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Biomedical subjects

Hiroshi Hashimoto

Publications and source records attributed to Hiroshi Hashimoto.

At least 127 records · Page 7Linked to original sources
PubMed2003

Genetic background of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: association of HLA-DRB1*0901 with microscopic polyangiitis.

OBJECTIVE: To examine association of 8 candidate genes with susceptibility to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japanese patients. Little is known on the genetic background of AAV in Japanese patients mainly because of the difficulty in collecting a sufficient number of samples for the genetics study. METHODS: Sixty-nine patients, including 50 with microscopic polyangiitis (MPA), were recruited in a multicenter study. Among them, 64 patients were positive for myeloperoxidase (MPO)-ANCA. Associations of HLA-DRB1, tumor necrosis factor-alpha promoter (TNF), TNF receptor 2 (TNFR2), Fcgamma receptor IIa (FCGR2A), IIb (FCGR2B), IIIa (FCGR3A), IIIb (FCGR3B), and CTLA-4 (CTLA4) polymorphisms were examined in a case-control analysis. RESULTS: A significant association of HLA-DRB1*0901 with MPA (p = 0.0037, OR 2.44, 95% CI 1.33-4.46), as well as with MPO-ANCA positivity (p = 0.0014, OR 2.44, 95% CI 1.41-4.22), was detected. There was no difference in the TNF promoter haplotype frequencies between patients with MPA and controls, excluding the possibility that the association of DRB1*0901 was secondarily caused by linkage disequilibrium with TNF. No association was observed for TNFR2, FCGR, or CTLA4 with MPA, nor with the presence of MPO-ANCA, although the combined genotype FCGR2A-131H/H and 3A-176F/F was increased in patients with MPA (p = 0.025). CONCLUSION: There was an association of HLA-DRB1*0901 with MPA and MPO-ANCA positive vasculitis in Japanese patients.

Adult↗
PubMed2003

[A case of penile malignant melanoma].

A 79-year-old male presented in December. In January, 2001, with complaints of black nodules and bleeding from the glans of the penis to the foreskin. Inguinal lymph nodes were palpable bilaterally. Clinical diagnosis was penile malignant melanoma. Cystoscopy and urethrography revealed urethral invasion of malignant melanoma, and magnetic resonance imaging (MRI) of the penis revealed invasion to prostate, and pelvic lymph node metastases in abdominal compuled tomography (CT) but no organ metastases. Total cystectomy, total penectomy, bilateral inguinal and pelvic lymph node dissection and bilateral ureterocutaneostomy were performed in February, 2002. The pathological findings were nodular malignant melanoma, pT4bN2bM1a, and the surgical margin was positive. After these therapies, chemotherapy was performed. Five months later, CT revealed multiple lung and brain metastases, and radiation therapy and chemotherapy were performed. Twelve months after the operation, he died of cancer. Review of the literature revealed that our patient is the thirtieth reported case of penile malignant melanoma in Japan since 1924. In 30 cases, stage III, IV were 20 cases and 16 cases performed operation.

Aged↗
PubMed2002

HMGIC alterations in smooth muscle tumors of soft tissues and other sites.

The HMGIC gene, which codes a protein that acts as an architectural transcription factor, is frequently rearranged in a variety of benign or locally aggressive mesenchymal tumors. In tumors of smooth muscle differentiation, only uterine leiomyoma and lipoleiomyoma are known to be associated with the altered HMGIC. We investigated molecular and genetic alterations of the HMGIC in 36 benign and malignant smooth muscle tumors arising at various anatomical sites, including 13 uterine leiomyomas, two leiomyomas of the kidney with a t(12;14), one pelvic lipoleiomyoma, one vascular leiomyoma of the foot, two uterine leiomyosarcomas, six retroperitoneal leiomyosarcomas, one leiomyosarcoma of the urinary bladder, and 10 leiomyosarcomas of external soft tissues. HMGIC gene expressions were detected in both uterine (73.3%) and extrauterine (57.1%) smooth muscle tumors by reverse transcriptase polymerase chain reaction (RT-PCR), and benign tumors (70.5%) more frequently expressed the HMGIC than leiomyo-sarcomas (57.8%). Variant transcripts of the HMGIC containing cryptic exonic sequences previously described were found in one renal and three uterine leiomyomas and four leiomyosarcomas arising in the uterus and soft tissues by RT-PCR. Southern blot analysis identified a rearranged HMGIC in one soft tissue leiomyosarcoma. Thus, the HMGIC alterations in smooth muscle tumors are not confined only to uterine leiomyoma or lipoleiomyoma. Our data expand the variety of mesenchymal tumors associated with HMGIC alterations.

