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Biomedical subjects

K Takatsuki

Publications and source records attributed to K Takatsuki.

At least 487 records · Page 27Linked to original sources

Blast crisis of chronic myelogenous leukemia with tumor formation characterized by T-cell features--a case report.

We report a case of chronic myelogenous leukemia (CML) associated with pronounced peripheral lymphadenopathy, with the cells having the philadelphia (Phl) chromosome and T-cell features. A 23-year-old man who was diagnosed as having CML and treated with busulfan was admitted to our hospital because of increasing hepatosplenomegaly and pronounced lymphadenopathy. An axillary lymph node biopsy disclosed that the malignant cells formed rosettes with neuraminidase-treated sheep red blood cells (En) (95.0%) and were positive for Leu 1 (91.8%). Of the cytochemical reactions, peroxidase was negative and periodic acid-Shiff, acid alpha-naphthyl acetate esterase and beta-glucuronidase were all positive. The karyotype of the bone marrow cells was 46 XY Phl positive (22q-), and that of the lymph node cells was 51 XY Phl positive +8, +9, +18, +19, +21, 22q-. He was treated with various anti-leukemic agents and irradiation. Despite such treatments, he died of pneumonia. This is a report of a CML patients with blast crisis and tumor formation characterized by T-cell features.

Adult↗

[Parathyroid function and uric acid metabolism].

In order to elucidate the influence of the parathyroid function on the uric acid metabolism, 24 patients (14 males, 10 females) with primary hyperparathyroidism (PHP) and 17 patients (9 males, 8 females) with idiopathic hypoparathyroidism (IHP) were extensively studied. The mean age was not significantly different between these groups, being 40.3 +/- 2.8 and 39.0 +/- 3.5 respectively. Hyperuricemia was found in 4 patients with PHP, but none of the patients had experienced gout. The serum uric acid levels were significantly higher and uric acid clearances were significantly lower in PHP than in IHP. There was no difference in daily urinary excretion of uric acid and in creatinine clearance between the two groups. In PHP, a positive correlation was observed between the levels of serum uric acid and calcium, both of which negatively correlated to renal uric acid clearance. Although the serum uric acid levels did not correlate to serum PTH levels in PHP, the removal of parathyroid adenoma resulted in a significant fall of serum uric acid levels. In IHP, the administration of PTH induced a small but significant decrease in serum uric acid levels with a coincidental increase in urinary uric acid excretion. Four hours of calcium infusion had no effect on the serum uric acid levels and urinary uric acid excretion. Treatment of IHP with 1 alpha-OH D3 to restore normal serum calcium levels caused significant increase in serum uric acid levels. These data indicate that the parathyroid function influences uric acid metabolism, even in the absence of renal insufficiency, mainly through changes of uric acid clearance. Levels of active vitamin D or chronically abnormal calcium levels in the circulation may be major determinant for uric acid metabolism in parathyroid disorders.

Adolescent↗

Evidence for the existence of a substance P-containing pathway from the nucleus laterodorsalis tegmenti (Castaldi) to the medial frontal cortex of the rat.

A long ascending substance P (SP)-containing pathway from the nucleus laterodorsalis tegmenti (TLD) to the medial frontal cortex (MFC) has been demonstrated by means of experimental immunohistochemical procedures. The unilateral destruction of the TLD, which contains numerous SP-like immunoreactive (SPLI) cells, resulted in a marked ipsilateral decrease in the SPLI fibers in the MFC.

Afferent Pathways↗

Experimental immunohistochemical studies on the distribution and origins of substance P in the medial preoptic area of the rat.

Distribution of substance P (SP)-positive fibers in the medial preoptic area (POM) of the rat and their origins were examined using indirect immunofluorescence. A very high density of SP-positive fibers was seen in the POM throughout its entire rostro-caudal extent. However, the distribution of these fibers was not even; the highest density was detected in the medial part of the POM, with less dense but still numerous fibers in the lateral part. On the other hand, in this area a small number of SP-positive cells could be found; a few cells were scattered in the rostral part and, in the caudal part, several cells could be seen in the ventral part of the POM. The origins of SP-positive fibers in the POM were experimentally examined. Since the destruction of the ventro-lateral part of the anterior hypothalamus (vlAH), where numerous SP-positive cells were seen, resulted in a marked decrease of SP-positive fibers in the POM on the operated side, the majority of these fibers may originate from SP-positive cells in the vlAH. The fine structure of SP-positive terminals in the POM were investigated by electron-microscopic immunohistochemical techniques. Immunoreactive terminals contained a few large granular vesicles together with numerous small vesicles, and they made synaptic contacts mainly with dendrites which were devoid of immunoreactive materials. Two different synaptic contacts could be distinguished: one asymmetrical (Gray's type I) and the other symmetrical (Gray's type II), with the latter being predominant.

Animals↗

Experimental and immunohistochemical studies concerning the major origins of the substance P-containing fibers in the lateral lemniscus and lateral parabrachial area of the rat, including the fiber pathways.

The origins and pathways of substance P-containing fibers in the lateral lemniscus and lateral parabrachial area of the rat were investigated by means of the indirect immunofluorescence technique. Following the placement of various knife cuts or lesions, the following could be concluded: (1) The cells of origin of substance P-containing fibers in the lateral lemniscus and lateral parabrachial area are localized in the ventral reticular formation of the rhombencephalon from the level of P2.8 to P7.0 in the atlas of Palkovits and Jacobowitz; (2) The fibers from these origins pass the ventral reticular formation of the rhombencephalon to form a dense bundle; (3) the fibers turn dorsally at the mid-rhombencephalon junction to reach the lateral lemniscus and lateral parabrachial area. The present study demonstrates the linking of the functions of the parabrachial area and lateral lemniscus via substance P innervation.

Animals↗

Ontogeny of neurotensin-containing neuron system of the rat: immunohistochemical analysis--II. Lower brain stem.

The ontogeny of the neurotensin neuron system in the lower brain stem of the rat was investigated by means of indirect immunofluorescent method. Neurotensin-like immunoreactivity-containing cells first appear in the primordium of the n. tractus solitarii, n. tractus spinalis nervi trigemini, reticular formation just medial to the latter nucleus, n. reticularis parvocellularis, n. laterodorsalis tegmenti, and midbrain reticular formation of the fetus at gestational day 17. At gestional day 18, neurotensin-immunoreactive cells newly appear in the n. raphe dorsalis. Between gestational day 19 and postnatal day 7, the animals show a remarkable increase in number of immunoreactive cells and fibers in various lower brain stem areas except for n. tractus spinalis nervi trigemini and n. tractus solitarii. Moreover, during this stage, neurotensin-immunoreactive cells located in the n. prepositus hypoglossi and n. vestibularis lateralis appear for the first time at birth and postnatal day 5, respectively. Since postnatal day 7, although the majority of immunoreactive cells located in the lower brain stem decrease in number as the rats grow, immunoreactive cells in the n. tractus spinalis nervi trigemini, on the contrary, increase in number from after birth until postnatal day 10, and maintain more or less their immunoreactivity even in the adult rat. In addition, neurotensin-immunoreactive cells in the nucleus of the solitary tract increase in number during the fetal period, reach the maximum content at postnatal day 7-10, and maintain their immunoreactivity even in the adult rats. Thus, the present study demonstrated that neurotensin-like immunoreactive structures appear at a very early ontogenetical stage, suggesting that neurotensin plays an important role in the development of the lower brain stem of the rat. In addition, the present study further showed that neurotensin-immuno-reactivity shows various fluctuations during the ontogeny, suggesting multiple functions of neurotensin in the central nervous system.

Animals↗

Homologous radioimmunoassay for human carboxyl-terminal parathyroid hormone and its clinical evaluation.

An homologous radioimmunoassay for human carboxyl-terminal parathyroid hormone (PTH) was developed using the antiserum raised against synthetic human PTH (46-84) and its clinical evaluation was attempted. Antisera were produced in guinea pigs by immunization with synthetic human PTH (46-84) conjugated with BSA. One of the antisera was used at a final concentration of 1 : 10,000 in the assay, and synthetic human PTH (53-84) for a standard and 125I-Tyr45 human PTH (46-84) for a tracer were used. A standard curve was obtained at concentrations from 0.001 to 10 ng per tube of human PTH (53-84). The displacement curves for human PTH (51-84), human PTH (46-84), Tyr45 human PTH (46-84) and bovine PTH (1-84) were almost identical with the standard curve made by synthetic human PTH (53-84). This antiserum, however, did not recognize the human PTH (1-34) fragment at all. Using this assay system, circulating immunoreactive PTH was measured in normal subjects and patients with parathyroid disorders. Normal PTH values in serum ranged from 0.47 ng/ml to an undetectable level (undetectable in two out of 32 normal subjects) and serum PTH values in patients with primary or secondary hyperparathyroidism or idiopathic hypoparathyroidism were almost completely discriminated from normal values. These results suggest that this homologous radioimmunoassay is a carboxyl-terminal specific assay for human PTH and can be quite useful in clinical practice.

Cross Reactions↗

Cell surface phenotype and in vitro function of adult T-cell leukemia cells.

The cell surface phenotypes of leukemic cells obtained from 30 patients with adult T-cell leukemia (ATL) were examined by means of a panel of OKT monoclonal antibodies and an anti-Tac monoclonal antibody. These leukemic cells were reactive with OKT1, OKT3, OKT4, OKT10, and OKT11 but not with OKT5, OKT6, OKT8 antibodies, suggesting that they were derived from peripheral mature cells included in the OKT4+ "helper/inducer" T-cell subset. Functionally, leukemic cells from none of the nine patients studied stimulated pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by normal B cells. Suppressor cell activity, however, was found in 17 of 25 patients in PWM-induced Ig production. Fresh or cultured ATL cells from 22 of 23 patients tested expressed Tac antigen (interleukin-2 receptor) on the cell surface. The significance of Tac antigen on ATL cells is discussed in relation to the abnormal regulation of Tac antigen and leukemogenesis.

Adult↗

A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases.

We have observed five patients with smoldering adult T-cell leukemia (ATL) who had skin lesions as premonitory symptoms. The illness developed slowly, but flared up after several years. Skin lesions appeared in the form of erythema, papules, or nodules. Infiltration of the skin by ATL cells was slight, and the proportion of ATL cells in the peripheral blood was 0%-2%. The serum lactate dehydrogenase (LDH) value was within normal range and was not associated with hypercalcemia; lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration were very slight. In most cases, hypergammaglobulinemia was seen, and in one case, monoclonal hypergammaglobulinemia was observed. All five patients had lived in an area in which ATL was endemic, and their anti-ATLA antibodies were positive; none had ever received a blood transfusion. One patient developed typical ATL after more than 13 yr of illness and died of renal insufficiency. Another patient developed typical ATL after 5 yr of illness and died of cryptococcus meningitis. Based on clinical and pathologic differences, we believe that these cases should be distinguished from typical ATL cases for the purposes of prognosis and treatment.

Antibodies↗

Altered expression of lymphocyte Fc alpha receptor in selective IgA deficiency and IgA nephropathy.

To study the expression of FcR specific for IgA (Fc alpha R) on human peripheral lymphocytes (PBL), PBL from normal donors were incubated with 300 to 500 micrograms/ml MOPC 315 IgA having anti-trinitrophenyl (TNP) antibody activity at 4 degrees C or 37 degrees C for 60 min. Under this condition, less than 2% of total cells could form rosettes with TNP-coated ox red blood cells (TNP-ORBC). When cultured with MOPC 315 IgA at 37 degrees C for 18 hr, however, there was a dose-dependent increase of the rosette-forming cells (RFC) binding TNP-ORBC. Because 15 to 20% of the total cells bound TNP-ORBC but not unsensitized ORBC, the rosette formation appeared to be due to the cytophilic binding of IgA to the cells. The binding of MOPC 315 IgA was competed by TEPC 15 IgA and human myeloma IgA, but not by murine myeloma proteins of other classes, indicating that the receptor is specific for IgA. Fc alpha R was induced on 15 to 20% of fractionated T and B cells, as well as on 15 to 18% of concanavalin A-(Con A) activated lymphocytes when cultured with IgA. The induction of the receptor was dependent on protein and RNA synthesis, but not on DNA synthesis as suggested by the sensitivity to metabolic inhibitors, such as mitomycin C, actinomycin D, puromycin, and cycloheximide. In five patients with selective IgA deficiency (serum IgA, 0 to 4 mg/dl), only 5.1% +/- 1.7 of PBL formed rosettes with TNP-ORBC after culture with MOPC 315 IgA, whereas 12.5% +/- 2.5 of PBL from normal donors (serum IgA, 90 to 330 mg/dl) formed rosettes. Fc alpha R was induced on more than 15% of the cells from these patients, however, when cultured with IgA in the presence of a conditioned medium obtained from mixed lymphocyte culture from two normal donors. The results suggested that the abnormality in the patients' PBL might be in the induction mechanism rather than in the number of precursor cells that could express Fc alpha R in the presence of IgA. On the other hand, Fc alpha R was induced on 10.4% +/- 1.5 of PBL from the patients with IgA nephropathy (serum IgA, 382 +/- 11 mg/dl) when they were incubated with IgA for 1 hr at 37 degrees C. Because Fc alpha R on normal PBL was not induced by 1 hr of incubation with IgA, it appeared that the receptor was already expressed in vivo on the cells of these patients.

Animals↗

Decrease in the zinc turbidity test values in patients with liver cirrhosis: a possible indicator for impending hepatocellular carcinoma.

A retrospective investigation of 21 cases of hepatocellular carcinoma with liver cirrhosis presumably of viral origin revealed a significant fall in the value of the zinc turbidity test from 15.5 +/- 6.9 (mean +/- SD) at 1 year to 11.2 +/- 2.5 units at 6 months before the discovery of the carcinoma (p less than 0.05), and a return to 16.8 +/- 7.2 units one month after the diagnosis (p less than 0.05). The values at 6, 2 and 1 month before the diagnosis were significantly lower than that for 120 control cirrhotics without hepatocellular carcinoma at 16.3 +/- 7.2 units (p less than 0.05). The fall in value occurred before or concurrently with a rise in the alpha-fetoprotein level in three patients, in whom it has been determined serially. Based on the results obtained, the decrease in the zinc turbidity test value may be used as an indicator for impending hepatocellular carcinoma in patients with liver cirrhosis.

Adult↗

Plasma cell dyscrasia with polyneuropathy and endocrine disorder: clinical and laboratory features of 109 reported cases.

We reviewed a series of 109 reported Japanese cases of "plasma cell dyscrasia with polyneuropathy and endocrine disorder." This syndrome shows 1) polyneuropathy with increased protein level in the cerebrospinal fluid and sometimes papilledema, 2) endocrinological symptoms, including skin pigmentation, sclerosis, hypertrichosis, gynecomastia, impotence, amenorrhea, decreased glucose tolerance, edema, pleural effusion and ascites, 3) hepatomegaly, splenomegaly and lymphadenopathy, 4) polycythemia, leukocytosis and thrombocytosis, 5) osteosclerotic changes and 6) plasma cell dyscrasia. Plasma cell dyscrasia is considered to be the cardinal change in this syndrome. Most of the patients have low levels of IgG lambda or IgA lambda M-protein in the serum and a slightly increased number of plasma cells in the bone marrow. The clinical course is usually chronic. Surgical excision or irradiation of the local lesion and administration of corticosteroids and/or anti-cancer drugs are effective in improving polyneuropathy and other systemic symptoms. This syndrome is apparently more common in Japan than in the United States and European countries. The pathogenesis of the association of a variety of symptoms in this syndrome is still unclear.

Adult↗

Cytogenetic studies and clinical aspects of patients with plasma cell leukemia and leukemic macroglobulinemia.

Chromosomes of six patients with plasma cell leukemia and one patient with leukemic macroglobulinemia were examined from peripheral blood, bone marrow, and/or pleural fluid. All the patients had a clonal chromosomal abnormality. The modal chromosome number was near tetraploid in two, pseudodiploid in two, and hypodiploid in three patients. Rearrangements of chromosome 1 were found in all the patients. The most consistent abnormality was a large marker involving the long arm of No. 1, found in six patients, including the patient with macroglobulinemia. Each patient had one to four large markers which resulted in partial trisomy to hexasomy for the long arm of No. 1. The translocations occurred with No. 9 in two, with No. 16 in two, and Nos. 8, 17, and 18 each in one patient. The survival time from the diagnosis was less than 1 year in five of them and over 2 years in one. The only patient whose cells lacked an extra 1q lived for over 3 years. Five 14q+ marker chromosomes were detected in three patients. The donor chromosome was No. 11 in one of these and was undetermined in the others; the size of each 14q+ marker seemed quite different which suggested different donor chromosomes. Loss of a sex chromosome was found in five patients. Loss of No. 13 and gain of No. 7 or 7q were each found in two patients. Rearrangement or deletion of the short arm of No. 8 was found in five patients. A rearrangement of 9p was found in three patients. The myeloma cells had a different morphology in the peripheral blood, bone marrow, and/or pleural fluid before and after the leukemic phase of one patient; however, chromosome analysis revealed the same clone despite the altered morphology.

Adult↗

A proposal for smoldering adult T-cell leukemia--diversity in clinical pictures of adult T-cell leukemia--.

We have observed five patients with smoldering adult T-cell leukemia (ATL) who had skin lesions as premonitory symptoms. The illness developed slowly but flared up after several years. Skin lesions appeared in the form of erythema, papules or nodules. Infiltration of the skin by ATL cells was slight, and the proportion of ATL cells in the peripheral blood was from 0% to 2%. The serum lactic dehydrogenase value was within normal range, and was not associated with hypercalcemia, lymphadenopathy, or hepatosplenomegaly, and bone marrow infiltration was very slight. In most cases, hypergammaglobulinemia was seen, and in one case monoclonal hypergammaglobulinemia was observed. All five patients had lived in an area in which ATL was endemic, and their sera were positive for anti-ATL-associated antigen antibodies. None of them had ever received a blood transfusion. One patient developed typical ATL after more than 13 yr of illness, and died of renal insufficiency. Another patient developed typical ATL after 5 yr of illness, and died or cryptococcus meningitis. These cases were clinically and pathologically different from typical ATL cases already reported, and we feel it necessary to make distinctions from the viewpoints of prognosis and treatment. In discussing these cases, we compared smoldering ATL with typical ATL, and deliberated upon the causes of both.

Antibodies, Viral↗

[Clinical and hematologic features of adult T cell leukemia].

Adult T cell leukemia (ATL) is a new disease entity with the following characteristic clinical and hematologic flutures: 1) Acute or subacute T cell leukemia in adulthood 2) Endemic in Kyushu and Southwest of Shikoku 3) Frequent skin infiltration 4) Common hepatosplenomegaly and lymphadenopathy (not so marked) 5) Mild or moderate bone marrow infiltration 6) Hypercalcemia 7) Typical leukemia cells with deeply-indented or lobulated nuclei and heterogeneous(pleomorphic) cells 8) No mediastinal mass 9) Ineffective ordinary treatment and short survival time Surface phenotypes of ATL cells were OKT 3(+) 4(+) 5(-) 8(-) Tac(+) and leukemia cells suppressed PWM-induced Ig synthesis in about half cases. Chromosome analysis showed the high incidence of abnormalities such as trisomy 7 and 14q +. ATL was compared with cutaneous T cell leukemia, T-cell chronic lymphocytic leukemia and lymphosarcoma cell leukemia in clinical features, hematologic and immunologic characteristics and the association with type C retrovirus.

Adult↗