Biomedical subjects

H Yamamoto

Publications and source records attributed to H Yamamoto.

At least 217 records · Page 12Linked to original sources

PubMed2001

Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer.

Vascular endothelial growth factor C (VEGF-C) is the only factor known to cause lymphangiogenesis. We studied the correlation between VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression of 85 primary gastric cancers by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, and the results were correlated with the number of lymphatic vessels, stained with anti-VEGFR-3 antibody. RT-PCR and immunohistology demonstrated that VEGF-C was mainly produced from cancer cells, but not from stromal elements. Morphologically, VEGFR-3 expression was detected in the endothelial cells of the stromal lymphatic vessels. There was a statistically positive correlation between the incidence of VEGF-C and VEGFR-3 mRNA expression in the primary tumours (P=0.0002). The number of VEGFR-3-positive lymphatic vessels in VEGF-C mRNA positive tumours was significantly larger than that in VEGF-C-negative tumours. The number of VEGFR-3-positive vessels in the tumour stroma was closely related to the grade of lymphatic invasion of gastric cancer. These results strongly indicate that VEGF-C may induce the proliferation of lymphatic vessels in the stroma of primary gastric cancer via activation of VEGFR-3, expressed on the endothelial cells of lymphatic vessels. In these circumstances, cancer cells can easily invade the lymphatic vessel, because of the increase of the contact points of cancer cells with the lymphatic vessels.

Blotting, Western↗

PubMed2001

Orally active cephalosporins. Part 3: synthesis, structure-activity relationships and oral absorption of novel C-3 heteroarylmethylthio cephalosporins.

A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-(heteroarytmethylthio)cephalosporins was designed, synthesized and evaluated for antibacterial activity and oral absorption in rats. Antibacterial activity was markedly influenced by the structure of the heteroaromatic ring moiety. Oral absorption was influenced by the heteroaromatic ring moiety as well as by the arrangement of heteroatoms. Among these compounds, FK041 (2o), having a 4-pyrazolylmethylthio moiety, showed potent antibacterial activity against both gram-positive and gram-negative bacteria including Haemophilus influenzae. Further, it showed higher oral absorption than CFDN.

Administration, Oral↗

PubMed2001

A leukocyte depleting filter reduces endothelial cell dysfunction and improves transplanted canine heart function.

BACKGROUND: To date leukocytes have been known to play a major role in reperfusion injury and have directed attention to leukocyte-endothelium interaction. This study was designed to investigate how much graft viability and the coronary microcirculatory function could be preserved by leukocyte depletion (LD) in a model of orthotopic cardiac transplantation. METHODS: The heart in 10 beagle dogs was arrested by introducing a 4 degrees C St. Thomas' cardioplegic solution. They were harvested, immersed in the cold saline for 3 hours, and then orthotopically transplanted. Five recipients underwent LD (LD group) at reperfusion with the use of a Pall BC1B leukocyte depleting filter inserted into the cardiopulmonary bypass (CPB) circuit. The other 5 dogs without filtration served as a control group. RESULTS: Leukocytes were about 80% filtrated and neutrophils were also 85% filtrated during the first 30 minutes of reperfusion in the LD group. A high level of adenosine triphosphate was maintained after transplantation in the LD group. The polymorphonuclear elastase level was significantly lower in the LD group. The cardiac function assessed by the slopes of the end-systolic pressure volume relation after transplantation was significantly higher in the LD group than in the control group (p < 0.05). The coronary vascular resistance responses to acetylcholine and nitroglycerin after transplantation were preserved significantly better in the LD group than in the control group (p < 0.05). CONCLUSIONS: These results suggest that a leukocyte depleting filter placed in the CPB circuit would prevent leukocyte-mediated endothelial cell injury, improve microcirculation of the myocardium, and lead to excellent graft function.

Animals↗

PubMed2001

Effect of a neutrophil elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using the left-sided heterotopic canine heart transplantation model.

