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Biomedical subjects

M Setoyama

Publications and source records attributed to M Setoyama.

At least 19 recordsLinked to original sources

Human T-cell lymphotropic virus type I infects eccrine sweat gland epithelia.

Human T-cell lymphotropic virus type I (HTLV-I) is known to be associated with several non-neoplastic inflammatory disorders such as HTLV-I-associated myelopathy/tropical spastic paraparesis, arthropathy, uveitis and lymphadenitis, in addition to neoplastic adult T-cell leukemia/lymphoma (ATLL). A strong relation between HTLV-I infection and Sjögren's syndrome (SS) has been reported, and impaired sweating in SS is well known. We have often encountered dry skin in patients with ATLL. On the basis of these observations, we aimed to determine whether HTLV-I infection is present in isolated sweat glands. Eccrine gland epithelia were isolated from full thickness skin biopsies from 8 HTLV-I-seropositive and 7 seronegative individuals using dispase in Eagle's minimum essential medium supplemented with 13% fetal calf serum. We detected HTLV-IpX sequences in samples of eccrine sweat gland epithelia from 4 samples of the 8 seropositive individuals using nested polymerase chain reaction, but all 7 samples from the seronegative donors had no signal corresponding to the sequence. Our results were confirmed by dot blot hybridization. Our results suggest that eccrine epithelium is one of the target organs of HTLV-I infection.

Adult

Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25).

Chromosome translocations involving band 12p13 are known to be involved in a variety of hematologic malignancies, some of them resulting in rearrangement of the ETV6/TEL gene. Applying the fluorescence in situ hybridization (FISH) method, we found a cryptic translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia (AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A patient-specific cDNA library was screened with ETV6 cDNA, and a novel fusion transcript was identified between the ETV6 and TRKC/NTRK3 gene located on 15q25. TRKC is a receptor tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known to be expressed broadly in neural tissues but not in hematologic cells, so far. ETV6-TRKC chimeric transcript encoded the pointed (PNT) domain of the ETV6 gene that fused to the protein-tyrosine kinase (PTK) domain of the TRKC gene. Two types of fusion transcript were determined, one that included the entire PTK domain of TRKC and the other in which the 3'-terminal 462 bp of TRKC was truncated within the PTK domain. Western blot analysis showed the expression of both chimeric proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK expressed in the leukemic cells may contribute to cellular transformation by abnormally activating TRK signaling pathways. Moreover, this is the first report on truncated neurotrophin receptors associated in leukemia.

Acute Disease

Significant expression of G-CSF-induced gene-1 (GIG-1) protein in myeloid cells and NK cells.

The granulocyte colony-stimulating factor (G-CSF)-induced gene, GIG-1, was originally cloned from G-CSF-stimulated bone marrow mononuclear cells obtained from a patient with chronic myelogenous leukemia (CML). We have characterized the GIG-1 gene and its protein product. Expression of GIG-1 mRNA was elevated by treatment with G-CSF in normal bone marrow mononuclear cells, as well as in some cases of blast cells obtained from patients with acute myelogenous leukemia (AML) and CML. Western blot analysis with anti-GIG-1 peptide antiserum showed the molecular mass of GIG-1 product was about 17 kDa. Immunostaining of the hematopoietic cells demonstrated that GIG-1 product was mainly localized to the cytoplasm of both myeloid and natural killer (NK) cells. These results suggested that GIG-1 protein is an integral component that is accumulated during the differentiation of myeloid cells toward the stage of mature neutrophils. Expression of GIG-1 gene in mature neutrophils was tightly regulated and reactivation of GIG-1 gene by G-CSF in mature neutrophils may represent a compensation process for the protein lost through the activation of these cells, thus implying an important role for this protein in host defense mechanisms.

Antigens, CD34

A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis.

A nerve growth factor receptor encoded by the TRKA gene plays an important part in the formation of autonomic neurons and small sensory neurons in dorsal root ganglia and in signal transduction through its intracytoplasmic tyrosine kinase domain. Recently, three mutations in the tyrosine kinase domain of TRKA have been reported in patients with congenital insensitivity to pain with anhidrosis, which is an autosomal recessive disorder characterized by recurrent fever due to absence of sweating, no reaction to noxious stimuli, self-mutilating behavior, and mental retardation. We examined the TRKA gene in five generations of a large Japanese family with many consanguineous marriages who live in a small remote island of the southern part of Japan. We found a novel point mutation at nucleotide 1825 (A-->G transition) resulting in Met-581-Val in the tyrosine kinase domain. Two of the three affected patients were homozygous for this mutation; however, the third affected patient was heterozygous. Further analysis revealed that the third patient was a compound heterozygote with the Met-581-Val mutation in one allele and with a single base C deletion mutation at nucleotide 1726 in exon 14 in the other allele, resulting in a frameshift and premature termination codon.

Adult

A case of sarcoidosis involving the tongue.

Sarcoidosis is a systemic granulomatous disorder which commonly affects the skin. Involvement of the tongue is rare; a review of the previous literature over the last 30 years revealed only six cases of sarcoidosis affecting the tongue. We studied a case of sarcoidosis involving the tongue in a 32-year-old Japanese woman with characteristic clinical and pathological findings. She visited our department with a complaint of a tongue lesion of which she had been aware for a month. A diagnosis of sarcoidosis was made for the lesion by clinical and pathological examinations. Oral involvement by sarcoidosis is rare, however this disorder should be considered as a possible cause of intraoral granulomatous lesions.

Adrenal Cortex Hormones

Clinicopathologic analysis of 124 cases of adult T-cell leukemia/lymphoma with cutaneous manifestations: the smouldering type with skin manifestations has a poorer prognosis than previously thought.

Adult T-cell leukemia/lymphoma (ATLL) commonly involves the skin as well as peripheral blood and lymph nodes. During the last 15 years we have studied 124 cases of ATLL with specific skin manifestations. Twenty-one patients (16.9%) were classified as acute, 21 (16.9%) as chronic, 26 (21.0%) as lymphoma, and 56 (45.2%) as smouldering according to Shimoyama's classification. Many patients had nodules/tumors (34.7%), erythematous plaques (22.6%), and erythematous papules (19.4%) similar to those occurring with other cutaneous T-cell lymphomas. Some patients displayed characteristic skin manifestations resembling non-neoplastic cutaneous disorders. The median survival time (MST) of all patients was 12.0 months. The MSTs of individual clinical types were: acute type, 4 months; chronic type, 14 months; lymphoma type, 7 months; and smouldering type, 16 months. In the smouldering type, cases with a deeper infiltration pattern (MST, 14 months) had a more aggressive course than those with a superficial infiltration pattern (MST, 24 months) (p < 0.05). The results indicate that smouldering type ATLL with skin manifestations may have a worse prognosis than without skin manifestations. Moreover, some cases of the smouldering type with specific skin lesions should be classified into another group with a much poorer prognosis.

Adult

Two cases of gigantic dystrophic calcinosis cutis caused by subcutaneous and/or intramuscular injections.

We describe two female patients with gigantic dystrophic calcinosis cutis caused by a large number of subcutaneous and/or intramuscular injections which they received when they were much younger. Laboratory data and physical examinations were generally within normal limits, and we detected no disease which might induce cutaneous calcification. There are many reports of dystrophic calcinosis cutis caused by injection of several kinds of drugs. However, we found no previous report describing a patient with calcinosis cutis induced by local tissue injury from a large number of injections and with extraordinarily widespread calcification at the injection sites. Because we do not know the exact drugs injected, it is difficult to say if a specific ingredient in the injections was related to this condition. We do know that a large number of subcutaneous or intramuscular injections were frequently administered to patients who had difficulty in maintaining venous infusions in the past, so there may be similar cases of dystrophic calcinosis cutis which have not been reported.

Aged

Morphological, biochemical and molecular biological characteristics of a granulocyte colony-stimulating factor-producing human eccrine carcinoma cell line.

We describe here a newly established cell line from an eccrine carcinoma which produced an abundant amount of granulocyte colony-stimulating factor (G-CSF). An eccrine carcinoma of the scalp of a 69 year-old-Japanese female had metastasized to the pleura. Clinically, she had marked neutrophilia (up to 60,000/mm3), and a high level of G-CSF (38.7 x 10(3) pg/ml) was detected in the pleural effusion, as determined by enzyme-linked immunosorbent assay (ELISA). We established a cell line in vitro and maintained the cells in culture for 30 months in 90 subcultures. We investigated whether these tumor cells were able to produce G-CSF in culture and found that they were. We also found that the amount of G-CSF produced paralleled the rise in cell number (26.5 x 10(3) pg/ml at confluency). When culture media were administered to rabbits (25 ml/rabbit), the amount of circulating neutrophils increased until the number was equal to or greater than that resulting from injection of recombinant human G-CSF (rhG-CSF)(75 micrograms). This effect persisted for 7 days. When tumors were induced in SCID and nude mice by injecting cultured cells (1 x 10(7) cells/mouse), the number of circulating neutrophils also correlated well with tumor size in these mice (200,000/mm3, 3 cm tumor). After tumor removal, the neutrophil number returned to normal within 30 days. G-CSFmRNA in cultured, cells was detected by RT-PCR. Based on these results, it was confirmed that the marked neutrophilia observed in the patient was caused by the tumor-generated G-CSF. This is the first G-CSF-producing cell line developed from a cancer of the skin.

Adenocarcinoma

Prurigo as a clinical prodrome to adult T-cell leukaemia/lymphoma.

