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Biomedical subjects

K Oikawa

Publications and source records attributed to K Oikawa.

At least 19 recordsLinked to original sources

Circular dichroism studies of native and chemically modified Ca2+-dependent protein modulator.

The structural features of the native Ca2+-dependent protein modulator and two chemically modified derivatives, namely, nitrotyrosyl modulator and alkylated modulator, were examined by circular dichroism. The binding of Ca2+ to the native molecule was accompanied by an increase in helical content from 40 to 49%, with little effect on the local environments of aromatic residues in the modulator. The Mg2+ and Mn2+ do not elicit the conformational change induced by the binding of Ca2+, which also stabilizes the modulator against urea denaturation. The overall secondary structure of nitrotyrosyl modulator is indistinguishable from that of the native protein and undergoes a similar conformational change upon binding Ca2+. These observations are in agreement with the fact that nitration has no effect on modulator functions. Furthermore, nitrotyrosyl modulator interacts with troponin I only in the presence of Ca2+, as detected by circular dichroism (cd). On the other hand, alkylation of five methionine residues on the modulator with benzyl bromide affects protein conformation, as evidenced by a reduced helical content of only 35%. Alkylated modulator retains the ability of the native protein to bind Ca2+ although the affinity of this derivative for Ca2+ is reduced some three orders of magnitude relative to the native protein, with Kd = 3.2 X 10(-4) M. The results with the alkylated modulator, in conjunction with previous cd studies on N-chlorosuccinimide oxidized modulator are utilized to advance a model for the Ca2+ activation of modulator protein, based on three conformational states of the molecule.

Alkylation

A scanning electron microscopic study on the liver of mice.

The three-dimensional fine structures of several tissue components of the liver in normal mice were studied by scanning electron microscopy. The tissue components observed were as follows: hepatocytes, sinusoidal endothelial cells, the Kupffer cells, fat-storing cells, reticulin fibers and epithelial cells of the bile duct. Two types of fenestrations were found in the sinusoidal endothelial cells. One was smaller and clustered, and the other larger and scattered. Both of them were distributed equally throughout the hepatic lobule. Intercellular gaps were found at the endothelial junction. The Kupffer cell which was localized in a large gap between the endothelial cells was characterized by numerous villous projections, and by the absence of fenestrations which were observed in the endothelial cells. Fat-storing cells were located between hepatocytes. They elongated their processes into the space of Disse, but never protruded into the sinusoidal lumen. They were clearly distinguished from the endothelial cells and the Kupffer cells by their morphological feature and location. No transitional form was seen among the endothelial cells, the Kupffer cells, and the fat-storing cells.

Animals

A scanning electron microscopic study on hepatic changes induced by mouse hepatitis virus-2.

No significant changes in the structure of the liver were seen until 9 hr after the inoculation of mouse hepatitis virus-2 (MHV-2) into mice. At the 24 hr stage, distinct swelling of hepatocytes and narrowing of sinusoidal lumina were observed from the middle to the central area of the hepatic lobules. Most of the Kupffer cells were swollen. Their villous projections were decreased in number, and the remaining projections became like blebs. Virus particles appeared from this stage in the hepatocytes, the Kupffer cells and the space of Disse. At the 48 hr stage, parenchymal necrotic foci were present in the central and the middle area of the lobules. The necrotic change was increased from 72 hr after inoculation, and was followed by submassive or massive necrosis. It is suggested that hepatic necrosis in both the central and the middle area, or in either area, of the lobules was advanced by aggravation of the sinusoidal microcirculation, as a result of the swelling of the hepatocytes and the Kupffer cells in addition to the direct affection by virus. Fine granulation was observed on the surface of most of the central flagella of the bile duct. Some flagella were degenerated, and came in part to be a fibrillar net.

Animals

Circular dichroism studies on Ca2+-dependent protein modulator oxidized with N-chlorosuccinimide.

The structural features and Ca2+-binding properties of native and N-chlorosuccinimide-oxidized modulator protein were compared by circular dichroism. In the presence of Ca2+,the far-UV spectra of native and oxidized modulator protein are virtually indistinguishable, indicating that oxidation of surface methionine residues does not alter the overall conformation of the molecule. In the absence of Ca2+, however, the circular dichroism spectra of native and oxidized modulator are different with calculated helical contents of 40% and 26%, respectively. As judged by circular dichroism titration studies, the native modulator contains both high-(Kd = 1.9 X 10(-7) M) and low-affinity (Kd = 4 X 10(-4) M) Ca2+-binding sites, whereas the modified modulator appears to possess only low-affinity sites (Kd = 3.8 X 10(-4) M). The reduced secondary structure in Ca2+-free oxidized modulator protein may account for the absence of high affinity Ca2+ binding sites.

