Lecithin-cholesterol acyltransferase (LCAT) deficiency without mutations in the coding sequence: a case report and literature review.

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure. In all FLD cases, a mutation has been found in the coding sequence of the LCAT gene. FLD is clinically distinguished from an acquired form of LCAT deficiency by the presence of corneal opacities. Here we describe a 36-year-old woman presenting with clinical, pathological, and laboratory data compatible with FLD. Her mother and elder sister had corneal opacities. However, genetic analysis revealed there were no mutations in the LCAT coding sequences and no alterations in LCAT mRNA expression. Furthermore, we were unable to find any underlying conditions that may lead to LCAT deficiency. The present case therefore demonstrates that LCAT deficiency may be caused by factors other than mutations in the coding sequence and we suggest that a translational or posttranslational mechanism may be involved.

Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice.

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by thrombus-like substances in markedly dilated glomerular capillaries, dysbetalipoproteinemia, and elevated plasma concentrations of apoE. Recent studies identified several apoE mutations in patients with LPG, including apoE2(R145P) Sendai (apoE-Sendai). Virus-mediated transduction of apoE-Sendai in apoE-deficient hypercholesterolemic mice resulted in insufficient correction of hypercholesterolemia and a marked and temporal induction of plasma triglyceride levels. In vitro binding studies showed that apoE-Sendai has a reduced affinity for the low density lipoprotein receptor, suggesting that dysbetalipoproteinemia in LPG is caused by the apoE mutation. Furthermore, histological examination revealed marked intraglomerular depositions of apoE-containing lipoproteins in mice injected with apoE-Sendai virus. These LPG-like depositions were detected 6 days after virus injection and were sustained for at least 60 days. Our results demonstrated that apoE-Sendai is an etiological cause of LPG.

Enhanced human tumor cell transplantability in a new congenic immunodeficient mouse; KSN-BNX.

We introduced two mutant genes (beige; bg that induces the deficiency of natural killer (NK) activity and xid that decreases the production of immunoglobulin) into KSN nude mice with high reproductive performances. We produced KSN bg/bg(nu/nu) (KSN-bg), KSN-xid/xid(nu/nn) (KSN-xid), KSN xid/xid,bg/bg(nu/nu) (KSN-BNX) and KSN-nu/+ (KS) mice by back-cross (cross-intercross method). All strains showed as high a reproductivity rate as the parental KSN mice. KSN-xid and KSN-BNX mice had a reduced percentage of B220 positive cells in the spleens compared to KSN and KSN-bg mice, but they showed increased percentages of Thy-1 and asialo GM1 positive cells. The serum immunoglobulin concentrations of KSN-BNX were as low as KSN-xid. Both KSN-bg and KSN-BNX mice showed deficient NK activity in spleens, whereas KSN-xid mice showed an elevated NK activity. Compared to nude mice, the growth of both human tumor cell TCO-1 and BxPc-3 transplanted subcutaneously was enhanced in KSN-BNX mice. However Panc-1 cells that was rejected in nude mice was not accepted in KSN-BNX mice. Liver metastasis of human pancreatic tumor cells; Capan-1, BxPc-3 and MIAPaCa-2 were studied. No significant difference was observed in the percentage of metastasis formed mice between nude and KSN-BNX mice.

Anti-angiogenic effect of TGFbeta in aqueous humor.

Neovascularization is mediated by various factors in ocular tissues. Recent studies have emphasized the role of vascular endothelial growth factor in the induction of angiogenesis. We have previously reported that aqueous humor (AH) suppressed vascular endothelial cell growth and angiogenesis. We speculated that the anti-angiogenic effect of AH is mediated by transforming growth factor beta (TGFbeta). In order to clarify the presence of TGFbeta in bovine AH, we applied it on the heparin-sepharose affinity column and prepared two fractions (bound and unbound fractions). We measured TGFbeta concentration in each fraction and examined how the anti-TGFbeta antibody decreased the inhibitory effect of AH on human umbilical vein endothelial cell growth and on in vitro angiogenesis. We found the presence of TGFbeta2, but not TGFbeta1, in the heparin bound fraction, and the inhibitory effect was detected in the heparin-bound fraction. Anti-TGFbeta antibody completely and dose-dependently extinguished the inhibitory effect of AH. We propose that the inhibitory effect of AH on endothelial cell growth and in vitro angiogenesis are both mediated by TGFbeta2. Our results indicate TGFbeta2 is normally present in AH and protects the eye tissue against abnormal neovascularization.

A comparison of UVB-carcinogenesis between nude mice and nude beige mice.