Adult↗
PubMed2002

C1q regulatory region polymorphism down-regulating murine c1q protein levels with linkage to lupus nephritis.

Much of the pathology of systemic lupus erythematosus (SLE) is caused by deposition of immune complexes (ICs) into various tissues, including renal glomeruli. Because clearance of ICs depends largely on early complement component C1q, homozygous C1q deficiency is a strong genetic risk factor in SLE, although it is rare in SLE patients overall. In this work we addressed the issue of whether genetic polymorphisms affecting C1q levels may predispose to SLE, using the (NZB x NZW)F(1) model. C1q genes are composed of three genes, C1qa, C1qc, and C1qb, arranged in this order, and each gene consists of two exons separated by one intron. Sequence analysis of the C1q gene in New Zealand Black (NZB), New Zealand White (NZW), and BALB/c mice showed no polymorphisms in exons and introns of three genes. However, Southern blot analysis revealed unique insertion polymorphism of a total of approximately 3.5 kb in the C1qa upstream region of NZB mice. C1q levels in sera and culture supernatants of LPS-stimulated peritoneal macrophages and C1q messages in spleen cells were all lower in disease-free young NZB and (NZB x NZW)F(1) mice than in age-matched non-autoimmune NZW and BALB/c mice. Quantitative trait loci analysis using (NZB x NZW)F(1) x NZW backcrosses showed that NZB microsatellites in the vicinity of the C1q allele on chromosome 4 were significantly linked to low serum C1q levels and the development of nephritis. These data imply that not only C1q deficiency but also regulatory region polymorphisms down-regulating C1q levels may confer the risk for lupus nephritis by reducing IC clearance and thus promoting IC deposition in glomeruli.

Animals↗
PubMed2002

Extraskeletal myxoid chondrosarcoma arising in the finger.

Extraskeletal myxoid chondrosarcoma (EMCS) is a rare soft tissue sarcoma and usually occurs in deep soft tissues, especially of the proximal extremities and limb girdles. We present an unusual case of the tumor arising in the finger. The diagnosis was confirmed by molecular detection of a characteristic EWS-CHN/TEC fusion gene transcript. Molecular detection of the tumor specific fusion gene could be a valuable aid for the final diagnosis of EMCS, particularly in cases with unusual clinicopathological features.

Artificial Gene Fusion↗
PubMed2002

Selective accumulation of CCR4+ T lymphocytes into renal tissue of patients with lupus nephritis.

OBJECTIVE: Some chemokine receptors, such as CCR5 and CCR4, are differentially expressed on Th1 and Th2 cells. To determine whether differential expression of the chemokine receptors occurs in patients with lupus nephritis, we examined the expression of CCR4 and CCR5 on peripheral blood lymphocytes and mononuclear cells infiltrated into the renal tissue of patients with lupus nephritis. METHODS: The expression of CCR4 and CCR5 on CD4+,CD45RO+ cells was analyzed by flow cytometry and compared between patients with systemic lupus erythematosus (SLE) and healthy controls. Correlation between the absolute number of CCR4+ or CCR5+ cells and clinical parameters was also analyzed. Mononuclear infiltrates in the renal tissue of SLE patients were analyzed for the expression of CCR4, CCR5, and CD4 by immunohistochemical staining. RESULTS: The absolute number of CCR4+, but not CCR5+, T lymphocytes in the peripheral blood was significantly decreased in the patients with SLE compared with that in the healthy controls, and this positively correlated with the serum levels of C3 and CH50. Most of the CD4+ T lymphocytes that infiltrated into the renal tissue of the patients with lupus nephritis expressed CCR4, but not CCR5. CONCLUSION: These results suggest that CCR4+ T lymphocytes in peripheral blood, which represent Th2 cells, preferentially migrate into the renal tissue of patients with lupus nephritis. The maldistribution of CCR4+ T lymphocytes might be involved in the pathogenesis of lupus nephritis.

Adolescent↗
PubMed2002

Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility.

OBJECTIVE: Human low-affinity Fcgamma receptors (FcgammaR) constitute a clustered gene family located on chromosome 1q23, that consists of FcgammaRIIA, IIB, IIC, IIIA, and IIIB genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals, and recent animal studies demonstrated a role for FcgammaRIIB deficiency in the development of autoimmunity. Genetic variants of FcgammaRIIA, IIIA, and IIIB and their association with systemic lupus erythematosus (SLE) have been extensively studied in various populations, but the results were inconsistent. To examine the possibility that another susceptibility gene of primary significance exists within the FcgammaR region, we screened for polymorphisms of the human FCGR2B gene, and examined whether these polymorphisms are associated with SLE. METHODS: Variation screening of FCGR2B was performed by direct sequencing and polymerase chain reaction (PCR)-single-strand conformation polymorphism methods using complementary DNA samples. Genotyping of the detected polymorphism was done using genomic DNA, with a specific genotyping system based on nested PCR and hybridization probing. Association with SLE was analyzed in 193 Japanese patients with SLE and 303 healthy individuals. In addition, the same groups of patients and controls were genotyped for the previously known polymorphisms of FCGR2A, FCGR3A, and FCGR3B. RESULTS: We detected a single-nucleotide polymorphism in FCGR2B, (c.695T>C), coding for a nonsynonymous substitution, Ile232Thr (I232T), within the transmembrane domain. The frequency of the 232T/T genotype was significantly increased in SLE patients compared with healthy individuals. When the same patients and controls were also genotyped for FCGR2A-131R/H, FCGR3A-176V/F, and FCGR3B-NA1/2 polymorphisms, FCGR3A-176F/F showed significant association. Two-locus analyses suggested that both FCGR2B and FCGR3A may contribute to SLE susceptibility, while the previously reported association of FCGR3B was considered to be secondary and derived from strong linkage disequilibrium with FCGR2B. CONCLUSION: These results demonstrate the association of a new polymorphism of FCGR2B (I232T) with susceptibility to SLE in the Japanese.

Adolescent↗
PubMed2002

Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus.

OBJECTIVE: To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation. METHODS: PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK-PCNA) were purified using anti-PCNA serum AK. The reactions to these antigens of 10 anti-PCNA-positive and 40 anti-PCNA-negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assays (ELISAs). RESULTS: With one exception (serum OK), anti-PCNA-positive sera reacted exclusively with only the 34-kd polypeptide. In contrast, 14 of 40 anti-PCNA-negative sera reacted with multiple proteins within PCNA complexes. Most anti-PCNA-positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK-PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58-kd polypeptide and the 34-kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes. CONCLUSION: Intermolecular-intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.

Antibodies, Monoclonal↗
PubMed2002

Gene expression of TrkC (NTRK3) in human soft tissue tumours.

TrkC is a member of the Trk family of tyrosine kinase receptors and plays an important role in the development and maintenance of neural tissues. Although a variety of non-neuronal tissues have also been shown to express TrkC, the status of TrkC in soft tissue tumours has been poorly investigated, except for a small fraction of tumours including congenital/infantile fibrosarcoma characterized by an ETV6-NTRK3 (also known as Tel-TrkC) fusion gene. To broaden knowledge about the TrkC status in human neoplasms, the expression of TrkC transcripts was assessed in 51 soft tissue tumours of variable lines of differentiation by reverse transcription-polymerase chain reaction (RT-PCR), using primer sets flanking their extracellular domain, the tyrosine kinase domain, and the intracellular domain of a truncated variant (Trunc 1) described previously. In 44 of the 51 tumours, TrkC transcripts, including alternatively spliced isoforms, were detected. The truncated transcripts (Trunc 1) were co-expressed in 40 of the 44 tumours and were expressed in one tumour without native TrkC gene expression. In two of the remaining six tumours, part of the sequence coding the tyrosine kinase domain of TrkC appeared to be truncated. Using a 3' rapid amplification of cDNA ends (3'RACE) method, another truncated isoform (Trunc 2) was isolated from one of the tumours, in which the TrkC transcript was terminated with a novel 160-base pair sequence. This truncated isoform was identified in nine of the 51 tumours examined by RT-PCR using primers for Trunc 2. There was no clear correlation between the types of TrkC isoforms detected and histological types or grades of the tumours. These results suggest that human soft tissue tumours widely express TrkC, irrespective of their cellular lineage, morphology, and biological behaviour. Dysregulated TrkC expression may enhance overgrowth or transformation of various mesenchymal cells.

Amino Acid Sequence↗
PubMed2002

Juxta-articular myxoma and intramuscular myxoma are two distinct entities. Activating Gs alpha mutation at Arg 201 codon does not occur in juxta-articular myxoma.

Juxta-articular myxoma is a rare myxoid tumor of soft tissue that bears a close histologic resemblance to intramuscular myxoma but is distinguished from the latter by its clinical setting and behavior. Activating missense mutations at the Arg 201 codon of the Gs alpha gene ultimately leading to increased levels of cyclic adenosine monophosphate have been implicated in McCune-Albright syndrome and sporadic fibrous dysplasia of bone. Recently, we have demonstrated that the same Gs alpha mutations occur in intramuscular myxomas associated with fibrous dysplasia of bone (Mazabraud's syndrome) as well as in sporadic intramuscular myxoma. The overlapping histologic appearances of juxta-articular myxoma and intramuscular myxoma prompted us to investigate whether there is a relationship between the two entities. We studied this possibility by looking for Gs alpha mutations in juxta-articular myxoma using polymerase chain reaction (PCR) to amplify appropriate genomic DNA fragments extracted from formalin-fixed, paraffin-embedded specimens of five juxta-articular myxomas, followed by single-strand conformation polymorphism analysis. Using these techniques, no aberrant bands were detected in any of the five juxta-articular myxomas, indicating that they lack Gs alpha mutations. Moreover, DNA sequencing of the PCR products of two JAMs showed no abnormalities. We conclude that juxta-articular myxomas, in contrast to intramuscular myxomas, do not involve Arg 201 mutations of the Gs alpha gene, indicating that they represent distinct entities with different underlying molecular mechanisms.

Adult↗
PubMed2002

Immunohistochemical expression of metallothionein in human bladder cancer: correlation with histopathological parameters and patient survival.

PURPOSE: We assessed metallothionein expression and its patterns of distribution as possible prognostic variables in bladder cancer with regard to histopathological parameters. MATERIALS AND METHODS: We stained 91 formalin fixed, paraffin embedded tissue specimens of bladder cancer from 91 patients with no history of treatment using an immunohistochemical technique for metallothionein. Relationships between immunoreactivity for metallothionein and histopathological parameters were examined. In addition, these parameters, including metallothionein, were evaluated as potential prognostic markers. RESULTS: Metallothionein was detected in 33 of 91 bladder cancers (36.3%). There were significant relationships of metallothionein expression with high grade, high stage and nonpapillary growth pattern tumors. There was no specific correlation of metallothionein expression with the interval to intravesical recurrence. In the 31 patients who underwent radical cystectomy a significant relationship between metallothionein immunoreactivity and cancer specific survival was found. CONCLUSIONS: Our findings suggest that a close correlation exists of metallothionein expression with histopathological parameters and metallothionein expression can be a useful prognostic variable for bladder cancer.

Adult↗
PubMed2002

Relationship between CD4(+)/CD8(+) T cell ratio and T cell activation in multiple myeloma: reference to IL-16.

We found that the ratio of CD4(+) to CD8(+) T cells (CD4/CD8 ratio) was decreased in patients with multiple myeloma (MM) and that this decrease was significantly related to an increase of human leukocyte antigen (HLA)-DR expression by CD8(+) (but not CD4(+)) T cells (P<0.005). In addition, the serum level of interleukin (IL)-16 was significantly higher in stage III MM patients than in healthy controls (P<0.001). The decrease of CD4(+) T cells in MM may be mediated by activation of CD8(+) T cells derived cytokine IL-16. In addition, these T cell phenotypic changes and the IL-16 level appear to be useful indicators of disease activity.

Biomarkers↗
PubMed2002

Immunohistochemical and ultrastructural observations of desmoplastic trichoepithelioma with a special reference to a morphological comparison with normal apocrine acrosyringeum.

BACKGROUND: Desmoplastic trichoepithelioma is a benign neoplasm considered to have follicular differentiation. Its sweat gland- or sebaceous-lines of differentiation have been also reported. There have been, however, only a few reports regarding extensive immunohistochemical and ultrastructural investigations of this neoplasm. METHODS: Histopathological and immunohistochemical studies were performed on three cases of desmoplastic trichoepithelioma, comparing it with normal skin. One of these cases was ultrastructurally investigated. RESULTS: The cord-like basaloid nests were reacted with the anti-cytokeratin (CK)1/5/10/14, -CK5/8, -CK14 and -CK15 antibodies, but not with the anti-CK6 antibody. Similar findings were observed in the outer layers of the normal follicular outer root sheath. Basaloid cell nests in one case, which showed ductal structures in the nests, also expressed CK7, CK8/18 and CK19. These keratins were also detected in the normal sweat glands. In addition, CK8/18 and CK19 were expressed in the basal cells of the outer root sheath. Keratinous cysts had inner reactions with the anti-CK10/11 and -CK6 antibodies, and outer reactions with anti-CK5/8 and -CK14 antibodies. Ultrastructurally, the cells in the cord-like nests were basically immature and basaloid in appearance. A few cells contained Odland bodies, which were also observed in the normal apocrine acrosyringeum. The ductal structure was lined by the cells which bore numerous microvilli in the luminal surface. CONCLUSION: The cells in desmoplastic trichoepithelioma are suggested to be in close association with the basal cells in the outer root sheath, which can differentiate into various parts of the folliculosebaceous apocrine unit.

Adolescent↗
PubMed2002

Roles of angiogenic factors and endothelin-1 in gastric ulcer healing.

Endothelins (ETs) participate directly and indirectly in angiogenesis via ET receptors. During early fetal angiogenesis, vascular endothelial growth factor (VEGF) and its receptors kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 (Flt-1) are required for the development of the systemic vasculature. In late angiogenesis, stromal-cell-derived factor (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) act in an organ-specific manner to promote the formation and development of large blood vessels supplying the gastrointestinal tract. We studied the roles of these ligand receptors in angiogenesis during healing of gastric ulcers. We studied the following five groups, each consisting of ten cases of endoscopically confirmed gastric ulcer: active stage (GA), healing stage (GH) and scar stage (GS) of gastric ulcers located in the angulus; Helicobacter pylori (Hp)-positive gastritis (gast+); and Hp-negative gastritis (gast-). All cases in the ulcer groups were Hp-positive. The study materials consisted of frozen biopsy specimens of lesions arising in the angulus. ET-1 was measured by enzyme immunoassay. The other factors were assayed by reverse-transcription-PCR. The distributions of ET-1, ETA receptor (ETAR), SDF-1 and CXCR4 in the gastric mucosa were evaluated by enzyme immunoassay. ET-1 and ETAR reached peak levels during the GH (ET: P<0.05, ETAR: P<0.01). VEGF mRNA increased slightly during the GA, but did not differ significantly among the groups. KDR and Flt-1 levels were high during the GA, the level being significantly higher than those during the GH and GS (P<0.05). SDF-1 levels significantly decreased during the GH and GS compared with levels during the GA, and CXCR4 significantly increased during the GH and GS (P<0.01). On immunostaining, ET-1-positive cells and ETAR-positive cells were found in the endothelium, vascular smooth muscle and gastric epithelium, and CXCR4-positive cells were found in the endothelium and gastric epithelium during the GH and GS. Our results suggest that VEGF receptors are mainly expressed early in ulcer development and participate in the initial stage of angiogenesis. SDF-1 receptors and ETAR are primarily expressed during the GH and GS and are involved in vascular maturation and gastric mucosal regeneration during late angiogenesis.

Chemokine CXCL12↗
PubMed2002

DNA copy number changes in carcinoma in pleomorphic adenoma of the salivary gland: a comparative genomic hybridization study.

Pleomorphic adenoma is the most common benign tumor of the salivary glands and is rarely associated with concurrent epithelial malignancy, which is designated as carcinoma in pleomorphic adenoma (CPA). Genetic abnormalities potentially related to the development of CPA have not been fully investigated. We analyzed DNA copy number changes in each of the adenomatous and carcinomatous components of seven CPA by comparative genomic hybridization using DNA extracted from microdissected tissues of formalin-fixed, paraffin-embedded tumor samples. Carcinomatous components of CPA showed multiple DNA copy number changes at 1-18 different genomic sites (mean 13 sites). Adenomatous components displayed less frequent DNA copy number changes (0-13 sites; mean, 5). In both components, the majority of the changes were gains. The most common recurrent gains in carcinomatous components were seen at 6q (four cases in each), whereas gains at 13q1-2 and 15q1 were most frequently detected in adenomatous components (three cases in each). In five CPA, the same chromosomal regions were involved in the DNA copy number changes detected in both components. Our data suggest that an accumulated or increased number of chromosomal changes including 6q abnormalities may be associated with the development of carcinomatous components in a subset of CPA.

Adenocarcinoma↗
PubMed2002

Plasma adsorption in critical care.

Plasmapheresis therapies such as plasma exchange (PE), double filtration plasmapheresis (DFPP), or immunoadsorption plasmapheresis (IAPP) have become therapeutic tools in critical care. PE or DFPP are limited by their non- or semiselective removal of all plasma components. Replacement fluids such as fresh frozen plasma and albumin are necessary during PE or DFPP. There is the risk of infection and allergic reactions whenever such fluids are used. On the other hand, IAPP is superior to PE and DFPP because it does not require any replacement fluid. There has been development of many adsorbent columns used for removing specific pathogenic substances, and patients with various kinds of critical illness have been treated with IAPP. However, IAPP can be applied only for certain diseases because of the limitations of the commercially available columns. It is concluded that the development of new adsorption therapy may improve the high mortality and morbidity rate in critically ill patients.

ABO Blood-Group System↗
PubMed2002

Fluctuations in the peripheral blood leukocyte and platelet counts in leukocytapheresis in healthy volunteers.

Leukocytapheresis (LCP) for the treatment of patients with diseases that involve an abnormal autoimmune reaction aims to improve the condition of the patient's pathology and to correct imbalances in immunological regulation mechanisms by removing the responsible leukocytes from the peripheral blood. To clarify the mechanism of therapeutic effect, LCP was conducted in healthy volunteers to investigate changes in peripheral blood leukocyte and platelet counts over time during the treatment. The subjects were 10 healthy male volunteers. LCP was performed once in each volunteer for 3,000 ml of blood volume. The peripheral blood counts decreased significantly, reaching a minimum of 20.0% of the baseline number of leukocytes, 10.1% of the baseline number of neutrophils, and 40.3% of the baseline number of lymphocytes. The number of removed leukocytes was about 6.6 x 10(9) cells, including about 3.5 x 10(9) neutrophils, as well as about 5.0 x 10(11) platelets. After the completion of LCP, the peripheral leukocyte levels increased transiently (overshoot), and at 2 h after the completion of the treatment, they reached 193.4% of the baseline value. Since LCP is capable of reducing the peripheral blood leukocyte count over a short period of time, its impact on peripheral blood is great. In addition, in view of the overshoot phenomenon and the appearance of immature granulocytes, the LCP may affect not only the peripheral blood, but also the bone marrow pool, the marginal pool, and the leukocytes present in the tissues.

Adult↗