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Biomedical subjects

M Koga

Publications and source records attributed to M Koga.

At least 379 records · Page 21Linked to original sources
PubMed1988

Regulation of epidermal growth factor receptor levels by 1,25-dihydroxyvitamin D3 in human breast cancer cells.

Specific, high affinity receptors for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have been demonstrated in human breast cancer cells. In addition, 1,25-(OH)2D3 has been shown to inhibit replication in some human breast cancer cell lines, although the mechanism(s) of this anti-tumor activity remain undefined. There is currently considerable interest in the role of autocrine growth factors in the control of breast cancer cell proliferation and the effects of steroid hormones on their production, receptor binding, and action. Since the epidermal growth factor (EGF) receptor mediates the effects of both EGF and the autocrine growth factor, alpha-transforming growth factor, we investigated the effect of 1,25-(OH)2D3 on EGF receptor levels in several human breast cancer cell lines. Preincubation of T-47D cells with 1,25-(OH)2D3 for 24 h resulted in a significant concentration-dependent decline in the specific binding of [125I]EGF. The effect was observed when EGF binding was assayed at either 0 or 37 degrees C, both before and after treatment with acid to remove receptor bound endogenous ligand. This indicated that the effect on [125I]-EGF binding was not due to effects of 1,25-(OH)2D3 on receptor internalization and degradation or receptor occupancy. The half-maximal inhibitory concentration of 1,25-(OH)2D3 was approximately 2 nM. The decrease in EGF binding was due to a decrease in receptor number from 2,900 sites/cell in control cultures to 2,330 and 1,730 sites/cell in cells treated for 24 h with 10(-8) and 10(-6) M 1,25-(OH)2D3, respectively. There was no change in the affinity of the receptor for EGF following treatment with 1,25-(OH)2D3 [Kd = 0.075 +/- 0.006 nM (+/- SEM) for control and Kd = 0.083 +/- 0.004 nM for treated cells]. Decreased EGF receptor levels were also achieved with a number of analogues of 1,25-(OH)2D3 in accordance with their affinities for the 1,25-(OH)2D3 receptor, i.e., potencies for decreasing EGF binding in T-47D cells were in the order: 1,25-(OH)2D3 greater than 1,24,25-trihydroxyvitamin D3 greater than 1,25,26-trihydroxyvitamin D3 greater than 24,25-dihydroxyvitamin D3 greater than or equal to 25-hydroxyvitamin D3. Specific, saturable EGF binding to MCF-7 cells was also reduced by 1,25-(OH)2D3 while binding to BT-20 and HBL-100 cells was unaffected by this treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗
PubMed1988

Porcine follistatin gene structure supports two forms of mature follistatin produced by alternative splicing.

Follistatin (FS), a novel gonadal protein which inhibits specifically the secretion of pituitary follicle stimulating hormone (FSH), has recently been isolated from porcine follicular fluid. cDNA cloning of the porcine ovarian FS precursor revealed two populations of cDNAs which differed at the 3'-region of the open reading frames; one population encodes a precursor of 317 amino acids while the other encodes another precursor having the same 317 amino acids, but with an additional 27 amino acids at the carboxy-terminal. Herein, we report the cloning of the porcine FS gene whose DNA structure reveals that the two populations of mRNA are generated by alternative splicing. In addition, restriction endonuclease mapping and DNA sequencing show that the FS gene is approximately 6 Kb long and consists of six exons separated by five introns. The first exon encodes the putative signal sequence, followed by four exons which encode the four domains of FS, three of which are highly homologous to each other. The last exon encodes the extra 27-amino acid carboxy-terminal domain of the 344-residued precursor.

Amino Acid Sequence↗
PubMed1988

Primary structure of the human follistatin precursor and its genomic organization.

Follistatin is a single-chain gonadal protein that specifically inhibits follicle-stimulating hormone release. By use of the recently characterized porcine follistatin cDNA as a probe to screen a human testis cDNA library and a genomic library, the structure of the complete human follistatin precursor as well as its genomic organization have been determined. Three of eight cDNA clones that were sequenced predicted a precursor with 344 amino acids, whereas the remaining five cDNA clones encoded a 317 amino acid precursor, resulting from alternative splicing of the precursor mRNA. Mature follistatins contain four contiguous domains that are encoded by precisely separated exons; three of the domains are highly similar to each other, as well as to human epidermal growth factor and human pancreatic secretory trypsin inhibitor. The genomic organization of the human follistatin is similar to that of the human epidermal growth factor gene and thus supports the notion of exon shuffling during evolution.

