• The Korean Journal of Quaternary Research
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• v.20 no.1 s.26
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• pp.51-66
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• 2006

The climate of the last glacial maximum (LGM) in northeast Asia is simulated with an atmospheric general circulation model of NCAR CCM3 at spectral truncation of T170, corresponding to a grid cell size of roughly 75 km. Modern climate is simulated by a prescribed sea surface temperature and sea ice provided from NCAR, and contemporary atmospheric CO2, topography, and orbital parameters, while LGM simulation was forced with the reconstructed CLIMAP sea surface temperatures, sea ice distribution, ice sheet topography, reduced $CO_2$, and orbital parameters. Under LGM conditions, surface temperature is markedly reduced in winter by more than $18^{\circ}C$ in the Korean west sea and continental margin of the Korean east sea, where the ocean exposed to land in the LGM, whereas in these areas surface temperature is warmer than present in summer by up to $2^{\circ}C$. This is due to the difference in heat capacity between ocean and land. Overall, in the LGM surface is cooled by $4{\sim}6^{\circ}C$ in northeast Asia land and by $7.1^{\circ}C$ in the entire area. An analysis of surface heat fluxes show that the surface cooling is due to the increase in outgoing longwave radiation associated with the reduced $CO_2$ concentration. The reduction in surface temperature leads to a weakening of the hydrological cycle. In winter, precipitation decreases largely in the southeastern part of Asia by about $1{\sim}4\;mm/day$, while in summer a larger reduction is found over China. Overall, annual-mean precipitation decreases by about 50% in the LGM. In northeast Asia, evaporation is also overall reduced in the LGM, but the reduction of precipitation is larger, eventually leading to a drier climate. The drier LGM climate simulated in this study is consistent with proxy evidence compiled in other areas. Overall, the high-resolution model captures the climate features reasonably well under global domain.

• The korean journal of orthodontics
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• v.41 no.2
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• pp.76-86
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• 2011

Objective: To investigate whether the accuracy of 3D laser scanning is influenced by the angles and number of scans. Methods: Using a 3D laser scanner, 10 manikins with facial markers were scanned at 7 horizontal angles (front view and at $20^{\circ}$, $45^{\circ}$, and $60^{\circ}$ angles on the right and left sides). Three-dimensional facial images were reconstructed by 6 methods differing in the number and angles of scans, and measurements of these images were compared to the physical measurements from the manikins. Results: The laser scan images were magnified by 0.14 - 0.26%. For images reconstructed by merging 2 scans, excluding the front view; and by merging 3 scans, including the front view and scans obtained at $20^{\circ}$ on both sides; several measurements were significantly different than the physical measurements. However, for images reconstructed by merging 3 scans, including the front view; and 5 scans, including the front view and scans obtained at $20^{\circ}$ and $60^{\circ}$ on both sides; only 1 measurement was significantly different. Conclusions: These results suggest that the number and angle of scans influence the accuracy of 3D laser scanning. A minimum of 3 scans, including the front view and scans obtained at more than $45^{\circ}$ on both sides, should be integrated to obtain accurate 3D facial images.

• Journal of Chest Surgery
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• v.33 no.9
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• pp.697-706
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• 2000

Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

• Journal of Chest Surgery
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• v.33 no.3
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• pp.221-229
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• 2000

Background: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. Material and Method: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. Result: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28$\pm$0.20, 1.82$\pm$0.23, 1.90$\pm$0.19, 2.14$\pm$0.18 in control group, 1.58$\pm$0.18, 1.73$\pm$0.01, 1.66$\pm$0.10, 1.50$\pm$0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4$\pm$61.9, 529.3$\pm$197.6, 578.3$\pm$255.8, 493.3$\pm$171.3 in control group, 323.8$\pm$118.0, 422.6$\pm$75.6, 412.3$\pm$59.9, 394.5$\pm$154.0 in aprotinin group. Left atrial concentrations were 339.3$\pm$89.2, 667.0$\pm$65.7, 731.2$\pm$192.7, 607.5$\pm$165.9 in control group, 330.0$\pm$111.2, 468.4$\pm$190.3, 425.4$\pm$193.6, 4.7.3$\pm$142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84$\pm$0.31, 13.2$\pm$0.51, 15.0$\pm$1.22, 16.3$\pm$1.73 in control group, 7.76$\pm$0.12, 15.3$\pm$0.71, 22.6$\pm$6.62, 14.9$\pm$1.11 in aprotinin group. Left atrial concentrations were 7.61$\pm$17.2, 57.1$\pm$28.4, 18.9$\pm$18.2, 31.5$\pm$20.5 in control group, 5.61$\pm$7.61, 37.0$\pm$26.2, 28.6$\pm$21.7, 37.8$\pm$30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. Conclusion: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.

• Childhood Kidney Diseases
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• v.2 no.1
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• pp.14-19
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• 1998

Purpose : Hypocalcemia is one of the major causes of convulsion in infants. The causes of hypocalcemia are hypoparathyroidism, deficiency and metabolic abnormalities of vitamin D, or increased uptake of inorganic phosphorous, etc. We analyzed the causes, symptoms and signs, treatment, and clinical courses of hypocalcemia as, recently, there were many clinical experiences of hypocalcemic infants under age of 6 months in the department of pediatrics, Kyungpook University Hospital. Objects and Methods : The authors observed 11 infants with hypocalcemia who had been admitted to the department of pediatrics, Kyungpook University Hospital, during the period of February 1992 to April 1997. Various clinical and laboratory data concerning causes, clinical courses and treatment of hypocalcemia were analyzed retrospectively Results : (1) The sex incidence revealed male predominance with male to female ratio 4.5 : 1. The mean age at onset of symptoms was $2.2{\pm}1.1$ months old. (2) The causes of hypocalcemia were vitamin D deficiency in 8 cases and excessive inorganic phosphate intake in 3 cases. (3) All eleven patients manifestated convulsion which was generalized tonic-clonic in 9, and focal clonic in 2 cases. (4) Serum calcium concentrarion increased from $6.3{\pm}0.9$ mg/dL to $9.9{\pm}1.7$ mg/dL after therapy of $1,25(OH)_{2}D_{3}$ with or without calcium(P=0.0008), and serum ALP concentration decreased from $1,418{\pm}864$ U/L to $772{\pm}503$ U/L (P=0.0112). Serum iPTH levels were high in all 11 patients initially. All showed decreased $25(OH)D_3$ levels initially. (5) All patients were treated successfully with $1,25(OH)_{2}D_{3}$ and/or calcium supplement. Conclusions : Vitamin D deficiency should be considered as one of the causes of hypocalcemia even in formula(known as vitamin fortified) feeding infants. Fortunately, they were successfully treated with $1,25(OH)_{2}D_{3}$.

• Korean Journal of Veterinary Research
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• v.15 no.2
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• pp.147-152
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• 1975

Although considerable research has been done on the blood picture of the horse, hot-blooded and cold-blooded, little work has been made of the blood picture of the army pack horse, Jeju horse. The object of the present investigation was to make good this deficiency, and to suggest standard for the blood picture of army pack horses kept under the regular military training and the ideal feeding in the heart of a mountain. Blood samples were drawn from the jugular vein through a 15-gauge bleeding needle from 41 males and 28 females, aging 3 to 9 years old. It was taken between seven and nine o'clock in the morning. Animals were handled as quietly as possible to avoid any excitation. No restraint other than a halter was used. Enumeration of erythrocyte, total and differential leukocyte count, determination of hemoglobin in blood, and the value of packed cell volume were male in the usual manner, and erythrocytic constant was calculated by the method of Wintrobe. Erythrocyte count was $7.83{\pm}0.20(4.95{\sim}11.05){\times}10^6/mm^3$(SE). This value was much lower than hot-horses, but slightly higer than the values of cold-horse reported from foreign country. Concentration of hemoglobin in blood was $13.0{\pm}0.33(9.5{\sim}17.8)g/100ml$. This value was much higher than that of cold-horses observed by the other authors, approaching to the values of hot-horses. Packed cell volume was $32.1{\pm}0.92(22{\sim}42)ml/100ml$. This vague was a little higher than that of the other cold-horses. Mean corpuscular volume was $41.5{\pm}1.20(26.6{\sim}59.3){\mu}m^3$. This value matched so well with the other results recorded by various investigators. Mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were $16.9{\pm}0.43(12.3{\sim}25)$ pg and $41.0{\pm}0.45(29.1{\sim}51.1)g/100ml$, respectively. These values were significantly higher than the values found by the other investigations. Total leukocyte enumeration was $10.5{\pm}0.41(5.6{\sim}17.9){\times}10^3/mm^3$, being considered as normal. And differential leukocyte count of neutrophil was $44.5{\pm}2.23(15{\sim}76)%$, $5,527{\pm}234(2,231{\sim}9,144)/mm^3$, of lymphocyte $50.5{\pm}1.19(19{\sim}77)%$, $4,307{\pm}125(1,456{\sim}11,098)/mm^3$, of monocytel (0~4)%, $105(0{\sim}352)/mm^3$, of eosiophil 3.2(0~14)%, $340(0{\sim}1,232)/mm^3$ and of basophil 0.25(0~3)%, $23(0{\sim}236)/mm^3$. The percentage of the differential count obtained from the present work showed a good agreement with the results of various authors. Of the horses examined monocyte was found from 42 horses, eosinophil from 62 horses and basophil from 10 horses. No significant differences recognized between male and female horses, and the effect of age was not observed between three to nine years old. Judging from the blood picture of the present investigation, it could be stated that the army pack horses on training were kept better than the average farming conditions.

• Clinical and Experimental Pediatrics
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• v.46 no.3
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• pp.271-276
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• 2003

Purpose : Granulocyte-colony stimulating factor(G-CSF) and granulocyte macrophage-colony stimulating factor(GM-CSF) are principal cytokines in granulopoiesis and their physiologic effects are mediated through binding to specific cell surface receptors. Although it is known that the level of serum G-CSF and GM-CSF, and presentation of the receptors are increased in infectious diseases, there have been no studies to find the correlation between the granulopoiesis and leukocytosis. This study was designed to measure G-CSF and GM-CSF in leukocytosis and in control and to demonstrate the possible pathogenesis of granulopoiesis in leukocytosis using quantitative analysis of G-CSF, GM-CSF and their CSFr. Methods : The plasma levels of G-CSF, GM-CSF of 13 children without leukocytosis and 14 children with leukocytosis were measured. Counts of cell surface G-CSFr and GM-CSFr were measured by combining anti G-CSFr and anti GM-CSFr monoclonal antibodies to their respective receptors by using quantitative flow cytometric assay. Results : There was no significant difference betweeen the plasma concentration of G-CSF and GM-CSF in acute leukocytosis and in the control group. However, levels of G-CSFr in acute leukocytosis decreased significantly compared to the control(P=0.012) and the levels of GM-CSFr in both groups revealed no significant difference. Conclusion : Increase in the number of leukocyte in leukocytosis was mediated by increasing the number of neutrophil, and increased plasma concentration of G-CSF may be the cause of neutrophilia. But GM-CSF did not have any influence on leukocytosis.

