopic spines on fungiform papillae, taste axons maintain a thinly keratinized apical surface that can be breached by the taste receptor cells.