Characterization of fungi in office dust: Comparing results of microbial secondary metabolites, fungal internal transcribed spacer region sequencing, viable culture and other microbial indices.

Recent developments in molecular and chemical methods have enabled the analysis of fungal DNA and secondary metabolites, often produced during fungal growth, in environmental samples. We compared 3 fungal analytical methods by analysing floor dust samples collected from an office building for fungi using viable culture, internal transcribed spacer (ITS) sequencing and secondary metabolites using liquid chromatography-tandem mass spectrometry. Of the 32 metabolites identified, 29 had a potential link to fungi with levels ranging from 0.04 (minimum for alternariol monomethylether) to 5700 ng/g (maximum for neoechinulin A). The number of fungal metabolites quantified per sample ranged from 8 to 16 (average = 13/sample). We identified 216 fungal operational taxonomic units (OTUs) with the number per sample ranging from 6 to 29 (average = 18/sample). We identified 37 fungal species using culture, and the number per sample ranged from 2 to 13 (average = 8/sample). Agreement in identification between ITS sequencing and culturing was weak (kappa = -0.12 to 0.27). The number of cultured fungal species poorly correlated with OTUs, which did not correlate with the number of metabolites. These suggest that using multiple measurement methods may provide an improved understanding of fungal exposures in indoor environments and that secondary metabolites may be considered as an additional source of exposure.

Influence of Aspergillus fumigatus conidia viability on murine pulmonary microRNA and mRNA expression following subchronic inhalation exposure.

BACKGROUND: Personal exposure to fungal bioaerosols derived from contaminated building materials or agricultural commodities may induce or exacerbate a variety of adverse health effects. The genomic mechanisms that underlie pulmonary immune responses to fungal bioaerosols have remained unclear. OBJECTIVE: The impact of fungal viability on the pulmonary microRNA and messenger RNA profiles that regulate murine immune responses was evaluated following subchronic inhalation exposure to Aspergillus fumigatus conidia. METHODS: Three groups of naïve B6C3F1/N mice were exposed via nose-only inhalation to A. fumigatus viable conidia, heat-inactivated conidia (HIC), or HEPA-filtered air twice a week for 13 weeks. Total RNA was isolated from whole lung 24 and 48 h postfinal exposure and was further processed for gene expression and microRNA array analysis. The molecular network pathways between viable and HIC groups were evaluated. RESULTS: Comparison of data sets revealed increased Il4, Il13 and Il33 expression in mice exposed to viable vs. HIC. Of 415 microRNAs detected, approximately 50% were altered in mice exposed to viable vs. HIC 48 h postexposure. Significantly down-regulated (P ≤ 0.05) miR-29a-3p was predicted to regulate TGF-ß3 and Clec7a, genes involved in innate responses to viable A. fumigatus. Also significantly down-regulated (P ≤ 0.05), miR-23b-3p regulates genes involved in pulmonary IL-13 and IL-33 responses and SMAD2, downstream of TGF-ß signalling. Using Ingenuity Pathway Analysis, a novel interaction was identified between viable conidia and SMAD2/3. CONCLUSIONS AND CLINICAL RELEVANCE: Examination of the pulmonary genetic profiles revealed differentially expressed genes and microRNAs following subchronic inhalation exposure to A. fumigatus. MicroRNAs regulating genes involved in the pulmonary immune responses were those with the greatest fold change. Specifically, germinating A. fumigatus conidia were associated with Clec7a and were predicted to interact with Il13 and Il33. Furthermore, altered microRNAs may serve as potential biomarkers to evaluate fungal exposure.

Subchronic exposures to fungal bioaerosols promotes allergic pulmonary inflammation in naïve mice.

