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Biomedical subjects

K Kuki

Publications and source records attributed to K Kuki.

At least 19 recordsLinked to original sources

Engraftment of tonsillar mononuclear cells in human skin/SCID mouse chimera--validation of a novel xenogeneic transplantation model for autoimmune diseases.

Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical tonsillar focal infections, based on the marked clinical improvement of the skin lesions after tonsillectomy. Despite the accumulation of data showing the clinical efficacy of tonsillectomy for this skin lesion, fundamental etiological and pathophysiological issues have yet to be addressed. One primary obstacle hindering investigators has been the lack of an appropriate animal model for this human skin disorder. In the early stage of PPP, it has been reported that lymphocytes, predominantly CD4+ T lymphocytes, infiltrate the palmar and plantar skins. However, the origin and mechanism of infiltration by these lymphocytes is not clear and there are very few reports on whether tonsillar mononuclear cells react directly with the skin. We have been intrigued by the ability to engraft human cells onto severe combined immunodeficiency (SCID) mice, together with the opportunity for long-term graft survival and ability to adoptively transfer various human immunocompetent cells. In this review, we addressed the existing deficiencies in our understanding of the relationship between tonsils and PPP by using emerging transplantation technology involving SCID mice.

Animals↗

[An experimental study for qualitatively diagnosing stapes lesions by helical 3-dimensional CT].

To evaluate qualitative diagnosis of stapes lesions by 3-dimensional computed tomography (3D-CT) combined with superselective image processing (3D-SS) of stapes, we studied helical 3D-CT on a phantom model of the temporal bone. Two stapes models were used-1 made from the bone filler, Celatite, consistent in bone density but changing in cross sectional area, and the other made from an apacerum rod used in quantitative computed tomography (QCT), consistent in cross sectional area but changing in bone density. These stapes models were put into a skull phantom and analyzed by helical 3D-CT. The influence of the tympanic cavity conditions on CT images of stapes was evaluated by filling the phantom model with Vaseline following 3D selective reconstruction. In all stapes models, lowering the lower CT window width threshold resulted in an enlarged cross-sectional area of the model. The higher the bone density, the lower the increase in cross-sectional area in the image. The stapes model with lower density had greater influence on the imaging by tympanic cavity conditions and was likely to be misdiagnosed as showing higher bone density. Based on the experimental study, 3D-SS by helical 3D-CT appears to be a useful measure for qualitatively diagnosing stapes lesions.

Hearing Loss, Conductive↗

Middle ear adenoma with neuroendocrine differentiation.

The lining of the middle ear cleft is normally a thin modified respiratory type mucosa. Normal mucosa of the middle ear is devoid of salivary type seromucous glands. Middle ear adenoma is a rare tumor that seems to be derived from the middle ear mucosa. This tumor has been previously described under a variety of names because of its different nature and biological behavior. We herein report a case of middle ear tumor that shows adenomatous and neuroendocrine features. A 64-year-old woman presented with a history of hearing loss, tinnitus and stuffy feeling of the right ear. The patient was treated two times for ear polyp. She finally underwent a tympanomastoidectomy and there was no evidence of recurrence 18 months after the procedure. Histopathological examination displayed cuboidal and columnar cells, arranged as glands, trabeculae and solid sheets. Neuroendocrine differentiation was revealed by immunohistochemical staining with polyclonal antibodies against neuron specific enolase and chromogranin antigens.

Adenoma↗

[Molecular analysis of pathogens of upper respiratory tract infections in children--a study of nasopharyngeal S. pneumoniae and PBP genes in acute otitis media].

We have recently been confronted with refractory upper respiratory infections with an increasing prevalence of penicillin (Pc)-resistant S. pneumoniae. There has been a broad consensus that acute otitis media (AOM) is caused by migration of pathogens from nasopharynx and proliferation in the middle ear space, and thus it is, very important to study the bacterial environment in the nasopharynx as the source of middle ear infections. Eighty pneumococcal isolates from the nasopharynx of children with acute otitis media were evaluated by polymerase chain reaction (PCR) for mutation of Pc-binding protein (PBP) genes. The results showed mutation of all three PBP genes, pbp 1a, pbp 2x, and pbp 2b, in 30% of the isolates, while 74% were found to possess various PBP gene mutations, mostly in one-year-old children. Of the 46 isolates whose minimum inhibitory concentration (MIC) of Pc was < or = 0.06 microgram/mL, 43% were found to possess a pbp 2x mutaion, which affects cefem resistance. We genotyped each pneumococcal isolate from the nasopharynx of children with recurrent AOM by pulsed-field gel electrophoresis (PFGE). In 9 of 11 pairs (82%) of consecutive AOM episodes, the nasopharyngeal isolate in the second episode was different. In addition, discrimination of each isolate based upon the mutation profile of its PBP genes in 8 pairs (72%) of consecutive AOM episodes showed that the isolates were different, and there was little difference between the results of PBP gene mutation and PFGE analysis. These findings suggest that most nasopharyngeal isolates from children with AOM possess PBP mutations and that children with increased numbers of drug-resistant bacteria in their nasopharynx during AOM has been colonized or recolonized by different strains during each episode. We therefore emphasize that clinicians should assess the antibiotic susceptibility of nasopharyngeal isolates from children during each episode. PBP gene mutation analysis of S. pneumoniae is useful not only in providing valuable information on the antibiotic susceptibility of each strain but for assessing changes in causative strains in the sequential episodes of pneumococcal infection.

Acute Disease↗

[A study of the pathogenesis of tonsillar focal infection--transplantation of human tonsillar lymphocytes and human skin into SCID mice].

Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical tonsillar focal infections, based on the marked clinical improvement of the skin lesions after tonsillectomy. In early-stage of PPP, it has been reported that lymphocytes, predominantly CD4-positive cells, infiltrate the palmar and plantar skin. However, the origin and mechanism of infiltration by these lymphocytes is not clear and there are very few reports on whether tonsillar cells react directly with the skin, possibly due to the difficulty of establishing adequate animal models. In this study, we established an experimental animal model of mice with severe combined immunodeficiency (SCID) and observed the reactions of the tonsillar lymphocytes (TL) or peripheral blood lymphocytes (PBL) of patients with PPP to their own plantar skin by transplanting the lymphocytes and skin of the patient into the mice. The results revealed that TL infiltrated the skin to a significantly greater extent than PBL. Most of these lymphocytes were T lymphocytes, and no B lymphocytes were detected in the transplanted skin. Strong expression of LFA-1 and ICAM-1 was observed in the skin after the TL transplantation. These results suggest that TL have a strong affinity for the skin in PPP, and that the adhesion molecules may play an important role in the infiltration by lymphocytes of the skin.

Animals↗

Squamous cell carcinoma arising in a Warthin's tumor.

Warthin's tumor is a well-defined salivary gland neoplasm consisting of epithelial and lymphoid components. However, malignant transformation is extremely rare. Such a patient who developed squamous cell carcinoma within a Warthin's tumor of the parotid gland is described and possible pathogenesis is discussed.

Adenolymphoma↗

Severe antecollis during antipsychotics treatment: a report of three cases.

1. The authors report on three patients with severe antecollis that developed after chronic treatment with antipsychotics. These patients had been treated with neuroleptics for their delusions and hallucinations. Antecollis is a rare form of tardive dystonia that has drawn little attention. To our knowledge, there have been no reports on this disorder. 2. The patients developed the symptom after receiving a number of antipsychotics for 4 months to 14 years. Neither discontinuation of antipsychotics nor administration of anticholinergic agents affected the symptom. 3. Although spontaneous improvement of dystonia was obtained after several months without any specific treatment in one patient, the symptom persisted for several years in another. The last patient could not be followed after discharge from our hospital since she and her family did not come to the hospital. 4. Severe antecollis may cause disturbances in various functions, such as vision, speaking and swallowing. Forward bending of the neck may cause inspiratory obstruction. Severe antecollis may not be unusual and psychiatrists should be aware of this symptom in routine clinical practice.

Aged↗

[Role of adhesion molecules in tonsillar focal infection].

Pustulosis palmaris et plantaris (PPP) is a pustular skin disease that is closely related to tonsillar focal infection. Patients with this skin disease have shown marked improvements of skin lesions after tonsillectomy. In this study, we evaluated the role of adhesion molecules in the pathogenesis of tonsillarfocal infection related to PPP. The results were that tonsillar lymphocytes of patients with PPP adhered to vessels in the dermis, to vessels running through the dermal papilla, and to vessels in the epidermis at the base of pustules. The adhesion of tonsillar lymphocytes to endothelial cells were significantly blocked by anti-LFA-1 antibody. An immunohistological study revealed that cells infiltrating the dermis expressed LFA-1, whereas ICAM-1, the ligand of LFA-1, was detected on endothelial cells and keratinocytes. It is interesting to note that cells infiltrating the dermis of the erythema stage or the pustule stage of PPP expressed ICAM-1, and the vessels in these stages expressed E-selectin. ICAM-1 was also detected on vessels in the dermis of skin that seemed to be macroscopically normal. These results suggest that tonsillar lymphocytes may have an affinity for the skin of PPP-expressing adhesion molecules such as LFA-1, ICAM-1, and E-selectin. These adhesion molecules seem to be easily activated, not only in skin lesions of PPP, but also in macroscopically normal areas resulting in cellular infiltration and pustule formation.

Adult↗

Study on specific mucosal immunity by intranasal immunization of outer membrane protein P6 of Haemophilus influenzae with cholera toxin B subunit.

Effective induction of the specific mucosal immunity against the outer membrane protein P6 of Haemophilus influenzae was investigated. Twenty-four BALB/c mice were intranasally immunized with P6, twice, with 2 weeks in between, with or without intranasal cytokine treatment. The intranasal immunization evoked both anti-P6 specific mucosal IgA immunity and systemic IgG immunity. In addition, intranasal administration of rIL-2 and rIL-5 enhanced anti-P6 specific immune response was maintained for 3 weeks after the final immunization with the intranasal cytokine treatment. These suggest the possibility of intranasal immunization and the advantage of intranasal administration of cytokines for eliciting both mucosal and systemic immunity.

Administration, Intranasal↗

Animal model of focal tonsillar infection: human tonsillar lymphocytes induce skin lesion in SCID mice.

Based mainly on clinical evidence, a concept of focal tonsillar infections affecting certain skin diseases has been established. In such disorders as pustulosis palmaris et plantaris (PPP), there have been significant improvement of clinical manifestations following tonsillectomy. However, the pathophysiological mechanism of PPP due to focal tonsillar infections has not been made clear. In order to clarify the relationship between tonsil and PPP, an in vivo experimental model of this disease was developed by reconstituting severe combined immunodeficiency (SCID) mice with tonsillar lymphocytes (TL) from patients with PPP. The results can be summarized as follows: i) The SCID mice reconstituted with PPP-TL developed skin lesions with fur-loss and eruption around their cheek and forehead; ii) The reconstituted SCID mice showed long-term presence of human IgG in their sera, reaching maximum level at 6-8 weeks after the transfer; iii) Human anti-keratin antibody was found in the sera of reconstituted SCID mice reflecting that of the donors; iv) A section of the skin lesions showed thickened epidermis and blister formation. A few CD4(+) human lymphocytes were seen around the lesions, whereas CD8(+) lymphocytes and B cells were hardly seen; v) Human IgG deposits were observed in skin lesions of SCID mouse.

Animals↗

Laboratory suncus: a new model animal for tonsil research.

Palatine and tubal tonsils of normal and horseradish peroxidase (HRP) sensitized laboratory suncuses (Suncus murinus) were examined by immunoelectron microscopy. The individual tonsil consisted of lymphoepithelial symbiosis containing M cells and a lymph nodule. The high-endothelial venules and efferent lymphatics were situated in the parafollicular region of the nodule. Staining of the frozen tonsil sections by our recently developed anti-Suncus T and B lymphocyte monoclonal antibodies revealed that T cells occupied the parafollicular zone and B cells localized within the follicles. In the present intra-tympanic cavity HRP sensitization, numerous HRP-antibody producing cells were seen not only in the tubal tonsils but also in their regional lymph nodes, spleen and palatine tonsils. The same HRP-antibody was rarely detected within the submesangial regions of the kidney. These findings presume that Suncus tonsil is homologous to the human tonsil. The Suncus is, therefore worthy as a model animal for tonsil research.

Animals↗

A study of apoptosis in the human palatine tonsil.

Apoptosis is a morphological involution caused by a cellular suicide program which is associated with programmed cell death. Several reports have shown that Fas antigen mediated apoptosis and death of immunocytes in lymphoid tissues are induced through apoptotic mechanisms. The present study was designed to investigate apoptotic cells in human palatine tonsils by using in situ end-labeling (ISEL) technique and flow cytometric analysis with anti-Fas antibody. The ISEL technique showed that a number of apoptotic cells were present in the subepithelial area of the tonsil. Flow cytometric analysis showed that the number of anti-Fas positive cells in the tonsil was larger in adults than in children. Further, tonsillar lymphocytes were examined for mRNA expression of the Fas antigen using reverse transcription polymerase chain reaction (RT-PCR) method. Fas mRNA expression was confirmed in tonsillar lymphocytes. The results suggest that apoptosis may be related to morphological and immunologic involutions of the tonsil.

Apoptosis↗

Analysis of viral infection in patients with IgA nephropathy.

We investigated viral infections in the tonsils, pharynx and renal tissues of patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR) and immuno-fluorescent techniques, and measured antibody titers against numerous types of viruses. Neutralization tests found no significant inhibition of growth of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2, B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal tissues and mouthwashings from patients with IgA nephropathy. On the other hand, EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14 patients with IgA nephropathy (42%). Immunohistological and serological analyses were done to examine the relationship between EBV and IgA nephropathy. No evidence was obtained that EBV-infected B lymphocytes were producing IgA. It seems unlikely that the viral infections examined in this study play a significant role in the pathogenesis of IgA nephropathy.

Adult↗

[Clinical evaluation of local administration of RIL-2 in head and neck cancer].

Recombinant Interleukin-2 (rIL-2) was administered locally to 20 patients with head and neck cancer. 800 thousand units of TGP-3 were injected around the tumor mass every day for about 4 weeks. Complete response (CR) was obtained in two cases with lip cancer and one with lingual cancer showed partial response (PR), and minor response (MR) in oral floor cancer. No recurrence of tumors was observed in the two cases of lip cancer. Chemotherapy was performed with rIL-2 in cases responding only insufficiently to rIL-2. It was interesting that arterial infusion of anticancer drugs subsequent to local administration of rIL-2 resulted in a dramatic decrease in tumor size in a short time. It is suggested that local administration of rIL-2 may play an important role in multimodal treatment for head and neck cancer.

Adult↗

[Clinical evaluation of immunosuppressive factors (IAP-immunosuppressive acidic protein, IS-immunosuppressive substance) in head and neck cancer].

It is reported that the levels of serum IAP and IS are useful parameters to evaluate the prognosis along with the clinical course of tumor bearing patients. Serum IAP and IS were examined in 149 patients with head and neck cancer. The level of serum IAP and IS increased in patients with not only advanced stages, but also poor prognosis. In general, the patients with death or recurrence had higher levels of serum IAP and IS than those with good prognosis. It is concluded that serum IAP and IS well reflect the immunological condition and clinical course of patients with cancer and may be one of the useful parameter for them.

Adolescent↗

An architecture of capillary vessels of the palatine tonsils studied by scanning electron microscope--with special references to comparison with the tonsillar cryptscopic images.

The three-dimensional structure of capillary vessels in the human palatine tonsil using corrosion casting techniques was investigated and compared to recently developed cryptscopic images. The postcapillary venules and arterioles were distinguishable from the nuclear impressions on their walls. The configuration of vessels around the micropores of crypts is similar to the images from the cryptscope.

Capillaries↗