PubMed Health⌕ Search

Biomedical subjects

K Aya

Publications and source records attributed to K Aya.

15 recordsLinked to original sources
PubMed2001

A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast function.

Osteoclastic bone resorption requires cell-matrix contact, an event mediated by the alpha v beta 3 integrin. The structural components of the integrin that mediate osteoclast function are, however, not in hand. To address this issue, we generated mice lacking the beta 3 integrin gene, which have dysfunctional osteoclasts. Here, we show the full rescue of beta 3(-/-) osteoclast function following expression of a full-length beta 3 integrin. In contrast, truncated beta 3, lacking a cytoplasmic domain (h beta 3c), is completely ineffective in restoring function to beta 3(-/-) osteoclasts. To identify the components of the beta 3 cytoplasmic domain regulating osteoclast function, we generated six point mutants known, in other circumstances, to mediate beta integrin signaling. Of the six, only the S(752)P substitution, which also characterizes a form of the human bleeding disorder Glanzmann's thrombasthenia, fails to rescue beta 3(-/-) osteoclasts or restore ligand-activated signaling in the form of c-src activation. Interestingly, the double mutation Y(747)F/Y(759)F, which disrupts platelet function, does not affect the osteoclast. Thus similarities and distinctions exist in the mechanisms by which the beta 3 integrin regulates platelets and osteoclasts.

Amino Acid Sequence↗
PubMed2001

Nephrin is an important component of the barrier system in the testis.

Nephrin, a gene product of the congenital nephrotic syndrome of the Finnish type (NPHS1), is a 1242-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules. The expression of this gene is localized in rat and human glomerular epithelial cells. Here we report the expression of nephrin in various tissues other than the kidneys in mice. The expression of nephrin mRNA in various tissues of mice, including the kidneys, testes, spleen, thymus and brain, were first investigated by the RT-PCR method, and it was shown that a high level of nephrin mRNA could be detected in the testes of mice 1-6 weeks old. In situ hybridization revealed the expression of the nephrin gene in the Sertoli cells. Additionally, immunofluorescent staining studies indicated that nephrin was colocalized with anchoring protein ZO-1 in the mouse testis. From these results, it is inferred that nephrin is an important component of the barrier system in testes.

Animals↗
PubMed2000

Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type.

BACKGROUND: Congenital nephrotic syndrome (CNS) of the Finnish type is a rare autosomal-recessive disorder. Kestila et al reported that a positionally cloned gene for a novel glomerular protein nephrin is mutated in CNS. Most Finnish patients have one of two mutations. In this study, we described a Japanese CNS family associated with a novel missense point mutation in the nephrin gene. METHODS: Reverse transcription-polymerase chain reaction, polymerase chain reaction, and sequence analysis were used. RESULTS: The patient had the three missense mutations homozygously. One mutation was already reported as sequence variant. The two other novel mutations were the GAG to AAG transition, leading to a Glu447Lys and the GAC to GTC transition, predicting an Asp819Val substitution in the nephrin protein. CONCLUSION: Our findings indicate that an abnormality of nephrin may cause CNS of the Finnish type in Japanese subjects.

Asian People↗
PubMed2000

Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads.

In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor alpha and beta were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.

Animals↗
PubMed1999

Expression of parathyroid hormone-related peptide messenger ribonucleic acid in developing kidney.

BACKGROUND: Parathyroid hormone (PTH)-related peptide (PTHrP), originally identified as a causative agent of hypercalcemia of malignancy, has been implicated in the regulation of growth and differentiation of endochondral bone, hair follicle, and breast as an autocrine/paracrine factor. Although some experiments indicate that PTHrP works as a growth factor for primary renal cells in vitro, the role of PTHrP in the kidney in vivo is not yet known. METHODS: We examined the amounts of PTHrP and PTH/ PTHrP receptor (PTHR) mRNA in the mouse kidney developmental process by reverse transcription-polymerase chain reaction, and investigated which cells produce PTHrP and PTHR in vivo by in situ hybridization. RESULTS: We observed high levels of PTHrP mRNA during mouse kidney maturation. PTHrP mRNA was expressed in the collecting duct, urothelium of the pelvis, and immature elements in the cortex of the developing kidney, including the S-shaped body, ureteric bud, and glomerulus. However, the expression of PTHR mRNA was lower during maturation than after the completion of the maturation process, and it was not detected in the collecting duct, urothelium of the pelvis, or nephrogenic zone in embryonic day 16 or 0-day-old mouse kidneys. CONCLUSION: These findings suggest that PTHrP has a role in mouse kidney maturation or glomerular development.

Animals↗
PubMed1997

Two novel missense mutations in calcium-sensing receptor gene associated with neonatal severe hyperparathyroidism.