BACKGROUND: Epidemiological surveys indicate that occupants of mold contaminated environments are at increased risk of respiratory symptoms. The immunological mechanisms associated with these responses require further characterization. OBJECTIVE: The aim of this study was to characterize the immunotoxicological outcomes following repeated inhalation of dry Aspergillus fumigatus spores aerosolized at concentrations potentially encountered in contaminated indoor environments. METHODS: Aspergillus fumigatus spores were delivered to the lungs of naïve BALB/cJ mice housed in a multi-animal nose-only chamber twice a week for a period of 13 weeks. Mice were evaluated at 24 and 48 h post-exposure for histopathological changes in lung architecture, recruitment of specific immune cells to the airways, and serum antibody responses. RESULT: Germinating A. fumigatus spores were observed in lungs along with persistent fungal debris in the perivascular regions of the lungs. Repeated exposures promoted pleocellular infiltration with concomitant epithelial mucus hypersecretion, goblet cell metaplasia, subepithelial fibrosis and enhanced airway hyperreactivity. Cellular infiltration in airways was predominated by CD4(+) T cells expressing the pro-allergic cytokine IL-13. Furthermore, our studies show that antifungal T cell responses (IFN-γ(+) or IL-17A(+) ) co-expressed IL-13, revealing a novel mechanism for the dysregulated immune response to inhaled fungi. Total IgE production was augmented in animals repeatedly exposed to A. fumigatus. CONCLUSIONS & CLINICAL RELEVANCE: Repeated inhalation of fungal aerosols resulted in significant pulmonary pathology mediated by dynamic shifts in specific immune populations and their cytokines. These studies provide novel insights into the immunological mechanisms and targets that govern the health outcomes that result from repeated inhalation of fungal bioaerosols in contaminated environments.

Setting Occupational Exposure Limits for Chemical Allergens--Understanding the Challenges.

Chemical allergens represent a significant health burden in the workplace. Exposures to such chemicals can cause the onset of a diverse group of adverse health effects triggered by immune-mediated responses. Common responses associated with workplace exposures to low molecular weight (LMW) chemical allergens range from allergic contact dermatitis to life-threatening cases of asthma. Establishing occupational exposure limits (OELs) for chemical allergens presents numerous difficulties for occupational hygiene professionals. Few OELs have been developed for LMW allergens because of the unique biological mechanisms that govern the immune-mediated responses. The purpose of this article is to explore the primary challenges confronting the establishment of OELs for LMW allergens. Specific topics include: (1) understanding the biology of LMW chemical allergies as it applies to setting OELs; (2) selecting the appropriate immune-mediated response (i.e., sensitization versus elicitation); (3) characterizing the dose (concentration)-response relationship of immune-mediated responses; (4) determining the impact of temporal exposure patterns (i.e., cumulative versus acute exposures); and (5) understanding the role of individual susceptibility and exposure route. Additional information is presented on the importance of using alternative exposure recommendations and risk management practices, including medical surveillance, to aid in protecting workers from exposures to LMW allergens when OELs cannot be established.

Domestic exposure to fungal allergenic particles determined by halogen immunoassay using subject's serum versus particles carrying three non-fungal allergens determined by allergen-specific HIA.

UNLABELLED: Studies that estimate indoor aeroallergen exposure typically measure a pre-selected limited range of allergens. In this study, inhalable aeroallergen particles were quantified using the halogen immunoassay (HIA) to determine the contribution of fungal and non-fungal aeroallergens to total allergen exposure. Bioaerosols from 39 homes of fungal-allergic subjects were sampled using inhalable fraction samplers and immunostained by HIA using resident subject's immunoglobulin E (IgE) to detect allergen-laden particles. Fungal aerosols as well as particles carrying mite, cat, and cockroach allergens were identified and enumerated by HIA. Reservoir dust-mite (Der p 1), cat (Fel d 1), and cockroach (Bla g 1) allergen concentrations were quantified by ELISA. Fungal particles that bound subject's IgE in the HIA were 1.7 (bedroom)- and 1.4 (living room)-fold more concentrated than Der p 1, Fel d 1, and Bla g 1 allergen particles combined. Predominant fungal conidia that bound IgE were derived from common environmental genera including Cladosporium and other fungi that produce amerospores. Airborne mite, cat, and cockroach allergen particle counts were not associated with reservoir concentrations determined by ELISA. This study demonstrates that inhalable fungal aerosols are the predominant aeroallergen sources in Sydney homes and should be considered in future exposure assessments. PRACTICAL IMPLICATIONS: Indoor allergen exposure assessment studies have primarily focused on a limited range of allergen sources in samples derived from reservoir dust samples. Using an innovative immunodiagnostic approach, this study demonstrates that fungal bioaerosols are the dominant source of aeroallergen exposure in the domestic environment, providing unique insight into domestic aeroallergen exposure.

Occupational sensitization to soy allergens in workers at a processing facility.