Adult↗
PubMed1988

Experimental infection in a monkey with Gnathostoma hispidum larvae obtained from loaches.

Since the 1908s gnathostomiasis has occurred sporadically in Japanese who have eaten loaches, fresh-water fish imported from southeast Asia. Symptoms include creeping skin eruptions and eosinophilia. The symptoms disappeared in most patients within three months after the onset and the patients then remained symptom-free. To elucidate the causative factors, we fed one monkey with 80 gnathostome larvae collected from loaches and autopsied the animal 466 days later. Fifty-one viable larvae (64%) were recovered from muscle; these were in the advanced third stage and were encapsulated.

Animals↗
PubMed1988

Clinical features and course of type A and type B vitiligo.

Four hundred and eighty one cases of vitiligo (acquired idiopathic depigmentation) were studied clinically. They were divided into two types, type B, in which depigmented patches are confined to a definite dermatome in the same manner as herpes zoster, and type A, which included all cases of vitiligo not classified as type B. The ratio of type A:type B was approximately 3:I. Onset of type A vitiligo could occur at any age, whereas type B generally affected the young. The activity of type B vitiligo usually ceased after one year, following rapid spread over the particular dermatomal area. However, in type A vitiligo new depigmented patches continued to appear throughout the patients' lives. Association with halo naevus and Köbner's phenomenon were observed exclusively in type A. Association with diseases with a proven or suggested allergic or immunological aetiology was more often found in type A. These findings support our hypothesis that type A and type B vitiligo have a different pathogenesis and that autoimmune mechanisms play a role only in type A.

Age Factors↗
PubMed1988

[A simple method for calculation of free metal ion concentrations in the presence of a chelating agent and multiple metal ions by successive approximation].

Calculation of free metal ion concentrations in the presence of a chelating agent (ligand) and multiple metal ions is complicated. In this paper we describe a simple method for calculation of free ion concentrations from given total ion concentrations. The outline of this method is as follows: i) Using an arbitrarily chosen provisional value of free ligand concentration (p-Lf), calculate a total ligand concentration (Lt). ii) Divide the p-Lf by the ratio, the calculated Lt (c-Lt)/the specified Lt (s-Lt). Take the resulting value as the next p-Lf and repeat the calculation until c-Lt is close enough to s-Lt. At this point, p-Lf is supposed to be set to a good approximation of true free ligand concentration. iii) Finally, calculate free metal concentrations from the above approximation.

Chelating Agents↗
PubMed1988

Epidermal grafting using the tops of suction blisters in the treatment of vitiligo.

Fourteen patients with nondermatomal and 31 patients with segmental vitiligo were treated by epidermal grafting using the tops of suction blisters. Epidermis of the vitiliginous area was removed by a blister induced by methoxsalen plus ultraviolet A, and the tops of suction blisters were placed next to one another, resembling paving stones. Reepithelialization was completed in about two weeks, and skin color normalized in most cases about half a year later. Repigmentation persisted in most cases of segmental vitiligo, whereas loss of pigmentation occurred again in nonsegmental vitiligo. Scars were not observed on either the graft site or the donor site.

Blister↗
PubMed1988

[Clinical studies of rokitamycin dry syrup on Chlamydia trachomatis infections in the neonate and infant].

A dry syrup preparation for infants and children of a newly developed 16-membered macrolide antibiotic, rokitamycin, was administered to 5 neonates and low birth weight infants of 6 to 25 days after births at a dose level of 10 mg/kg on an empty stomach then plasma drug levels were determined. The dry syrup preparation was also given to a total of 19 Chlamydia trachomatis infection cases of 7 days to 8 months old neonates, low birth weight infants and infants including 12 cases of pneumonia, 2 cases of conjunctivitis and 5 non-symptomatic carriers at an average daily dose level of 48.1 mg/kg in 2 to 4 doses for an average of 19 days and its clinical effects, bacteriological effectiveness, side effects and effects on laboratory test values were examined. The obtained results are summarized as follows. 1. Because the test subjects were neonates and premature infants, obtainable amounts of blood samples were limited, thus it was not possible to determine time courses of plasma drug levels to reach their peaks. Peak plasma levels, however, were speculated to be similar to those in children. Plasma half-lives of the drug were also not determinable, but they seemed to be somewhat longer than those in children. 2. Clinical efficacies were determinable in the 2 cases of conjunctivitis and 10 of the 12 cases of pneumonia, with excellent or good results in both cases of the former and with excellent or good results in 9 of the 10 determinable cases of the latter. Thus, the overall efficacy rate was high, 91.7%. 3. Bacteriological efficacies were determinable in 18 cases including non-symptomatic carriers. C. trachomatis was eradicated in 16 of the cases with an overall efficacy rate of 88.9%. 4. Diarrhea was observed in 2 cases, which were suspected as side effects of the drug. 5. No abnormalities were observed in the laboratory test results. Judging from the above results, this drug appears to be useful for the treatment of C. trachomatis infections of neonates, low birth weight infants and infants.

Chlamydia Infections↗
PubMed1987

Epidermal growth factor partially reverses the inhibitory effects of antiestrogens on T 47D human breast cancer cell growth.

When T 47D human breast cancer cells were treated with 10 nM of the potent antiestrogen, 4-hydroxyclomiphene, growth rate was reduced to about 50% of control. Simultaneous treatment with epidermal growth factor (EGF) and 4-hydroxyclomiphene led to a partial reversal of the growth inhibitory effect of the antiestrogen. The effect of EGF was concentration-dependent being half-maximal at 0.10 ng/ml (0.02 nM) and maximal at concentrations greater than 0.5 ng/ml (greater than 0.08 nM). Furthermore, EGF partially reversed the growth inhibitory effects of several other antiestrogens including tamoxifen, 4-hydroxytamoxifen, and LY 117018. These results are compatible with the hypothesis that part of the growth inhibitory effects of antiestrogens on breast cancer cell proliferation are mediated by inhibition of autocrine secretion of growth stimulatory peptides acting through the EGF receptor.

Breast Neoplasms↗
PubMed1987

[Analysis of urinary metabolites of rats exposed to ethylene oxide].

Urinary metabolites of rats exposed to ethylene oxide(EO) were analyzed by gas chromatography-mass spectrometry(GC/MS). Male Wister rats(220-240 g) were exposed to EO for 6 hours. The urine was collected during 18 hours after the exposure and extracted with ethyl acetate. For the water-soluble metabolites, ethanol was added to the urine centrifuged and the supernatant fraction was evaporated to dryness. The residue of the extract was methylated with diazomethane and trimethylsilylated with bis(trimethylsilyl)trifluoroacetamide. Ethylene glycol, 2-hydroxymercapturic acid, 2-methylthioethanol and 2-mercaptoethanol were identified as the metabolites of EO. These results suggest that the inhaled EO was hydrolyzed to ethylene glycol, and conjugated with glutathion to form the mercapturic acid and methylthio metabolite.

Animals↗
PubMed1987

Early third-stage larvae of Gnathostoma hispidum in cyclops. Surface topography revealed by scanning electron microscopy.

Surface structures of the early third-stage larvae were examined by scanning electron microscopy. There were hemispherical head-bulbs at the apical ends. These bulbs could be clearly distinguished from the bodies. The head-bulbs (52 X 29 micron) had four transverse rows of sharp hooklets. The number of hooklets in each row was 37, 36, 38, and 43, posteriorly. The larvae posessed a pair of lateral lips in the head-bulb. Each of the lips had two labial papillae and an amphid between the papillae. Small unidentate cuticular spines were present along the entire length of larvae on their transverse striations. The number of these cuticular striations was 175-217. A pair of cervical papillae and an excretory pore were present on the anterior part of the body. Another pair of papillae was detected laterally on the posterior one-third of the body. The shape of the posterior body papillae resembled that of cervical papillae. The cuticular spines were absent around the anus.

Animals↗
PubMed1987

Cerebellar efferent fibers around the dentate nucleus. Pathological anatomy in olivo-ponto-cerebellar and dentato-pallido-luysian atrophy.

