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Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 397 records · Page 22Linked to original sources

Clinical course of human T-lymphotropic virus type I carriers with molecularly detectable monoclonal proliferation of T lymphocytes: defining a low- and high-risk population.

To characterize the prodromal phase of adult T-cell leukemia (ATL), a prospective follow-up study was conducted on 50 carriers in a putative pre-ATL state. This state was defined by the presence of molecularly-detectable monoclonal proliferation of human T-lymphotropic virus type I (HTLV-I)-infected T lymphocytes, and the absence of clinical symptoms of leukemia. The median observation time was 50 months. The pre-ATL subjects were divided into two groups according to initial white blood cell (WBC) counts: group A, those with a normal WBC count (9,000/microL) (n = 30), and group B, those with an increased WBC count (9,000 to 15,000) (n = 20). Comparisons were made between the two groups and with a group of 25 patients with chronic ATL (group C) who had WBC counts of more than 15,000. Significant differences in survival rate were found between groups A and B (10-year survival 65.7%) and group C (32.8%) (P < .01), and between group A (10-year survival 90.0%) and group B (52.1%) (P < .05). The incidence of transformation to overt ATL was 10% (3 of 30) in group A and 50% (10 of 20) in group B (P < .01). In six transformed cases (one in A and five in B) we found exactly the same integration sites in pre-ATL and overt ATL phases, confirming the multistep leukemogenesis hypothesized for this disease. However, the pre-ATL subjects could be divided into two distinct prognostic groups based on the initial WBC count; those with good and those with poor prognosis. Although the 10% transformation rate (2.5% annually) in group A seemed to be extremely high compared with that in the general population of HTLV-I carriers (around 0.06% to 0.4% annually), the majority of group A subjects and some in group B showed stable clinical courses without transformation. Further, development of ATL was not observed in four group A subjects with HTLV-I-associated myelopathy (HAM), which is rarely associated with ATL. We propose to call this group of rather benign HTLV-I carriers "HTLV-I carriers with monoclonal proliferation of T lymphocytes (HCMPT)." Thus far we have been unable to identify reliable parameters other than WBC counts that prospectively distinguish HCMPT from the true pre-ATL state, in which there is a high probability of developing ATL. Further clinical and biologic approaches should elucidate the natural history of the HTLV-I carrier state and early events in ATL leukemogenesis.

Adult↗

Association of the antibodies against human papillomavirus 16 E4 and E7 proteins with cervical cancer positive for human papillomavirus DNA.

Occurrence of the antibodies against human papillomavirus (HPV) 16 proteins E4 and E7 is specifically but independently associated with cervical cancer. To correlate HPV DNA and antibody data, we examined the biopsy specimens and sera, by polymerase chain reaction (PCR) and by ELISA, respectively, from 51 patients with cervical cancer (including 3 recurrent cases) and 22 with cervical intra-epithelial neoplasia. Consensus primers for the L1 region were used for PCR and bacterially expressed, purified fusion protein HPV-16 E4 and non-fusion protein HPV-16 E7 were used for ELISA. HPV-16 DNA and other HPV types were detected in 17 and 25, respectively, out of 51 cases of cervical cancer. Ten out of the 17 HPV-16-DNA-positives were positive either for anti-E4 or for anti-E7: positivities for anti-E4, for anti-E7, and for both were 6/17, 5/17 and 1/17 respectively. Three anti-E7-positives consisted of those for HPV-33, -52 and -58 DNA, suggesting that limited cross-reaction occurred between the HPV types. Among the HPV-16-DNA-positive cases of cancer, lymph-node or distant metastasis was recorded more frequently in the seropositives than in the seronegatives. Our results show that the HPV-16 anti-E4 or anti-E7 occurs in some, but not in all, of the HPV-16-DNA-positive cases, and support the hypothesis that the presence of the HPV-16 antibodies can be used as a marker for possible metastasis.

Adult↗

Chimeric reverse transcriptase of Moloney murine leukaemia virus, having the YXDD box of a Drosophila retrotransposon, 17.6.

All reverse transcriptases (RTs) so far examined are known to possess in common a stretch of 7 amino acids called the YXDD box. Various mutations were introduced in vitro into the nucleotide sequence coding for this box of Moloney murine leukaemia virus (Mo-MuLV) RT. The YXDD box of Mo-MuLV could be replaced by the counterpart of a Drosophila retrotransposon, 17.6, without loss of activity, while virtually complete loss of activity was detected in the case of replacement of the YXDD box of Rous sarcoma virus RT. Amino-acid substitution at position X resulted in significant change in divalent metal ion preference and enzyme activity, thus indicating that the YXDD box possibly constitutes a part of the active center of RT through metal ion binding.

Amino Acid Sequence↗

Relationship between the anti-HTLV-1 antibody level, the number of abnormal lymphocytes and the viral-genome dose in HTLV-1-infected individuals.

Two distinct diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), develop in a minor population of HTLV-1 carriers. We examined the relationship between the viral genome dose in the peripheral-blood mononuclear cells and the serological response in HTLV-1 carriers and patients with HAM/TSP. The antibody titer to HTLV-1 gag and env proteins, as well as the frequency of an antibody response to viral protein p40tax and the titer, increased with increasing viral genome dose. However, the number of abnormal lymphocytes was not directly related to the host viral load. Patients with HAM/TSP generally showed a higher genome dose than healthy carriers and also had higher antibody titers than healthy carriers with the same HTLV-1 load, supporting the existence of an augmented immune response in these patients. These findings suggest that the antibody titer to HTLV-1 genome products, and not the number of abnormal lymphocytes, intimately reflects the approximate viral load in HTLV-1-infected individuals.

Adolescent↗

Cloning of a cDNA encoding rat intestinal 15 kDa protein and its tissue distribution.

A cDNA encoding rat intestinal 15 kDa protein was isolated and sequenced from a rat ileum-specific cDNA library. This cDNA was found to contain an open reading frame of 384 nucleotides as well as 5' (27 nucleotides) and 3' (46 nucleotides) non-coding regions. The deduced sequence of 127 amino acids was identical to that of rat I-15P which was purified from rat intestinal epithelium. The nucleotide sequence of the open reading frame exhibited 79% identity to that of the porcine gastrotropin. Northern blot analysis indicated that the same size of transcript as that of the ileum was detected in the ovary, suggesting that I-15P or a homologous protein might be involved in the metabolism of steroids in steroid hormone-producing tissues.

Amino Acid Sequence↗

A giant tumor of the mesocolon found to be metastasis from an alpha-fetoprotein-producing gastric carcinoma: report of a case.

We present herein an extremely rare case of metastasis from a gastric carcinoma to the mesocolon. A 71-year-old woman underwent a laparotomy for gastric cancer with an intra-abdominal mass. Her serum alpha-fetoprotein level was very high at 3,560 ng/ml. The abdominal mass was subsequently revealed to be a metastatic tumor of the transverse mesocolon derived from an alpha-fetoprotein-producing gastric carcinoma, but no other metastatic focus was found. An immunohistochemical study revealed alpha-fetoprotein-positive cells in both lesions. The serum alpha-fetoprotein level became normal after the operation which was followed by a course of chemotherapy, and no recurrence has been observed thus far in 6 months of follow up.

Adenocarcinoma↗

Low-dose combination therapy with metoprolol and captopril for congestive heart failure in mice.

We assessed the therapeutic efficacy of a low-dose combination of metoprolol and captopril given orally to C3H/Hej mice that developed dilated and hypertrophied hearts after being inoculated with the encephalomyocarditis virus. Mice were randomly assigned to one of six 8-week oral regimens: 1 mg/kg/day of metoprolol (group 1); 10 mg/kg/day of metoprolol (group 2); 1.2 mg/kg/day of captopril (group 3); 12 mg/kg/day of captopril (group 4); 1 mg/kg/day of metoprolol plus 1.2 mg/kg/day of captopril (group 5); or distilled water (control group). Group 4 exhibited a significantly lower survival rate and body weight than the control group (p < 0.01). Survival rates and body weights were similar in groups 1, 2, 3, 5, and the control group. Low-dose metoprolol plus captopril is superior to low-dose metoprolol, high-dose metoprolol, and low-dose captopril with regard to heart weight and the heart weight/body weight ratio. The left and right ventricular cavity dimensions as well as myocardial necrosis, calcification, and fibrosis were less severe in groups 4 and 5 than in the control group. The left ventricular free wall showed significantly more thinning in group 4 than in the control group (p < 0.01). Our results show that the administration of low-doses of metoprolol and captopril given in combination was effective in this animal model of congestive heart failure and was associated with a reduction in biventricular cavity dimensions and myocardial necrosis.

Animals↗

Myocardial atrial natriuretic factor gene expression after coronary ligation in rats.

The atrial natriuretic factor (ANF) messenger RNA (mRNA) content was determined in a rat model of acute myocardial infarction. Non-infarcted tissue of left and right ventricles were examined soon after ligation of the left descending anterior coronary artery. In the left ventricles, ANF mRNA/alpha-actin mRNA ratio increased to reach a maximum on day 7 and was sustained while in the right ventricle, the maximum was reached on day 1. The plasma ANF was significantly (p < 0.01) elevated from days 1 to 28 after coronary ligation. The primary compensatory response of ANF within the first 7 days may be attributed not only its synthesis in the left ventricle but also to its generation in the right ventricle in acute heart failure.

Actins↗

Mode of action of exo- and endo-type cellulases from Irpex lacteus in the hydrolysis of cellulose with different crystallinities.

The mode of action of two highly purified cellulases of exo- and endo-types from Irpex lacteus was investigated by using pure cellulosic substrates with different crystallinities derived from cellulose I. Exo-type cellulase saccharified all celluloses more effectively than endo-type enzyme, and the saccharification activities of both cellulases similarly increased with decreasing crystallinity of cellulose. The DP-lowering activity of exo-type cellulase remained similar for celluloses with higher crystallinity, while this cellulase showed a degradation mode resembling that of the endo-type enzyme for the substrates with lower crystallinity. Compared with exo-type cellulase, endo-type cellulase remarkably decreased the DP of cellulose with higher crystallinity, while this activity was abated for cellulose with lower crystallinity. Thus, the effects of both cellulases became similar in the degradation of amorphous substrates such as H3PO4-treated cellulose. Endo-type cellulase produced several kinds of cellooligosaccharide from all kinds of cellulose used, while the product of the exo-type enzyme was only cellobiose from crystalline cellulose such as cotton and cotton linter even after a 12-h incubation period. The results indicate that each cellulase shows a typical mode of action (exo or endo) for crystalline cellulose, but that their characteristic modes of attack may change with decreasing crystallinity of cellulose.

Cellulase↗

Electron microscopic observation of cotton cellulose degradation by exo- and endo-type cellulases from Irpex lacteus.

The interaction of two highly purified cellulases, exo- and endo-type cellulases from Irpex lacteus, with pure cotton and amorphous cellulose was investigated by electron microscopy. The morphological observations indicated that exo- and endo-type cellulases are both strongly adsorbed on the internal microfibril of cotton fiber before enzymatic hydrolysis, and then initiate their action toward the internal cellulose microfibrils with retention of the original shape. The two cellulases, however, caused considerably different morphological changes in cotton cellulose, and each cellulase seems to degrade native cellulose with a distinct mode of action. In the hydrolysis of cotton with exo-type cellulase, deep transverse cracks were produced and they extended from the fiber surface to the lumen structure located inside the fibers. In contrast, it was found that there were no deep cracks on fibers treated with endo-type cellulase, but severe internal erosion and cavitation occurred along fibril or microfibril layers inside the fibers. Thus, the degradation of cotton by exo- and endo-type cellulases yielded quite different morphological patterns, while little difference was found for regenerated celluloses. The mode of enzymatic hydrolysis of cellulose shown by cellulases with different degrees of randomness (exo and endo types) appears to be markedly affected by the fine structure of cellulose fibers.