BACKGROUND: Exposure to soy antigens has been associated with asthma in community outbreaks and in some workplaces. Recently, 135 soy flake processing workers (SPWs) in a Tennessee facility were evaluated for immune reactivity to soy. Allergic sensitization to soy was common and was five times more prevalent than in health care worker controls (HCWs) with no known soy exposure. OBJECTIVE: To characterize sensitization to soy allergens in SPWs. METHODS: Sera that were positive to soy ImmunoCAP (n=27) were tested in IgE immunoblots. Wild-type (WT) and transgenic (TG) antigens were sequenced using nanoscale Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry (nanoUPLC MS/MS). IgE reactivity towards 5-enolpyruvylshikimate-3-phosphate synthase (CP4-EPSP), a protein found in TG soy, was additionally investigated. De-identified sera from 50 HCWs were used as a control. RESULTS: Immunoblotting of WT and TG soy flake extracts revealed IgE against multiple soy antigens with reactivity towards 48, 54, and 62 kDa bands being the most common. The prominent proteins that bound SPW IgE were identified by nanoUPLC MS/MS analysis to be the high molecular weight soybean storage proteins, ß-conglycinin (Gly m 5), and Glycinin (Gly m 6). No specific IgE reactivity could be detected to lower molecular weight soy allergens, Gly m 1 and Gly m 2, in soybean hull (SH) extracts. IgE reactivity was comparable between WT and TG extracts; however, IgE antibodies to CP4-EPSP could not be detected. CONCLUSIONS AND CLINICAL RELEVANCE: SPWs with specific IgE to soy reacted most commonly with higher molecular weight soybean storage proteins compared with the lower molecular weight SH allergens identified in community asthma studies. IgE reactivity was comparable between WT and TG soy extracts, while no IgE reactivity to CP4-EPSP was observed. High molecular weight soybean storage allergens, Gly m 5 and Gly m 6, may be respiratory sensitizers in occupational exposed SPWs.

Adverse respiratory outcomes associated with occupational exposures at a soy processing plant.

This study aimed to characterise the relationship between adverse health outcomes and occupational risk factors among workers at a soy processing plant. A questionnaire, spirometry, methacholine challenge, immune testing and air sampling for dust and soy were offered. Prevalence ratios (PRs) of respiratory problems from comparisons with the US adult population were calculated. Soy-specific immunoglobulin (Ig)G and IgE among participants and healthcare worker controls were compared. Associations between health outcomes and potential explanatory variables were examined using logistic regression. 147 (52%) out of 281 employees, including 66 (70%) out of 94 production workers, participated. PRs were significantly elevated for wheeze, sinusitis, ever-asthma and current asthma. Participants had significantly higher mean concentrations of soy-specific IgG (97.9 mg·L(-1) versus 1.5 mg·L(-1)) and prevalence of soy-specific IgE (21% versus 4%) than controls. Participants with soy-specific IgE had three-fold greater odds of current asthma or asthma-like symptoms, and six-fold greater odds of work-related asthma-like symptoms; the latter additionally was associated with production work and higher peak dust exposures. Airways obstruction was associated with higher peak dust. Work-related sinusitis, nasal allergies and rash were associated with reported workplace mould exposure. Asthma and symptoms of asthma, but not other respiratory problems, were associated with immune reactivity to soy.

Relationship of aluminum to neurocognitive dysfunction in chronic dialysis patients.

Aluminum has been proposed as the causative agent in dialysis encephalopathy syndrome. We prospectively assessed whether other, less severe, neuropsychologic abnormalities were also associated with aluminum. A total of 16 patients receiving chronic dialytic therapy were studied. The deferoxamine infusion test (DIT) was used to assess total body aluminum burden. Neurologic function was evaluated by quantitative measures of asterixis, myoclonus, motor strength, and sensation. Cognitive function was assessed by measures of dementia, memory, language, and depression. There were four patients with a positive DIT (greater than 125 micrograms/L increment in serum aluminum) that was associated with an increase in the number of neurologic abnormalities observed, as well as an increase in severity of myoclonus, asterixis, and lower extremity weakness. Patients with a positive DIT also showed significant impairment in memory; however, no differences were noted on tests of dementia, depression, or language. There was no significant correlation between sex, age, presence of diabetes, mode of dialysis, years of chronic renal failure, years of dialysis or years of aluminum ingestion and any neurologic or neurobehavioral measurement, serum aluminum level, or DIT. These changes may represent early aluminum-associated neurologic dysfunction.

