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Biomedical subjects

Y Koide

Publications and source records attributed to Y Koide.

At least 163 records · Page 9Linked to original sources

The unique nucleotide sequence of the A beta gene in the NOD mouse is shared with its nondiabetic sister strains, the ILI and the CTS mouse.

It is generally held that one of the recessive genes controlling diabetes in the NOD mouse is linked to the major histocompatibility complex (MHC). Unique substitution of Asp57 with Ser in the A beta chain is considered to make the A beta gene the MHC-linked susceptibility gene. We therefore analysed the nucleotide sequences of the A beta second exon in ILI, CTS, and NON mice, which are nondiabetic inbred strains but are derived from the same Jcl-ICR mice as the NOD mouse. The DNA sequence analyses revealed that the A beta second exon sequences in the ILI and CTS mice, but not in the NON mouse, are identical to that of the NOD mouse. Possible roles of Ser57 of the A beta chain in the nondiabetic sister strains are discussed.

Amino Acid Sequence↗

Endocrine and immunohistochemical studies on thyrotropin (TSH)-secreting pituitary adenomas: responses of TSH, alpha-subunit, and growth hormone to hypothalamic releasing hormones and their distribution in adenoma cells.

Endocrine and immunohistochemical studies were performed in two cases of TSH-secreting pituitary adenomas. The patients had elevated serum TSH and alpha-subunit concentrations despite high serum thyroid hormone levels. In addition, one patient (no. 1) had elevated serum GH levels with clinical evidence of acromegaly. GH-releasing hormone infusion increased serum levels of TSH, alpha-subunit and GH in the two patients. TRH injection increased serum TSH levels in both patients and, concomitantly, serum alpha-subunit and GH levels in patient 1. Basal TSH levels and their responses to TRH changed reciprocally to changes in serum thyroid hormone levels, although TRH-induced GH release did not. The administration of GnRH also increased serum TSH, alpha-subunit, and GH levels in patient 1. In accordance with these in vivo results, pituitary adenoma cells in culture obtained from patient 1 responded to GH-releasing hormone, TRH, or GnRH to secrete TSH, alpha-subunit, and GH. Incubation of cells with dexamethasone resulted in inhibition of TSH and stimulation of GH secretion without a significant change in alpha-subunit secretion. On the basis of light microscopic and electron microscopic double gold immunohistochemistry, the tumor from patient 1 was a bimorphous adenoma composed of two separate cell types: cells with TSH beta-subunit (TSH beta) and alpha-subunit, and those with GH and alpha-subunit. The remainder consisted mainly of cells with TSH beta and alpha-subunit. The coproduction of the unusual combination of two hormones such as GH and alpha-subunit in a single-type of adenoma cell and the coexistence of thyrotrophs and somatotrophs in one pituitary adenoma along with the aberrant responses of TSH beta, alpha-subunit, and GH to multiple hypothalamic hormones suggest the dedifferentiation of pituitary cells to multipotential progenitor cells by neoplastic transformation.

Adenoma↗

Successful treatment of a metastatic hormone-producing adrenal cancer by a combination of mitotane, tegafur and surgical resection.

A 34-year-old man had a huge hormone-producing adrenal cancer with multiple lung metastases, direct liver invasion and a tumor thrombus in the inferior vena cava. Initial treatment was mitotane alone. The dose of mitotane was 2 g/day initially and gradually increased to 15 g/day in combination with 600 mg of tegafur per day. During the initial phase of chemotherapy, the serum mitotane level was relatively low (2.9-4.6 micrograms/ml) and the pulmonary metastases tended to grow in size in spite of a gradual decline in urinary 17-KS and 17-OHCS and a regression of the primary tumor. A seemingly marked increase in serum mitotane (20.5-34.5 micrograms/ml) was coincident with the addition of tegafur. Rapid and consistent regression of the primary tumor occurred. This excellent response to the chemotherapy made the primary tumor with liver invasion and the metastases resectable. The adverse effect of mitotane, central nervous toxicity, appeared to be serum mitotane level dependent. The present results, together with previous reports in the literature, seem to recommend the following therapeutic approaches to advanced adrenal cancer: monitoring of the serum level may be useful in predicting the efficacy as well as the occurrence of side effects of mitotane, surgical treatment of the lesions should be performed whenever possible, even though it may be only palliative, and the combination of mitotane and tegafur is a choice of chemotherapy which should be evaluated in future studies.

17-alpha-Hydroxypregnenolone↗

[A case of fatal graft-versus-host disease following blood transfusion in esophageal cancer documented by homozygous changes of HLA typing].

A 72 year-old Japanese male with esophageal cancer underwent esophagectomy. After seemingly uneventful recovery, he developed high fever on 11 post-operative day (POD), rashes over the whole body on 13 POD and leukopenia on 15 POD. On 22 POD, thrombopenia and parenchymal bleeding of lungs were noted. He died on 26 POD after progressive hypoxia and hypotension. HLA type of peripheral lymphocytes on him changed homozygously to that of the transfused fresh blood. Skin biopsy showed mild leukocyte infiltration in the epidermis and the dyskeratotic keratinocytes were associated with a contiguous lymphocyte, the so-called satellite cell necrosis. In the findings of autopsy, aplastic bone marrow and atrophied spleen, whose weight was 14g, were noted. Based on the clinical picture, skin biopsy and HLA study findings, we diagnosed this case as post-transfusion GVHD. We think that high age, operative injury and preoperative irradiation might be inducement to reveal post-transfusion GVHD in this case.

Aged↗

[Paradoxical response of blood pressure to salt loading in renovascular hypertension].

We studied the effect of high salt intake on blood pressure in two cases with renovascular hypertension. They had hypertension with hyperreninemia and marked difference in plasma renin activity between both renal veins. Blood pressure significantly decreased after single oral administration of captopril. Renal arteriogram revealed significant stenosis in the main artery to the left (case 1) and right (case 2) kidney. Blood pressure response was evaluated after seven (case 1) and five (case 2) days of low salt and seven days (both cases) of high salt intake. Mean blood pressure in two patients was significantly decreased (case 1; 118 +/- 5.5 to 108 +/- 6.1 mmHg and case 2; 150 +/- 3.8 to 138 +/- 3.1 mmHg). Plasma renin activity was also decreased (case 1; 6.25 to 0.77 ng/ml/hr and case 2; 22.8 to 6.3 ng/ml/hr). In case 2, blood pressure elevated markedly during low salt intake, compared with blood pressure level during normal salt intake. The results suggest that excessive salt intake in patients with unilateral renovascular hypertension produces blood pressure reduction because of suppression of renin-angiotensin system. We concluded that in patients with unilateral renovascular hypertension dietary sodium depletion may be harmful, whereas salt supplement may have a beneficial effect.

Adult↗

[Effect of high dose etoposide, adriamycin, cisplatin (EAP) therapy with autologous bone marrow transplantation in gastric cancer].

A clinical usefulness of high dose EAP therapy with autologous bone marrow transplantation for gastric cancer was investigated. Three patients with advanced gastric cancer (one recurrent and 2 inoperable) with measurable lesions were treated with high dose EAP therapy consisting of VP-16 1200 mg/m2, ADM 80 mg/m2 and CDDP 80-120 mg/m2, and then 1 x 10(7)/kg of cryopreserved autologous bone marrow cells were transfused intravenously. All patients were recovered from aplastic period without any severe complications. Measurable lesions, namely, stenosis of prepyloris lesion, lymph node metastasis and invasion into pancreas in 3 patients with gastric cancer were reduced or diminished. It seemed that high dose EAP therapy with autologous bone marrow transplantation was safe and an useful strategy, especially for advanced gastric cancer.

Adult↗

[Immunotherapy and quality of life].

In order to examine the quality of life with immunotherapy, a survey was conducted on 17 advanced gastric or colon cancer patients receiving LAK immunotherapy and on 10 patients receiving EAP chemotherapy as a control. Performance status of patients at the time of treatment was similar between the groups. Many patients on EAP therapy complained of severe side effects, such as loss of hair, nausea and vomiting, and appetite loss. None of the patients on LAK therapy complained of such effects on the contrary, favorable effects were found. Appetite increased in some patients and tenderness of the liver disappeared in others. As for the continuance of the treatment, two thirds of EAP patients declined, and all LAK patients replied in the affirmative. The data suggest that LAK immunotherapy is better than EAP chemotherapy from the standpoint of the quality of life.

Antineoplastic Combined Chemotherapy Protocols↗

Continued high albumin production by multicellular spheroids of adult rat hepatocytes formed in the presence of liver-derived proteoglycans.