• Korean Journal of Veterinary Research
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• v.14 no.1
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• pp.115-133
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• 1974

Although considerable research has been done on the changes associated with age in the blood picture of domestic and laboratory animals, little work has been made of the changes occurring at different age in the blood picture of goats. And a comprehensive survey of the bood picture of Korean native goats has not been made. The object of the present investigation was to suggest standards for the blood picture of Korean native goats at frequent intervals from birth to maturity. The goats were kept under average farming conditions in this country. Observations were made at the following ages: at birth; 2,4 and 7 days; 2, 3, 4, 5, 6, 7, 8 and 9 weeks; 2.5, 3,6 and 12 months. Blood samples were drawn from the jugular vein. It was taken between 8 and 9 a.m. except those for the at-birth period. Erythrocyte and leukocyte enumerations and, determinations of hemoglobin in blood and hematocrit value were made in the usual manner. Reticulocytes were enumerated per 1,000 erythrocytes in blood smears stained with briIliant cresyl blue and counterstained with Wright's stain. Erythrocytes counts declined from $8.7{\times}10^8/mm^3$ at birth to a low of 7.0 at 4 days of age. These values increased to 11.5 at 5 weeks and reached a maximum of 14.0 at 3 months of age; it then fell to 11.5 at 12 months of age. Concentrations of hemoglobin in blood and hematocrit values were not related to the changes of erythrocyte counts. The values at birth were higher than at any other period during the first year of life. These fell from highs of 12.3 g/100 ml and 38.0 ml/100 ml to lows of 9.2 and 29 at 4 weeks for concentration of hemoglobin in blood and hematocrit value, respectively. There was a common pattern for the hematocrit value and hemoglobin in blood which showed three phases-a fall during the first month, a rise to the third month, and a fall to the mature level at 12 months of age. Mean corpuscular volume and mean corpuscular hemoglobin showed a common pattern. The values were $44.2{\mu}m^3$ and 14.2 pg at birth and fell, at first slowly and then rapidly, to reach adult levels of 24.1 and 7.9 at 6 weeks of age for mean corpuscular volume and mean corpuscular hemoglobin, respectively. Mean corpuscular hemoglobin concentration was little affected by age. Reticulocyte was observed from birth to 4 weeks of age. Percentage of reticulocyte decreased from 0.85% at birth to 0.06% at 4 weeks of age. Total leucocyte counts increased from $5.64{\times}10^3/mm^3$ at birth to a maximum of 13.4 at 3 months; it then fell to 11.5 at 12 months of age. In differential counts myelocyte, juvenile and band form decreased with advancing age. No myelocyte and juvenile were seen after the age of 7 and 9 weeks, respectively, and band forms were rare after the age of 3 months. Percentage of mature neutrophil showed a quick decline from 52.5% at birth to reach a minimum level (34.5%) at 3 months of age; it then rose to 38% at 12 months of age. Percentage of lymphocyte increased from 39.2% at birth to maximum of 59% at 3 month of age; it then fell to 54.9% at 12 months of age. Percentage of monocyte was not affected with advance of age. Percentage of eosinophil and basophil were increased with advance of age to reach a maximum at 2 to 3 month of age. It then fell to adult level at 12 month of age.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.135-140
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• 2013

Objective: To evaluate correlations between serum anti-M${\ddot{u}}$llerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. Methods: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ${\geq}25kg/m^2$ (n=34). Results: The mean age was $25.9{\pm}5.7$ year and mean AMH level was $10.1{\pm}5.4$ ng/mL. The BMI ($kg/m^2$) was higher in group 1 ($24.2{\pm}6.3$) than in group 2 ($21.9{\pm}4.3$, p=0.046) or group 3 ($21.6{\pm}3.3$, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH ($7.7{\pm}3.9$ ng/mL vs. $10.7{\pm}5.6$ ng/mL), p=0.004) and low-density lipoprotein levels ($93.1{\pm}21.2$ mg/dL vs. $107.5{\pm}39.3$ mg/dL, p=0.031), and showed higher total T ($0.74{\pm}0.59$ L vs. $0.47{\pm}0.36$ ng/mL, p=0.001), free T ($2.01{\pm}1.9$ vs. $1.04{\pm}0.8$ pg/mL, p=0.0001), and free androgen index ($6.2{\pm}7.9$ vs. $3.5{\pm}3.0$, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. Conclusion: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.