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Biomedical subjects

K Kakudo

Publications and source records attributed to K Kakudo.

At least 109 records · Page 6Linked to original sources

Calcitonin gene-related peptide in patients with endocrine tumors.

The plasma level of calcitonin gene-related peptide (CGRP) was measured by RIA in 41 patients with endocrine tumors [22 medullary thyroid carcinomas (MTC), seven parathyroid adenomas, four benign insulinomas, five carcinoids, and three pheochromocytomas]. Of the 22 patients with MTC, all five preoperative patients had elevated CGRP levels. The correlation between CGRP and calcitonin levels was significant (P less than .001) in 22 patients with MTC. Six of 19 patients with endocrine tumors other than MTC showed elevated CGRP levels. Immunohistochemical study showed that tumor tissues from all 22 cases of MTC and seven from other endocrine tumors contained immunoreactive CGRP. CGRP reactivity was found in only small numbers of tumor cells. Thus, although CGRP appeared to be a useful additional marker for MTC, the role of CGRP in the pathophysiology of endocrine tumors was not elucidated.

Adenoma↗

An autopsy case of a cystic variant of thymic carcinoma mimicking a thymic cyst.

An autopsy case of thymic carcinoma is reported. The surgically excised cystic tumour from a 38-year-old Japanese male mimicked a thymic cyst pathologically. After a clinical course of 6 years, postmortem examination disclosed extensive metastases, including cystic lesions lined by benign-looking squamous epithelium. This evidence suggested that the present tumour was not of the specific variants of thymic carcinoma and not a thymic cyst with malignant transformation.

Adult↗

Superficial esophageal carcinoma. With special reference to basaloid features.

A total of 200 surgically resected esophageal carcinomas were reviewed and 50 cases (25.0%) were identified as "superficial esophageal carcinoma" (depth of invasion limited to mucosa or submucosa). The age, sex, location, tumor size, histological features, and prognosis were studied in 49 of these cases. The carcinomas were classified into four histological groups: 1) squamous cell carcinoma (SCC), 2) squamous cell carcinoma with basaloid features and expansive growth (BE), 3) squamous cell carcinoma partially mixed with the basaloid type (mixed), and 4) other types of tumors. There were 25 cases (51.0%) of SCC, 14 BE cases (28.6%), 8 mixed cases (16.3%), and 2 (4.1%) other tumors (malignant melanoma, adenoacanthoma). Among 133 advanced cancers (invasion into and beyond the muscularis propria), there were 123 cases (92.4%) of SCC, 9 (6.8%) mixed cases, and one (0.8%) adenoacanthoma. No BE lesions were identified. In superficial carcinoma there was a statistically significant difference between BE and mixed carcinoma by the chi-square test (p less than 0.05) with regard to the maximum longitudinal diameter. None of the BE carcinoma showed nodal metastasis, while 3 (12.0%) of SCC and 5 (62.5%) of mixed lesions had nodal metastases. The difference in cumulative survival rate between BE and mixed carcinoma was statistically significant by the Z and Wilcoxon tests (p less than 0.05). We conclude that the BE type of superficial esophageal carcinoma had a better prognosis, and should be separated from the ordinary SCC with infiltrative growth from a clinicopathological view point.

Age Factors↗

Carcinoembryonic antigen and nonspecific cross-reacting antigen in medullary carcinoma of the thyroid.

Carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) were studied immunohistochemically in formalin-fixed, paraffin-embedded tissues of 73 cases of medullary carcinoma of the thyroid (MTC) using 2 polyclonal antibodies (CEA antisera cross-reactive with or without NCA), 3 monoclonal antibodies recognizing epitopes only on CEA, and one monoclonal antibody against NCA. The staining patterns of the 5 antibodies against CEA in MTCs were not different, and they reacted with 86.3% of all cases. With regard to the effects of fixatives on the staining patterns, samples fixed with formalin or 4% paraformaldehyde demonstrated CEA immunoreactivity in both the cell membrane and cytoplasm. In Bouin-fixed tissue, the immunoreactivity was predominant on the cell membrane, whereas cytoplasmic positivity predominated in alcohol-fixed specimens. Thus the difference in fixatives used in previous studies does not appear to be a major reason for the difference in the reported incidence of CEA-positive MTCs. It is concluded that CEA is still a useful tumor marker for MTC and that it is detectable only in thyroid tumors originating from C cells, as seen in our series. The epitope defined by monoclonal antibody F106-88, present only on NCA, was found in 42.5% of all cases (49.2% of CEA-positive MTCs). The NCA immunoreactivity was located in the tumor cell cytoplasm as globular aggregates, which were also labeled for CEA.

