Biomedical subjects
Publications and source records attributed to K Kuki.
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.
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.
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.
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.
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.
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.
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.
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.
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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.
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.
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.
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In this study, two experiments were made to investigate the immunological pathogenesis of PPP, a skin disease of so-called focal infections. One was the immunohistological study on tonsils with PPP and recurrent tonsillitis. In the investigation, monoclonal antibodies against T lymphocytes and anti-immunoglobulin antibodies were used to reveal the distribution of T and B cell subsets on frozen sections of tonsils. But no difference between tonsils with focal infection and recurrent tonsillitis was observed in the distribution of T and B cell subsets. The other was the identification of a common antigen between tonsillar epithelium of PPP and hand-sole skin by use of one monoclonal antibody against PPP-tonsillar epithelium, which was made in our laboratory. Monoclonal antibody ATE-3 was in IgM, and recognized about 35 kilo dalton molecular weight protein of a tonsillar epithelium of PPP. This antibody reacted with the basal layer cells of the tonsillar epithelium and the suprabasilar cells of plantar skins of PPP. But ATE-3 did not react with normal tonsillar epithelium and normal plantar skin.
We have reported a case of malignant lymphoma in associated with Hashimoto's disease arising in the right lobe of thyroid of a 57-year-old woman. The pre-operative aspirated biopsy was valuable for diagnosis Immuno-histochemical observations revealed the localization of anti B cell antibody in the cell surface of lymphoma cells and anti thyroglobulin antibody in intactly follicular epithelium within the lymphoma tissue. This lymphoma was diagnosed as diffuse, medium cell and B cell type. Radiation and chemotherapy were performed for multiple metastasis of liver and brain, but this case had died of DIC and diffuse hyaline membrane disease of lung.
The biological property of human gastric cancer was studied by morphological and immunohistochemical observations. The cytoplasmic mucin of cancer cells was mainly neurtromucin in the mucosa. However, acid mucin was increased in the cancer cells of signet-ring cell carcinoma with submucosal infiltration. Immunohistochemically, CEA was localized in the plasma membrane of matured signet-ring cells and the cytoplasm of immature cancer cells. On electron microscopic observation, the cytoplasmic organellae were prominent in the immature cells which were dominant in submucosal infiltrating region. In vitro, the cancer cell line established from signet-ring cell carcinoma revealed that CEA production was associated with cell growth property showing 3H-TdR and BrdU uptake. This results may suggest that CEA production was an important indicator for the decision of prognosis in signet-ring cell carcinoma.