A radioimmunoassay for 3',5'-diiodothyronine.

The present report describes a RIA for 3',5'-diiodothyronine (T2) that can be performed on unextracted serum and which has a lower limit of detectability of 2 ng/dl. Cross-reactivity with other iodothyronines was negligible, except for rT3 which began to demonstrate cross-reactivity when rT3 levels were elevated to 180 ng/dl. Employing this RIA for T2, we have determined that 83 healthy individuals had a mean (+/-SE) serum T2 concentration of 5.0 +/- 0.3 ng/dl, thyrotoxic subjects (n = 12) had a mean T2 level that was elevated to 10.8 +/- 0.8 ng/dl, and each of 6 hypothyroid subjects had undetectable (less than 2 ng/dl) concentrations. Athyreotic patients (n = 8), receiving 0.4 mg T4 daily, had serum T2 concentrations of 15.0 +/- 3.0 ng/dl. Fasting in obese subjects was associated with an increase in serum T2 to 6.9 +/- 0.6 ng/dl from a basal level of 4.4 +/- 0.4 ng/dl in the fed state (P less than 0.01). Despite the fact that rT3 levels may be elevated in amniotic fluid and that rT3 is expected to represent the major source from which extrathyroidal T2 arises, T2 levels were low in amniotic fluid, being undetectable (less than 2 ng/dl) in 9 of 19 samples; the mean (+/-SE) T2 concentration in the 10 detectable samples was 5.4 +/- 1 ng/dl. These data indicate T2 is a normal component of serum and that the majority of serum T2 is probably derived from peripheral conversion. Furthermore, these observations suggest that situations associated with elevated rT3 levels (e.g. thyrotoxicosis and fasting) may also have increased T2 values.

Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay.

A new TSH immunoenzymometric assay was found to be capable of discriminating between the serum TSH values of normal subjects [2.28 +/- 1.02 (+/-SD); range, 0.6-6.5 microU/ml] and those of clinically euthyroid, antithyroid drug-treated (n = 22) or clinically thyrotoxic (n = 34) patients. While a wide spectrum of basal TSH values was found in the antithyroid drug group [ranging from undetectable (less than 0.05 microU/ml: 57%) to 17.9 microU/ml], all clinically thyrotoxic patients had undetectable values. In 33 patients receiving chronic oral T4 therapy for treatment of goiter (n = 15) or thyroid cancer (n = 18), 48% (6 of 33) had undetectable basal TSH levels and no TSH response to TRH stimulation. Detectable TSH levels were found in 42% (14 of 33), and TRH responsiveness was found in 52% (17 of 33). The TSH response to TRH stimulation was less than 2.0 microU/ml in 7 patients. Serum free T4 index, free T3 index, and free T4 levels and oral T4 dosage were inferior predictors of TRH responsiveness compared to the basal TSH value. No patient receiving more than 0.2 mg T4 daily or having a free T4 index above 18, a free T3 index above 205 or a free T4 level above 3.0 ng/dl had a TSH response to TRH. Seventy-six percent (16 of 21) of the patients, when reevaluated 1-6 weeks after increased oral T4 dosage, had a significant reduction in their serum thyroglobulin level. This was true of both patients with initially detectable (11 of 14) as well as undetectable (5 of 7) basal serum TSH levels. These findings support the concept that subnormal and, for that matter, as yet undetectable levels of circulating TSH may exert stimulatory effects on thyroid tissue.

Serum IgM monoclonal autoantibody binding to the 301 to 314 amino acid epitope of beta-tubulin: clinical association with slowly progressive demyelinating polyneuropathy.

