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H Yoshida

Publications and source records attributed to H Yoshida.

At least 595 records · Page 33Linked to original sources
PubMed1999

Genetic background determines the nature of immune responses and experimental immune-mediated blepharoconjunctivitis (EC).

PURPOSE: Experimental immune-mediated blepharoconjunctivitis (EC) was induced in Lewis rats by immunization with ovalbumin (OVA) in complete Freund's adjuvant (CFA) or aluminum hydroxide [Al(OH)3]. To investigate the affect of genetic factors on the susceptibility of EC, we tested different strains of rats for the development of EC. METHODS: Lewis and Brown Norway (BN) rats were immunized once with 100 microg of OVA in CFA or Al(OH)3. Three weeks later they were challenged with OVA in eye drops; 24 hours after the challenge they were sacrificed and their eyes, blood, and lymph nodes were harvested for histological studies, measurement of OVA-specific antibodies (IgG, IgG1, IgG2a, IgE), and proliferation or cytokine assay, respectively. ELISA was used to detect OVA-specific IgG; passive cutaneous anaphylaxis was used for detecting IgE. RESULTS: EC, OVA-specific IgG, and cellular immunity were induced in Lewis rats by using either adjuvant, whereas IgE was not produced by either adjuvant. In contrast, IgE was produced in BN rats using either adjuvant, whereas cellular immunity was evoked only when CFA was used. Less cellular infiltration as well as cellular proliferation was detected in BN rats immunized with Al(OH)3. In both strains, Al(OH)3 induced a higher IgG1/IgG2a ratio than did CFA. More interferon-gamma by stimulation with OVA was noted in Lewis rats compared to BN rats, whereas interleukin-4 was detected only in BN rats. CONCLUSIONS: The severity of EC evaluated by cellular infiltration was dependent on OVA-specific cellular immunity. Genetic background is more important than adjuvants in determining the nature of EC and immunity.

Aluminum Hydroxide↗
PubMed1999

Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress.

The unfolded protein response (UPR) controls the levels of molecular chaperones and enzymes involved in protein folding in the endoplasmic reticulum (ER). We recently isolated ATF6 as a candidate for mammalian UPR-specific transcription factor. We report here that ATF6 constitutively expressed as a 90-kDa protein (p90ATF6) is directly converted to a 50-kDa protein (p50ATF6) in ER-stressed cells. Furthermore, we showed that the most important consequence of this conversion was altered subcellular localization; p90ATF6 is embedded in the ER, whereas p50ATF6 is a nuclear protein. p90ATF6 is a type II transmembrane glycoprotein with a hydrophobic stretch in the middle of the molecule. Thus, the N-terminal half containing a basic leucine zipper motif is oriented facing the cytoplasm. Full-length ATF6 as well as its C-terminal deletion mutant carrying the transmembrane domain is localized in the ER when transfected. In contrast, mutant ATF6 representing the cytoplasmic region translocates into the nucleus and activates transcription of the endogenous GRP78/BiP gene. We propose that ER stress-induced proteolysis of membrane-bound p90ATF6 releases soluble p50ATF6, leading to induced transcription in the nucleus. Unlike yeast UPR, mammalian UPR appears to use a system similar to that reported for cholesterol homeostasis.

Activating Transcription Factor 6↗
PubMed1999

Inhibitory effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats.

We have investigated the effect of clonidine on ketamine-induced norepinephrine release from the medial prefrontal cortex in rats using microdialysis. Twenty-one male Wistar rats weighing 200-300 g were allocated randomly to one of four groups: i.p. injection of ketamine 100 mg kg-1 with clonidine 0 (saline: group C0, n = 6), 3 (group C3, n = 5), 30 (group C30, n = 5) and 300 micrograms kg-1 (group C300, n = 5). As reported previously, ketamine increases norepinephrine release. In groups C0 and C3, marked increases in norepinephrine release were observed with maximum values of mean 483 (SEM 55)% and 412 (53)% compared with basal values, respectively. Although significant increases in norepinephrine release were also observed (276 (43)%) in group C30, they were significantly lower than those in groups C0 and C3 (P < 0.01 and P < 0.05, respectively). In group C300, there was a significant reduction in norepinephrine release (62 (13)%) compared with basal and the three other groups (P < 0.01). This inhibitory effect of clonidine on norepinephrine may be related to reduction in undesirable emergence reactions after ketamine anaesthesia.

