Successful Single-Lung Transplant for the Dominant Side: A Case Report

Although single-lung transplant on the side with better lung function is challenging in patients with significantly asymmetrical lung function between the right and left sides, it sometimes can be a realistic option because of the recipient's condition and from the viewpoint of organ sharing. We report our experience with a successful case of single-lung transplant on the side with a pulmonary perfusion ratio of 89%. The transplant was performed with the patient under central venoarterial extracorporeal membrane oxygenation through a clamshell incision, and the patient had an acceptable short- and long-term outcome with a remarkable improvement of lung function.     

Hereditary pressure-sensitive neuropathy: demonstration of "tomacula" in motor nerve fibers.

By studying intramuscular nerves in 2 patients from 2 families with hereditary pressure-sensitive neuropathy (HPSN), the occurrence of abnormal thickening of myelin sheaths ("tomacula") was for the first time demonstrated in motor nerve fibers. Furthermore, the tomacula were found to line up on certain axons instead of being randomly distributed. These results indicate that the recurrent mononeuropathies of HPSN arise from an underlying asymptomatic motor and sensory polyneuropathy. It is also suggested that some signals emanating from the axons might be related to the formation of tomacula on the basis of the genetically determined myelination disorder.     

Urinaryα 1 as an index of proximal tubular function in early infancy

Urinary ₁-microglobulin (U-A₁M) was measured in healthy term infants on days 1, 4, 7, 14, 28, 90 and 180 of life. U-A₁M was high until day 14 and declined thereafter. It was significantly correlated with urinary ₂-microglobulin (U-B₂M) throughout the study, but not with serum A₁M on days 1 or 7. Similar to U-B₂M, U-A₁M in the clinically stable term infants with intrauterine growth retardation (n=4–7) was not elevated on days 1–7. In the sick infants who needed immediate resuscitatio at birth (n=4–8), U-A₁M as well as U-B₂M was high on days 1–7 and then decreased to normal levels, suggesting that U-A₁M can be used as a sensitive marker of acute proximal tubular damage and its recovery. These observations indicate that U-A₁M is a useful index of proximal tubular function in early infancy.     

Isolated avulsion fracture of the lesser tuberosity of the humerus: A case report

Isolated avulsion fractures of the lesser tuberosity are extremely rare. A 24-year-old woman fell on her back as her arm was forcibly extended and adducted. Radiographs revealed a small fragment of bone beneath the glenoid. Axillary radiography showed the bone fragment and a bone defect of the lesser tuberosity. Computed tomography scan clearly demonstrated those findings. Surgery was performed 3 weeks after the occurrence of the injury. The bone fragment was reduced and fixed by means of two screws. After 3 weeks, light exercise was started. At follow-up 7 months later she had no complaints. Most reported cases involved sudden contraction of the subscapularis tendon. This type of fracture is sometimes misdiagnosed; computed tomography scan is useful for diagnosis. Previously reported cases have similarly demonstrated a good outcome after surgery, except in cases involving children.     

Surgical and preoperative treatment of soft tissue sarcoma

Preoperative therapy effects, resected margin and local radicality were investigated in 40 cases of soft tissue sarcoma in which preoperative therapy (mainly radiation therapy) had been given. The results indicated that there was no effect upon prognosis due to postponement of surgery in order to perform preoperative treatment. In cases in which radiation therapy was used for preoperative treatment, even when a surgical margin resulted with in a tumor, no recurrence was found. However, histologically there was concern that some portion of the living tumor cell in marginal area of the tumor might have remained. Thus, at the present stage in cases having undergone initial treatment, radiation limited to the specific area of the resected margin causing non-curative margin should be given. If combined with preoperative radiation therapy, surgical intervention involving "wide margin" can be considered radical. On the other hand, cases having undergone surgery before and receiving preoperative therapy that show good response nevertheless show numerous recurrences. These recurrences, however, invariably occur outside of the irradiated area, and may be attributed to the fact that tumor cell dissemination from the earlier surgery was not within the radiation field. Hence, it was considered that the area for radiation in the case of a recurrence should extend well beyond the scar area.     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

Clinical results and prognostic factors of radiotherapy for bone metastases from breast cancer

The purpose of this study was to analyze the results of initial radiotherapy for bone metastases (BM) from breast cancer and to investigate the prognostic factors. Between 1981 and 1995, 65 women (109 lesions) received initial radiotherapy for BM, aiming at a total dose of 50 Gy/25 Fr. Significant relief of pain was obtained in 61 (88.4%) of 69 estimable lesions according to the RTOG score. The control rates of pain including the prevention of pathological fractures or myelopathy were 80.4% at 5 years and 64.3% at 10 years. The median survival time of all patients was 11 months, and the survival rates were 56% at 1 year, 31.6% at 3 years, 17.9% at 5 years and 10.7% at 10 years, with five long-term survivors. Univariate analysis showed that a normal state of LDH, no other metastatic organs, a disease-free interval longer than two years, good performance status (0 or 1), BM limited to the axial bones, maintenance chemo-hormonal therapy and an age of more than 55 years were good prognostic factors. Multivariate analysis showed that LDH, age and performance status were significant predictors of prognosis. It is important to note the prognostic factors at the initial treatment of BM from breast cancer. We consider that further prospective studies are needed to determine the optimal treatment schedule, including radiotherapy and its combination with chemohormonal therapy, for BM.     

Case report of 14-year survival after radiotherapy for clinical T3 esophageal carcinoma, with local recurrence finally rescued by surgery

A 51-year-old man with increasing dysphasia was admitted to our hospital on March 18, 1985. Several examinations revealed thoracic esophageal squamous cell carcinoma 11 cm in length staged T3N0M0 (stage IIA) by UICC 1987. As he rejected our proposal of surgery, definitive radiotherapy (60 Gy) was delivered, and complete response was obtained. The patient had been doing well for 5 years after radiotherapy until superficial local recurrence was discovered at a periodic endoscopic examination. High-dose-rate intraluminal brachytherapy (10 Gy/2 Fr) was administered. After a 3-year disease-free interval, superficial recurrence developed in the same location, and early gastric cancer was detected as a secondary cancer. Radical salvage surgery was performed. The patient was alive and disease free 5 years and 5 months after surgery. We present this rare case of a patient who survived 14 years after the initial radiotherapy. The present case demonstrated the importance of long-term follow-up after radiotherapy, long-term local controllability of relatively low doses of intraluminal brachytherapy after superficial recurrence, and the feasibility of salvage surgery as long as local recurrence is limited to within the mucosal layer.     

Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells is differentially regulated by transforming growth factor-beta and platelet-derived growth factor-BB

Pathologic remodeling of mesangial matrix after glomerular injury is the central biologic feature of glomerular scarring (sclerosis). Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB have been implicated in the development of glomerular scarring in rat and human glomerulonephritis. To clarify molecular and cellular mechanisms involved in abnormal mesangial remodeling, this study focused on the role of alpha1beta1 integrin, a collagen/laminin receptor, in rat mesangial cells, using collagen gel contraction as an experimental model of in vivo collagen matrix remodeling and scar formation. In addition, the influence of TGF-beta and PDGF-BB on mesangial cell (MC)-mediated collagen gel contraction in association with the alpha1beta1 integrin expression was evaluated. Integrin function blocking studies using anti-alpha1, beta1 subunit antibodies indicated that MC-alpha1beta1 integrin is essentially required not only for collagen-dependent adhesion/migration, but also for gel contraction. Protein synthesis and mRNA analysis experiments demonstrated that TGF-beta, but not PDGF-BB, increases the expression of alpha1beta1 integrin in mesangial cells cultured on plastic surface and in collagen gels. The upregulation of alpha1beta1 integrin expression by TGF-beta correlated with increases in gel contraction and collagen-dependent adhesion but not migration of mesangial cells. On the other hand, PDGF-BB enhanced MC-mediated gel contraction and migration without affecting cell adhesion to collagen I. Growth factor-induced collagen-dependent adhesion, migration, and gel contraction were significantly attenuated by incubation with anti-alpha1, beta1 subunit antibodies. Thus, these data indicate that alpha1beta1 integrin-mediated collagen matrix remodeling can be modulated by TGF-beta and PDGF-BB via different mechanisms. Alpha1 integrin-mediated mesangial matrix remodeling induced by TGF-beta or PDGF-BB may be a pathogenic mechanism leading to glomerular scarring.     

Constitutive and cytokine-regulated expression of presenilin-1 and presenilin-2 genes in human neural cell lines

To investigate the role of pleiotropic neuronal and glial cytokines in the regulation of presenilin (PS) gene expression in human neural cells, both presenilin-1 (PS1) and presenilin-2 (PS2) mRNA levels were analysed by Northern blotting in SK-N-SH neuroblastoma, IMR-32 neuroblastoma, NTera2 teratocarcinoma-derived differentiated neurones (NTera2-N) and U-373MG astrocytoma cells following exposure to proinflammatory cytokines (TNF-alpha, IFN-gamma, or IL-1beta), anti-inflammatory cytokines (IL-10 or TGF-beta1), dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate (PMA). The constitutive expression of PS1 (3.0 kb) and PS2 (2.3 kb) mRNA was identified in all these cell lines, in which PS1 mRNA levels were unaltered following treatment with any cytokines and factors examined. By contrast, PS2 mRNA expression was upregulated substantially in SK-N-SH cells by exposure to TNF-alpha and in U-373MG cells by treatment with IFN-gamma, whereas it was downregulated in both NTera2-N and U-373 MG cells following exposure to IL-1beta or PMA. The levels of PS2 mRNA remained unchanged in IMR-32 cells after these treatments. These results indicate that PS1 and PS2 genes are expressed constitutively in a panel of human neural cell lines where PS2 mRNA expression is affected by a distinct set of cytokines via cell type-specific mechanisms that do not alter PS1 mRNA levels, suggesting the existence of separated regulatory systems controlling the expression of PS1 and PS2 genes in human neural cells.