We identified five patients with IgM monoclonal autoantibodies that bound to human brain tubulin. In a companion study, we found that IgM in these sera selectively recognized one of three epitopes on tubulin. IgM from three patients bound selectively to a small epitope on human beta-tubulin comprising amino acids 301 to 314. The other two sera recognized tubulin amino acids 215 to 235 and 315 to 336. In this study, we compared the clinical syndromes in these patients with the tubulin epitope recognized by their serum IgM. The three patients with IgM binding to tubulin amino acids 301 to 314 all had chronic inflammatory demyelinating polyneuropathy (CIDP) syndromes with slowly progressive weakness, hyporeflexia, and electrophysiologic studies consistent with demyelination. Two of these patients had significant asymmetry to their weakness. The two other patients had diagnoses of polyradiculopathy and amyotrophic lateral sclerosis with no evidence of peripheral nerve demyelination. We conclude that IgM monoclonal anti-tubulin antibodies have some association with demyelinating polyneuropathy syndromes, but may occur in patients with other clinical syndromes as well. A stronger association with demyelinating polyneuropathies may occur if the anti-tubulin antibodies recognize the 301 to 314 amino acid epitope on tubulin. This tubulin epitope, or a similar one on another molecule, could play an important antigenic role in the development of demyelinating polyneuropathies with features of CIDP.

Spatiotemporal patterns and symmetry breaking on a ring electrode.

A series of experiments on a ring electrode with changes in a parameter, the applied potential, are described. Spatiotemporal patterns are investigated in a region of parameter space in which relaxation oscillations occur. The simplest state is a period 2Pi oscillation that has full O(2) symmetry so that at each instant the pattern is unchanged by rotations or reflections of the ring. With change in parameter a spatiotemporal period doubling occurs to period 4Pi. This is followed by a symmetry breaking to another state with period 4Pi and subsequently by a second period doubling to period 8Pi. Proper orthogonal decomposition is used as an aid in elucidating the nature of the transitions.

Suppressing spatiotemporal disorder via local perturbations in an electrochemical cell.

We report experimental results depicting suppression of complex spatiotemporal dynamics under the influence of local periodic stimulations. In an experimental electrochemical system, applying a continuous forcing signal to one of the sites in an array of eight coupled oscillators, the naturally complex behavior of the remaining seven electrodes can be converted to periodic responses. The oscillations remain periodic as long as the forcing is active and revert back to exhibiting chaotic dynamics after the control is switched off. These results can also be interpreted as experimental realization of "phase-synchronization" induced via local driving in an extended system. A possible relevance to the experimentally observed calcium wave patterns is pointed out.

Normative and reliability data for the Children's Depression Inventory.

The present study was undertaken to examine some of the psychometric properties of the Children's Depression Inventory (CDI), a self-report inventory devised by Kovacs and Beck (1977) to measure depression in children and adolescents. Normative and reliability data were obtained from three independent samples taken from eight public schools in central Pennsylvania. Age- and gender-related differences in reported characteristics of depression were also investigated. The subjects were 594 males and 658 females whose ages ranged from 8 to 16 years and whose combined mean age was 11.67 years (SD = 1.91). The CDI was group-administered to all 1,252 subjects; 155 fifth-grade subjects (77 males and 78 females) were retested after 3 weeks, and 107 seventh- and eight-grade subjects (45 males and 62 females) were retested after 1 year. The distribution statistics for the combined samples yielded an overall CDI mean of 9.09, a standard deviation of 7.04, and a cutoff score of 19 for the upper 10% of the distribution. Reliability assessed through coefficient alpha, item-total score product-moment correlations, and test-retest coefficients proved acceptable. Gender differences were obtained for several item-total score correlations and for test-retest reliability of CDI scores.

Mollusc/algal chloroplast symbiosis: how can isolated chloroplasts continue to function for months in the cytosol of a sea slug in the absence of an algal nucleus?

A marine sea slug, Elysia chlorotica, has acquired the ability to carry out photosynthesis as a result of forming an intracellular symbiotic association with chloroplasts of the chromophytic alga, Vaucheria litorea. The symbiont chloroplasts (kleptoplasts) are functional, i.e. they evolve oxygen and fix CO(2) and actively transcribe and translate proteins for several months in the sea slug cytosol. Considering the dependency of plastid function on nuclear genes, the level of kleptoplast activity observed in the animal cell is quite remarkable. Possible factors contributing to this long-lasting functional association that are considered here include: the presence of an algal nuclear genome in the sea slug, autonomous chloroplasts, unusual chloroplast/protein stability, re-directing of animal proteins to the kleptoplast, and lateral gene transfer. Based on our current understanding, the acquisition and incorporation of intact algal plastids by E. chlorotica is aided by the robustness of the plastids and the long-term functional activity of the kleptoplasts appears to be supported by both plastid and protein stability and contributions from the sea slug.

Measuring environmental fungal exposure.

Airborne fungi are ubiquitous in the environment and human exposure is inevitable. Such fungi differ greatly in their taxonomic, physical, ecological, behavioral, and pathogenic characteristics. Many strategies have evolved to sample, identify and interpret fungal exposure and their choice is determined by the hypotheses involved. While fungi can be sampled directly from surfaces, results do not generally reflect human exposure. For this reason, airborne spores are commonly sampled, by either filtration or impaction, using volumetric air samplers. Identification is commonly performed by either culture on nutrient medium or light microscopy using morphological criteria, although new techniques using DNA probes or characteristic antigens or toxins continue to be developed. Interpretation of such exposure data is both complex and contentious, but while there are numerous recommendations there is no consensus on exposure thresholds. A better understanding of the complex pathogenic roles of fungi and susceptibilities of their hosts will enable refinement of techniques for sampling and interpretation.

Defect in production of B cell differentiation factor-like activity by mononuclear cells from a boy with hypogammaglobulinemia.

The case history of a boy who presented at 6 mo of age with pneumocystis carinii pneumonia is described. Hypogammaglobulinemia was detected. His T lymphocytes and B lymphocytes proliferated with mitogens but no immunoglobulin was secreted secondary to polyclonal stimulation with pokeweed mitogen. His peripheral blood mononuclear cells secreted interleukin 2 and B cell growth factor (BCGF) but failed to secrete detectable levels of B cell differentiation factor (BCDF). Studies of his B lymphocytes showed that they would secrete immunoglobulin in vitro after exposure to a supernatant containing BCDF activity. Hence regulatory control of these lymphokines appears to be independent, and this case illustrates the pathologic sequellae of a defect in BCDF-like production.

Relationship between depressed mood and sex-typed personality characteristics in adolescents.

The current study investigated the relationship between self-reports of depressed mood, self-esteem, and endorsement of sex-typed personality characteristics in a normal adolescent population. For positively valenced (socially desirable) sex-typed characteristics, masculinity was inversely related to depression while femininity was not significantly related. In contrast, for negatively valenced sex-typed characteristics the masculine and feminine scales showed similar effects: all were positively correlated with depression. Self-esteem was the best single predictor of depression and none of the sextyped characteristics contributed significantly beyond that accounted for by self-esteem. The results support previous findings with younger children and high school students by demonstrating that sex-typed characteristics in adolescents are significantly associated with depression, although this relationship is accounted for by the variance shared with self-esteem, a more general measure of mental health. However, the presence of negative feminine-typed characteristics was as highly correlated with depression as the absence of positive masculine characteristics and both relationships were stronger for females than males. Thus the linkages between sex-role socialization, sex-typed characteristics, self-esteem, depressed mood, and clinical depression bear further investigation, and may prove useful in understanding the development of depression in males and females.

The CMRF-35H gene structure predicts for an independently expressed member of an ITIM/ITAM pair of molecules localized to human chromosome 17.

The CMRF-35 monoclonal antibody recognizes an epitope found on at least two cell surface molecules, differentially expressed by many leukocytes. These molecules, the CMRF-35H (9) and CMRF-35A (CMRF-35) antigens are both members of the immunoglobulin (Ig) superfamily with a single V-like Ig domain. The function of these molecules is unknown, however the presence of putative immunoreceptor tyrosine-based inhibitory motifs (ITIM) in the cytoplasmic domain of the CMRF-35H molecule suggests that this molecule may play a regulatory role in leukocyte function. The CMRF-35H and CMRF-35A molecules show several similarities to the family of molecules containing ITIM or immunoreceptor tyrosine-based activatory motifs (ITAM) suggesting that CMRF-35H/CMRF-35A may be new members of this family. This would further indicate that, like other ITIM/ITAM containing molecules, CMRF-35H/CMRF-35A will also play an important role in the immune response. To further characterize these molecules, we have isolated genomic clones for the CMRF-35H gene and determined its intron-exon organization. The gene spans approximately 12 kb and consists of seven exons. Furthermore, this gene has been mapped to chromosome 17 and thus is not linked to the known human ITIM containing genes which map to human chromosome 19 or the recently characterized molecule, NKp44, localized to human chromosome 6.