Antigens, Differentiation, Myelomonocytic↗

Neuroendocrine differentiation in a case of acinic cell carcinoma of the parotid gland.

We report a case of acinic cell carcinoma of the parotid gland with neuroendocrine differentiation. Light microscopically, the tumor appeared as clear cell-type acinic cell carcinoma. In addition, the tumor showed neurosecretory features such as Grimelius positivity and the presence of neurosecretory granules by electron microscopy. We suggest that a tumor cell arising from a stem cell can show simultaneous differentiation to both neuroendocrine and acinic cells.

Carcinoma↗

Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs.

A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so-called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemical results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. Immunohistochemistry may be of great help in setting this issue.

Carcinoid Tumor↗

Pigmented dermatofibrosarcoma protuberans (Bednár tumor). An autopsy case with systemic metastasis.

An autopsy case of pigmented dermatofibrosarcoma protuberans (Bednár tumor) with systemic metastasis is reported. No previous example of this tumor showing widespread metastasis has been reported in the literature. The patient, a 45-year-old man, developed a tumor on the right upper arm. The tumor recurred twice and metastasized to other parts of the skin, lungs and brain during the 8-year clinical course. The primary tumor contained melanin-laden tumor cells and showed a storiform growth pattern. Autopsy confirmed multiple metastatic lesions in the skin, lungs, brain, thyroid, pancreas, stomach, small intestine and thigh muscles. The recurrent and metastatic tumors lacked both melanin production and the storiform arrangement, and instead revealed "fibro-sarcomatous" change with a herring-bone or interlacing pattern of growth.

Adult↗

Functional interpretation of the kidney juxtaglomerular apparatus using renin immunohistochemistry in Bartter's, pseudo-Bartter's and Conn's syndromes.

A comparative study of renin immunoreactivity in the juxtaglomerular apparatus of the human kidney was performed using the indirect immunoperoxidase method on a random microscopic sections. In renal biopsies taken from a case of Bartter's syndrome and a case of pseudo-Bartter's syndrome, the number of renin-positive juxtaglomerular apparatus (JGA) and the number of renin-positive cells in each JGA were significantly greater than in five renal specimens from control autopsy cases. In Conn's syndrome, none of the glomeruli contained renin-immunoreactive JGA. The number of renin-positive cells/mm2 in the renal cortex in cases of Bartter's and pseudo-Bartter's syndromes were 17.5 and 20.3, respectively, while in the control group, the range was 0.78-1.77 (mean 1.08). Together with other histochemical findings routinely examined in renal specimens, renin immunohistochemistry on random sections may be helpful in diagnostic renal pathology.

Adult↗

Deletion of histo-blood group A and B antigens and expression of incompatible A antigen in ovarian cancer.

Expression of histo-blood group ABH antigens in 53 cases of ovarian cancer was examined by immunoperoxidase staining of Formalin-fixed as well as frozen histological sections with various monoclonal antibodies, including those defining type 1, 2, 3, and 4 chain A. Findings of major interest were (a) deletion of A and B determinants in tumors from histo-blood group A and B individuals, and a high incidence of H antigen deletion in tumors from group O individuals were observed and (b) strong expression of incompatible A antigen in two of 10 samples from group B patients and in two of nine samples from group O patients was demonstrated. A antigen expression was defined by monoclonal antibody AH21, which reacts with monofucosyl type 1 chain A (ALed), but not by other types of anti-A antibodies directed to difucosyl type 1 chain A (ALeb), mono- or difucosyl type 2 chain A, or type 3 or type 4 chain A. The reactivity of monoclonal antibody AH21 was abolished by alpha-N-acetylgalactosaminidase from chicken liver. These findings clearly identified the specific expression of incompatible A antigen with the structure monofucosyl type 1 chain A (ALed) in tumors from histo-blood group B and O individuals.

ABO Blood-Group System↗

Calcifying odontogenic cysts: co-expression of intermediate filament proteins, and immunohistochemical distribution of keratins, involucrin, and filaggrin.

The epithelia lining the cyst of five cases of calcifying odontogenic cyst (COC) were evaluated immunohistochemically with the use of monoclonal antibodies (MoAb's) against keratin (PKK1, KL1, K4.62, K8.12) and vimentin, and polyclonal antisera agonist involucrin and filaggrin. Epithelial lining of COC was classified into 1) thin squamous-cell epithelium, 2) ameloblastoma-like, and 3) thin or 4) thick calcifying odontogenic epithelium. Foci consisting of ghost cells or calcified cells were categorized as calcifying epithelial odontogenic tumor (CEOT). Thin squamous-cell epithelium reacted with PKK1, KL1, K4.62, K8.12, and anti-vimentin MoAb's, thus demonstrating the co-expression of keratin and vimentin. Ameloblastoma-like cells showed positive staining with PKK1, KL1, and sometimes with anti-vimentin. Thick calcifying odontogenic epithelial lining showed stratification of cell layers, and the most strikingly reactive zone was the upper intermediate layer, which showed the presence of keratin, involucrin, and a small amount of filaggrin. Cells of this layer might be the most differentiated type of cells in COC. Undifferentiated odontogenic cells of COC masses were characterized by co-expression of keratin and vimentin, and by the absence of involucrin and filaggrin. All ghost cells were devoid of any immunostaining except for filaggrin, which was rarely positive, but eosinophilic or basophilic cells surrounding the ghost cells showed intense staining for all keratin proteins except vimentin.

Adolescent↗

C cell carcinoma of the thyroid. Follicular variant.

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immunohistochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma.

Adenocarcinoma↗

Effects of synthetic salmon calcitonin on C cells of the thyroid.

The effects of long-term administration of synthetic salmon calcitonin (TZ-CT) on thyroid C cells of rats were evaluated immunohistochemically and electron microscopically. Low dose (0.075, 0.75 and 7.5 IU/kg/day) administration caused no significant changes in the C cell population, whereas high doses (30 and 120 IU/kg/day) caused C cell suppression. The area ratio of C cells to total cells in the thyroid was measured on sections immunoperoxidase stained for calcitonin. The average C cell ratio was compared among the experimental groups. This morphometric analysis of the high-dose and control groups confirmed the differences in C cell populations statistically (30 IU/kg vs. control, p less than or equal to 0.05; 120 IU/kg vs. control, p less than or equal to 0.05). The suppressive effect of TZ-CT on C cells was reversible after cessation of administration for one month. Electron microscopic examination on the C cells in the high-dose groups revealed no particular ultrastructural differences. These results may suggest a negative feedback mechanism on C cells by exogenous CT.

Animals↗

Electron-immunocytochemical localization of calcitonin and calcitonin-gene-related peptide in human c cells of the thyroid.

A preembedding immunocytochemical technique enabled us to demonstrate normal human parafollicular (C) cells at the electron-microscopic level. The normal human C cells had numerous large secretory granules with a diameter of approximately 200 nm, well-developed rough endoplasmic reticulum and Golgi complex in their cytoplasm. Calcitonin immunoreactivity and calcitonin-gene-related peptide (CGRP) immunoreactivity were present only in the C cells whose secretory granules were heavily labeled. Both calcitonin and CGRP immunoreaction deposits were seen in the cytosol but not in the cisterna of endoplasmic reticulum, Golgi apparatus or mitochondrial matrix. The two peptides produced from a single calcitonin gene were stored in the secretory granules of the C cells.

Calcitonin↗

Application of video surgery to orthodontic diagnosis.