Adrenergic alpha-Agonists↗
PubMed1999

IL-7 receptor alpha+ CD3(-) cells in the embryonic intestine induces the organizing center of Peyer's patches.

Peyer's patch (PP) organogenesis proceeds through three histologically distinct steps: formation of organizing centers expressing VCAM-1 and ICAM-1 in segregated regions of the intestine at 15.5 days post-coitus (d.p.c.) (step I), accumulation of blood cells expressing different sets of surface markers to this region at 16.5-17.0 d.p.c. (step II), and entry of CD3+ and B220+ lymphocytes just before birth (step III). PP formation of both Il7ra-/- and Lta-/- mice is impaired from step I, suggesting involvement of the two molecules at the same timing in PP organogenesis. Expression of lymphotoxin (LT) alpha and LTbeta in IL-7 receptor (IL-7R) alpha+ cells in the intestine indicates that defects of Il7ra-/- and Lta-/- mice are due to functional inability of IL-7Ralpha+ cells in the induction of PP anlage. Blocking of IL-7Ralpha function by a single injection of the antagonistic mAb in 15.5 d.p.c. embryos suppressed appearance of VCAM-1(+) spots and expression of LTalpha and LTbeta in the intestine, which eventually resulted in mice without PP but are otherwise normal. Intestinal IL-7Ralpha+ cells are lymphoid in morphology but CD3(-) and functional in both nu/nu and Rag2-/- mice. These results implicate IL-7Ralpha+ CD3(-) cells as the direct inducer of the organizing center of PP.

Animals↗
PubMed1999

Long-term treatment results of elderly patients with prostate cancer in Japan: an analysis of prognostic factors.

BACKGROUND: The management of elderly patients with prostate cancer is an important issue because the incidence of prostate cancer is high in old men, and people are also living longer today. The present retrospective study was therefore conducted to evaluate the long-term clinical outcome of elderly patients with prostate cancer and to analyze the prognostic factors. METHODS: Between 1980 and 1992, 151 patients aged 75 to 89 years old were diagnosed as having prostate cancer. The patients were initially managed by hormonal therapy in 117, radical prostatectomy in 11, external radiotherapy in 20, chemotherapy in 1 and no treatment in 2 cases. The clinical outcome of the patients was analyzed in relation to clinical stage, histological grade and treatment methods received. RESULTS: By univariate analysis, the stage and treatment methods were significant variables for overall and cause-specific survival rates, and grade was a significant variable for cause-specific survival rate of the patients. However, multivariate analysis revealed that stage was the only independent prognostic factor for overall as well as cause-specific survival of the patients. Among the patients with stage A2-B disease, a comparison between those treated definitively and non-definitively revealed no difference in terms of overall and relative survival rates. CONCLUSIONS: The presence of advanced prostate cancer disease had the greatest impact on the survival of the elderly patients. On the other hand, localized prostate cancer was satisfactorily managed with non-definitive almost as well as with definitive treatment.

Aged↗
PubMed1999

Does circulating erythropoietin reflect progression of IgA nephropathy? Comparison with urinary N-acetyl-beta-D-glucosaminidase.

