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Biomedical subjects

M Horiguchi

Publications and source records attributed to M Horiguchi.

At least 19 recordsLinked to original sources

Human placental trophoblast cells express alpha-tocopherol transfer protein.

Alpha-tocopherol transfer protein (alpha-TTP), a 30 kDa cytosolic protein first described to be present in the liver and important for alpha-tocopherol trafficking, plays a major role in maintaining alpha-tocopherol levels in plasma, while alpha-tocopherol is known as the major lipid-soluble antioxidant. Expression of alpha-TTP has not only been described in animal model liver, but also in diverse other tissues such as rat brain or pregnant mouse uterus, the latter finding stressing the importance of alpha-TTP for embryogenesis and foetal development. In this study, we report the identification of alpha-TTP in human liver by anti-human alpha-TTP monoclonal antibodies made in rat and the cellular localization of alpha-TTP in term human placenta. By immunohistochemistry, intense staining of alpha-TTP was seen in syncytiotrophoblast as well as in villous and invading extravillous cytotrophoblast, while basal decidual cells showed slighter, but present staining of alpha-TTP. Foetal vessel endothelium remained unstained. It is therefore suggested that alpha-TTP may play a major role in supplying alpha-tocopherol to the foetus prior to delivery and is likely involved in maintaining adequate alpha-tocopherol levels in the foetus.

Adult↗

Molecular nature of ultraviolet B light-induced deletions in the murine epidermis.

Depletion of the stratospheric ozone layer leads to an increase in ambient UV loads, which are expected to raise skin cancer incidences. Tumor development in the skin could be a multistep process in which various genetic alterations, such as point mutations and deletions, occur successively. Here, we demonstrate that UVB irradiation efficiently induces deletions in the epidermis using a novel transgenic mouse, gpt delta. In this mouse model, deletions in lambda DNA integrated in the chromosome are preferentially selected as Spi(-) (sensitive to P2 interference) phages, which can then be subjected to molecular analysis. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5, and 2.0 kJ/m(2). After 4 weeks, lambda phage was rescued from the genomic DNA of the epidermis by in vitro packaging reactions. The mutant frequencies of Spi(-) with large deletions in the epidermis increased >15-fold at a UVB dose of 0.5 kJ/m(2) over the control. Molecular sizes of most of the large deletions were >1000 bp. More than one-half of the large deletions occurred between short direct-repeat sequences from 1 to 6 bp, and the remainder had flush ends. In the unirradiated mouse, almost all of the Spi(-) mutants were 1-bp frameshifts in runs of identical bases. These results suggest that UVB irradiation induces deletions in the murine epidermis, and most of the deletions are generated through end-joining of double strand breaks in DNA.

Animals↗

The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development.

We have used confocal microangiography to examine and describe the vascular anatomy of the developing zebrafish, Danio rerio. This method and the profound optical clarity of zebrafish embryos make it possible to view the entire developing vasculature with unprecedented resolution. A staged series of three-dimensional images of the vascular system were collected beginning shortly after the onset of circulation at 1 day postfertilization through early- to midlarval stages at approximately 7 days postfertilization. Blood vessels in every region of the animal were imaged at each stage, and detailed "wiring patterns" were derived describing the interconnections between every major vessel. We present an overview of these data here in this paper and in an accompanying Web site "The interactive atlas of zebrafish vascular anatomy" online at (http://eclipse.nichd.nih.gov/nichd/lmg/redirect.html). We find a highly dynamic but also highly stereotypic pattern of vascular connections, with different sets of primitive embryonic vessels severing connections and rewiring in new configurations according to a reproducible plan. We also find that despite variation in the details of the vascular anatomy, the basic vascular plan of the developing zebrafish shows strong similarity to that of other vertebrates. This atlas will provide an invaluable foundation for future genetic and experimental studies of vascular development in the zebrafish.

Angiography↗

Hypoplasia of the left lobe of the liver.

In a forensic autopsy, hypoplasia of the left lobe (lateral segment) of the liver was found. Although the cause was unknown, the morphologic anomaly observed in this case was regarded as congenital because there was no history of surgery. Moreover, the main vessels of the left lobe were present despite complete absence of the parenchyma.