BACKGROUND: Ischemia/reperfusion injury is a major cause of transplanted heart dysfunction. Several reports have demonstrated that polymorphonuclear neutrophil (PMN) elastase derived from the activated neutrophils might play an important role in this injury. Herein, we investigated the protective effects of PMN elastase inhibitor (ONO-5046 Na) on ischemia/reperfusion injury using a left-sided canine heterotopic heart transplantation model. METHODS: We used 10 pairs of adult beagle dogs. The donor heart was transplanted heterotopically into the left thoracic cavity of the recipient without cardiopulmonary bypass. A bolus of ONO-5046 Na (10 mg/kg) was introduced intravenously to 5 recipients (group II) at 15 minutes before reperfusion and was followed by continuous infusion (10 mg/kg per hour) for 180 minutes. Five dogs (group I) did not receive ONO-5046 Na and thus served as a control. After reperfusion, we evaluated transplanted heart function and obtained blood samples from the coronary sinus over a 360-minute period. RESULTS: E(max) and pre-load recruitable stroke work in group II showed significantly better recovery than group I. Blood levels of PMN elastase, creatine kinase MB, lactate and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-8) were significantly lower in group II. Depletion of myocardial concentration of adenosine triphosphate at 120 minutes after reperfusion and myocardial water content was significantly lower in group II. CONCLUSIONS: ONO-5046 Na, which inhibits PMN elastase, could reduce ischemia/reperfusion injury in heart transplantation. These results indicate that clinical application of ONO-5046 Na should be considered.

Animals↗

PubMed2001

Lysyl oxidase-catalyzed cross-linking and insolubilization reactions of Lys-containing polypeptides and synthetic adhesive proteins.

The lysyl oxidase- (LO-) mediated insolubilization reactions of the Lys-containing polypeptides have been examined using poly(L-Lys) with degrees of polymerization (Dps) ranging 1 from 2300, copoly(LysxAlay) (x:y = 1:4, 1:3; 1:1, 2:1, and 3:1), copoly(LysxGlyy) (x:y = 1:1 and 2:1), and synthetic adhesive proteins with sequential repetitive units enriched in the Lys residues, poly(Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys), poly(Ala-Gly-Tyr-Gly-Gly-Ala-Lys), and poly(Gly-Gly-Gly-Tyr-Gly-Gly-Tyr-Gly-Lys). All of the substrates were insolubilized by the LO-catalyzed oxidation of the epsilon-amino group in the Lys residues. The Dps of the polypeptide substrates did not affect the kinetic constants, the Km and Vmax values. The Km and Vmax values and the insolubilization rates varied depending on the Lys contents in the substrate polypeptides, which were enriched in Gly and Ala residues. As the Lys content increased, the Km and Vmax values became lower and higher, respectively. The insolubilization rates decreased with increase of the Lys content. The time-dependent changes in the LO-catalyzed aldehyde production, the insolubilization, and remaining LO activity demonstrated that the cross-linking and the insolubilization steps occurred along with LO deactivation, indicating that the enzymatic and chemical processes in the LO-mediated insolubilization occur in order.

Adhesives↗

PubMed2001

Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer.

PURPOSE: To evaluate a new prognostic factor of breast cancer, bone marrow micrometastases which was detected by RT-PCR for mammaglobin, a sensitive molecular marker of breast cancer, was examined. MATERIALS AND METHODS: One hundred and eleven samples from stage I-III breast cancer patients were examined. Bone marrow micrometastases and clinicopathological parameters, which were age, tumor size, lymph node metastasis and status of the estrogen receptor, were evaluated for the prognostic factor by statistical analysis. RESULTS: Median follow-up time was 21.1 months. Thirty-three (29.7%) out of 111 samples were RT-PCR positive. Eight cases (24.2%) in this group showed recurrent lesions in the distant organs. Whereas six (7.7%) out of 78 RT-PCR negative patients had distant recurrences. In the premenoposal patients, and in the patients with axillary lymph node metastases, RT-PCR positive cases showed significantly higher distant recurrent rate. Bone marrow micrometastases, axillary nodal status, and estrogen receptor were independent prognostic factors for breast cancer by both univariate and multivariate analysis. CONCLUSIONS: Bone marrow micrometastases detected by RT-PCR for mammaglobin can be a useful predictive marker for early distant recurrence of breast cancer.

Adult↗

PubMed2001

Quinapril with high affinity to tissue angiotensin-converting enzyme reduces restenosis after percutaneous transcatheter coronary intervention.