Animals

Familial balanced translocation 4p+/17q- as a suggested cause of primary trisomy-21 Down's syndrome.

A case is presented in which a 4p+/17q- familial balanced reciprocal translocation in the mother produced a son with primary trisomy-21, as well as the structural chromosomal anomaly. A number of similar situations have been reported, suggesting that the two events are related. In practice, this (as well as other direct risks) should be taken into account when counseling those families in which one parent carries a balanced translocation. A hypothesis, based on experiments in Drosophila, has been put forward by Grell to explain the mechanism which links the balanced structural abnormality to an aneuploidy of chromosomes not taking part in the structural change, and this has been extended to similar human situations.

Child, Preschool

Circular dichroism of intermediate subviral particles of reovirus. Elucidation of the mechanism underlying the specific monovalent cation effects on uncoating.

1. Circular dichroic (CD) spectra of purified intermediate subviral particles of reovirus were determined in the presence of different monovalent cations. 2. The CD spectra reveal that reo intermediate subviral particles can exist in two conformationally different forms. The two forms are readily distinguished by comparison of their ellipticities in the wavelength regions 210 nm and 220 nm, with a Na+-induced form exhibiting a reduced negative ellipticity relative to a Cs+-induced form. 3. The transition between the Na+- and Cs+-induced forms is reversible by manipulation of the species of monovalent cation present and appears to be temperature independent. 4. Temperature variation studies on dilute suspensions of particles indicate that the Na+-induced form is stable, whereas the Cs+-induced from undergoes a second transition, temperature dependent and irreversible, to become a viral core. 5. A model is presented relating these observations to the known properties of reovirus uncoating and transcriptase activation.

Cesium

Malignant lymphoma initiated with malabsorption syndrome due to Isospora belli infection and lymphocytosis.

A 47-year-old man had diarrhea in 1965. Four years later, malabsorption syndrome was diagnosed and the patient was found to have mild lymphocytosis. Abdominal lymphoma was suspected, but exploratory laparotomy was normal except for partial villous atrophy of small intestine and slightly enlarged mesenteric lymphnodes which were normal microscopically. In vitro lymphocyte blastformation with phytohemagglutinin was depressed markedly throughout the course and the result predicted the developement of malignancy of the lymphocytic system. Infection of Isospora belli was found thereafter, and sulfamethoxazole was quite effective for diarrhea. In August, 1974, he noticed cervical lymphadenopathy for the first time and it was diagnosed as undifferentiated type of malignant lymphoma. He died in December, 1974. In this case diarrhea was most probably caused by the intestinal infection of Isospora belli without obvious lymphoma. The symptom was swept away by peroral sulfamethoxazole. In this patient coccidiosis was presumably induced and prolonged by suppression of cellular immunity which might have already begun to progress at the onset of diarrhea.

Biopsy

Treatment of multiple myeloma and macroglobulinemai Waldenström: A long-term follow-up study.

Fifteen cases of multiple myeloma and 6 cases of macroglobulin emia Waldenstrom were followed up from 1957 to 1974. As for administration of drugs a low continuous dose regimen was mainly employed instead of a high intermittent dose regimen. 50% survival time from the onset of the disease was 18 months for multiple myeloma and 25 months for macroglobulinemia Waldenstrom. 3 cases of multiple myeloma are still living 44 months after the onset of symptoms. Cyclophosphamide and melphalan seem to have contributed much to the prolonged survival of these patients as well as improved supportive care.

Adult

Electron microscopic observation of inclusion bodies in plasma cells of multiple myeloma and Waldenström's macroglobulinemia.

Intracellular inclusion bodies in the plasma cells were sought by electron microscopy in 32 cases of multiple myeloma and 3 of Waldenström's macroglobulinemia. In some cases, round shaped intranuclear inclusions and intranuclear fibrillar bundles were observed. In other cases, Russell bodies and crystalline structures were found in the cisternae of rough surfaced endoplasmic reticulum (rER), and dense bodies, myelin-like structures, fibrillar formations, polysome lamellae complexes, crystalline structures, virus-like particles and phagocytosis were observed in the cytoplasm of plasma cells. The detailed ultrastructure of these inclusions was described, and their functional significance, origin and appearance rate were discussed. Finally, the presence of true viral particles in the plasma cells was ruled out.

Aged