We report a case of adult T-cell leukaemia/lymphoma (ATLL) with prurigo as a prodromal skin manifestation. The patient was a 52-year-old woman with a 2-year history of a fluctuating skin condition consisting of pruritic papules and pigmentation on her lower legs and right buttock. Prurigo was diagnosed at her first visit in October 1995, and she was found to be seropositive for human T-cell lymphotropic virus type 1 (HTLV-1). Two years later, the skin lesions had spread over the patient's forearms and dorsa of the hands, and abnormal lymphoid cells had appeared in her peripheral blood. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus in the peripheral blood, but not in a skin lesion. Based on these results, a diagnosis of overt ATLL of the smouldering type was made. The findings in this case indicate that in healthy HTLV-1 seropositive carriers, prurigo requires careful follow-up as a cutaneous prodrome of ATLL.

Blotting, Southern

Membranocystic lesions in a patient with cytophagic histiocytic panniculitis associated with subcutaneous T-cell lymphoma.

A 51-year-old Japanese woman had erythematous, tender subcutaneous nodules on her lower legs and buttocks, as well as fever, pancytopenia, and liver dysfunction. Histopathologic examination of the nodules showed subcutaneous T-cell lymphoma with cytophagocytosis and membranocystic lesions. Our patient was unique in having the combination of cytophagic histiocytic panniculitis due to subcutaneous T-cell lymphoma and membranocystic lesions.

Cell Membrane

Squamous cell carcinoma of the skin associated with sarcoid reactions in the regional lymph nodes.

Sarcoid reactions in lymph nodes with or without metastasis from a primary malignant neoplasm are well-known. However, it is extremely rare to find these reactions associated with cutaneous solid tumors; only one such case has appeared in the literature. Here we describe a case of an 83-year-old man with cutaneous squamous cell carcinoma accompanied by sarcoid reactions and metastatic foci in the regional lymph nodes. The possibilities of systemic sarcoidosis and tuberculosis were excluded after extensive examinations specific for these diseases. Some authors regard the sarcoid reaction to be a sign of a good prognosis on the basis of studies of a few patients with solid tumors. In our case, however, the patient died of pulmonary metastasis with pleuritis carcinomatosa shortly after surgery. Systematic analysis of a sufficient number of cases should be carried out to evaluate the clinical significance of this type of reaction.

Aged

Linear lichen planus in the region of the mandibular nerve caused by an allergy to palladium in dental metals.

We observed a case of linear lichen planus extending from the right cheek to the jaw, which was accompanied by itching and an unusual sensation in the mouth. The eruption was located along the mandible and aligned with the mandibular nerve. The right molars of the patient contained metal compounds and these were considered to be the cause of his disease. Patch testing with various dental metals showed positive reactions to palladium and platinum. A biopsy specimen showed a lichenoid reaction in the lesional tissue, and dermal contact dermatitis was noted at the palladium patch test site. His dentist reported that palladium-silver-gold or nickel-chrome alloys without platinum had been used in the crown and bridge of his molars. After removal of the dental alloys, the skin eruption resolved with some residual hyperpigmentation. In addition, the peculiar mouth sensation disappeared dramatically within 2 months.

Allergens

Elastofibroma dorsi.

Elastofibroma dorsi is a rare benign soft-tissue tumor which is solid, ill-defined and marked by slow growth. It is usually found in the subscapular region of older individuals. We report here the case of a 56-year-old Japanese man with elastofibroma dorsi which was located in the left subscapular region and measured 50 x 70 mm in size. The mass was very similar to tumors previously reported, both clinically and histologically. This entity has only rarely been described in the dermatological literature, but it should be considered in the differential diagnosis of subscapular complaints elderly patients.

Back

Detection of HTLV-1 by polymerase chain reaction in situ hybridization in adult T-cell leukemia/lymphoma.

A method for nonradioactive polymerase chain reaction in situ hybridization was developed and used to determine the distribution of human T-lymphotropic virus type I (HTLV-I) proviral DNA in paraffin-embedded surgical specimens of adult T-cell leukemia/lymphoma (ATLL). As controls, we used biopsy samples of five cases of mycosis fungoides, cells of an HTLV-I-infected cell line (MT2), as well as HTLV-1-negative cells (YAS). We successfully detected the amplicon of the HTLV-1 tax sequence in the nuclei of the cutaneous infiltrating lymphoid cells in 90% (9/10) of ATLL cases. Studies also revealed the existence of HTLV-1 provirus DNA in nuclei of sweat gland epithelial cells and vascular endothelial cells as well as lymphoid cells in ATLL patients. Mycosis fungoides and YAS cells were negative for the HTLV-I tax sequence, but MT2 cells were strongly positive. The results indicated that this technique was more sensitive in detecting intracellular amplicons than was the previous in situ hybridization method. Through its use, we were able to easily determine the distribution of HTLV-I-positive cells among the various cells and tissues of paraffin-embedded archival materials.

Adult