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Biomedical subjects

M Tsukuda

Publications and source records attributed to M Tsukuda.

At least 73 records · Page 4Linked to original sources

Neuropeptide-containing nerve fibres in the human parotid gland: a semiquantitative analysis using an antibody against protein gene product 9.5.

The occurrence and distribution of neuropeptide-containing fibres in the human parotid gland were examined by the peroxidase-antiperoxidase method with attention to the quality of fixation and the condition of patients. Many fibres immunoreactive for neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) and a moderate number of galanin-positive (GAL) fibres were distributed around the acini. A moderate number of NPY and VIP fibres were distributed around the intercalated ducts. The semiquantitative mean densities (+/- SD) of periacinar NPY, VIP and GAL fibres expressed as a percentage of the total protein gene product (PGP) 9.5 immunoreactive fibres were 75.62 +/- 7.25%, 70.52 +/- 9.33% and 41.76 +/- 5.45%, respectively, whereas those of substance P (SP), calcitonin gene-related peptide (CGRP) and FMRF amide (FMRF) fibres were below 10%. The mean densities of NPY and VIP fibres around the intercalated ducts expressed as the percentage of PGP 9.5 fibres associated with these ducts were 52.37 +/- 6.19% and 59.62 +/- 7.02% respectively. Those of SP, CGRP, GAL, and FMRF fibres were below 10%. The densities of NPY, VIP, SP, CGRP, GAL and FMRF fibres around the striated and excretory ducts were also below 10%. In the vasculature, NPY fibres were the most prominent. Similarly, the mean density of perivascular NPY fibres was 93.76 +/- 2.03%. No somatostatin or leucine or methionine enkephalin immunoreactivity was detected around the acini, duct system or blood vessels. These findings suggest that, in this gland, the periacinar NPY, VIP and GAL fibres may participate in regulating the synthesis of saliva and its secretion and that perivascular peptidergic fibres, especially NPY fibres, may be involved in controlling local blood flow.

Adult↗

Peptidergic innervation in human von Ebner's glands: an immunohistochemical study.

The occurrence and distribution of several neuropeptides were studied in human von Ebner's glands. Immunoreactivity for substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin, and somatostatin was found in the nerve fibers around the acini, ducts, and blood vessels. VIP-immunoreactive varicose fibers were numerous compared with the other five neuropeptides. Most NPY fibers were associated with the vasculature in the gland. These findings suggest that the neuropeptides may regulate the secretion and vascular tone in human von Ebner's glands.

Humans↗

[Chemoradiotherapy for patients with advanced head and neck cancer].

At diagnosis of head and neck cancer, over half of all patients show advanced stages. Cure rates for patients with advanced head and neck carcinomas remain low. Because of the poor outcome of unresectable patients with head and neck cancer after radiation therapy alone, concomitant chemoradiotherapy has been used for these advanced cases in order to improve locoregional and systemic tumor control. On the other hand, a recent treatment modality for resectable head and neck cancer has a new goal to preserve organ functions, i.e., speech, swallowing and appearance, which are affected by surgical resection. For both of these reasons, various concomitant administrations of chemotherapy and radiotherapy have been applied for advanced tumors. In this paper, the clinical results of the past and present reports are reviewed and summarized in terms of chemoradiotherapy using single and combination chemotherapeutic drug therapy. In conclusion, some aggressive concurrent chemoradiotherapy trials suggest an improved locoregional control rate, prolonged disease-free interval and a better overall survival rate.

Antineoplastic Combined Chemotherapy Protocols↗

Ontogeny of the peptidergic fibers in the male mouse submandibular gland.

