Showing papers by "Kumamoto University published in 1986"

A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs

Abstract: We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.

Precipitation processes in near-equiatomic TiNi shape memory alloys

Abstract: Metallographic studies have been made of precipitation processes in Ti-50 pct Ni and Ti-52 pct Ni (at. pct) shape memory alloys. The eutectoid and peritectoid reactions previously reported for near-equiatomic and Ni-rich TiNi alloys were not observed for either composition. In the Ti-52Ni alloy, diffusional transformations take place, similar to those in supersaturated alloys. The precipitation sequence can be written asβ 0 → Ti11Ni14 → Ti2Ni3 → TiNi3. The solidus line of the TiNi phase in the Ti-52Ni alloy lies at 812 ± 22 °C. Morphological characteristics of the various precipitate phases are described in detail.

Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II

Abstract: Proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors are functionally divided into two groups: B-cell growth factor (BCGF), thought to be involved in B-cell proliferation; and B-cell differentiation factor (BCDF), responsible for maturation of activated B cells into immunoglobulin-secreting cells. This classification needs to be re-examined in the light of the recent cloning of complementary DNA encoding IgG1 induction factor (interleukin-4, IL-4) from the 2.19 mouse T-cell line. Recombinant IL-4 has BCGF and BCDF activities and affects B cells, T cells and mast cells (refs 7, 8; our unpublished data). Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells. Although TRF from B151K12 was classified as BCDF, purified TRF has BCGF-II activity. To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine.

The Current Mode Fuzzy Logic Integrated Circuits Fabricated by the Standard CMOS Process

Abstract: Nine basic fuzzy logic circuits employing p-ch and n-ch current mirrors are presented, and the fuzzy information processing hardware system design at a low cost with only one kind of master slice (semicustom fuzzy logic IC) is described. The fuzzy logic circuits presented here will be indispensable for a "fuzzy computer" in the near future.

Studies of hypothyroidism in patients with high iodine intake

Abstract: Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state Twelve (545%) became euthyroid after restriction of iodine intake for 3 weeks (reversible type) In the remaining 10 patients, thyroid function did not improve with restriction of iodine alone, and thus, replacement therapy was required, (irreversible type) In the reversible type, 1) radioactive iodine uptake after 1 week of restricted iodine intake was higher than in the irreversible type [500 +/- 122% (+/- SD) vs 43 +/- 32%; P less than 001], 2) the perchlorate discharge test was positive in 2 of 10 patients, and 3) the iodine-perchlorate discharge test, carried out in 7 of 8 patients with negative perchlorate discharge test, was positive in 6 Seven patients with the reversible type were given 25 mg iodine daily for 2-4 weeks; all became hypothyroid again Two patients had a history of habitual ingestion of seaweed (254 and 431 mg iodine, respectively), but the remaining 10 patients ingested ordinary amounts of iodine (1-5 mg) daily The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone

Anterior basal encephalocele of the neonatal and infantile period.

Abstract: Diagnosis of occult basal encephalocele is not difficult if the peculiar clinical and radiological signs of this anomaly are borne in mind. Recent surgery for transsphenoidal encephalocele has had better results than realized. However, high surgical risks may still be encountered in transsphenoidal encephalocele of the early infantile period, because the pituitary-hypothalamic structures are usually incorporated in the herniated encephalocele of this age group. Surgical indications for and operative approaches to transsphenoidal encephalocele in the infantile period are discussed on the basis of the authors' failure in transcranial repair, which resulted in early postoperative death due to hypothalamic dysfunction. Reviewing the reported cases of anterior basal encephalocele, a high correlation between transsphenoidal encephalocele, particularly in the pediatric age group, and allied malformations of the face, eye, and brain was disclosed. This characteristic malformation complex may be explained by a common pathogenetic mechanism operating in the embryonal period at about the stage of the anterior neuropore closure and occurring in the ventral surface of the cephalic end of the neural tube. Three cases of transsphenoidal encephalocele diagnosed in the neonatal period with progressive obstruction in the nasopharyngeal airway are also reported. A characteristic malformation complex consisting of median cleft face syndrome, optic nerve dysplasia, and agenesis of the corpus callosum was associated in two cases; the other patient had an extremely rare combination of septooptic dysplasia. Two patients died pre- and postoperatively, respectively; the other patient did not undergo operation because of grave multiple anomalies.

Recurrence after Initial Dislocation of the Shoulder

Abstract: Recurrence after primary traumatic anterior dislocation of the shoulder is common. The rate of recurrence is generally thought to be about 20%, and to be related to factors of age, force and situation of injury, length of immobilization complications of primary dislocations, and instability of the shoulder joint. However, a case of recurrence is still a matter of speculation and few reports to be concerned with the rate of recurrence of primary dislocation have yet been in Japan.About 170 cases were assesed at our University and neighboring hospitals, and the relation between primary dislocation and recurrence were investigated. We studied and examined 104 cases of traumatic dislocation, age, force and situation of injury, length of immobilization, complication of dislocation, and of 66 cases of recurrence, we studied the situation of primary injury and interval of recurrence.

Effects of intracoronary injection of acetylcholine on coronary arterial diameter.

Abstract: The effects of intracoronary injection of acetylcholine on coronary arterial diameter was examined by coronary arteriography in 30 adult patients (13 men, 17 women), aged 23 to 67 years (mean 51), with normal or almost normal coronary arteriographic findings. Patients with angina pectoris, myocardial infarction and other severe cardiac diseases were excluded. Two minutes after injection of 30 to 100 micrograms of acetylcholine into the left coronary artery, significant diffuse narrowing (more than 25% reduction in diameter) of the left main trunk, the proximal, mid- and distal left anterior descending artery, and the proximal, mid- and distal left circumflex artery occurred in 1 (4%), 5 (20%), 3 (12%), 9 (36%), 6 (24%), 8 (32%) and 3 (12%) of 25 patients, respectively. After injection of 30 to 50 micrograms of acetylcholine into the right coronary artery, significant diffuse narrowing of the proximal, mid- and distal right coronary artery occurred in 5 (25%), 7 (35%) and 10 (50%) of 20 patients, respectively. However, significant diffuse dilatation (more than 25% increment in diameter) appeared in the left main trunk, left anterior descending, left circumflex and right coronary arteries in a few patients. These results indicate that acetylcholine induces coronary vasoconstriction in a significant number and coronary vasodilatation in a small number of adult humans, and that response of the coronary artery to acetylcholine varies along the course of the coronary artery.

Determination by the SRID Method of Normal Values of Serum Apolipoproteins (A-I, A-II, B, C-II, C-III, and E) in Normolipidemic Healthy Japanese Subjects

Abstract: The normal levels of apolipoproteins in Japanese were investigated by the single radial immunodiffusion method. No differences were seen between the males and females in the apolipoprotein A-I, B, and C-III levels. However, the levels of apolipoproteins A-II and C-II were higher in the males, while that of apolipoprotein E was higher in the females. These differences were statistically significant. Except for apolipoprotein E, the apolipoprotein levels tended to increase with age more in the females than in the males. The apolipoprotein E level showed a statistically significant positive correlation not only with the total cholesterol level but also with the high density lipoprotein-cholesterol level.

HTLV-I seroprevalence in patients with malignancy.

Abstract: Since many malignancies often occur in patients with smoldering type adult T-cell leukemia (ATL) (5 of 18 cases in this report), the relationship between HTLV-I (human T-cell leukemia virus type I) infection, which is closely associated with ATL, with other malignancies in an HTLV-I endemic area was examined. Among the 394 patients with malignancies and who had not had blood cell transfusions, 61 (15.5%) tested positive for HTLV-I antibody. The prevalence was significantly higher in males older than age 40 years and females of all ages compared to age- and sex-matched healthy individuals. The overall seroprevalence (26.1%) in 291 patients with malignancies and who had had blood cell transfusions was higher than that of those who had not had blood transfusions. There was no significant correlation between the site of malignancy and antibody prevalence. These results suggest the possibility that development of malignancy may contribute to expression of latent HTLV-I infection and that HTLV-I infection may contribute to the risk of other malignancies.