Familial hypocalciuric hypercalcemia (FHH) is characterized by lifelong asymptomatic hypercalcemia without PTH hypersecretion and is inherited as an autosomal dominant trait with near 100% penetrance. In contrast, neonatal severe hyperparathyroidism (NSHPT) is a life-threatening disorder characterized by marked hypercalcemia and PTH hypersecretion. FHH/NSHPT results from inactivating mutations of the human calcium-sensing receptor (Casr) gene on chromosome 3q13.3-24. Nearly 30 different mutations of the Casr gene associated with FHH/NSHPT have been reported previously. In this report, genetic analysis of 1 Japanese NSHPT family revealed 2 novel mutations at codon 185 (CGA-->TGA/Arg-->Ter) in exon 4 of the Casr gene and at codon 670 (GGG-->GAG/Gly-->Glu) in exon 7. The Arg185Ter change was shown to occur in the proband's unaffected father and paternal grandmother as well as in the proband. The other mutation in exon 7 was shown in the proband's unaffected mother of Philippine origin as well as in the proband. This family is the first case of manifestation of more than 1 mutation in a proband's chromosomes; 1 mutation was obtained from the unaffected father, and the other was from the unaffected mother. Our observations have given us important keys to help elucidate the structure-function relationships of the Casr.

Arginine↗
PubMed1991

Two movement-related foci in the primate cingulate cortex observed in signal-triggered and self-paced forelimb movements.

1. Single-unit activity in the cingulate cortex of the monkey was recorded during the performance of sensorially (visual, auditory, or tactile) triggered or self-paced forelimb key press movements. 2. Microelectrodes were inserted into the broad rostrocaudal expanse of the cingulate cortex, including the upper and lower banks of the cingulate sulcus and the hemispheric medial wall of the cingulate gyrus. 3. A total of 1,042 task-related neurons were examined, the majority of which were related to the execution of the key press movements. In greater than 60% of them, the movement-related activity preceded the activity in the distal flexor muscles. 4. The movement-related neurons were distributed, in two foci, in the posterior and anterior parts of the cingulate cortex, both including the upper and lower banks of the cingulate sulcus. The posterior focus was found to largely overlap the area projecting to the forelimb area of the primary motor cortex by the use of the horseradish peroxidase (HRP) method. 5. About 40% of the cingulate cortical neurons showed equimagnitude responses during the signal-triggered and self-paced movements. The neurons exhibiting a selective or differential response to the self-paced motor task were more frequently observed in the anterior than in the posterior cingulate cortex. 6. The long-lead type of changes in activity, ranging from 500 ms to 2 s, were observed mainly before the self-paced and, much less frequently, before the triggered movements. They were particularly abundant in the anterior cingulate cortex. 7. Only a few of the neurons showed activity time-locked to the onset of the sensory signals. 8. These observations indicate that the anterior and posterior parts of the cingulate cortex are distinct entities participating in the performance of limb movements, even if the movements are simple, such as those in this study.

Animals↗
PubMed1989

Activity of digital area neurons of the primary somatosensory cortex in relation to sensorially triggered and self-initiated digital movements of monkeys.

Single-cell activity was examined in digital areas of the primary somatosensory cortex (SI) of monkeys performing sensorially triggered and self-initiated digital movements with the aim of rigorously determining the relative timing of onset of the neuronal activity with respect to movement onset. The activity of prime mover muscles for execution of a key-press movement was recorded simultaneously with the neuronal activity; movement onset was defined as the onset of muscle activity. Neuronal receptive fields were also identified. The following findings emerged from this study: (1) Few neurons, if any, in the SI(areas 3b, 1, 2), including pyramidal tract neurons, were active prior to movement onset. (2) The movement-related activity of SI neurons was basically similar in cases of signal-triggered and self-initiated movement. (3) No neuron in the SI showed activity associated with ipsilateral digital movement. (4) A majority of movement-related neurons in the precentral motor cortex, in contrast, started their activity before movement onset. These findings suggest that SI neuronal activity participates little in providing information necessary for developing motor responses in the initial phase of simple digital movements.

Afferent Pathways↗
PubMed1985

A maximum entropy criterion of filtering and coding for stationary autoregressive signals: its physical interpretations and suggestions for its application to neural information transmission.

The operations of encoding and decoding in communication agree with filtering operations of convolution and deconvolution for Gaussian signal processing. In an analogy with power transmission in thermodynamics, an autoregressive model of information transmission is proposed for representing a continuous communication system which requires a pair of an internal noise source and a signal source to encode or decode a message. In this model transinformation (informational entropy) equals the increase in stationary nonequilibrium organization formed through the amplification of white noise by a positive feedback system. The channel capacity is finite due to the existence of inherent noise in the system. The maximum entropy criterion in information dynamics corresponds to the 2nd law of thermodynamics. If the process is stationary, the communication system is invertible, and has the maximum efficiency of transformation. The total variation in informational entropy is zero in the cycle of the invertible system, while in the noninvertible system the entropy of decoding is less than that of encoding. A noisy autoregressive coding which maximizes transinformation is optimum, but is also ideal.

Animals↗
PubMed1983

Quantitative analysis of the sympathetic efferent activity to characterize the integrative function of the sympathetic ganglion.

Using the concept of the Markov dependency, we analyzed the spontaneous activity in the pre- and postganglionic nerve trunks of the feline superior cervical ganglion. The time structure (order and value of time dependency) of the sequence of compound action potentials was determined. The analysis revealed that the time dependency of the postganglionic activity is of higher order and is generally more consistent than that of the preganglionic one. The difference in orders and values between the pre- and postganglionic activities was found to be a measure of the integrative function of the ganglion. A transformation by the ganglion of some additional information, inaccessible in the time structure of the preganglionic activity, seems to underlie this difference.

Action Potentials↗
PubMed1982

Nociceptive and non-nociceptive responses of neurons in the medial subthalamic region and lateral hypothalamic area of cats and their relationship to the effects of morphine and pentazocine.

Single neuronal activity was recorded extracellularly from the Forel's field (FH), subthalamic region immediately rostral to the FH (STRF), rostral end of the medial subthalamic region (RE) and lateral hypothalamic area (LHA) of the anesthetized cats. Many of the FH, RE and LHA neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intra-arterial injection of bradykinin. These nociceptive neurons were also excited by non-nociceptive stimulation such as tap of deep tissues, bending hairs with an air-puff and/or joint rotation. On the other hand, inhibition by both nociceptive and non-nociceptive stimuli was seen in and around the rostral end of the FH including STRF. Their receptive fields were large. After intravenous administration of either morphine or pentazocine, most nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non-nociceptive stimuli. This suggests that morphine and pentazocine have a specific antinociceptive action on these nociceptive neurons. Intravenous naloxone reversed the antinociceptive action of morphine, but failed to reduce the action of pentazocine. This differentiation has an important functional significance.

Animals↗
PubMed1981

Peripheral somatic activation and spontaneous firing patterns of neurons in the periaqueductal gray of the cat.

A total of 50 neurons in the periaqueductal gray (PAG) of the cat were studied. Sixty percent of the units were excited by nociceptive pinch stimulation. These units were also excited by non-nociceptive stimulation such as tapping, hair movement and/or joint rotation. Non-nociceptive stimulation excited 20% of the units, whereas nociceptive stimulation did not drive these units. Their receptive fields were large, and often encompassed the entire body. Spontaneous discharges of PAG neurons revealed great irregularity.

Animals↗
PubMed1981

Regularity of the spontaneous discharge of neurons in the nucleus raphe dorsalis of the cat.

Impulse discharges were recorded from 43 neurons in the nucleus raphe dorsalis of the cat. Of these neurons examine for spontaneous activity, 23 fired in remarkable regular rhythm (clock-like neurons); 18 fired irregularly (non-clock-like neurons); and 2 fired with an unclassified pattern. Almost all clock-like neurons were unresponsive to any kind of peripheral somatic stimuli, while the majority of non-clock-like neurons were excited by both nociceptive and non-nociceptive stimuli or by non-nociceptive stimuli. The somatic receptive fields were large, spanning the entire body.

Animals↗
PubMed1977

Dependency representing Markov properties of spike trains recorded from central single neurons.

Neuronal spike trains are regarded as stochastic point processes. To estimate the order and the vale of Markov properties of the adjacent interspike interval sequences, we have proposed new statistics "dependency" Dm for discrete variable and "simplified dependency" Dm for continuous variable in the stationary point processes, and Dm(t) for discrete variable in the non-stationary point processes. With the use of Dm it was shown that the maintained activity of the neurons of the mesencephalic reticular formation and red nucleus (tonic neuron groups) revealed higher order and larger values of Markov properties than that of the optic tract (OT) fibers and lateral geniculate nucleus neurons (phasic neuron groups) in cats. By employing Dm(t) it was shown that the value of the 1st order Markov properties of OT spike trains induced by the light spot presentation became to increase earlier in Y-fibers than in X-fibers; and that the value for Y-fibers returned to the maintained level in a short time, while the maximum value for X-fibers continued up to the light-off. The differentiation is considered to have a decided functional significance. From these results it is suggested that dependency code represents the stability of neuronal functions.

Action Potentials↗