Experimental studies have demonstrated that vascular injury resulted in an induction of vascular angiotensin-converting enzyme (ACE), and have suggested that inhibition of vascular ACE might be important in the prevention of restenosis. The present study aimed to determine the effect of quinapril, an ACE inhibitor with high affinity to tissue ACE, on restenosis following coronary intervention. The design of this study was a prospective, randomized, open, and non-placebo controlled trial. Patients with ischemic heart disease were enrolled after successful percutaneous transluminal coronary angioplasty or stent implantation at 7 participating institutions. Two hundred and fifty-three patients with 294 lesions were randomly assigned to the quinapril (10-20 mg per day) group or control group. Administration of quinapril was continued for 3-6 months of the follow-up. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Core laboratory measurements were performed independently and blinded. Follow-up angiography was performed in 108 patients with 124 lesions in the quinapril group and in 107 patients with 130 lesions in the control group. The baseline characteristics and findings of angioplasty showed no significant differences between the two groups. However, in the quinapril group, restenosis per patient and per lesion was significantly lower (34.3% vs. 47.7%, p < 0.05 and 30.6% vs. 43.8%, p < 0.05). Multivariable analysis revealed that administration of quinapril independently contributed to reducing the restenosis per patient and per lesion (odds ratio, 0.73; 95% confidence interval, 0.54-0.99 and odds ratio, 0.75; 95% confidence interval, 0.57-0.99). In conclusion, quinapril significantly reduces restenosis following coronary intervention.

Aged↗

PubMed2001

Development of pigment cells in the brain of ascidian tadpole larvae: insights into the origins of vertebrate pigment cells.

In vertebrates, melanins produced in specialized pigment cells are required for visual acuity, camouflage, sexual display and protection from ultra violet (UV) radiation. There are three pigment cell types that are classified based on their distinct embryonic origins. Retinal pigment epithelium (RPE) cells originate from the outer layer of the optic cup. Pigment cells of the pineal organ are formed from the developing diencephalon. Melanocytes are derived from the neural crest unique to vertebrate embryos. Some of these pigment cells also play roles that are independent of the activity of tyrosinase, the key melanogenesis enzyme, or melanin: production of substrate(s) for catecholamine synthesis, maintenance of endolymph composition in the cochlea, maintenance of photoreceptor cells in the retina and retinoid metabolism essential for the visual cycle. To deduce the evolutionary origins of vertebrate pigment cells and a possible archetypal genetic circuitry, which may have been modified and utilized to generate multiple pigment cell types, comparison of developmental mechanisms of pigment cells between vertebrates and closely related invertebrate ascidians are proposed to provide useful information. The tadpole-type larva of ascidians possesses two melanin-containing pigment cells, termed the otolith and ocellus pigment cells, in the brain that are believed to be required for photo- and geotactic responses during swimming. In this review, current knowledge on the development of the two ascidian pigment cells is summarized, i.e. complete cell lineage, structure and expression of genes encoding two melanogenesis enzymes, and molecular developmental mechanisms involving BMP-CHORDIN antagonism, and possible evolutionary relationships between ascidian and vertebrate pigment cells are discussed.

Animals↗

PubMed2001

Exon 3 of tyrosine hydroxylase gene: lack of association with Japanese schizophrenic patients.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) biosynthesis. Exon 3 of the human TH gene encodes the sequence from Ser31 to Glu104 of type 1 enzyme, which contains the critical parts for regulation of the catalytic activity. The amino acid residues Gly36-Arg37-Arg38 were identified as a key sequence for DA to exert its inhibitory effect on catalytic activity. Therefore, we screened the nucleotide sequences of exon 3 from 201 Japanese patients with schizophrenia to explain the elevation in the synaptic or presynaptic DA concentrations in the schizophrenic brain, based on the hypothesis that any mutation changing the amino acid sequence Gly36-Arg37-Arg38 would result in the elevation of DA synthesis, due to a reduced inhibitory effect of DA on the catalytic activity. However, no mutated sequences of exon 3 and both exon-intron boundaries were detected in any of the patients examined. Polymorphisms generating Val81 and Met81 were compared of the distributions of genotype and allele between the patients and 175 Japanese healthy controls, which did not suggest an association between the polymorphism and schizophrenia. These results indicate that exon 3 of the human TH gene lacks association with schizophrenia in Japanese patients.

Adult↗

PubMed2001

Functional conservation of the promoter regions of vertebrate tyrosinase genes.

Tyrosinase is the key enzyme for synthesizing melanin pigments, which primarily determine mammalian skin coloration. Considering the important roles of pigments in the evolution and the adaptation of vertebrates, phylogenetic changes in the coding and flanking regulatory sequences of the tyrosinase gene are particularly intriguing. We have now cloned cDNA encoding tyrosinase from Japanese quail and snapping turtle. These nonmammalian cDNA are highly homologous to those of the mouse and human tyrosinases, whereas the 5' flanking sequences are far less conserved except for a few short sequence motifs. Nevertheless, we demonstrate that the 5' flanking sequences from the quail or turtle tyrosinase genes are capable of directing the expression of a fused mouse tyrosinase cDNA when introduced into cultured mouse albino melanocytes. This experimental method, which reveals the functional conservation of regulatory sequences in one cell type (the melanocyte), may be utilized to evaluate phylogenetic differences in mechanisms controlling specific gene expression in many other types of cells. We also provide evidence that the 5' flanking sequences from these nonmammalian genes are functional in vivo by producing transgenic mice. Phylogenetic changes of vertebrate tyrosinase promoters and the possible involvement of conserved sequence motifs in melanocyte-specific expression of tyrosinase are discussed.

5' Flanking Region↗

PubMed2001

Differential responsiveness of cord and adult blood monocytes to hepatocyte growth factor.

Monocytes as antigen-presenting cells play an important role in host defence. There are several cytokines affecting monocyte function. We demonstrate that both adult and cord blood monocytes constitutively express hepatocyte growth factor (HGF) receptor, MET. HGF significantly down-regulated MET expression of adult blood monocytes, compared with cord blood monocytes, when cultured either in RPMI-1640 containing 10% FBS or serum-free medium. Surface levels of MET correlated with c-met mRNA levels both in adult and cord blood when cultured. MET expression was down-regulated by treating with actinomycin D or cycloheximide. HGF stimulated DNA synthesis of adult monocytes, but not cord blood. HGF enhanced antigen-presenting capacity of adult blood monocytes but not cord blood monocytes. HGF up-regulated HLA class I expression in adult monocytes but not in cord blood monocytes. The current results suggest that the failure of cord blood monocytes to respond to HGF may be responsible, in large part, for their functional immaturity.

Adult↗

PubMed2001

Characterization of premature atherosclerosis of carotid arteries in acromegalic patients.

OBJECTIVE: Acromegalic patients have increased mortality from vascular diseases. Although atherosclerotic risk factors such as hypertension, diabetes mellitus and dyslipoproteinaemia are highly associated with acromegaly, the prevalence of premature atherosclerosis in acromegalic patients and its relationship to these risk factors have not been reported. DESIGN: We measured mean intima-media thickness (IMT) of the carotid arteries in 21 acromegalic patients without symptomatic atherosclerotic vascular disease, by ultrasound high-resolution B-mode imaging. In analysis 1, it was compared with the predicted mean IMT based on data from existing risk factors (age, male sex, dyslipoproteinaemia, hypertension, diabetes mellitus, smoking status) in 282 non-acromegalic subjects. In analysis 2, the mean IMT in the 21 acromegalic patients was compared with that in 42 non-acromegalic subjects matched for age, sex and the other atherosclerotic risk factors. We also analysed clinical characteristics between the acromegalic patients with and without the atherosclerosis. RESULTS: Mean IMT in 21 acromegalic patients was 0.92 +/- 0.21 (mean +/- SD) mm. It was significantly (P < 0.05) lower than the mean IMT (1.03 +/- 0.12 mm) predicted from their existing risk factors (analysis 1). It was also less than that in 42 non-acromegalic subjects matched for atherosclerotic risk factors (1.07 +/- 0.37 mm; P < 0.05) (analysis 2). Among the acromegalic patients, 10 patients (48%) had increased mean IMT (> or = 1.1 mm) and/or plaque lesions whereas the other 11 had no such atherosclerotic changes. In the patients without the atherosclerotic changes, plasma insulin-like growth factor-I (IGF-I) concentration was significantly (P < 0.01) higher, and the prevalence of hypertension was significantly (P < 0.05) lower than in those with the atherosclerotic changes. CONCLUSIONS: The extent of carotid atherosclerosis in the acromegalic patients was not higher than that in non-acromegalic subjects, considering their atherosclerotic risk factors. Increased concentration of IGF-I might be involved in the lack of susceptibility to atherosclerosis in some acromegalic patients.

Acromegaly↗

PubMed2001

Terminal deoxynucleotidyltransferase directly interacts with a novel nuclear protein that is homologous to p65.

BACKGROUND: Terminal deoxynucleotidyltransferase (TdT) is a DNA polymerase that enhances Ig and TcR gene diversity in the N region in B- and T-cells. TdT is found as a member of a large protein complex in the lysate of the thymocytes. To elucidate the molecular mechanism of the synthesis of the N region, we first attempted to isolate the genes with products that are interacting directly with TdT. RESULTS: Using a yeast two-hybrid system, we isolated a cDNA clone encoding a novel nuclear protein that interacts with TdT. This protein was designated as TdT interacting factor 1 (TdIF1). TdIF1 has a high degree of homology to the transcription factor p65, which belongs to the nuclear receptor superfamily. TdIF1 contains HMG-I and HMG-Y DNA binding domains (AT-hooks) and can bind to single- and double-stranded DNA. TdT and TdIF1 were co-eluted at position 232 kDa by gel filtration of MOLT4 lysate. TdIF1 can enhance TdT activity fourfold in vitro assay system using oligo(dT)16 as primers. CONCLUSIONS: TdIF1 binds directly to TdT, both in vitro and in vivo. TdIF1 and TdT exist as the members of a 232 kDa protein complex. TdIF1 can enhance TdT activity maximum fourfold in vitro assay system, suggesting that it positively regulates the synthesis of the N region during V(D)J recombination in the Ig and TcR genes.

Amino Acid Sequence↗

PubMed2001

Terminal deoxynucleotidyltransferase is negatively regulated by direct interaction with proliferating cell nuclear antigen.

BACKGROUND: The repertoires of Ig and TcR are generated by a combinatorial rearrangement of variable (V), diversity (D), and joining (J) segments (V(D)J recombination) in B- and T-cells. Terminal deoxynucleotidyltransferase (TdT) adds extra nucleotides (N nucleotides) at the junctions of the gene segments to enhance the Ig and TcR genes diversity. Using an anti-TdT antibody column, TdT has been purified as a member of a megadalton protein complex from rat thymus. The N region would be synthesized with the large protein complex. RESULTS: The cDNAs for proliferating cell nuclear antigen (PCNA) were isolated by yeast two-hybrid screening as the gene products which directly interacted with TdT. The interaction between PCNA and TdT was confirmed by co-immunoprecipitation, both in vitro and in vivo. TdT binds directly to a PCNA trimer, as shown by gel filtration. TdT interacts with PCNA in its DNA polymerization domain (DPD), but not in its BRCA-1 C-terminal (BRCT) domain. TdT activity was reduced to 17% of the maximum value by TdT/PCNA complex formation. CONCLUSION: TdT interacts directly with PCNA through its DPD. A functional consequence of this interaction is the negative regulation of TdT activity. These findings suggest that TdT catalyses the addition of N nucleotides under the negative control of PCNA during V(D)J recombination.

Binding Sites↗

PubMed2001

Adrenalectomy-induced potentiation of morphine action in guinea-pig ileum: possible decrease in the release of endogenous opioids from opioidergic neurones.

1. The effects of adrenalectomy on exogenous and endogenous opioid actions in guinea-pig isolated myenteric plexus-longitudinal muscle (MPLM) were investigated. 2. A decrease in serum cortisol level to about 37% of the level in the sham-operated group was obtained in adrenalectomized animals (sham: 53.5 +/- 7.2 microg 100 ml(-1); adrenalectomized: 20.0 +/- 3.6 microg 100 ml(-1)). 3. The concentration-response curve of twitch inhibition, which was induced by electrical field stimulation (0.1 Hz, 0.5 ms pulse width, maximum intensity), caused by a low concentration of morphine (5 x 10(-9)-5 x 10(-7) M) was not affected, but at high concentration (10(-6)-10(-5) M) there was an upward shift in the adrenalectomized group compared with the sham-operated control, although the basal twitch contraction was not changed by adrenalectomy. 4. The twitch inhibition induced by a high concentration of morphine (10(-6) M) in the adrenalectomized group was antagonized to the same level as that in sham-operated controls by naloxone (NLX) (3 x 10(-7) M). 5 Post-tetanic twitch inhibition, an indicator of endogenous opioid release, induced by tetanic stimulation (10 Hz, 0.5 ms pulse width, maximum intensity, for 1 min) was inhibited in the adrenalectomized group compared with the sham-operated controls. The antagonism of inhibition in both groups was equivalent to that exerted by NLX (10(-7) M). 6. Acetylcholine-evoked contraction of the muscle was not influenced by adrenalectomy. 7. These results suggested a possible mechanism for the increase in sensitivity of the opioid receptors to morphine by adrenalectomy, resulting from a decrease in the release of endogenous opioids from the opioidergic neurones in the ileum.

Acetylcholine↗

PubMed2001

Craniofacial abnormalities in Japanese patients with severe obstructive sleep apnoea syndrome.

OBJECTIVE: To clarify that factors besides obesity play an important role in the development of obstructive sleep apnoea syndrome (OSAS) in Japanese patients, we compared craniofacial structures in patients with severe OSAS with those of normal controls. METHODOLOGY: The craniofacial structures of 60 Japanese patients with severe OSAS and 30 normal controls were evaluated using standard cephalometric analysis. Patients were stratified according to body mass index (BMI): non-obese, BMI < 25; moderately obese, BMI = 25-30, severely obese, BMI > 30. RESULTS: The SNA (sella to nasion to subspinale angle) was significantly smaller in the patient groups than in the controls. The SNB (sella to nasion to supramentale angle) and NSBa (cranial base flexure) were significantly smaller in the non-obese and moderately obese patients than in controls. The MP-H (distance from the mandibular plane to the hyoid bone) and the PNS-P (distance from the posterior nasal spine to the tip of the soft palate) were significantly longer in the patient groups than in the controls. The PNS-P was significantly longer in the severely obese patients than in the non-obese patients. CONCLUSIONS: Japanese patients with severe OSAS have enlargement of the soft tissues and palate as well as craniofacial bony structural abnormalities. This is particularly apparent in non-obese patients.

Body Mass Index↗

PubMed2001

Functional immaturity of cord blood monocytes as detected by impaired response to hepatocyte growth factor.

BACKGROUND: Monocytes as antigen-presenting cells play an important role in host defense and transplantation. However, there are little reports on cord blood monocytes, and the role of monocytes in cord blood transplantation is largely unknown. METHODS AND RESULTS: There are several cytokines affecting monocyte function. These include interferon-gamma, interleukin-4, interleukin-10, granulocyte macrophage-colony stimulating factor and hepatocyte growth factor (HGF). We investigated the effect of these cytokines on antigen-presenting capacity (APC) of cord and adult blood monocytes. Using either mononuclear cells or purified CD4+ T cells as responder cells, HGF enhanced APC of adult monocytes most effectively among these cytokines. In contrast, cord blood monocytes failed to respond to HGF. As HLA, costimulatory and adhesion molecules may affect APC function, we examined these antigens of monocytes following HGF stimulation. The HGF upregulated integrin alpha5 subunit (CD49e) and intercellular adhesion molecule-1 (CD54) was expressed in adult blood monocytes, but not in cord blood. In kinetic studies, HGF downregulated c-met protein/HGF receptor expression of adult monocytes in lower concentrations and at shorter incubation time as compared with that of cord blood. CONCLUSIONS: The results suggest that impaired response of cord blood monocytes to HGF may be responsible, in large part, for their functional immaturity.

Adult↗

PubMed2001

Intrathymic lymph nodes in humans.

An unusual lymph node exists in the centre of the human thymus. This lymph node, which we call an intrathymic lymph node (ITLN), possesses some interesting morphological characteristics. In ontogeny, this node seems to appear at the latter half of fetal period. The function of the ITLN is still unknown, but it is assumed that it may play a different role in the immune system than other peripheral lymph nodes by its characteristics.

Adolescent↗