Adult rat hepatocytes formed floating multicellular spheroids, when they were cultured with proteoglycan fraction isolated from rat liver reticulin fibers. Cells in the spheroid showed only low growth activity. Albumin production by the spheroids increased up to 1.5 micrograms/micrograms DNA/day (180 micrograms/mg Protein/day) during the first 6 days and remained constant thereafter. In contrast, the albumin production by the monolayer markedly decreased after 4 days. The spheroid culture appears to be more suitable than the monolayer in studying differentiated functions of adult hepatocytes.

Albumins↗

Restriction fragment length polymorphism analysis of major histocompatibility complex genes in the non-obese diabetic mouse strain and its non-diabetic sister strains.

It has been suggested that one of the recessive genes controlling diabetes in non-obese diabetic mice is linked to the major histocompatibility complex. We, therefore, performed restriction fragment length polymorphism studies of major histocompatibility complex genes (class I, II, and III) in non-obese diabetic mice in comparison with those of their non-diabetic sister strains, non-obese non-diabetic, cataract, and ILI mice which were derived from the same Jcl-ICR mice as the non-obese diabetic mouse was. When class II and III probes and a minimum of four restriction enzymes were used, class II and III genes of non-obese diabetic mice were indistinguishable from those of cataract and ILI mice but totally different from those of non-obese non-diabetic mice. The studies also indicated that A beta, E beta, and C4-Slp genes of non-obese diabetic, cataract, and ILI mice, and A alpha, A beta, E beta and C4-Slp genes of non-obese non-diabetic mice are different from those of BALB/c and C57BL/6 mice, respectively. While non-obese non-diabetic mice expressed the E alpha gene, non-obese diabetic, cataract, and ILI mice appeared to carry a deletion in the 5' end of the E alpha gene resulting in failure to transcribe the E alpha gene. When class I probe was used, cataract mice showed very different band patterns from those of the other ICR-derived mice. It is suggested that non-obese diabetic, non-obese non-diabetic, and ILI mice contain only a single class I D region gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The oncogenicity of avian adenoviruses. IV. Confirmatory evidence for recombination between viral and cellular DNA sequences and repetition of the recombinant in cells of a tumor line.

On the basis of hybridization analyses with viral DNA fragments as probes, we previously concluded that, in DNAs of many fowl adenovirus type 1-induced rodent tumors, units consisting of viral DNA segments flanked on both sides by cellular DNA segments are repeated more than 100 times per diploid genome of cell. Molecular cloning of virus-cellular junction fragments and analyses of their sequence arrangement in the present study confirmed that the previous conclusion was basically correct.

Adenoviridae↗

Synthesis and antitumor properties of N1-acyloxymethyl derivatives of bis(2,6-dioxopiperazines).

Many N1-acyloxymethyl derivatives VI of bis(2,6-dioxopiperazine) I, ICRF-154, were prepared and tested for antitumor activity. The treatment of I with formaldehyde gave a crystalline bis(N1-hydroxymethyl) derivative VII, which was acylated under various conditions to give bis(N1-acyloxymethyl) derivatives VI. Antitumor activity of VI against P388 leukemia in mice was studied. Several bis(N1-acyloxymethyl) compounds such as phenylacetyloxymethyl VI-6, methoxycarbonyloxymethyl VI-41, isobutoxycarbonyloxymethyl VI-44, and furancarboxymethyl VI-38 compounds were found to have potent antitumor activities. On the other hand, water-soluble esters having an amine or a carboxylic acid function in their acyl groups showed rather reduced activity. These bis(N1-acyloxymethyl) derivatives VI were presumably hydrolyzed into the parent bis(2,6-dioxopiperazine) I by nonspecific esterase in the body to exhibit their antitumor activity.

Animals↗

Characterization of secondary structure of neocarzinostatin apoprotein.

Characteristics of the secondary structure of neocarzinostatin apoprotein (apo-NCS) were examined by various means. Gaussian analysis of the Fourier-transform infrared (FT-IR) curve and curve-fitting of the circular dichroism (CD) spectrum for apo-NCS revealed that this peptide was abundant in beta-structures. In the presence of sodium dodecyl sulfate (SDS), the CD bands of NCS originating from phenylalanyl, tyrosyl, and cystinyl residues decreased, indicating a conformational change around the chromophore (CNS-chr). On the other hand, apo-NCS, in the SDS system, showed no change of these bands. We showed that the major parts of the protein moiety consist of beta-structures by measurements of the FT-IR and CD spectra of apo-NCS and a prediction of the secondary structure based on the amino acid sequence of the peptide. It seems that properties of the protein may be important to the hydrophobic interaction between NCS-chr and apo-NCS.

Amino Acid Sequence↗