In patients with olivo-ponto-cerebellar atrophy (OPCA), the deep cerebellar white matter showed evidence of severe degeneration and gliosis. However, the circumferential white matter enclosing the dentate nucleus was less involved. In addition, the Holzer stain verified the presence of mild gliosis inside the wrinkled band of the dentate gray matter. In contrast, dentato-rubro-pallido-luysian atrophy (DRPLA) affected the mantle layer covering the dentate nucleus. The fibers encircling the dentate nucleus, which degenerate in DRPLA and are spared in OPCA, are anatomically noticeable to be dentatofugal pathways. Moreover, the afferent fibers from the cerebellar cortex and other systems may reach the dentate nucleus partly from the medial aspect via the hilus, as was noted in cases of OPCA.

Cerebellar Ataxia↗
PubMed1987

Ventricular septal defect associated with aortic regurgitation.

The effectiveness of aortic valvuloplasty and the indications for aortic valve replacement were examined in 76 patients with ventricular septal defect associated with aortic regurgitation. Results of this study indicate aortic regurgitation is associated with rapid deterioration and that aortic valvuloplasty should be performed as soon as aortic regurgitation is detected. The data also suggest that aortoplasty is indicated if aortic valvuloplasty alone is inadequate for coaptation of the aortic cusps with thickening.

Adolescent↗
PubMed1987

Japanese patients with leukaemia following the use of Thorotrast including a patient with marked chromosomal rearrangements.

It is estimated that 20,000-33,000 persons have been injected with Thorotrast in Japan. By August 1984, 12 patients with leukaemia following the use of Thorotrast have been reported. Their clinical and haematological data indicate that most of the patients were males over 50 years of age and that the most frequent type of leukaemia involved the stem cells common to the granulocytic, erythroid and/or megakaryocytic lines. This assumption was supported by the evidence of marked chromosomal rearrangements in 100% of the cells from the bone marrow in our case. The median latent period from the administration of Thorotrast to the onset of leukaemia in Japan was 35 years, ranging from 16 to 45 years, which indicates that patients who were injected with Thorotrast should be carefully followed up in the future.

Acute Disease↗
PubMed1987

Musical cooing murmurs in degenerated porcine valves--a report of three cases.

Three cases with typical cooing murmurs in degenerated porcine valves at mitral positions were studied. An echophonocardiogram disclosed that the origin of cooing murmur was due to cusp vibration with fixed cycle in frequency. Three failed xenografts were replaced with mechanical valves and the removed prostheses were examined. The first valve had a torn cusp, the second had a perforated cusp and the third had both a torn and perforated cusps. The failed leaflets were all pliable and not thickened in properties. These common findings are suspected to relate closely to the occurrence of a musical cooing murmur. Since all cases with cooing murmurs suddenly developed severe or progressive heart failure, we recommend prompt evaluation and reoperation when a cooing murmur appears in the patients with xenografts.

Adult↗
PubMed1987

A case of von Recklinghausen's disease associated with pheochromocytoma and papillary carcinoma of the thyroid gland.

A 58-year-old woman was admitted to our hospital complaining of headache, dizziness and intermittent elevation of blood pressure. Multiple café-au-lait spots and neurofibromas had appeared on the back and the limbs since the age of 30 years. At the age of 54 years she underwent total thyroidectomy because of papillary carcinoma of the thyroid gland. On admission, the levels of plasma norepinephrine and epinephrine, urinary norepinephrine and normetanephrine were all within the normal range. However, urinary excretion of metanephrine was markedly increased to 1.49 +/- 0.45 (Mean +/- SD) mg/day and that of epinephrine was also slightly increased. The computed tomographic scans of the abdomen and the scintigraphy with 131I-metaiodobenzylguanidine revealed a tumor mass in the region of the right adrenal gland. The tumor was histologically confirmed to be pheochromocytoma at the operation. In her family history, her mother and one of her two sisters had von Recklinghausen's disease and another sister suffered from follicular carcinoma of the thyroid gland. As far as we know, this paper is the first report of a patient with von Recklinghausen's disease associated with both pheochromocytoma and non-medullary carcinoma of the thyroid gland, and her family.

Carcinoma, Papillary↗