The purpose of this project was to develop a practical methodology for predicting the visual facial changes resulting from the movement of anterior teeth. The armamentarium includes an 8-bit audiovisual computer, a video camera, a digitizer, and a cephalogram of the patient. The system outputs the patient's profile on a personal computer video display. The image is superimposed on the soft tissue line of a digitized cephalogram plot on the same display. The video profile image is transformed from analog to digital signals. The profile image digitized by the computer is modified according to average ratios of soft tissue to hard tissue changes induced by modifications to the hard tissues. The program incorporates the spline function to smooth the profile image.

Audiovisual Aids↗

[Diagnosis and treatment of the precancer state in hereditary medullary thyroid carcinoma].

We attempted to elucidate the diagnosis and treatment in 11 patients with hereditary medullary thyroid carcinoma which were inherited as autosomal dominant traits. The oncogens are thought to be supported by the two-mutational event theory; the C cell hyperplasia, the first step, is the expression of the genetic mutation, which requires a subsequent somatic mutation to transform the initially mutated cell into a cancer cell. The C-cell hyperplasia was thought to be precancer state. The definitive diagnosis was established by measurement of calcitonin and CEA levels in sera. In patients with normal levels of calcitonin and CEA, the provocative test (Ca-gluconate plus pentagastrin) was useful such as in pt. no. 11,K.N.). The principle of surgery is total thyroidectomy because of multicentric occurrence in both lobes. Two patients (pt nos. 10, 11) with normal postoperative levels of provocative test underwent total thyroidectomy.

Adult↗

Immuno-electron microscopic study of calcitonin gene-related peptide (CGRP) in axis cylinders of the vagus nerve. CGRP is present in both myelinated and unmyelinated fibers.

The localization of immunoreactive calcitonin gene-related peptide (IR-CGRP) in vagus nerve fibers of the rat was studied with pre-embedding electron immunocytochemistry. IR-CGRP was localized in a small number (approximately 5%) of myelinated fibers and approximately 50% of unmyelinated fibers of the vagus. The immumoreactivity was observed in the dense cored vesicles (75-150 nm) and in the axoplasm, but absent in the clear vesicles.

Animals↗

Carcinoma of possible thymic origin presenting as a thyroid mass: a new subgroup of squamous cell carcinoma of the thyroid.

Intrathyroidal thymoma is a rare tumor that occurs in the thyroid gland and has been reported as a low-grade malignant tumor. The present report describes a 59-year-old male patient with this tumor, who was treated with subtotal thyroidectomy followed by radiation and chemotherapy. The tumor was located in the lower pole of the left lobe and the isthmus of the thyroid, and it had invaded the thyroid parenchyma, thyroid capsule, adjacent connective tissue, and neck muscles. Continuity between the cervical thymus and the tumor was noted. Subsequently, the patient developed widespread metastases in the liver, lungs, bones, and lymph nodes without local recurrence. Histologic examination disclosed a solid growth of epithelial cells with squamous cell differentiation and keratinization. The tumor cells had an ill-defined cell border and large nuclei with large nucleoli. Moderate mitoses and slight necrosis of the tumor were seen. Immunohistochemical examination showed that the tumor cells were stained positively for keratin but not for calcitonin or thyroglobulin. There were infiltrations of lymphocytes in the tumor and fibrous stroma, and most of them proved to be T cells.

Carcinoma, Squamous Cell↗

Paget's extension of esophageal carcinoma. Immunohistochemical and mucin histochemical evidence of Paget's cells in the esophageal mucosa.

A 68-year-old male with Paget's disease of the esophagus is reported. The underlying primary esophageal carcinoma was diagnosed as adenosquamous cell carcinoma on the basis of the presence of both adenocarcinoma and epidermoid carcinoma components. There was invasive growth of clear Paget's cells in the esophageal epithelium. Mucin histochemistry disclosed common characteristics of mucin between Paget's cells and adenosquamous cell carcinoma. It was histochemically confirmed that the existence of mucin was a general feature of extramammary Paget's disease. In 13 control esophageal carcinomas including three with adenocarcinomatous elements, Paget's cells were not found in the epithelium. To date only one case of Paget's disease of the esophagus has been described in the literature.

Aged↗