Abnormalities, Multiple↗

Na(+) action potentials in human photoreceptors.

Mammalian photoreceptors are hyperpolarized by a light stimulus and are commonly thought to be nonspiking neurons. We used the whole-cell patch-clamp technique on surgically excised human retina to examine whether human photoreceptors can elicit action potentials. We discovered that human rod photoreceptors express voltage-gated Na(+) channels, and generate Na(+) action potentials, in response to membrane depolarization from membrane potentials of -60 or -70 mV. Na(+) spikes in human rods were elicited at the termination of a light response that hyperpolarized the potential well below -50 mV. This served to amplify the release of a neurotransmitter when a bright light is turned off, and thus selectively amplify the off response to the light signal.

Action Potentials↗

Association of angiotensinogen gene polymorphism with erythropoietin-induced hypertension: a preliminary report.

The association of the angiotensinogen (AGT) gene variation at codon 235, the T235 variant, with hypertension induced by erythropoietin (Epo) was investigated in patients with progressive renal disease requiring treatment for renal anemia with Epo. The subjects for the study were patients with renal diseases with serum creatinine concentration exceeding 2 mg/dl and a hematocrit (Ht) of less than 30%. During the run-in period, blood pressure was well controlled with an appropriate salt restricted diet and/or antihypertensive treatment. The patients were then given 6,000 IU of Epo once a week until the Ht rose by 5%. For the overall patient group, AGT gene polymorphism analysis revealed T235T (T/T) in 31 cases (61%), M235T (M/T) in 19 cases (37%), and M235M (M/M) in 1 case (2%). In response to treatment with Epo, hypertension (defined as an increase in mean blood pressure greater than 10 mmHg) was found in 11 cases (22%), all of who carried the homozygous T allele (T/T). On the other hand, the frequency of T/T in patients who did not develop hypertension was 50% (T/T:T/M=20:19 cases), indicating a significant difference (p=0.003 by Chi-square). Variables estimated to be associated with Epo-induced hypertension were the T allele, gender (male), and the degree of increase in Ht, in descending order. Our preliminary research indicates that individuals who carry two copies of the T allele, i.e., who are homozygous for T, are highly susceptible to development of hypertension when subjected to Epo. These results suggest that the AGT T235 variant may be the primary gene responsible for the development of Epo-induced hypertension.

Adult↗

Multifocal ERG findings in complete type congenital stationary night blindness.

PURPOSE: To study the multifocal electroretinogram (mfERG) in patients with the complete type of congenital stationary night blindness (cCSNB), which is thought to be due to a defect in neurotransmission from the photoreceptors to the ON-bipolar cells. METHODS: mfERGs were recorded with the VERIS recording system from four patients with cCSNB, none of whom had nystagmus. The stimulus array consisted of 61 hexagons, and the total recording time was approximately 4 minutes. The amplitudes and implicit times of the first- and second-order kernels of the local responses were compared with those from 20 myopic controls. Waveforms of the summed response from all locations were also compared between the two groups. RESULTS: The first-order kernels of the mfERGs of cCSNB patients had normal amplitudes but delayed implicit times for nearly the whole field tested. The second-order kernel was severely attenuated in amplitude in cCSNB patients. The ratios of the second- to first-order kernel amplitudes were significantly reduced in cCSNB and clearly separated the cCSNB group from the control group without any overlap of the values. CONCLUSIONS: The second-order kernel, which is involved in adaptative mechanism of the retina to repeated flashes, is selectively reduced in cCSNB. The delay of the implicit times of the first-order kernel in patients with cCSNB may be related to the severe amplitude reduction of the second-order kernel.

Adolescent↗

A contact lens electrode with built-in high intensity white light-emitting diodes. A contact lens electrode with built-in white LEDs.

We determined the clinical usefulness of a new contact lens electrode with built-in, white light-emitting diodes (LEDs) for full-field electroretinograms (ERGs). Three, high-brightness white LEDs were incorporated into a contact lens electrode and served as the source for the stimulus and the background. The stimulus intensity, stimulus duration and background illumination were regulated by a small LED control device. Maximum stimulus and background intensities were 3.9 and 3.6 log cd/m2, respectively. We successfully recorded intensity-response series for scotopic and photopic ERGs. We also recorded a duration-series for photopic ERGs, and ERGs that were comparable to the ISCEV standardized ERGs. The compactness and ease of using this system suggest that it will be clinically useful under different conditions.

Adult↗

New visual acuity chart for patients with macular hole.

PURPOSE: To evaluate the usefulness of a new multiple-letter visual acuity chart (MLAC) for the measurement of visual acuity in patients with macular hole. METHODS: Visual acuity was measured using a standard visual acuity chart (Landolt rings, also referred to as C's) and with the MLAC in normal subjects and in patients with a cataract or a macular hole. The MLAC has 14 plates (45 x 45 cm), and on one plate, many Landolt C's were printed with the gaps pointing in the same direction and all of one size. The sizes of the letters and gaps were made to give equivalent visual acuities of 0.1, 0.15, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.5, and 2.0. The spacing between the letters was 33.3% of the diameter of the C's. Each chart projected many C's onto the macular area (5 degrees x 5 degrees ), which permitted the measurement of visual acuity at an extrafoveal point without the patient having to search for the extrafoveal point with the best acuity. RESULTS: There was no difference in the acuity measurement determined with the standard chart and the MLAC in normal subjects and patients with cataracts. Twelve of 16 patients with open macular hole, however, demonstrated higher acuity measurement (more than two lines) on the MLAC than on the standard chart. The improvement of visual acuity measurement after successful macular hole surgery was significantly less with the MLAC than with the standard chart. CONCLUSIONS: Our results suggest that the standard acuity chart, when administered before surgery, underestimates the patient's potential visual acuity after surgery, whereas the MLAC provides a better estimate of the patient's postoperative acuity. The MLAC can be a useful tool for measuring visual acuity in patients with macular hole.

Aged↗

Tumour necrosis factor-alpha up-regulates the expression of BMP-4 mRNA but inhibits chondrogenesis in mouse clonal chondrogenic EC cells, ATDC5.

Tumour necrosis factor (TNF)-alpha causes the degradation of articular cartilage in arthritis via direct actions on chondrocytes. However, it remains unknown whether TNF-alpha affects chondrogenesis in chondroprogenitors. In the present study, we assessed the effects of TNF-alpha in vitro on chondrogenesis using mouse clonal chondrogenic EC cells, ATDC5. TNF-alpha (10 ng/ml) stimulated [3H] thymidine incorporation in undifferentiated ATDC5 cells, and suppressed cartilaginous nodule formation and the accumulation of cartilage-specific proteoglycan. We recently showed that undifferentiated ATDC5 cells express BMP-4 and that exogenously administered BMP-4 promotes chondrogenesis in these cells. Interestingly, TNF-alpha up-regulated the expression of BMP-4 mRNA in undifferentiated ATDC5 cells in time- and dose-dependent manners. However, exogenously administered BMP-4 was not capable of reversing the inhibitory action of TNF-alpha on chondrogenesis in ATDC5 cells. These results indicate that TNF-alpha stimulates both cell proliferation and BMP-4 expression but inhibits chondrogenesis in chondroprogenitor-like ATDC5 cells.

Animals↗

Stenotrophomonas maltophilia endophthalmitis after intraocular lens implantation.

BACKGROUND: Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus. Endophthalmitis induced by S. maltophilia has been described in only two cases after intraocular lens implantation. We report S. maltophilia endophthalmitis in two patients with diabetes mellitus after intraocular lens implantation and compare the characteristics of the S. maltophilia-induced endophthalmitis with two previous cases. METHODS: A 68-year-old woman and a 74-year-old man with diabetes mellitus developed S. maltophilia endophthalmitis within 5 days of intraocular lens implantation. We performed intraocular lens removal and vitrectomy, which resolved the inflammation. No recurrences were found. RESULTS: Cultures grew S. maltophilia in both cases, and one of the organisms was multi-resistant. The final visual acuity was counting fingers and 0.3. The first case revealed a tractional retinal detachment during vitrectomy. CONCLUSIONS: S. maltophilia is a potential opportunistic intraocular pathogen, and the incidence of multiresistant S. maltophilia is increasing. S. maltophilia causes acute endophthalmitis, and its prognosis may not be poor unless the eye has a history of serious disease before the cataract surgery. The combined procedure of intraocular lens removal and vitrectomy was useful in resolving the inflammation and preventing recurrences.

Aged↗

Nutrient canal of the fibula.

OBJECTIVE: To investigate the radiological features of the nutrient canal in the fibula. DESIGN AND PATIENTS: One hundred and seventy-nine dried fibulae were studied regarding the type, number, location, and direction of the nutrient canal. They were classified into a usual type (type I: a radiolucent line confined to the cortex) and an atypical type (type II: a radiolucent line extending beyond the cortex). RESULTS: Among the total of 230 nutrient canals seen on radiography, 197 (86%) were type I and 33 (14%) were type II. On CT scans, the ossified rim of the canal extended into the medullary cavity in type II canals. The most common site was the posteromedial aspect in both type I and type II canals. Type II canals were significantly more common in fibulae with two or three nutrient canals. The frequency of the upward direction was more common in type II canals. CONCLUSION: Nutrient canals with extension of the ossified rim into the medullary canal are the cause of linear lucency that may simulate a fracture. Their features are slightly different from those of usual canals.

Aged↗

The communicating branch of the 4th cervical nerve to the brachial plexus: the double constitution, anterior and posterior, of its fibers.

Twenty-four adult cadavers (48 sides) were used to investigate the incidence of a branch arising from the ventral ramus of the fourth cervical nerve (C4) with the phrenic nerve and subsequently joining the brachial plexus. Six brachial plexuses with spinal cords and phrenic nerves were dissected under a surgical microscope to investigate localization of fibers contained in the C4 branch to the brachial plexus. The incidence of the C4 branch was 23% (11/48 sides). Branches from C4 to the brachial plexus divided into anterior and posterior divisions on four sides (4/6 sides). On two sides, the branch did not divide but consisted entirely of an anterior division (2/6 sides). In the brachial plexus, anterior division fibers of the C4 branch were intertwined with fibers from the anterior divisions of the ventral rami of the fifth and sixth cervical nerves. They then passed to the suprascapular nerve and the anterior division of the superior trunk (6/6 sides). On the other hand, posterior division fibers of the C4 branch were intertwined with fibers from the posterior divisions of the ventral rami of the fifth and sixth cervical nerves. They then passed to the suprascapular nerve (2/6 sides) and the posterior division of the superior trunk (4/6 sides). The anterior division of the C4 branch received fibers from the ventral rootlets of the entire fourth cervical segment, whereas the posterior division received fibers from the ventral rootlets of the caudal half of the fourth cervical segment only. The fact that the suprascapular nerve received fibers from both the anterior and posterior divisions of the C4 branch was considered to support our claim that the human suprascapular nerve belongs to both the anterior and posterior divisions of the brachial plexus.

Adult↗

Characterization of mutations induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the colon of gpt delta transgenic mouse: novel G:C deletions beside runs of identical bases.

Mutations induced by one of the typical dietary mutagens/carcinogens, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), were characterized using gpt delta transgenic mice. This transgenic mouse model has two selection methods to efficiently detect different types of mutations, i.e. 6-thioguanine selection for point mutations and Spi(-) selection for deletions. The mice were fed with a diet containing 400 p.p.m. PhIP for 13 weeks and gpt and Spi(-) mutations were analyzed from the colon, where the highest mutant frequencies were detected. Concerning the types of gpt mutations from PhIP-treated mice, 81% were single base pair substitutions and G:C-->T:A transversions predominated; single base pair deletions at G:C base pairs were also observed. In untreated mice G:C-->A:T transitions predominated and >80% of these events involved 5'-CpG-3' sites. Concerning Spi(-) mutants from PhIP-treated mice, 76% were G:C base pair deletions and more than half of these events occurred in monotonic G or C run sequences. Interestingly, a novel type of frameshift motif, i.e. G:C base pair deletions beside run sequences, was observed. The most frequently observed mutation in this class was the 5'-TTTTTTG-3'-->5'-TTTTTT-3' event. These results suggest that PhIP induces point mutations, such as base substitutions and single base pair deletions, rather than larger deletions in vivo and that run sequences may play an important role in PhIP-induced G:C base pair deletions.

Animals↗

Circulating adrenomedullin in erythrocopietin-induced hypertension.

Levels of adrenomedullin (AM) have been shown to be elevated in hypertension and chronic renal failure, suggesting that AM plays a role in the pathogenesis of these diseases. The objective of the present study was to investigate whether circulating AM is involved in erythropoietin (Epo)-induced hypertension in patients with renal anemia due to progressive renal disease. Following treatment with 6,000 IU of Epo once a week, the hematocrit (Ht) rose significantly from 25.9+/-4.0 to 33.4+/-3.3% (n=54, p<0.001) with an overall rate of increase in Ht of 0.43+/-0.04%/week. In response to treatment with Epo, a rise in mean blood pressure of >10 mmHg (Epo-induced hypertension) was found in 22% (12/54 cases) of the patients enrolled. There was no difference in the rate of Ht increase between patients with and without Epo-induced hypertension. There was a significant positive correlation between mature AM and serum creatinine (Cr) concentration before treatment with Epo. However, no correlation was found between the plasma concentration of total AM and serum Cr concentration. Long-term treatment with Epo did not influence plasma concentration of either mature AM or total AM in patients developing hypertension during the study period. These results suggest that circulating AM may play a role in the progression of renal disease. However, the present study does not support the notion that circulating AM is associated with the pathogenesis of Epo-induced hypertension. It is too early yet to claim that there is no AM-mediated mechanism in Epo-induced hypertension.

Adrenomedullin↗

Different functional aspects of the group II subfamily (Types IIA and V) and type X secretory phospholipase A(2)s in regulating arachidonic acid release and prostaglandin generation. Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation.

We have recently reported that members of the heparin-binding group II subfamily of secretory PLA(2)s (sPLA(2)s) (types IIA and V), when transfected into 293 cells, released [(3)H]arachidonic acid (AA) preferentially in response to interleukin-1 (IL-1) and acted as "signaling" PLA(2)s that were functionally coupled with prostaglandin biosynthesis. Here we show that these group II subfamily sPLA(2)s and the type X sPLA(2) behave in a different manner, the former being more efficiently coupled with the prostaglandin-biosynthetic pathway than the latter, in 293 transfectants. Type X sPLA(2), which bound only minimally to cell surface proteoglycans, augmented the release of both [(3)H]AA and [(3)H]oleic acid in the presence of serum but not IL-1. Both types IIA and V sPLA(2), the AA released by which was efficiently converted to prostaglandin E(2), markedly augmented IL-1-induced expression of cyclooxygenase (COX)-2 in a heparin-sensitive fashion, whereas type X sPLA(2) lacked the ability to augment COX-2 expression, thereby exhibiting the poor prostaglandin E(2)-biosynthetic response unless either of the COX isozymes was forcibly introduced into type X sPLA(2)-expressing cells. Implication of phospholipid scramblase, an enzyme responsible for the perturbation of plasma membrane asymmetry, revealed that the scramblase-transfected cells became more sensitive to types IIA and V, but not X, sPLA(2), releasing both [(3)H]AA and [(3)H]oleic acid in an IL-1-independent manner. Thus, although phospholipid scramblase-mediated alteration in plasma membrane asymmetry actually led to the increased cellular susceptibility to the group II subfamily of sPLA(2)s, several lines of evidence suggest that it does not entirely mimic their actions on cells after IL-1 signaling. Interestingly, coexpression of type IIA or V, but not X, sPLA(2) and phospholipid scramblase resulted in a marked reduction in cell growth, revealing an unexplored antiproliferative aspect of particular classes of sPLA(2).

Annexin A5↗