Limitations of the Severe Combined Immunodeficiency (SCID) Mouse Model for Study of Human B-Cell Responses

Mice lacking functional T and B lymphocytes offer an in vivo animal model for the study of human immune functions. We have attempted to optimize the reconstitution of severe combined immunodeficiency (SCID) mice with human peripheral blood lymphocytes (PBL) using radiation, anti-asialo GM₁ antibody or cyclophosphamide (Cy) treatment of the mice and in vitro stimulation of human PBL with interleukin (IL)-2 prior to their transfer to the mice. Total human IgG and tetanus-toxoid (TT)-specific human IgG responses of the mice were used as parameters of successful reconstitution. Treatment of the mice with anti-asialo GM₁ antibody significantly enhanced total human IgG levels, but not TT-specific antibody responses, whereas irradiation or Cy treatment of the mice had no effect on human antibody production. In vitro treatment of human PBL with IL-2 prior to engraftment significantly decreased total human IgG responses of human PBL-grafted SCID mice. The immune responses of individual mice within a group were highly variable, which constitutes a major disadvantage of this model.     

3’-当归酰氧基-4’-乙酰氧基-3’,4’-双氢邪蒿内酯对麻醉犬短时缺血后心肌功能不良的影响(英文)

静脉输入3’-当归酰氧基-4’-乙酰氧基-3’,4’-双氢邪蒿内酯(0.15mg·kg~(-1)·min~(-1))30min对15min闭塞犬左前降枝伴3h再灌注后心肌收缩功能的影响被研究。用超声微测距法测定心肌节段收缩(SS)长度表明:该药迅速改善心肌收缩功能不良,再灌后5min即使SS％恢复到用药前的41±51％(P<0.05,n=8),对血流动力学无明显影响。     

Thrombocytopenia associated with platelet-associated immunoglobulin G in alcoholic hepatitis

Abstract A 45 year old Japanese man with alcoholic hepatitis developed thrombocytopenia together with an increase in the level of platelet-associated immunoglobulin G (PAIgG). Bone marrow aspiration revealed a normal nucleated cell count and a slight increase of megakaryocytes. After abstinence from alcohol, laboratory and symptomatic improvement occurred in association with a prompt increase in the platelet count and a corresponding decrease of PAIgG. These findings suggest that PAIgG may have been involved in the development of thrombocytopenia in this patient.     

Direct observation of the portal vein interior by intra-operative angioscopy in the dog and man

The purpose of this study was to develop the technique of intra-operative portal angioscopy using a portal angioscope, and to demonstrate its potential use in the therapy for patients with hepatocellular carcinoma (HCC) bearing a portal thrombus. Portal angioscopes, Olympus BF3C10 and CHFP10 of a diameter of 3.5 mm and 4.8 mm, respectively, were used during operation in five dogs, two patients with hepatic metastasis from colon cancer and three patients with HCC having a portal tumour thrombus. The portal vein and hepatic artery were ligated simultaneously, and the angioscope was immediately introduced under direct vision through a small portal venotomy. Blood in the portal vein was almost fully diverted by infusion of heparinized saline through a channel of the angioscope at a rate of 3 mL/min in dogs and 5 mL/min in patients with hepatic metastasis. Rates of 6 mL/min and 10 mL/min in dogs and patients, respectively, were adequate to clear completely the portal vein of blood. In patients with HCC, portal tumour thrombectomy was performed with a Fogarty balloon catheter by suctioning thrombi through a channel of the fibrescope after visual study of the portal thrombus. Observation and treatment of portal thrombus by angioscopy may become an important part of surgical treatment of HCC with portal invasion, but further technical improvement is desirable before this technique becomes a routine procedure.     

Effect of Ventricular Pacing on Coronary Blood Flow in Patients with Normal Coronary Arteries

Although ventricular pacing is thought to produce impairment of left ventricular function by altering the sequence of ventricular activation and AV dyssynchrony, little is known about the effect of ventricular pacing on coronary blood flow. We measured coronary blood flow and coronary flow reserve in the left anterior descending coronary artery during sinus rhythm, and during both atrial and ventricular pacing at a rate of 100 ppm in 14 patients with normal coronary arteries. The double product increased significantly during both types of pacing. Coronary arterial diameter during ventricular pacing significantly increased compared to that during both sinus rhythm and atrial pacing. Coronary flow velocity during ventricular pacing was significantly lower compared to that during both sinus rhythm and atrial pacing. Coronary blood flow increased significantly during atriai pacing (30.7%± 12.1%; P < 0.001), but not significantly during ventricular pacing (23.6%± 47.0%; P = ns). While coronary flow re-serve during both atrial (3.9 ± 1.3) and ventricular pacing (3.8 ± 0.9) was lower compared to its value during sinus rhythm (4,5 ± 1.5), the difference was not significant. There was a significant positive correlation between the coronary flow reserve during sinus rhythm and the increase of coronary blood flow during ventricular pacing (R²= 0.78; P < 0.001). We concluded that an increase in coronary blood flow during ventricular pacing is not a common finding regardless of the increase in metabolic demand. The increase of coronary blood flow during ventricular pacing was less in patients with a reduced coronary flow reserve. These findings suggest that preservation of AV synchrony and the presence of a normal sequence of ventricular activation may play an important role in preserving coranary blaod flow in this subset of patients.     

Erosion of a penile prosthesis due to an indwelling urethral catheter as a late complication

A case of erosion of a penile prosthesis caused by indwelling of a catheter in the urethra is reported. A 73-year-old man had maintained sexual intercourse with penile prostheses (Jonas prosthesis, 19 cm) for 11 years without any complications until he developed cerebral infarction. One month after starting an indwelling urethral catheter in a neurosurgery clinic, the left-side penile prosthesis eroded from the area of the fossa navicularis, and was immediately removed. This type of complication is not unusual in patients with a neurogenic bladder. However, it is not well recognized in patients who suddenly develop a neurogenic bladder following a long-term uneventful period after the implantation of penile prostheses. Therefore, urologists should inform patients who receive this type of treatment that erosion of the prosthesis may develop when they need an indwelling urethral catheter as a late complication.     

Two Cases of Malignancy-Associated Hypercalcemia Treated with Mithramycin

The hypocalcemic effect of mithramycin, an antitumor antibiotic,was studied in two consecutive hypercalcemic patients with malignancy.Case 1 was a 60-year-old woman with advanced breast cancer.Severe, generalized bone metastasis seemed to be the cause ofthe hypercalcemia. Serum calcium levels reached 14.6mg/dl (ionizedcalcium 3.84 mEq/I) despite continued therapy with saline (5liters/day) with frosemide (60mg/day, intravenously), high dosesof elcatonin (up to 440 MRC units/day) and prednisolone (30mg/day). Case 2 was a 49-year-old woman with recurrence of ovariancancer. Bone metastasis was not found on X-ray films. Hypercalcemiawas progressive in spite of extensive treatments with saline(2 liters/day) with frosemide (40 mg/day), indomethacin (150mg/day), elcatonin (160 MRC units/day) and prednisolone (30mg/day). Meantime, serum calcium rose to 14.6mg/dl (ionizedcalcium 3.57 mEq/I). In both cases, mithramycin (1.25 mg) wasthen administered intravenously. Serum calcium levels droppedto 9.6 and 9.4 mg/dl two days after the administration of mithramycinin case 1 and case 2, respectively. These observations indicate that mithramycin is more effectivethan any other drug tested for the treatment of hypercalcemiacaused by malignancy irrespective of the presence or absenceof bone metastasis. Therefore, it should be widely used forhypercalcemic emergency.     

Micro-determination of cyclic AMP levels in human epidermis, dermis and hair follicles

In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin.