Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle.

Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptors were present in circular smooth muscle cells of the guinea-pig gastric antrum. Nonselective cation channels (NSCC) activated by ACh or CCh are coupled to pertussis toxin (PTX)-sensitive Go protein through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach. CCh-activated currents (I(CCh)), especially the steady-state I-V relationship of I(CCh) showed a chracteristic U-shaped curve; reversal potential of around 0 mV and inward rectification at around +15 mV and a negative slope conductance at negative potential range. Under physiological conditions, the measured single channel conductance of NSCC was approximately 25 pS. The single channel conductance was modulated by external monovalent and divalent cations including Na+, Cs+, Li+, and Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of I(CCh) (f(Ca)) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, f(Ca) was 2.3%. Quinidine blocked I(CCh) potently in a reversible manner; IC50 was 0.25 microM. There were two kinds of I(CCh) modulations through Ca(2+)-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of I(CCh) via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of I(CCh) via Ca(2+)-dependent PKC pathway. In the mouse stomach, all seven types of TRPC mRNA were detected with RT-PCR. On the basis of electrophysiological, pharmacological, and molecular biological experiments, we reported the mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.     

Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.     

The use of cadaver kidneys for transplantation in young children

The role of cadaver kidney transplantation in the management of end-stage renal disease in young children is controversial. To assess the current risk-benefit ratio of cadaver first and second kidney transplants in recipients under 6 years of age, we compared the outcome of 19 transplants performed between 1984 and 1989 using a quadruple-drug regimen (Minnesota antilymphocyte globulin, azathioprine, prednisone, cyclosporine) with the outcome of 25 transplants performed prior to 1984 without the use of cyclosporine at a single institution. Twenty-five transplants were in children under the age of 3 years. In the last decade patient survival has significantly improved. One-year patient survival improved from 53% before 1979 to 90% since 1979 (P less than 0.05). The use of the quadruple-drug regimen since 1984 was associated with a significant improvement in one-year cadaver graft function from 40% before 1979 to 78% in recipients under 6 years of age, and from 22% to 82% in recipients under 3 years of age (P less than 0.05). With the quadruple-drug regimen, one-year and four-year graft function rates for children under 6 years of age were 83% for first cadaver transplants and 72% for second cadaver transplants, which were essentially the same results as in older children and adults. Children who received kidneys from donors over 4 years of age achieved the best result, with 87% one-year graft function compared with 50% for kidneys from donors under 4 years old. In 15 children with successful transplants, 8 (53%) showed accelerated growth, 5 (33%) had normal-velocity growth, and only 2 children (14%) with suboptimal renal function had poor growth following transplantation. Therefore, we believe that with a quadruple-drug immunosuppressive protocol, cadaver renal transplantation using kidneys from adults or pediatric donors over 4 years old is an acceptable form of treatment in young children with end-stage renal disease for whom there are no suitable living-related donors.     

Mycobacterium marinum infection of the hand and wrist. Results of conservative treatment in twenty-four cases

Inadequate débridement, extensive scarring, and breakdown of the wound have been commonly encountered after surgical débridement has been employed as the initial treatment of infection with Mycobacterium marinum involving the deep structures of the hand. Because of our disappointment with the results of this form of treatment, from 1982 to 1986 we treated twenty-four patients who had such an infection with rifampicin and ethambutol after a diagnostic biopsy was done. Surgical treatment was deferred until it was determined that the infection had not been controlled by the chemotherapy. The clinical outcome for these patients could be divided into three patterns: eleven patients (Group I) had a good result with no complications, three patients (Group II) had delayed healing of the wound, and ten patients (Group III) did not have a good response to conservative treatment and required one or more surgical débridements. Complications were sometimes associated with use of the drugs, and loss of visual acuity was a concern in three patients. In twenty-one (87 per cent) of the patients, at follow-up the function of the treated hand was equal to that of the other hand. Persistent pain, a discharging sinus, and previous local injection of steroids were unfavorable prognostic factors. If these factors are present, surgical débridement is advised.     

Clinicopathologic Study of Angiogenesis in Japanese Patients with Breast Cancer

p = 0.0007) and tumor necrosis (TN) (HMC: p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients ( p = 0.0086 and p = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.