To gain an insight into the relationship between UVB-carcinogenesis and natural killer activity, we examined ultraviolet light-induced carcinogenesis in mice with high natural killer, activity (KSN) and mice with natural killer deficiency (KSN-bg). We exposed mice six times a week to three levels of daily ultraviolet B (UVB) doses; 320, 160 and 0 J/m2/day. During the latency period of skin tumor development in KSN mice, we detected no suppression of the natural killer activity at both 320 and 160 J/m2/day. Even at 1340 J/m2/day, we could not detect any significant suppression of NK activity in KSN mice. When we irradiated spleen cells in vitro, we observed NK activity suppression. Next, we compared the carcinogenic effects of UVB-irradiation on KSN and KSN-bg mice. At 320 J/m2/day, we detected no significant differences between them. In contrast, at 160 J/m2/day, KSN-bg mice showed a significantly higher rate of skin tumor induction than KSN mice (p < 0.05). Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. Our results suggest that NK activity plays a protective role against UVB-carcinogenesis from low daily-doses of UVB-irradiation.

An UVB-carcinogenesis model with KSN nude mice.

We established and characterized a systematic ultraviolet light-induced carcinogenesis model using KSN nude mice. We prepared five groups of KSN mice and exposed them six times a week to five levels of daily ultraviolet B (UVB) doses; 1340, 670, 320, 160 and 0 J/m2/day. In 670, 320 and 160 J/m2/day, the latency period tended to become shorter in proportion to the daily doses and prevalence data fitted well to log-normal distribution. In the log-log plot of days till 50% prevalence versus daily dose, we saw a linear relationship for 1 mm tumor diameter. From this analysis, we determined that days necessary to reach 50% prevalence is in proportion to the -0.49 power of daily dose. The average number of tumors per survivor correlated with prevalence data. Direct measured rates of tumor growth were independent of daily UVB-dose. Therefore we speculated that UV-irradiation did not affect tumor growth after its appearance. Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. We concluded that our experimental data with nude mice was in accordance with data with hairless mice in nature.

Monitoring the free radial forearm flap in pharyngo-oesophageal reconstruction.

Monitoring the viability of the free radial forearm flap after pharyngo-oesophageal reconstruction poses technical problems. A method of monitoring using a small island flap elevated distal to the main forearm flap is presented. This monitor flap is easy to elevate. It is placed externally and provides information about the perfusion of the buried reconstruction flap. Postoperative management requires only assessment of tissue colour, turgor, capillary refill and bleeding, as for standard skin flap monitoring.

New immunodeficient mouse strains bred by introducing beige and xid mutations into the KSN nude strain.

We introduced two mutant genes (beige or bg, which induces a deficiency of natural killer activity, and xid, which decreases the production of immunoglobulins) into KSN nude mice with high reproductive performance. At first we produced the KSN-bg/bg(nu/nu) (KSN-bg) and KSN-xid/xid(nu/nu) (KSN-xid) congenic strain by backcross (cross-intercross method). After we identified homozygosity at the biochemical locus and polymorphic microsatellite loci, we mated KSN-bg and KSN-xid mice, and selected the KSN-xid/xid;bg/bg(nu/nu) (KSN-BNX) mice from the progeny. Furthermore we introduced the non-nude gene, which originated from CBA/N, into the KSN strain and produced KSN-nu/+ (KS) mice that have the same genetic background except for the nu locus. All strains had as high a reproductivity rate as the parental KSN mice. The KSN-xid and KSN-BNX mice had a reduced percentage of B220-positive cells in the spleen compared with KSN and KSN-bg mice, but they had increased percentages of Thy-1 and asialo GM1-positive cells. The serum immunoglobulin concentrations of BNX were as low as those of KSN-xid mice. Both KSN-bg and KSN-BNX mice had deficient natural killer activity in the spleen, whereas KSN-xid mice had increased natural killer activity. Compared with nude mice, the growth of the human thyroid tumor cell line transplanted subcutaneously was enhanced in BNX mice. These KSN, KSN-bg, KSN-xid, KSN-BNX, and KS nice not only are of value for use in various fields as the hosts of xenograft but also are good models of the combination effect of multiple immunodeficient genes.

[The effectiveness of discharge planning (DSP) in home care--comparison of conditions of cancer patient shifted to home treatment before and after DSP introduction].

We developed a discharge planning (DSP) procedure as a method to assess the family and cancer patient situation when making the shift to home care, and we herewith report its significance. DSP is intended to sustain the patient's quality of life (QOL) and improve it; for a smooth transition to treatment at home, the family and patient situation must be assessed from various perspectives. The prospective illness conditions, needed medical treatment and care should be appropriately planned, with due recognition of the roles to be played and the requisite pooling of professional information in order to handle emergencies and the like when such arise. In the present study, in order to clarify issues dealing with DSP effectiveness, we compared 34 patients on home care, 17 before DSP and 17 thereafter. The results indicated that following the introduction of DSP, the home care increased for patients with gastroenterological problems such as pain, general debilitation, poor appetite, constipation, diarrhea and the like and those impulsiveness, vomiting and mental symptoms overlapping. With the proper assessment at the time of the transition to home care, this care could be continued. Moreover, with patient satisfaction, there was the need for assessment over the course in order to evaluate treatment and care. In the days to come, there is the need to improve this approach with a scoring system in the evaluation.

[Factors affecting continuation of home medical care--based on the relationship between patient and caregiver status].

In recent years it has gradually become possible to have some control over the medical condition of the end-stage cancer patient. However, there are various problems involved in the continuation of home care. In order to clarify how the mutual relationship between patient and caregiver effects the continuation of home care, we conducted a study on 28 end-stage cancer patients who made the transition from our hospital to home care by means of our HOme Care Service. Using the Kaneda Assessment Score, we obtained information from patients' charts, added reasons for rehospitalizations and analyzed the data. The results showed that the group of patients who remained on home care, despite the fact that their condition was significantly poorer than that of the group who discontinued home care, showed a significantly higher proportion of "wishing to be cared for at home to the last," in the view of the caregiver, a joint commitment of the caregiver together with the family, and a suitable response to changes in the patient. As a direction for forthcoming support in this area, there is a need for sufficient assessment in order to evaluate the balance between caregiver and family. It was suggested that guidance in each case and the use of community resources will be very important.

Bilateral lateral vermilion border transposition flaps to correct the "whistling lip" deformity.

A simple method of transposing bilateral lateral vermilion border flaps into the midposterior line of the prolabium to correct the "whistling lip" deformity is presented. This method makes it possible to decrease the upper lip tension, deepen the labiogingival sulcus, and reconstruct a peaked tubercle.

Suppression of experimental autoimmune myasthenia gravis with new immunosuppressants: 15-deoxyspergualin and actinobolin.

In the search for a new drug to treat myasthenia gravis, we studied the efficacy of new immunosuppressants on experimental autoimmune myasthenia gravis (EAMG). 15-Deoxyspergualin (15-DSP), bactobolin and actinobolin were administered to some groups at the time of immunization and to other groups 10 days after. The most effective results were achieved with doses of 2.5 mg/kg daily of 15-DSP and 30 mg/kg daily of actinobolin administered from day 1. In both groups, the body weights of the rats increased as normally as those of controls and signs of myasthenia were mild. Immunoelectron microscopic examination of the neuromuscular junctions in rats treated with 2.5 mg/kg of 15-DSP appeared normal, even in the chronic phase (induced by a booster at week 4). Levels of anti-acetylcholine receptor antibodies were almost completely suppressed. Although the effects of these drugs were more remarkable when administered from day 1 than from day 10, the results suggest that they may prove useful in treating myasthenic patients.

[Toward effective cancer home therapy--from the nurses point of view].

Home cancer therapy is part of the palliative care intended to enhance the Quality of Life for patients. This treatment in the home should be maintained at the hospital level. The home could be called a "Hospital without walls." Cancer patients, both in the terminal and late stages prefer treatment in their own homes regardless of severity except patients whose cancer is in the early stage. Home treatment primarily relates itself to pain control, TPN, chemotherapy, and symptom control. Our hospital started Home Care Service in 1989, and has since continued work for 18 cancer patients with 122 home visits. Patients in the late stage receiving mostly chemotherapy were treated on an outpatient basis. From August 1990 through July 1991 the patients receiving chemotherapy were 28 in number. Informed consent is essential whenever chemotherapy is involved. Drugs used at home are mostly vescicant or irritant types, in which the route of administration plays a crucial part. But most home cases are given ip treatment. In this process, major efforts have been directed toward flexibility, efficiency, and optimality in providing a support system that responds effectively to multifaceted needs of the community. Clear findings ascertained so far from our experience in this pilot study are as follows. The most urgent needs are 1. Creation of a support system a. A Discharge Planning and Team approach. b. 24-hour support service and emergency care c. A medical and welfare network in the community 2. Education and Training 3. Informed consent 4. Nursing Manual 5. Extensive use of public health insurance, in order to achieve balanced cost sharing.

[Clinical application of dynamic CT].

10 patients with primary pulmonary cancer were performed using of dynamic CT scanning with dynamic curve and obtained radiograms were analyzed with computer. Blood is supplied usually via a bronchial artery to primary pulmonary cancer. But we could be analyzed four types on blood supplying to the primary pulmonary cancer which are via aorta, pulmonary artery, aorta and pulmonary artery and non classified type. This technique be able to suggest of effectiveness of radiotherapy with analyzing of exist of center necrosis of the tumor. Therefore we radiotherapist and radiation oncologist be able to avoid radiation-induced pulmonary pneumonia and pulmonary fibrosis especially high aged patients. We are recommended to take a this technique as preirradiative examination for patient with pulmonary cancer because of avoiding of no available radiotherapy.