Biomedical subjects

J Kishimoto

Publications and source records attributed to J Kishimoto.

At least 19 recordsLinked to original sources

PubMed2004

Interchange of the quantum states of confined excitons caused by radiative corrections in CuCl films.

The energy states of a particle confined in a narrow space are discrete and lined up in the order of n=1,2,3,.... However, if the particle interacts with a radiation field, modification of the energy, referred to radiative correction, will occur and quantum states are expected to interchange. We investigated the center-of-mass confinement of excitons in CuCl films by a new method based on "nondegenerate two-photon excitation scattering." The energies of confined excitons in a 19.3 nm thick film are found to be lined up in the order of n=1,3,5, because the radiative correction is very weak. On the other hand, in a 35.3 nm thick film, in which the radiative correction becomes large, the energies of quantum states are ordered n=2,3,4,1,5,7. This interchange is confirmed by comparing the calculated scattering spectra, in which radiative correction is taken into account, with the measured ones.

Journal Article↗

PubMed2002

Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G-CSF, a model protein.

A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designed for the oral delivery of protein drugs. The system consists of four layered films, 3.0 x 3.0 mm2, contained in an enteric capsule. The 40 microm backing layer is made of a water-insoluble polymer, ethyl cellulose (EC). The surface layer is made of an enteric pH-sensitive polymer such as hydroxypropylmethylcellulose phthalate (HP-55), Eudragit L100 or S100 and was coated with an adhesive layer. The middle layer, drug-containing layer. made of cellulose membrane is attached to the EC backing layer by a heating press method. Both drug and pharmaceutical additives including an organic acid, citric acid, and a non-ionic surfactant, polyoxyethylated castor oil derivative (HCO-60), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako 103). Fluorescein (FL), 30mg, was first used as a model drug for oral administration of GI-MAPS having different surface layers in beagle dogs. The plasma FL concentration vs. time profiles demonstrated that the targeting of the systems was obtained, because the Tmax, the time when plasma FL concentrations reaches to its maximum lelev, was 2.33+/-0.82 h for HP-55 system, 3.33+/-0.41 h for Eudragit L100 system and 5.00+/-0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs containing 125 microg of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in total white blood cell (WBC) counts were measured as the pharmacological index for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 microg) indicated the pharmacological availabilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins.

Administration, Oral↗

PubMed2001

A novel mechanism of matrix metalloproteinase-9 gene expression implies a role for keratinization.

To investigate the pathophysiological role of matrix metalloproteinase (MMP)-9 in the skin, we analyzed MMP-9 expression from human keratinocytes in culture. MMP-9 and the terminal differentiation marker involucrin were co-localized in the same keratinocytes with a high concentration of Ca(2+), a potent stimulator of differentiation. We identified the novel KRE-M9 element, further downstream to the previously reported TPA responsive element in the MMP-9 promoter, and both of these two elements were shown to be important for MMP-9 transcription and Ca(2+) induction. The concomitant upregulation of MMP-9 and involucrin transcripts was probably due to the very similar gene regulatory elements, KRE-M9 and KRE-4, in their respective promoters. These results indicate a novel mechanism of transcriptional regulation for MMP-9 in the process of keratinization, implying the probable association of apoptosis and differentiation of keratinocytes in epidermal skin tissue.

Calcium↗

PubMed2001

Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice.

Targeted ablation of the vitamin D receptor (VDR) results in hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, osteomalacia, and alopecia--the last a consequence of defective anagen initiation. To investigate whether the markedly elevated levels of 1,25-dihydroxyvitamin D led to the alopecia, we raised VDR-null mice in a ultraviolet light-free environment and fed them chow lacking vitamin D for five generations. Despite undetectable circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, alopecia persisted in the VDR-null mice, demonstrating that the alopecia was not secondary to toxic levels of 1,25-dihydroxyvitamin D interacting with an alternative receptor. Furthermore, alopecia was not seen in control littermates, suggesting that absence of ligand and absence of receptor cause different phenotypes. To identify the cell population responsible for the alopecia, we performed hair-reconstitution assays in nude mice and observed normal hair follicle morphogenesis, regardless of the VDR status of the keratinocytes and dermal papilla cells. However, follicles reconstituted with VDR-null keratinocytes demonstrated a defective response to anagen initiation. Hence, alopecia in the VDR-null mice is due to a defect in epithelial-mesenchymal communication that is required for normal hair cycling. Our results also identify the keratinocyte as the cell of origin of the defect and suggest that this form of alopecia is due to absence of ligand-independent receptor function.

Alopecia↗

PubMed2000

TT virus mRNAs detected in the bone marrow cells from an infected individual.

Although replicative forms of TT virus (TTV) DNA have been found in the liver and bone marrow cells, mRNAs of TTV have not yet been detected in these tissues. The entire nucleotide sequence of a TTV clone [TYM9 (3759 bases)] isolated from a patient with high TTV viremia (10(6) copies/ml) was determined, and the poly(A)(+) RNAs from bone marrow cells were subjected to reverse transcription-polymerase chain reaction with primers specific for the TYM9 sequence. Sequence analysis of the amplified products revealed the presence of three distinct species of spliced TTV mRNAs [2.9, 1.2, and 1.0 kilobases (kb)] with common 5' and 3' termini as well as splicing to bind nucleotide (nt) 181 to nt 283. The shorter mRNAs of 1.2 kb and 1.0 kb possessed another splicing to join nt 681 with nt 2341 or nt 2579. The transcription profile of TTV found in an infected human corroborates that observed in vitro.

3' Untranslated Regions↗

PubMed2000

Species-specific TT viruses in humans and nonhuman primates and their phylogenetic relatedness.

By means of polymerase chain reaction with a primer pair (NG133-NG147) deduced from the untranslated region (UTR) of TT virus (TTV), TTVs with markedly distinct genomic lengths were recovered from sera of humans and nonhuman primates, and their entire nucleotide sequences were determined. A human TTV [TGP96 of 2908 nucleotides (nt)] was obtained that was about 900 nt shorter than heretofore reported TTVs (3787-3853 nt). Likewise, TTVs of chimpanzee occurred in two distinct genomic sizes [Pt-TTV6 (3690 nt) and Pt-TTV8-II (2785 nt)]. Two TTVs of Japanese macaque [Mf-TTV3 (3798 nt) and Mf-TTV9 (3763 nt)] were comparable in genomic length, but only 55% similar in sequence. These five human and nonhuman primate TTVs, along with TTVs of tamarin [So-TTV2 (3371 nt)] and douroucouli [At-TTV3 (3718 nt)], were compared over the entire nucleotide sequence. Although the seven TTVs were only < or = 55% similar, they share a common genomic organization with two open reading frames (ORFs), designated ORF1 (654-735 amino acids) and ORF2 (91-152 amino acids). The N-terminal sequences of ORF1 proteins were rich in arginine, and sequence motifs necessary for transcription and replication were conserved among them all. Like the human prototype TTV (TA278), all seven TTVs from various animals possessed in common two 15-nt sequences (CGAATGGCTGAGTTT and AGGGGCAATTCGGGC) in the UTR that were covered by NG133 and NG147, respectively. These primers would be instrumental in research on TTVs in previously unexamined species for defining their virological characteristics and evolutionary relationships.

Amino Acid Sequence↗

PubMed2000

Wnt signaling maintains the hair-inducing activity of the dermal papilla.

The formation of the hair follicle and its cyclical growth, quiescence, and regeneration depend on reciprocal signaling between its epidermal and dermal components. The dermal organizing center, the dermal papilla (DP), regulates development of the epidermal follicle and is dependent on signals from the epidermis for its development and maintenance. GFP specifically expressed in DP cells of a transgenic mouse was used to purify this population and study the signals required to maintain it. We demonstrate that specific Wnts, but not Sonic hedgehog (Shh), maintain anagen-phase gene expression in vitro and hair inductive activity in a skin reconstitution assay.

Animals↗

PubMed2000

In vivo detection of human vascular endothelial growth factor promoter activity in transgenic mouse skin.

We have generated transgenic mice expressing green fluorescent protein (GFP) driven by 2.453-kb (-2,362 to +91) of the 5'-upstream region of the human vascular endothelial growth factor (VEGF) promoter to monitor changes of VEGF gene transcription in situ. Neonatal transgenic mice exhibited GFP-derived fluorescence in tissues that have been previously reported to express VEGF mRNA expression, including lung, cartilage, and brain. In normal skin during postnatal development, moderate fluorescence was observed in the upper epidermis and, more prominently, in the outer root sheath keratinocytes of hair follicles. Strong up-regulation of GFP fluorescence was observed in the hyperplastic epidermis of the wound edge at 48 hours after wounding, whereas little GFP fluorescence was detected in the dermis. In situ hybridization confirmed an identical expression pattern of VEGF mRNA in these wounds. Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced strong VEGF-GFP expression in suprabasal epidermis. Little or no fibroblast-derived fluorescence was seen both in the wound model and after TPA application. By confocal laser microscopy, increased GFP fluorescence was detectable in the epidermis of intact mouse ear skin as early as 6 hours after topical TPA treatment. Importantly, GFP fluorescence was also measurable in the skin of living transgenic mice. These results resolve the present controversy regarding the ability of VEGF-GFP transgenic mouse models to correctly reflect established patterns of VEGF expression, and show the model to be a powerful tool for the in vivo monitoring of VEGF gene expression.

Animals↗

PubMed2000

Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response.

PURPOSE: Photodynamic therapy (PDT), the light activation of photosensitizers to produce free radicals, is known to inhibit experimental intimal hyperplasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The aim of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response. METHODS: Rat carotid arteries were balloon-injured (BI), and for PDT, the arteries were irradiated with thermoneutral laser light (lambda = 660 nm, 100 J/cm(2)) after the photosensitizer methylene blue (MB) was delivered locally. Control rats included BI alone and MB after BI alone. Arteries were analyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybridization for versican and procollagen type I gene expression (digitized image pixel analyses, n = 3). RESULTS: No IH developed in PDT-treated arteries (0 +/- 0 mm(2); compared with BI, 0.192 +/- 0.006 mm(2); P <.0001). The diameters remained unchanged (PDT, 0.95 +/- 0.04 mm; BI, 0.94 +/- 0.05 mm; uninjured artery, 0.91 +/- 0.06 mm). Arterial injury resulted in an increase of versican and procollagen type I messenger RNA (mRNA) in the adventitia and neointima. In the repopulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PDT, 1.13% +/- 0.39%; BI, 2.93% +/- 0.61%; P <.02), but not in procollagen type I mRNA. CONCLUSION: The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific delivery of MB, a clinically appropriate photosensitizer, followed by PDT represents a suitable method to promote favorable healing after balloon intervention and further supports its role for inhibiting postinterventional restenosis.

Analysis of Variance↗

PubMed2000

Circular double-stranded forms of TT virus DNA in the liver.

TT virus (TTV) is an unenveloped, circular, and single-stranded DNA virus commonly infecting human beings worldwide. TTV DNAs in paired serum and liver tissues from three viremic individuals were separated by gel electrophoresis and characterized biophysically. TTV DNAs in sera migrated in sizes ranging from 2.0 to 2.5 kb. TTV DNAs in liver tissues, however, migrated at 2.0 to 2.5 kb as well as at 3.5 to 6.1 kb. Both faster- and slower-migrating forms of TTV DNAs in the liver were found to be circular and of the full genomic length of 3.8 kb. TTV DNAs migrating at 2.0 to 2.5 kb, from either serum or liver tissues, were sensitive to S1 nuclease but resistant to restriction endonucleases, and therefore, they were single-stranded. By contrast, TTV DNAs in liver tissues that migrated at 3.5 to 6.1 kb were resistant to S1 nuclease. They migrated at 3.7 to 4.0 kb after digestion with EcoRI, which suggests that they represent circular, double-stranded replicative intermediates of TTV. When TTV DNAs were subjected to strand-specific primer extension and then amplified by PCR with internal primers, those in serum were found to be minus-stranded DNAs while those in liver tissues were found to be a mixture of plus- and minus-stranded DNAs. These results suggest that TTV replicates in the liver via a circular double-stranded DNA.

Base Sequence↗

PubMed1999

Selective activation of the versican promoter by epithelial- mesenchymal interactions during hair follicle development.

Interaction between the epithelium and the mesenchyme is an essential feature of organogenesis, including hair follicle formation. The dermal papilla (DP), a dense aggregate of specialized dermis-derived stromal cells located at the bottom of the follicle, is a major component of hair that signals the follicular epithelial cells to prolong the hair growth process. However, little is known about DP-specific gene activation with regard to hair induction. In this study we demonstrate that a short fragment (839 bp) of the human versican (a core protein of one of the matrix chondroitin sulfate proteoglycans) promoter is sufficient to activate lacZ reporter gene expression in the DP of postnatal transgenic mice and also in the condensed mesenchyme (the origin of the DP) beneath the hair placode during hair follicle embryogenesis. Using the same versican promoter with green fluorescent protein (GFP), large numbers of fresh pelage DP cells were isolated from newborn transgenic skin by high-speed cell sorting. These GFP-positive DP cells showed abundant versican mRNA, confirming that the reporter molecules reflected endogenous versican gene expression. These sorted GFP-positive cells showed DP-like morphology in culture, but both GFP and versican expression was lost during primary culture. In vivo hair growth assays showed that GFP-positive cells could induce hair when grafted with epithelial cells, whereas GFP-negative cells grafted with epithelium or GFP-positive cells alone did not. These results suggest that versican may play an essential role both in mesenchymal condensation and in hair induction.

Animals↗

PubMed1998

Isolation of mouse vomeronasal receptor genes and their co-localization with specific G-protein messenger RNAs.

Four mouse vomeronasal receptors (mV1Rs) have been isolated by similarity to rat vomeronasal receptor (V1R) motifs. The four mV1Rs identified in this study are members of two distinct subfamilies. Specific in situ hybridization probes (ISH) derived from the 3' non-coding regions of the mV1R genes, were used to detect expression of a single receptor and probes from the homologous coding regions were used to detect expression of subfamily members. The ISH results showed that the mV1Rs expressing neurons were scattered in the middle/upper layer of the vomeronasal organ (VNO) sensory epithelium in serial VNO sections but were excluded from the deeper layers of the VNO sensory epithelium and these neurons were found to co-express the mRNA for the G-protein Galphai2, and were distinct from the deeper layers of the VNO sensory epithelium where the mRNA for Galphao positive neurons was located.

Amino Acid Sequence↗

PubMed1998

Expression of olfactory receptors, G-proteins and AxCAMs during the development and maturation of olfactory sensory neurons in the mouse.

Three mouse olfactory receptors have been cloned and sequenced and were found to be expressed in different zones of the olfactory epithelium. In situ hybridisation (ISH) results showed that each olfactory receptor was expressed at an early stage in development (E12), was not dependent on the maturation of the receptor neurons, and was present long before the onset of odour detection. Cells positive for these same olfactory receptors and the G-protein (Gbeta) were also found in non-neural regions of the nasal epithelium in the earlier stages of development (E12-16). Ncam, and Big-2 expression were, however, restricted to the region of developing olfactory neurons. Ncam expression appeared in advance of the olfactory receptor expression, while Big-2 appeared after olfactory receptor expression and neither were expressed in cells outside the olfactory epithelium. Both showed the highest number of positive cells in the early post-partum period when olfactory detection is functional. Ncam is known to be involved in guidance of the developing olfactory axons and was expressed earlier than any of the olfactory receptors, while Big-2 appears somewhat later (E14) at a time when developing axons reach the olfactory bulb. Moreover the highest periods of expression occur at post-natal day 7 when a proliferation of bulbar glomeruli are observed, suggesting the role of Big-2 to be primarily concerned with synaptogenesis.

Aging↗

PubMed1998

The entire nucleotide sequences of three hepatitis C virus isolates in genetic groups 7-9 and comparison with those in the other eight genetic groups.

We have proposed that hepatitis C virus should be classified into eleven genetic groups (types) which further divide into more than 80 genotypes (subtypes). However, only eight genetic groups (1-6, 10 and 11) have been defined on the basis of the full-length sequence. Hence, the entire nucleotide sequences of three HCV isolates in genetic groups 7-9 have now been determined. Phylogenetic analysis over the full-length sequences of these three isolates, along with 30 more in the other eight genetic groups, indicated that genetic groups 6-9 and 11 have bifurcated from a common branch and groups 3 and 10 from another. In the former branch groups 7 and 11, and groups 8 and 9, are closely related. Consequently, HCV can be classified into either eleven (1-11) or six groups (1; 2; 3 and 10; 4; 5; 6-9 and 11), allowing a clear separation of group and genotype similarity within the NS5b region or a subregion of 1093 nt. When pairwise comparison of 1093 nt in the NS5b sequence was performed on 106 HCV isolates of 36 genotypes in eleven genetic groups, they were classified into either eleven (1-11) or six (1; 2; 3 and 10; 4; 5; 6-9 and 11) genetic groups. However, group and genotype similarities were not clearly separable in either classification. The overlapping range was smaller using the classification into eleven genetic groups as compared to six genetic groups (2.7 vs 4-7%). These results indicate that HCV might not have evolved in the two-tiered fashion, at least in a strict sense.

Base Sequence↗

PubMed1997

Modulatory effect of L-NAME, a specific nitric oxide synthase (NOS) inhibitor, on stress-induced changes in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats: physiological significance of stress-induced NOS activation in hypothalamic-pituitary-adrenal axis.

We investigated whether NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric oxide synthase (NOS), can modify the stress-induced adrenocorticotropic hormone (ACTH) and corticosterone responses, because we found that immobilization-induced stress increases NOS mRNA and protein levels and enzyme activity in the adrenal cortex. The physiological significance of these phenomena, however, remains unknown. Plasma ACTH and corticosterone levels were determined by radioimmunoassay (RIA) of systemic blood samples and NOS enzyme activity was measured as the rate of [3H]arginine conversion to [3H]citrulline in the presence of tissue homogenate of adrenal cortex separated from the adrenal gland. The NOS enzyme activity in the adrenal cortex of rats pre-injected with saline at 2 h after the 2-h immobilization was significantly higher (P < 0.01) than that in the non-stressed controls. Pre-injection of L-NAME (100 mg/kg, s.c.) almost completely abolished the activity. This dose of L-NAME maintained a significantly elevated plasma corticosterone level (P < 0.05, compared with basal level) even 2 h after the 2-h stress, whereas the plasma corticosterone level in rats pre-injected with saline returned to the basal level at the same time point. Plasma ACTH level in L-NAME-pre-treated rats was higher than that in those pre-treated with saline 2 h after the stress, but the difference was not significant. This dose of L-NAME did not influence plasma ACTH or corticosterone levels under resting conditions without stress. These findings suggest that the stress-induced increase in NO synthesis in the adrenal cortex can modify the stress-induced corticosterone response to facilitate the recovery from the elevated corticosterone secretion by stress in the adrenal cortex to the resting basal level.

Adrenocorticotropic Hormone↗

PubMed1997

The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan.

Recently, putative viral agents responsible for human non-A to E hepatitis have been independently reported by two groups of investigators and designated GB virus C (GBV-C) and hepatitis G virus (HGV), respectively. The entire nucleotide sequences were determined for two viral genomes isolated from Japanese blood donors with GBV-C RNA. One of them (GT230) had a total genomic length of 9390 nucleotides (nt) with 5' and 3' untranslated regions of 551 and 313 nt, while the other (GT110) had genomic lengths of 9395, 281 and 315 nt, respectively. They both had a single long open reading frame, encoding 2842 amino acids (aa) in GT230 and 2933 aa in GT110. Surprisingly, they both lacked a clearly identifiable core gene, and possessed the E1/E2 gene with only four potential N-linked glycosylation sites. Pairwise comparison and phylogenetic analysis of the entire sequence indicated that the prototype GBV-C and two HGV isolates reported, as well as GT230 and GT110, are the same virus possibly of different genotypes. The five GBV-C/HGV isolates were variable up to 13.8% in the genomic nucleotide sequence, and contained deletions and insertions within the 5'-terminal 518-593 nt, which resulted in four different sizes of predicted polyproteins encoded by genomes of individual isolates. By contrast, the 3' untranslated region was well conserved. The high degree of sequence conservation within this region would favour it as a target for sensitive detection of GBV-C/HGV RNA.

Amino Acid Sequence↗

PubMed1996

Immobilization-induced stress activates neuronal nitric oxide synthase (nNOS) mRNA and protein in hypothalamic-pituitary-adrenal axis in rats.

The purpose of this study was to determine whether immobilization stress can cause changes in the enzyme activity and gene expression of neuronal nitric oxide synthase (nNOS) in the hypothalamus, pituitary, and adrenal gland in rats. NOS enzyme activity was measured as the rate of [3H]arginine conversion to citrulline, and the level of nNOS mRNA signal was determined using in situ hybridization and image analysis. NOS-positive cells were also visualized using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase) histochemistry and by immunohistochemistry using an anti-nNOS antibody. A significant increase of NOS enzyme activity in the anterior pituitary, adrenal cortex, and adrenal medulla (1.5-, 3.5-, and 2.5-fold) was observed in the stressed animals (immobilization of 6 h) as compared to non-stressed control rats. Up-regulation of nNOS mRNA expression in anterior pituitary and adrenal cortex was already detectable after stress for 2 h with 1.5- and 2-fold increase, respectively. The nNOS mRNA signals in hypothalamic paraventricular nucleus (PVN) significantly increased after the stress for 6 h. This increase in NOS enzyme activity was confirmed using NADPH-diaphorase staining and immunostaining in the PVN and adrenal cortex. An increase of NOS enzyme activity in adrenal medulla after immobilization for 6 h posited by far longer than in the adrenal cortex and anterior pituitary. The present findings suggest that psychological and/or physiological stress causes NO release in hypothalamic-pituitary-adrenal (HPA) axis and in sympatho-adrenal system. It is suggested that NO may modulate a stress-induced activation of the HPA axis and the sympatho-adrenal medullary system. The different duration of stress-induced NOS activity in HPA axis and the adrenal medulla may suggest NO synthesis is controlled by separate mechanism in the two HPA and the sympatho-adrenal systems.

Animals↗

PubMed1996

Marked increases in neuronal nitric oxide synthase (nNOS) mRNA and NADPH-diaphorase histostaining in adrenal cortex after immobilization stress in rats.

The changes of neuronal nitric oxide synthase (nNOS) mRNA expression in the rat adrenal gland following immobilization-induced stress were examined by the in situ hybridization technique. To introduce immobilization stress, the animals were wrapped with flexible wire gauze for 6 h. In the adrenal medulla and cortex, signals for nNOS mRNA were detected. In the adrenal medulla, the difference between non-stressed and stressed animals was not clear. In the adrenal cortex, the expression of nNOS mRNA markedly increased (2.5-fold) in the stressed animals. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase) histochemistry also showed an increase of staining in adrenal cortex after stress. This suggests that nitric oxide (NO) is involved in stress-induced activation in adrenal cortex function.

Adrenal Cortex↗