BACKGROUND: Recent reports describe that erythropoietin (Epo) is produced by peritubular interstitial fibroblast-like cells in response to a hypoxic stimulus. We studied serum Epo levels as a possible marker of tubulointerstitial damage in the progression of IgA nephropathy (IgAN), in comparison with urinary (u-) levels of N-acetyl-beta-D-glucosaminidase (NAG), which is mainly derived from proximal tubular cells and is used as a marker of tubular damage. METHODS: Thirty-eight patients with IgA nephropathy (IgAN) with relatively preserved renal function (serum creatinine: sCr, 0.5-2.2 mg/dl) were examined. The severity of glomerulosclerosis and interstitial fibrosis of the renal biopsy tissue was expressed by semiquantitative grading scores. Clinical parameters including serum creatinine (sCr), blood pressures, and 24-h proteinuria levels were obtained at the renal biopsy. Epo was measured by a radioimmunoassay (RIA) of sera obtained in the morning and u-NAG was measured by colorimetric method of 24-h urine samples. RESULTS: The mean Epo level of the patients (17.7+/-6.3 mU/ml) was not different from the control level (19.3+/-3.7 mU/ml). There were no significant correlations between Epo levels and red blood cell (RBC) counts, haematocrit (Hct), or haemoglobin (Hb) levels. The mean u-NAG level of the patients (6.7+/-6.2 U/gCr) was significantly higher than the control level (1.9+/-0.5 U/gCr). There was an inverse quantitative correlation between Epo and u-NAG levels in the patients (P<0.02). The u-NAG levels showed quantitative positive correlations with sCr (P<0.001), u-proteins (P<0.001), systolic (SBP) (P<0.001), and diastolic blood pressures (DBP) (P<0.05). Conversely, Epo levels were inversely correlated with sCr, SBP and DBP (each P<0.05). The patients with higher u-proteins (>2.0 g/day) showed significantly decreased Epo levels (P<0.05) than those with lower u-proteins (<2.0 g/day). The both scores of glomerulosclerosis and interstitial fibrosis were positively correlated with the u-NAG levels (each P<0.001), but were not correlated with the Epo levels. CONCLUSIONS: The significant correlation between u-NAG and serum Epo levels suggests that tubular damage and interstitial cell dysfunction are associated each other in the progression of IgAN. Serum Epo levels bearing inverse correlations with sCr, blood pressure levels and heavy proteinuria seem to reflect clinical severity of IgAN, whereas u-NAG can be more useful progression marker of IgAN bearing correlations with both clinical and histological findings.

Acetylglucosaminidase↗
PubMed1999

Engineering a chimeric pyrroloquinoline quinone glucose dehydrogenase: improvement of EDTA tolerance, thermal stability and substrate specificity.

An engineered Escherichia coli PQQ glucose dehydrogenase (PQQGDH) with improved enzymatic characteristics was constructed by substituting and combining the gene-encoding protein regions responsible for EDTA tolerance, thermal stability and substrate specificity. The protein region responsible for complete EDTA tolerance in Acinetobacter calcoaceticus, which is recognized as the indicator of high stability in co-factor binding, was elucidated. The region is located between 32 and 59% from the N-terminus of A. calcoaceticus PQQGDH(A27 region) and also corresponds to the same position from 32 to 59% from the N-terminus in E. coli PQQGDH, though E. coli PQQGDH is EDTA sensitive. We previously reported that the C-terminal 3% region of A. calcoaceticus (A3 region) played an important role in the increase of thermal stability, and that His775Asn substitution in E. coli PQQGDH resulted in an increase in the substrate specificity of E. coli PQQGDH towards glucose. Based on these findings, chimeric and/or mutated PQQGDHs, E97A3 H775N, E32A27E41 H782N, E32A27E38A3 and E32A27E38A3 H782N were constructed to investigate the compatibility of two protein regions and one amino acid substitution. His775 substitution to Asn corresponded to His782 substitution to Asn (H782N) in chimeric enzymes harbouring the A27 region. Since all the chimeric PQQGDHs harbouring the A27 region were EDTA tolerant, the A27 region was found to be compatible with the other region and substituted amino acid responsible for the improvement of enzymatic properties. The contribution of the A3 region to thermal stability complemented the decrease in the thermal stability due to the His775 or His782 substitution to Asn. E32A27E38A3 H782N, which harbours all the above mentioned three regions, showed improved EDTA tolerance, thermal stability and substrate specificity. These results suggested a strategy for the construction of a semi-artificial enzyme by substituting and combining the gene-encoding protein regions responsible for the improvement of enzyme characteristics. The characteristics of constructed chimeric PQQGDH are discussed based on the predicted model, beta-propeller structure.

Acinetobacter↗
PubMed1999

Snowboard head injury: prospective study in Chino, Nagano, for two seasons from 1995 to 1997.

BACKGROUND: The popularity of snowboarding has been growing rapidly throughout the world. To date, however, the risk of head injury associated with this relatively new winter sport, especially in comparison with alpine skiing, has not been well analyzed. This study was conducted to assess the risk of head injury in snowboarding and to elucidate its features in comparison with skiing head injury. METHODS: We prospectively analyzed 301 cases of head injuries related to snowboarding or skiing experienced from December of 1995 to May of 1997 at our institution, which is located close to the most popular skiing areas in Japan. Of those injuries, 143 cases were snowboard related and 158 cases were ski related. In addition to appropriate medical evaluation and medical care, detailed examination was performed on every patient to determine various factors, including sex, age, skill level, cause and mechanism of the accident, and the side of impact to the head. The data are statistically analyzed to elucidate unique features of snowboard head injury. RESULTS: During the study period, 2.2 million snowboarders and 4.2 million skiers visited the five skiing facilities that are covered by our hospital. Thus, the incidence of head injury was 6.5 per 100,000 visits for snowboarders and 3.8 per 100,000 visits for skiers. Beginning snowboarders more frequently sustained head injuries compared with beginning skiers (60 of 142 vs. 48 of 154, p = 0.022). Likewise, frequent causes of snowboarding head injuries were fall during jumping (43 of 139 vs. 2 of 147, p<0.0001), falling backward (67 of 127 vs. 49 of 144, p = 0.001), and occipital impact (67 of 126 vs. 49 of 147). More importantly, there were nine major head injury cases (6.3%) in snowboard head injuries in contrast to only two such cases found in skiing head injuries (1.3%). Of 11 major head injury cases, 10 were caused by occipital impact. CONCLUSION: These results indicate that snowboarders, particularly beginners, are at higher risk for head injury, frequently involving occipital impact, and could lead to more major head injuries. We propose that measures should be taken to protect the head, especially the occiput, in snowboarding.

Adolescent↗
PubMed1999

Mxi1 mutations in human neurofibrosarcomas.

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.

Adult↗
PubMed1999

Combination chemotherapy with nedaplatin and cyclophosphamide in human ovarian cancer model.

The antitumor efficacy of the combination of nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using human ovarian cancer models. Since NDP has been found to have greater antitumor activity and lower nephrotoxicity than cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM. Increasing doses of NDP (16.5, 33 and 66 mg/kg as a total dose) and a fixed amount of CPM (174 or 348 mg/kg as a total dose) were injected three times at intervals of 7 days via the tail vein into mice implanted with RMUG-S, OC9-JCK or KF-28 human ovarian cancer. Simultaneous administration of NDP with CPM resulted in markedly enhanced inhibition of tumor growth for all cancers tested. The growth inhibition and survival effect of the combination therapy of NDP with CPM against KF-28 and OC9-JCK were as potent as those of CDDP plus CPM. Neither increased hematotoxicity nor a significant difference in maximum concentration, half time or area under the curve of platinum or CPM in plasma between the single and combined treatment was found. These results suggest that the combination of NDP with CPM may be clinically effective.

Animals↗
PubMed1999

Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome.

INTRODUCTION: A new strategy to elucidate the molecular mechanisms underlying the long QT syndrome (LQTS) is now available with genetic mutational analyses and characterization of ion channel mutations. METHODS AND RESULTS: In a 26-year-old woman with LQTS, we identified a novel missense mutation in the pore of HERG by using polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and sequencing of her genomic DNA. The mutation resulted in an amino acid substitution of a positively charged lysine for a highly conserved uncharged asparagine at codon 629 (N629K). Whole cell, patch clamp studies were conducted in COS7 cells by transfecting with wild-type (WT) and/or the mutant N629K HERG. The WT HERG produced an I(Kr)-like, E-4031-sensitive conductance with an inward rectification. In contrast, the cells transfected with the N629K HERG did not display any time-dependent current. Cotransfection of WT and N629K HERG (at a ratio of 1:1) produced a significantly smaller conductance when compared with WT HERG (WT 59.9 +/- 7.3 pA/pF [n = 22] vs WT+N629K 5.5 +/- 2.3 pA/pF [n = 11]; P < 0.01), but did not alter K+ ion selectivity and tail current-voltage dependence. Because aprindine hydrochloride was effective in preventing ventricular tachycardias, we also tested the effect of the drug on WT HERG (I(Kr)) and KvLQT1/KCNE1 (I(Ks)) currents expressed in COS7. CONCLUSION: Functional analyses of a novel missense mutation in the pore of HERG suggest that the mutation causes marked reduction of I(Kr) via a dominant negative effect.

Adult↗
PubMed1999

Effect of epidermal growth factor administration on the development of mouse salivary gland carcinomas.

This study investigated whether epidermal growth factor (EGF) administration was capable of modifying salivary gland carcinogenesis. Two groups of mice were given 1 mg of 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received 2 microg of EGF and Group 2 mice received vehicle subcutaneously for 8 weeks. Mice in two other groups, 3 and 4, received either EGF or vehicle alone. Twelve weeks after the start of the experiment, the incidences of submandibular gland carcinomas in Groups 1 and 2 were 39% and 58%, respectively, although this difference was not statistically significant. Duct- and cyst-like structures and carcinomas in the left submandibular glands were weakly stained by anti-EGF receptor (EGFR) antibody. Immunoblot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed the expression of EGFR in the submandibular glands and carcinomas. However, EGFR was undetectable in YT cells that were derived from a submandibular gland undifferentiated carcinoma of a Group 2 mouse. These findings indicate that EGF does not promote tumor induction in mouse salivary gland carcinogenesis. This may be ascribed in part to the low expression level of EGFR in tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Angiogenesis in the human temporomandibular joint studied by immunohistochemistry for CD34 antigen.

The CD34 antigen is a sensitive marker of vascular endothelium and angiogenesis. Thus, we examined the expression of CD34 in 20 human temporomandibular joint (TMJ) samples with internal derangement and in 10 control specimens by an immunohistological technique using paraffin-embedded tissue and specific anti-human CD34 monoclonal antibody. In the control specimens, CD34 was observed sporadically within the TMJ discs. On the other hand, in the internal derangement specimens, CD34 was found frequently in the walls of blood capillaries within the TMJ discs. In the synovial membrane, CD34 was detected frequently in the walls of many blood capillaries in both the controls and the internal derangement specimens. Indeed, CD34 expression in internal derangement specimens was more intense than in control specimens. In the posterior loose connective tissue of the bilaminar zone, and in the anterior loose connective tissue between the upper and lower lamellae of the anterior capsular wall, CD34 was detected in abundance in the walls of blood capillaries both of the controls and the internal derangement specimens. Generally, CD34 was found rarely in the walls of large blood vessels. The presence of CD34 is suggested to be correlated with the process of angiogenesis induced by internal derangement of the TMJ.

Adult↗
PubMed1999

The localization of matrix metalloproteinase-3 and tenascin in synovial membrane of the temporomandibular joint with internal derangement.

OBJECTIVES: The aim of this investigation was to study the immunohistochemical localization of MMP-3 and tenascin in the temporomandibular joint and to compare it with control specimens. MATERIALS AND METHODS: Localizations of matrix metalloproteinase-3 (MMP-3) and tenascin in the temporomandibular joint disc and the synovial membrane in 26 human temporomandibular joint samples (internal derangement of TMJ; n = 16, and control; n = 10) by an immunohistological method with monoclonal antibodies specific to human MMP-3 and tenascin. RESULTS: MMP-3 was not distributed in control specimens while it was observed in the internal derangement cases. MMP-3 showed two staining profiles: (1) diffuse staining was observed within the stroma of severely deformed disc with osteophyte and/or disc displacement (three of 16 specimens); and (2) the localization was specifically detected on the surface of severely hypertrophic synovial membrane (six of 16 specimens). The latter localization pattern resembled that of the tenascin on the surface of the severely hypertrophic synovial membrane. CONCLUSION: Comparative localization of MMP-3 and tenascin revealed intense staining for both in the synovial membrane presenting inflammation, proliferation and hypertrophy. These findings suggest that tissue repair and remodeling in the temporomandibular joint disc and the inflammatory hypertrophic reaction in the synovial membrane might proceed at the same time.

Adult↗
PubMed1999

[Efficacy of immunized milk for preventing viral infection].

This paper investigated the efficacy of passive protection provided by milk (immunized milk) against enterovirus infection in mice experimentally infected with enterovirus. Milk with a high antibody titer against six enterovirus serotypes was prepared from hyperimmunized goat. In vivo and in vitro experiments were performed and the results showed that immunized milk has an antiviral activity against enterovirus infection. Further observation was performed using Coxsackie B 3 virus (CVB 3). When immunized milk was orally applied to mice prior to oral inoculation with CVB 3, preventive effects against viral infection such as reduction of histopathological changes in the heart and reduced detection of the virus genome in the organs were seen. The antiviral effect was also indicated by the increase of CD4+T cells proportion in the i-IEL. The proportion of virus specific CD4+T cells was increased in mice treated with immunized milk, whereas no such increase was detected in control mice. These results suggest that oral application of immunized milk is not only capable of preventing viral infection but also induces specific immunological responses. These phenomena may play an important role in host defense mechanisms.

Animals↗
PubMed1999

[A case of lymphocyst infection caused by vanB type VRE].

A case of post-operative abdominal lymphocyst infection caused by vanB type vancomycin resistant enterococcus (VRE) in reported. A 27-year-old female was diagnosed as pregnancy with uterine cervical carcinoma and underwent Cesarean section and radical hysterectomy. After discharge, she developed a high fever which was diagnosed as a lymphocyst infection. Microbiological examination demonstrated the presence of vanB type VRE in the cyst fluid. Cyst cleaning and minocyclin injection were effective. This is the first case of VRE infection in Japan.

Adult↗
PubMed1999

[Two cases of suspected Bartonella henselae infection from a dog].

A 55-year-old male was admitted to our hospital because of fever and left submaxillary, right axillary, and left inguinal lymphadenopathy. A presumptive diagnosis of rickettsiosis was made and treatment with oral doxycycline was started. Lymphadenopathy was partialy resolved after antibiotics treatment. Ablation of the left inguinal node was done and histopathological examination showed non-Hodgkin's lymphoma. Lymphadenopathy was resolved by chemotherapy. The second patient, a 40-year-old male, developed a tender submandibular node. Excisional biopsy of the node was performed to eliminate lymphoma. Histopathological examination revealed granulomatous lymphadenitis with follicular hyperplasia. The patients had no history of cat contact, but owned a dog. Diagnosis of both cases was confirmed by the detection of IgG antibodies to Bartonella henselae with an enzyme immunoassay. Our findings suggest that dogs are implicated in B. henselae infection and can serve as a reservoir of the organism as well as cats. In the abscence of other bacterial and especially after exposure to dogs, B. henselae should be included as possible cause of lymphadenopathy.

Adult↗