The first appearance of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), galanin (GAL), leucine-enkephalin (1-ENK), and methionine-enkephalin (m-ENK) in the male mouse submandibular glands were different for each. VIP immunoreactive fibers first appeared on embryonic day 15 (E15), SP on E16, and CGRP fibers on E18. GAL, 1-ENK, and m-ENK fibers appeared in the early postnatal period, and NPY fibers occurred on postnatal day 21 (P21). From P0 to P21, VIP fibers rapidly increased in number, but SP and CGRP fibers increased only slightly. After P21, VIP, SP, and CGRP fibers decreased in number. ENK fibers were found only from P0 to P14. The number of these immunoreactive fibers in the adult phase was low in comparison with that in early postnatal phase. Around the blood vessels, SP, VIP, CGRP, NPY, and GAL fibers appeared by at least P7. These findings suggested that the transient high activity of VIP, CGRP, SP, and GAL and the transient appearance of ENKs in the nerve fibers may be related to the cell proliferation and differentiation of the functionally important structures of the mouse submandibular glands, and that the peptidergic innervation around the vasculature is probably involved in controlling local glandular circulation.

Animals↗

Coexistence of nitric oxide synthase and neuropeptides in the mouse vomeronasal organ demonstrated by a combination of double immunofluorescence labeling and a multiple dye filter.

Nitric oxide synthase (NOS)-immunofluorescence techniques were applied to the mouse vomeronasal organ. Immunoreactivity for NOS was found in the nerve fibers distributed in the receptor-free epithelium, and around the blood vessels and glands in the cavernous tissue. No NOS fibers were seen in the receptor area. A combination of double immunofluorescence labeling and multiple dye filter revealed that a part of the substance P (SP)-immunoreactive nerve fibers in the cavernous tissue contained NOS and that all the vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers around the blood vessels and glands in the cavernous tissue contained NOS. A few SP-immunoreactive cell bodies in the trigeminal ganglion showed coexistence with NOS, and almost all VIP-immunoreactive cell bodies in the sphenopalatine ganglion showed coexistence with NOS. Immunoreactivity for NOS without VIP in the cell bodies in the sphenopalatine ganglion was also found. These results suggest that NOS-immunoreactive nerve fibers in the mouse vomeronasal organ originate from the trigeminal and the sphenopalatine ganglia, and may modulate the vascular tone and the glandular secretion. In addition, these functions may be controlled in part by the interaction of nitric oxide and neuropeptides.

Animals↗

Peritumoral angiogenesis in carcinomas of the head and neck.

In the present study, the relationship between peritumoral angiogenesis and the clinical stage or the DNA ploidy pattern in 37 cases of squamous cell carcinomas of the head and neck was examined. Vascular endothelial cells of biopsy specimens were immunohistochemically stained for factor VIII-related antigen and the number of micro-vessels counted. The DNA ploidy pattern was determined by flow cytometry. The number of micro-vessels increased significantly (p < 0.05) as the regional lymph node metastasis advanced. In terms of the DNA ploidy pattern, the tumors of aneuploid pattern contained a greater number of micro-vessels than did those of diploid pattern. These findings suggest that the number of micro-vessels at the primary site of squamous cell carcinoma of the head and neck may be closely associated with the metastatic potential to the regional lymph node.

Adult↗

Inhibition of head and neck metastatic and/or recurrent cancer by local administration of multi-cytokine inducer OK-432.

The multi-cytokine inducer OK-432 is a pulverized preparation of the low-virulence SU strain of Streptococcus pyogenes of human origin. A reduction of the tumour mass in the OK-432-injected areas was observed in 11 out of 13 patients with metastatic and/or recurrent head and neck cancer. Complete response (CR), partial response (PR) and minor response (MR) were noted in six, three and two cases respectively. OK-432 local administration therapy could create a new strategy for cancer therapy.

Adult↗

Differentiation between schwannoma of the vagus nerve and schwannoma of the cervical sympathetic chain by imaging diagnosis.

Ultrasonography, computed tomography, and magnetic resonance imaging were performed to differentiate preoperatively between schwannomas of the vagus nerve and schwannomas of the cervical sympathetic chain by observing the position of schwannomas in regard to the surrounding blood vessels. Ultrasonography also permitted direct visualization of the vagus nerve, so its position relative to the schwannoma could be examined. In schwannomas of the vagus nerve the schwannoma grew between the common carotid artery and the internal jugular vein or between the internal carotid artery and the internal jugular vein, resulting in an increase in the distance between the artery and vein (separation). In schwannomas of the cervical sympathetic chain, no separation was observed between the internal jugular vein and the common carotid artery or internal carotid artery. Ultrasonography with a 7.5-MHz transducer showed the derivation of the tumor from the vagus nerve in schwannomas of the vagus nerve but showed the vagus nerve on the tumor surface in schwannomas of the cervical sympathetic chain.

Adolescent↗

[Postoperative swallowing function in tongue and oral floor cancer patients reconstructed with a recto-abdominal myocutaneous free flap after glossectomy--quantitative assessment of reconstructed tissue movement].

We examined the postoperative swallowing function of 12 tongue and oral floor cancer patients reconstructed with a recto-abdominal myocutaneous free flap after glossectomy. On the basis of the resection site, the present cases were classified into either anterior type or lateral type. Subjective evaluation of postoperative swallowing function was obtained from self-reports from patients. The movement of the reconstructed tissue was evaluated videofluorographically during swallowing, by tracking the movement of two small pellets temporarily attached to the anterior and central portions of the reconstructed tongue. The trajectory of the two pellets and the selected point of the hyoid bone were recorded together with the distance between the plate and the tongue dorsum, and between the posterior pharyngeal wall and the tongue base. Using a personal computer, a quantitative study of the video images was performed. The results were summarized as follows. 1) The movement pattern of the reconstructed tissue was generally saccadic rather than smooth. It was suggested that the swallowing pattern of the patients was different to that of normal controls. 2) Postoperative swallowing function was poorer in cases of the anterior type when compared to the lateral type. 3) In general, cases which showed relatively wide movement range appeared to achieve subjectively satisfactory swallowing function.

Adult↗

[Case reports of mucosal melanoma of the head and neck].

Twelve patients with mucosal melanoma in the head and neck were treated at Yokohama city University from 1975 to 1994. The sex distribution was 5 male and 7 female, and the age ranged from 40 to 79 years-old. The highest number of patients were in their sixties. In 10 cases tumors arose in the nasal cavity, in one case in the maxillary sinus and in other case in the oral cavity. The treatment modality for this tumor consisted of various combination therapies including surgery, radiotherapy, chemotherapy and immunotherapy. Combination chemotherapy consisting of dimethyltriazeno imidazole carboxamide (DTIC, Dacarbazine), amino methyl pyrimidinyl methyl chlorethyl nitrorosourea hydrochloride (ACNU) and vincristine (VCR). Cisplatin (CDDP) was recently used for cases where other chemotherapy was not effective. Surgical treatment in the initial therapy was performed in 8 patients. In three of these 8 cases, the surgical margin was positive. One of them was dead after 9 months, another dead with complication after 1 year and the other survived free of any tumor. Immunotherapy using OK-432, interleukin-2, LAK therapy and low dose CPM was effective for some patients. The 5-year survival rate was 44%. Patients with surgical treatments in the initial therapy had longer survival than those without surgical treatments.

Adult↗

[Neuroendocrine carcinomas of the head and neck].

Neuroendocrine carcinomas (NECs) of the head and neck are rare. Between 1980 and 1995, only 163 cases of laryngeal and 30 cases of sinonasal NEC had been reported worldwide. We report two cases of sinonasal NEC. Case 1: A 49-year-old man complaining of left nasal obstruction was admitted to our hospital. A tumor with a tendency to bleed was seen in the left nasal cavity. CT scanning revealed an enhanced mass in the left nasal cavity and both maxillary and ethmoid sinuses. An open biopsy was performed to determine the diagnosis. The diagnosis of NEC was based on light microscopic and immunohistochemical findings. Chemotherapy and radiation were performed, but bone, liver and brain metastasis occurred 15 months after diagnosis and the patient died. Case 2: A 59-year-old man, complaining of right forehead swelling visited our department. CT scanning and MRI revealed that the right ethmoid sinus was filled by a tumor which had invaded the base of the skull. An open biopsy was performed. From the results of light microscopic and immunohistochemical investigations, NEC was highly suspected. Chemotherapy and radiation were performed, but the patient died 6 months after diagnosis. This study shows that there are aggressive types of nasal NEC, although these sinonasal carcinomas were reported in the literature to be not very lethal. The diagnosis, histopathological classification, treatment, and prognosis of sinonasal and laryngeal NECs were reviewed.

Carcinoma, Neuroendocrine↗

[Articulatory function in patients receiving glossectomy followed by reconstruction with a recto-abdominal myocutaneous free flap].

Postoperative articulatory functions of patients with tongue cancer have been improved by reconstructive surgery with a radial forearm or recto-abdominal myocutaneous free flap. We examined the postoperative articulatory functions of 10 patients who received reconstruction with a recto-abdominal myocutaneous free flap after glossectomy. The functions were investigated by standardized tests, i. e. a quentionnaires, the 100 Japanese monosyllable speech intelligibility test and a single-word intelligibility test. A confusion matrix was obtained from the results of the monosyllable test. On the basis of resection sites, the present cases were divided into two types: an anterior type and a lateral type. The results are summarized as follows. There was no significant difference in the results of the quentionnareis between the two types. The mean score of the 100 Japanese monosyllable speech intelligibility test in cases of the anterior type was 48% and in those of the lateral type it was 62%. The mean score of the single-word intellibibility test in cases of the anterior type was 75% and in those of the lateral type it was 83%. In cases of the anterior type, dental and alveolar sounds were often confused with fricatives, whereas in the lateral type, velars sounds were often confused with affricates or flaps. These results suggest that our classification based on resection site was useful for investigating postoperative articulatory functions after partial glossectomy.

Adult↗

[Two pediatric cases of facial palsy caused by masked mastoiditis].

Two children with otogenic facial palsy are reported. The tympanic membranes of a 15-month-old boy and a girl of the same age were hyperemic, dull, and bulging, and the children suffered from masked mastoiditis. The facial palsy had not been improved by myringotomy, and parenteral administration of antibiotics and steroids. Finally, tympanomastoidectomy and facial nerve decompression was performed and a tympanostomy tube was inserted. Both patients completely recovered facial nerve function within two months after the operation. On the basis of the results of those operations tympanomastoidectomy and the facial nerve decompression may become necessary in such cases as those caused by masked mastoiditis.

Facial Nerve↗

[Immunotherapy of patients with head and neck carcinomas].

The decline of immunity has been reported in head and neck carcinomas in the advanced stage. On the basis of this finding in head and neck carcinomas, additional immunotherapy in curative treatment, i.e., surgical therapy and/or radiation therapy, has been applied for patients with advanced tumors to improve their poor prognosis. Until now, only a few controlled randomized studies have evaluated the clinical efficacy of non-specific immunotherapy, i.e., Ubenimex and OK-432. Each result using these drugs showed that the survival rate in those receiving non-specific immunotherapy was higher than in the control. Cytokines, e.g., IFN-alpha, gamma, TNF-alpha, had immunologically modulating actions on the immunological conditions of patients and on the tumor cells, whereas immunotherapy using these cytokines has not shown a good clinical response, as with clinical administration of IL-2 alone. Furthermore, the clinical results of combined therapy of IL-2 and adoptive immunotherapy for head and neck carcinomas have not been satisfactory. In future, to improve the prognosis in patients with these carcinomas, it is indispensable to develop a new immunotherapy including transfer of cytokine-transfected cells having tumor-immunization ability and capable of inducing cytolytic effector cells in the peritumoral site, and specific antibody therapy against tumor cells.

Antineoplastic Agents↗

Analysis of an initial step of T cell adhesion to endothelial monolayers under flow conditions.

We analyzed an initial step of T cell adhesion to endothelial cells under flow conditions. An initial step in T cell-endothelial cell interactions was characterized either by a rolling phase, or by an immediate arrest without rolling. Anti-E- and P-selectin Abs inhibited T cell rolling on endothelial cells under flow conditions. The rolling velocity of T cells on endothelial cells increased after treatment of endothelial cells with anti-E- or P-selectin Abs. Also, rolling of T cells was observed on E-selectin-transfected CHO cells but not on ICAM-1-transfected CHO cells. Thus, rolling of T cells under flow condition was dependent on E-selectin as well as P-selectin expressed on endothelial cells. In contrast, neither anti-E- nor P-selectin Abs inhibited the immediate arrest of T cells on endothelial cells significantly and anti-ICAM-1 Abs also failed to inhibit the immediate arrest of T cells. Therefore, other adhesion molecules may play an important role in the immediate arrest of T cells under flow conditions. The number of CD45RA- T cells rolling on E-selectin-transfected CHO cells was much higher than that of CD45RA+ T cells.

Animals↗

A macromolecular multicomponent peptide vaccine prepared using the glutaraldehyde conjugation method with strong immunogenicity for HIV-1.

The immunogenicity of a newly constructed macromolecular multicomponent peptide vaccine candidate against human immunodeficiency virus type 1 (HIV-1) was compared with that of previously reported vaccine candidates. This vaccine candidate is composed of a macromolecular multicomponent peptide complex consisting of three V3 region peptides, one Gag region peptide, and CD4-binding site peptide and was constructed using the multiple-antigen peptide and glutaraldehyde methods. Sera from rabbits immunized with this newly constructed vaccine showed strong antibody titers against each constituent peptide antigen. Furthermore, these antibodies exhibited strong neutralizing and antifusion activity toward HIV-1IIB, HIV-1MN, and fresh isolates from Japanese HIV-seropositive individuals. These results show that this new vaccine candidate has the capacity to induce strong, polyvalent immunogenicity and therefore may prove to be a powerful peptide vaccine against HIV-1 infection.

AIDS Vaccines↗

Changes in glycoconjugates revealed by lectin staining and stage-specific embryonic antigen-1 immunostaining in hamster submandibular glands during the postnatal period.

Lectin binding and stage-specific embryonic antigen-1 (SSEA-1) immunoreactivity were studied in the developing submandibular glands of young Syrian golden hamsters (Mesocricetus auratus) from postnatal day 1 (the day of birth) to day 28. The submandibular glands were fixed in a solution containing 6% mercuric chloride, 1% sodium acetate, and 0.1% glutaraldehyde (HgCl2-G) or 4% paraformaldehyde (4P), and embedded in paraffin. Sections from HgCl2-G fixation were stained with three lectin-peroxidase conjugates: peanut agglutinin (PNA), Ulex europeus I agglutinin (UEA I), and wheat germ agglutinin (WGA). Sections from the 4P-fixed tissues were immunostained with monoclonal antibodies against SSEA-1, sialyl SSEA-1 and fucosyl SSEA-1. On the day of birth, the terminal unit of the submandibular gland was composed of fetal type secretory cells and proacinar cells. The secretory cells were PNA, UEA I, and WGA positive. The number of secretory terminal tubule cells decreased rapidly, and lectin-positive secretory cells were replaced by adult secretory cells that did not show PNA or UEA I stainings but were weakly positive for WGA. Fetal secretory cells were positively immunostained for SSEA-1 and sialyl SSEA-1, and immature ductal cells were stained for fucosyl SSEA-1. The positive stainings disappeared with regression of the fetal epithelial cells. Hence, modulation of glycoconjugate expression in the submandibular glands, which reflects changes in secretory cells from the fetal type to adult type during postnatal development, is revealed by lectin staining and immunostaining for SSEA-1 and related antigens.

Animals↗

Comparison of granisetron alone and granisetron plus hydroxyzine hydrochloride for prophylactic treatment of emesis induced by cisplatin chemotherapy.

The efficacy and safety of granisetron alone (group G) and granisetron plus hydroxyzine hydrochloride (group G/H) as prophylactic therapy for acute and delayed nausea and vomiting were evaluated in an open trial in head and neck cancer patients undergoing chemotherapy with cisplatin. The severity of nausea was significantly reduced on days 1 and 4 in patients receiving combination therapy, but the frequency of vomiting was not significantly different between the two groups. The only side-effect observed was headache in 1 patient from group G, and no drug-related laboratory test abnormalities were observed. These results suggest that the anti-emetic efficacy of granisetron can be augmented by hydroxyzine hydrochloride.

Acute Disease↗