F plasmid ccd mechanism in Escherichia coli.

Abstract: The ccd mechanism specified by the ccdA and ccdB genes of the mini-F plasmid determines fate of plasmid-free segregants in Escherichia coli (Jaffe et al., J. Bacteriol. 163:841-849, 1985). The killing function in plasmid-free segregants by the ccd mechanism did not affect cell growth of coexisting cells in the same culture. Elongated cells and anucleate cells caused by the ccd mechanism were clearly detected by flow cytometry in cultures of bacterial strains harboring Ccd+ Sop- mini-F plasmids defective in partitioning. This indicates that the defect in correct partitioning of plasmid DNA molecules into daughter cells also induces the ccd mechanism to operate.

Ultrastructural studies of amyloid fibrils and senile plaques in human brain.

Abstract: Amyloid fibrils and senile plaques in brains with Alzheimer's disease, senile dementia and Down's syndrome were examined by light and electron microscopy. In addition, replicas of amyloid fibrils, made by a quick freezing method from a brain with Down's syndrome, were examined. All amyloid masses forming the cores of senile plaques consisted of numerous amyloid fibrils spreading from the walls of small blood vessels to the surrounding parenchyma. The amyloid fibrils ran in various directions, forming bundle-like groups in a geometrical array. They appeared as rods with hollow structures consisting of an array of globular units in the replicas, while they showed bead-like structure in the tissue specimens of 500-nm thick sections. The ultrastructure of replicas reveals a new finding on the structure of amyloid fibrils in the human brain.

Wake interference of a row of normal flat plates arranged side by side in a uniform flow

Abstract: The wake characteristic of groups of normal flat plates, consisting of two, three, or four plates placed side by side with slits in between, have been investigated experimentally. When the ratio of the slit width to the plate width (slit ratio) was small, the gap flows were observed to be biased either upward or downward in a stable way, leading to multiple, stable flow patterns for a single slit-ratio value. Some regularities were recognized in the gap-flow directions and the appearance of the flow patterns. The plates on the biased side showed high drag and regular vortex shedding, while those on the unbiased side showed the opposite. The origin of the biased flow has also been investigated with water-tank experiments, numerical calculations and wind-tunnel experiments. The-results showed that the origin of biasing is strongly related to the vortex shedding of each plate of a row.

Familial amyloidotic polyneuropathy diagnosed by cloned human prealbumin cDNA

Abstract: A diagnosis of familial amyloidotic polyneuropathy (FAP) can be made by use of restriction endonuclease Nsi I, a cloned human prealbumin cDNA and Southern blot procedures. Digests of DNAs from 10 disease-free individuals showed two bands (6.6 kb and 3.2 kb) complementary to a human prealbumin cDNA, whereas digests from 11 individuals with FAP exhibited two additional bands (5.1 kb and 1.5 kb). We interpret these changes in pattern to be the result of a restriction site for Nsi I located in the altered codon and associated with the mutant prealbumin gene. All these individuals with FAP were heterozygous for the prealbumin gene, carrying one normal and one mutant gene.

Decreased bone density in severely handicapped children and adults, with reference to the influence of limited mobility and anticonvulsant medication

Abstract: Bone density and related biochemical parameters were investigatd in institutionalised children and adults with severe handicaps, who were classified according to the degree of limited mobility (group 1, bed-ridden; group 2, capable of crawling; group 3, capable of walking) and according to whether or not they were receiving anticonvulsants. As determined by microdensitometric analysis of radiograms of the second metacarpal bone, bone width (D), bone pattern area (ΣGS) and bone salt density (ΣGS/D) were decreased in the patients, the decreases being most prominent in group 1, followed by groups 2 and 3, in that order. Significant decreases of ΣGS and ΣGS/D, but not of D, were found in patients on anticonvulsant treatment in comparison to patients without therapy. Serum alkaline phosphatase (Al-p) and parathyroid hormone (iPTH) as well as urinary calcium and cyclic adenosine-3′,5′-monophosphate (cAMP) excretion were significantly increased in group 1. In comparison to patients without therapy, anticonvulsant-treated children showed significantly decreased levels of serum calcium (Ca), ionised Ca (Ca2-), 25-hydroxy vitamin D3 and urinary phosphate (PO4) excretion, and elevated levels of Al-p, iPTH and calcitonin (iCT). It is suggested that limited physical activity results in a mild hyperparathyroid state, which is aggravated in patients on anticonvulsant treatment.

Structure and expression of the mouse prealbumin gene.

Abstract: We cloned a genomic DNA fragment which covers the entire sequence of the mouse prealbumin gene and then studied the structure. The coding regions are separated into four exons by three introns, and these numbers, the sizes of the exons and the relative sites of the exon-intron junctions are all in complete agreement with those determined for the human gene. The sequences of four exons can be aligned perfectly with that of the previously determined mouse prealbumin cDNA. In addition to the exon regions, we found two highly conserved DNA regions between the mouse and human prealbumin genes, one in the 5'-flanking region of the gene and the other in the 3' end region of the first intron. These DNA regions contain several consensus glucocorticoid receptor-binding site sequences, and the latter also contains an enhancer sequence present in the immunoglobulin kappa-chain joining-constant kappa intron. RNA hybridizing to the mouse prealbumin cDNA was detected in the extracts from liver, brain, and kidney, but was not detected in testes, spleen, or heart. Little change was caused in the level of prealbumin mRNA in the liver by administration of dexamethasone to mice.

Attraction of chick primordial germ cells by gonadal anlage in vitro.

Abstract: The attraction of primordial germ cells (PGCs) by the gonadal anlage (germinal ridge; GR) in vitro has been demonstrated in the chick. PGCs were isolated from circulating blood of stage 13 embryos (Hamburger and Hamilton, 1951), placed between the GR and other embryonic tissues (neural tube, heart, allantois, liver) as controls separated by a distance of 170 microns on collagen-coated substrate, and cultured with modified medium 199 (Kuwana and Fujimoto, Anat. Rec., 209:337-343, 1984) containing 10% fetal calf serum (pH 7.3). The behavior of PGCs was observed for 3 hr by 16-mm time-lapse microcinematography. PGCs showed directional movement toward GR. Also, there was a stronger attractive effect on the PGCs by GR from stage 13 embryos than by GR from later stage embryos. These results suggest that PGCs are attracted by some factor emitted from GR.

Small mass lesions in cirrhosis: Transition from benign adenomatous hyperplasia to hepatocellular carcinoma?

Abstract: Ten patients with cirrhosis, in whom small mass lesions were detected by imaging techniques and histological diagnosis of the resected specimens was difficult, are described. There were 17 grossly discrete lesions measuring 10 × 8 mm to 27 × 22 mm. Four were compatible with so-called adenomatous hyperplasia showing no histological features of malignancy, and eight were equivocal as to whether they were benign or malignant. The other five lesions (in four patients) were hepatocellular carcinoma, co-existing with apparently benign lesions. The eight equivocal lesions were eventually judged to be highly differentiated hepatocellular carcinomas. These benign-appearing lesions, found by advanced imaging in patients with cirrhosis, create a serious problem in regions where primary liver cancer is endemic among cirrhotics, and hepatic resection is the preferred treatment. It is possible that these lesions represent a transition from adenomatous hyperplasia occurring in cirrhotic livers to hepatocellular carcinoma through a histologically equivocal state and that the current morphological methods are inadequate for differentiating malignant from benign lesions.