Antibody Specificity↗

Growth dependence of human papillomavirus 16 DNA-positive cervical cancer cell lines and human papillomavirus 16-transformed human and rat cells on the viral oncoproteins.

The dependence on human papillomavirus (HPV) oncoproteins of the growth of cervical cancer cell lines [C4-1, HeLa (both containing HPV 18 DNA), CaSki and SiHa (both containing HPV 16 DNA)], HPV 16-transformed human embryonic kidney cells, and HPV 16-transformed rat brain and 3Y1 cells was examined by using antisense RNA approaches. The cells were transfected with plasmids expressing RNA antisense to the HPV 16 or 18 open reading frames E6E7, together with plasmids expressing the hygromycin B resistance gene, and drug-resistant colonies were scored three weeks later. In all the human cell lines, the efficiency of colony formation was lowered by RNA antisense to the resident HPV type. Some of the rat cell lines responded to the antisense plasmids, but some did not. From a nonresponding rat tumor line (3Y1HP-1T), cell clones with various levels of E7 protein were isolated after transfection with the antisense plasmid, and were examined for anchorage-independent growth in soft agar. The colonies formed by the clones with lower E7 levels tended to be smaller and fewer than those formed by the clones with higher E7 levels. These findings strongly suggest that some of the transformed or cancer phenotypes of cells in vitro are dependent, even after extensive passages and malignant changes, on expression of the oncoproteins of the resident HPV.

Animals↗

GM3 regulates protein kinase systems in cultured brain microvascular endothelial cells.

The barrier function of endothelial cells is known to be positively regulated by protein kinase A (PKA) and negatively regulated by protein kinase C (PKC). We found that exogenously administered GM3(NeuAc) promoted PKA activity in cultured brain microvascular endothelial cells (BMECs). Other glycolipids, including GM1, sulfoglucuronyl paragloboside, and GM3(NeuGc), did not have any effect on the PKA activity of BMECs. PC12 cells did not respond to exogenously applied GM3(NeuAc). GM3(NeuAc) also suppressed the PKC activity of BMECs. Thus, GM3(NeuAc) may function as a modulator of blood-brain barrier function via the two different kinase systems.

Animals↗

[Application of PCR for isolation of Chlamydia pneumoniae].

Chlamydia pneumoniae was isolated from the throat swab of a 5-year-old girl with acute bronchitis. The titers of IgM and IgG antibodies to C. pneumoniae in the serum were 1:20 and 1:2560, respectively. C. pneumoniae genome was detected by polymerase chain reaction in the throat swab and the infected cells after three passages, while C. pneumoniae was isolated from the throat swab after five passages by cell culture. PCR is considered to be a helpful method to isolate C. pneumoniae efficiently in routine cell-cultures.

Acute Disease↗

Circulating autoantibody to mature neurons and astrocytes of humans and some mammals present in a demented patient with autoimmune disorder.

Circulating autoantibody to a 48-kD nuclear protein in neurons and astrocytes of the human and bovine cerebrum were present in the serum of a demented patient with an autoimmune disorder. Other human visceral organs, dorsal root ganglion cells, neuroblastoma and glioblastoma cell lines, and rat cerebrum did not react with the patient's serum. No sera from age-matched controls, including those with Alzheimer's disease, reacted with the 48-kD protein. Only the mature neurons and astrocytes of humans and some mammals express the 48-kD protein. This antibody may be responsible for the patient's demented condition.

Aged↗

Cardiac myxoma metastasized to the brain: potential role of endogenous interleukin-6.

Metastasis of a cardiac myxoma to the brain is extremely rare. We present the case of a 70-year-old man who had an atrial myxoma and two metastatic myxomas in the brain. The intracranial lesions were in fact diagnosed before the cardiac myxoma, since the patient developed hemiparesis before his cardiac symptoms occurred. Computerized tomography of the brain showed two high-density lesions, the larger of which was removed surgically. Follow-up computerized tomography revealed a progressive enlargement of the second lesion which was then resected. Histopathological examination showed all lesions to the benign myxomas. Interestingly, high concentrations of interleukin-6 were present in the patient's serum and cardiac myxoma. Interleukin-6 may possibly potentiate metastasis of cardiac myxoma.

Aged↗

Discrete cortical infarction with prominent impairment of thumb flexion.

BACKGROUND: Intracortical efferent zones in the primary motor cortex for thumb movements, namely thumb flexion, extension, adduction, and abduction, have been described in Macaca mulatta monkeys but not in humans. Even recent cortical mapping based on intraoperative monitoring does not provide information about intracortical efferent zones as it is not ethically possible to search the human motor cortex extensively by punctate electrodes. CASE DESCRIPTION: A 78-year-old man with discrete cortical embolism over the left central sulcus is described. Only a mild weakness of his right thumb was observed. Thumb flexion was affected to a greater degree than thumb extension, adduction, and abduction. The lesion ran along the bottom of the central sulcus and affected part of the precentral and postcentral gyri on both sides of it. Animal studies in Macaca mulatta monkeys have shown that the intracortical efferent zones for thumb movement, especially for thumb flexion, are located in the part of the motor cortex just adjoining the central sulcus that folds down from the "bank" to the depth of the central sulcus. It was possible to explain the prominent weakness of thumb flexion if we applied the results of the animal studies. CONCLUSIONS: Our case suggests that the same arrangement of intracortical efferent zones found in monkeys may also exist in human beings.

Aged↗

Indium 111-labeled platelets accumulation over abdominal aortic graft with chronic disseminated intravascular coagulation--a case history.

The authors describe a seventy-six-year-old man with aortic graft, which became the focus of chronic disseminated intravascular coagulation (DIC). The patient had abdominal aortic aneurysm (AAA) and the size had increased up to 38 mm in diameter. The AAA was excised and replaced by Dacron graft. Ten months later, the DIC became chronic with renal dysfunction. Indium 111-labeled platelets scintigraphy showed increased accumulation of radioactivity over the graft. In the treatment of chronic DIC, low-dose subcutaneous heparin injection (5,000-10,000/day) was effective, and he was discharged. In this case there was also suspicion of lung cancer and recurrent aortic aneurysm, which were a more reasonable cause of chronic DIC. This case suggests that an aortic graft prosthesis may be a cause of localized chronic DIC and that indium 111-labeled platelets scintigraphy is useful for the detection of localized chronic DIC. Moreover, subcutaneous heparin administration may be effective for chronic DIC in patients with an abdominal aortic graft prosthesis.

Aged↗

Two-step polymerase chain reaction for diagnosis of scrub typhus and identification of antigenic variants of Rickettsia tsutsugamushi.

Two-step polymerase chain reaction (nested PCR) method was examined for the diagnosis of scrub typhus. Primers were derived from the type-specific antigen (TSA) gene DNA sequences of Rickettsia tsutsugamushi, Gilliam strain. These primers served to produce rickettsia-specific products in the amplification of template DNA prepared from all serovariants, Gilliam, Karp, Kato, Kawasaki, Kuroki and Shimokoshi strains, and the fragments of product after digestion with several kinds of restriction endonuclease showed the respective patterns to strain in acrylamide or agarose gel electrophoresis. The rickettsia-specific DNAs were also derived, by this nested PCR, by amplifying DNA from patients' bloods and mites from endemic areas, and the serotype of rickettsiae infected to these hosts could be identified from fragment patterns of the amplified products observed after endonuclease treatment. These results indicate that this PCR is sensitive and specific method not only for detection of rickettsial DNA in patient specimens and in mites, but also for the typing of rickettsiae infected to these hosts.

Animals↗