A prospective, randomized study: day 3 versus hatching blastocyst stage

Hum. Reprod.,      

Study on extensive lymph node dissection: metastatic lymph nodes in papillary carcinoma of the thyroid

Bilateral cervical lymph node dissection was performed in 71 cases of papillary thyroid carcinoma, considered to be relatively early cases because of mobility, irrespective of the size of tumor or presence of node enlargement. Of these, 33 cases received additional node dissection of the anterosuperior mediastinum through longitudinal sternotomy. The number of lymph nodes examined per subject averaged 89.9, the number of metastatic nodes was 13.8, and metastasis was noted in 88.7% of all cases. Lymph node metastasis tended to be more frequent on the affected side, but was simultaneously scattered over the whole cervical area. As to sites, metastasis of paratracheal nodes on the affected side occurred at a frequency of 66.2%, inferior and superior jugular nodes at 62.0% and 59.0% respectively, pretracheal nodes at 50.7%, and tracheoesophageal nodes at 47.9%. The high incidence of para- and pretracheal nodes suggests that the lymph flow in this direction is of great importance in metastasis. In fact, lymph nodes in the mediastinum, which were directly continuous with these nodes, showed as high as 39.4% metastasis in cases of anterosuperior mediastinal extirpation. This extensive node dissection is considered to be very preferable as at least the agony of survival with carcinoma can be lessened.     

Effects of halothane on spinal dorsal horn WDR(wide dynamic range) neuronal activity in cats

The effects of halothane (0.2%, 0.5%, and 1.0%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity was studied in either spinal cord intact or spinal transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact or decerebrate, spinal cord transected (L 1-2) cats. When 10 micrograms of bradykinin was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, all of 7 WDR neurons gave excitatory responses which were not depressed by 0.2% and 0.5% halothane but were depressed significantly by 1.0%. On the other hand, when the injection of 10 micrograms of bradykinin into the femoral artery ipsilateral to the recording site was used in the intact cat, 7 of 14 WDR neurons (50%) gave excitatory responses, which were not depressed by 0.2% halothane but were significantly depressed by 0.5% and 1.0% halothane, and 7 of 14 WDR neurons (50%) gave inhibitory responses, which were significantly depressed by 0.2%, 0.5%, and 1.0% halothane. We have found that halothane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by bradykinin injection.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Differentiation of blast cells from a Down's syndrome patient with transient myeloproliferative disorder

A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.     

Muscle strength in patients with gastrointestinal carcinoma--an important role of muscle strength as a nutritional parameter

The relationship between nutritional status and muscle strength was examined in 73 patients with gastrointestinal carcinoma preoperatively. Nutritional status was assessed by measuring various nutritional parameters. Muscle strength was determined by measurements of %grip strength and respiratory muscle strength expressed as %maximal expiratory and inspiratory pressure (%MEP and %MIP). The results were as follows: %GS was significantly low in the patients who showed low values in body weight (%ideal body weight: %IBW), mid-arm muscle circumference (%AMC), serum albumin (Alb), serum prealbumin (PA), total peripheral lymphocyte count (TLC), and/or nutritional surgical risk index (NRI). %MEP was significantly low in the patients who showed low values in %IBW, %AMC, triceps skin fold, Alb, PA, retinol binding protein, NRI, and/or nutritional assessment index (NAI). %MIP was significantly low in the patients who showed low values in %IBW, %AMC, creatinine height index, Alb, PA, NRI, and/or NAI. %MEP and %MIP were significantly correlated with %GS. Preoperative %GS value was significantly low in the esophageal cancer patients with postoperative pulmonary complications. It was suggested that %GS was a simple and useful nutritional parameter for detecting depletion of the muscle mass and visceral proteins, for respiratory muscle strength, and for functional capacity of muscle.     

Antibodies to brain proteins in paraneoplastic cerebellar degeneration

A 68-year-old man had subacute cerebellar degeneration and a non-Hodgkin's lymphoma. Using an immunoblotting method, we found serum antibodies to rat cerebral 250-kd and 110-kd and cerebellar 110-kd acidic cytoplasmic proteins. The antibodies did not react unless the antigens were prepared soon after death with protease inhibitors. Two hundred fifty-kd and 110-kd proteins are minor components of soluble cytoplasmic proteins of the brain. The molecular weights differed from other soluble brain-specific proteins already characterized.     

Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis

We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis. To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions. Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated. Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients. Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls. The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome.