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Biomedical subjects

J Koch

Publications and source records attributed to J Koch.

At least 91 records · Page 5Linked to original sources

Cloning and characterization of the full-length cDNA and genomic sequences encoding murine acid ceramidase.

The full-length cDNA and genomic sequences encoding murine acid ceramidase (AC; E.C. 3.5.1.23) have been isolated and characterized. The 2176-bp cDNA was approximately 80% identical to the human cDNA (Koch et al., 1996) and predicted a 394-amino-acid polypeptide that was approximately 90% identical to the human protein. A fluorescence-based assay system was developed to determine AC enzymatic activity, and transfection of COS-1 cells with the full-length mouse cDNA led to increased AC activity, demonstrating its functionality. The murine AC gene, which spanned approximately 38 kb, consisted of 14 exons separated by 13 introns. The exons ranged in size from 46 to 1038 bp and were flanked by exon/intron junctions that adhered closely to known donor and acceptor splice site consensus sequences. Exon 1 encoded the putative translation start site and the signal peptide region, while exon 14 encoded the carboxy end of the AC polypeptide and all of the 3' untranslated region. Sequence analysis of a 497-bp region upstream from the first in-frame ATG revealed several features of a housekeeping promoter, as well as several tissue-specific and/or hormone-inducible regulatory sites. Insertion of this sequence into a chloramphenicol acyltransferase (CAT) expression vector led an approximately fivefold increase in CAT activity after transfection into NIH3T3 cells. Northern blot analysis and enzymatic assays also were carried out on various murine tissues to examine AC expression. Of the tissues studied, the highest AC activity and mRNA levels were found in the kidney, followed by the brain; almost no AC activity or mRNA was found in the testis or skeletal muscle. These latter studies provided clear evidence that despite the housekeeping function of AC, its expression was tissue-specific.

Acid Ceramidase↗

[Hypertensive derailment in marital crisis].

A 34-year-old man was admitted because of headache with neck pain, hypertension and tachycardia. The symptoms started 10 days prior to presentation. In the past the patient was treated because of different vegetative symptoms, which were interpreted in relation to excessive private problems. Despite suggestive clinical presentation, the diagnosis phaeochromocytoma was confirmed late. Following removal of the tumor, blood pressure came into the normal range. The operation also abolished all vegetative symptoms and lead to stabilisation of the psychosocial situation.

Adrenal Gland Neoplasms↗

[Fever, headache and weakness. Primary cytomegalovirus infection].

We report on an acute primary infection with cytomegalo virus in a 26 year old immunocompetent and hitherto healthy man. The course of the disease was characterized by prolonged febrile state, headaches, myalgias and markedly reduced general condition. Indicators leading to diagnosis were in view of otherwise unremarkable clinical findings, reactive lymphocytosis, mild splenomegaly as well as elevated transaminases interpreted as concomitant hepatitis. The evolution was benign under symptomatic treatment. The patient recovered rapidly and completely. The clinical picture of primary CMV infection in nonimmunosuppressed adults is discussed.

Adult↗

[Fatigue, general weakness, subcutaneous nodules].

A 58 year old female patient presented with subcutaneous nodules (adenocarcinoma on cytology) and general symptoms as first symptoms of advanced metastasizing cancer of the breast. The patient succumbed to metastatic disease and terminal bronchopneumonia a few months later. The path to diagnosis in a situation with diffusely metastasizing cancer, the differential diagnosis during evaluation and the rationale for the choice of investigations in a patient with far advanced metastasizing cancer but unknown primary site are discussed.

Adenocarcinoma↗

Improved detection and comparative sizing of human chromosomal telomeres in situ.

Telomeric length dynamics are thought to play an important role both in the processes of cellular aging and cancer progression. We have revised the primed in situ (PRINS) labeling technique to allow an estimation of the relative length of individual telomeres. We illustrate the applicability of the approach by demonstrating different telomeric sizes not only between blood lymphocytes from a young and an old donor, but also among bone marrow cells from hematological cancer patients. In the latter case we found general variations in telomeric sizes as well as individual telomeric variations that would have escaped detection by other methods. An interesting finding was the selective expansion of a single telomere within a specific subset of cells.

Adolescent↗

CpG islands detected by self-primed in situ labeling (SPRINS).

We have studied the distribution and methylation of CpG islands on human chromosomes, using the novel technique of self-primed in situ labeling (SPRINS). The SPRINS technique is a hybrid of the two techniques primed in situ labeling (PRINS) and nick translation in situ. SPRINS detects chromosomal DNA breaks, as in nick translation in situ, and not annealed primers, as is the case in PRINS. We analyzed in situ-generated DNA breaks induced by the restriction enzymes HpaII and MspI. These restriction enzymes enable the detection of chromosomal CpG islands. Both HpaII- and MspI-SPRINS produce a banding pattern resembling R-banding, indicating a higher level of CpG islands in R-positive bands than in R-negative bands. Our SPRINS banding observations also indicate differences in sequence copy number in the satellites of homologous acrocentric chromosomes. Furthermore, a comparison of homologous HpaII-SPRINS-banded X chromosomes of females from lymphocyte cultures grown without methotrexate or bromodeoxyuridine revealed methylation difference between them. The same comparison of homologous X chromosomes from the cell line GM01202D, which has four X chromosomes, one active and three inactive, revealed the active X chromosome to be hypermethylated.

Cells, Cultured↗

Trisomy 10 survival: a literature review and presentation of seven new cases.

Trisomy 10 as the only chromosome aberration is a rare phenomenon in malignant and premalignant hemopoietic disorders. We describe 7 new cases and have found another 12 in the literature. It appears that, whereas adult patients have myeloid disorders (acute myeloid leukemia, myeloproliferative, or myelodysplastic syndromes), in children the diagnosis is lymphocytic leukemia or lymphoma. The median survival was 122 months in the total material. Age above 60 years proved to be a significant adverse factor (median survival only 5 months; p = 0.003). None of the other clinical, cytogenetic, or hematological variables were of demonstrable prognostic importance. In contrast with the larger trisomy 10 clones, those of limited size were associated with nonleukemic diagnoses, normal or slightly elevated leukocyte counts, and few or no circulating blasts. This may suggest that expansion of the trisomy 10 clone is associated with clinical and hematological progression.

Adult↗

[Long-term results of autologous conjunctiva-limbus transplantation in pterygium].

BACKGROUND: Conjunctiva-limbus autografting is known as a safe surgical technique for the removal of pterygia, with a low rate of recurrence. However, the long-term effect of this surgical maneuver is not clear. This study now investigates the long-term efficacy of conjunctiva-limbus autografts to prevent pterygium recurrence. METHODS: Conjunctiva-limbus transplants for primary (n = 62) or recurrent (n = 8) pterygia were reevaluated 11 to 83 months after surgery (mean: 44.97 months). Slit-lamp appearance and photomicrographs were studied with respect to the configuration of the transplant and the recurrence of the fibrovascular tissue typical of pterygia. RESULTS: Corneal pterygium recurrence has been observed in 2 cases. Fibrovascular tissue was found at the peripheral transplant-margin in 15 cases, and transplant compression towards the limbal margins were detected in further 7 patients. These conjunctival changes have not been observed during the first postoperative months. CONCLUSIONS: Conjunctiva-limbus autografts in pterygia have excellent efficacy against recurrence within the first few years. The transplant compression and fibrovascular changes within the peripheral conjuctiva seen in this study suggest that recurrencies might, however, develop on the long-term.

Adult↗

Evaluation of the analytical performance of an enzyme immunometric assay (EIA) designed to measure endogenous thyroid-stimulating hormone (TSH) in canine serum samples.

The analytical performance of a commercially available enzyme immunometric assay (EIA) designed to measure endogenous thyroid-stimulating hormone (cTSH) concentration in canine serum samples was evaluated. The precision of the assay was acceptable with intra- and inter-assay coefficients of variation (CV) of 5 and 11%, respectively. The assay maintained linearity under dilution and recovered added cTSH in a linear and proportional manner. The limit of detection (0.03 microgram/L) was well below the values measured in serum from dogs with primary hypothyroidism (median value 1.52 micrograms/L). Further, the assay clearly distinguished dogs with primary hypothyroidism from clinically healthy dogs (P = 0.0004). Based on these findings, it was concluded that the analytical performance of the assay was acceptable.

Animals↗

Infection of human B lymphocytes with lymphocryptoviruses related to Epstein-Barr virus.

Lymphocryptoviruses (LCVs) naturally infecting Old World nonhuman primates are closely related to the human LCV, Epstein-Barr virus (EBV), and share similar genome organization and sequences, biologic properties, epidemiology, and pathogenesis. LCVs can efficiently immortalize B lymphocytes from the autologous species, but the ability of a given LCV to immortalize B cells from other Old World primate species is variable. We found that LCV from rhesus monkeys did not immortalize human B cells, and EBV did not immortalize rhesus monkey B cells. In this study, baboon LCV could not immortalize human peripheral blood B cells but could readily immortalize rhesus monkey B cells. Thus, efficient LCV-induced B-cell immortalization across distant Old World primate species appears to be restricted by a species-specific block. To further characterize this species restriction, we first cloned the rhesus monkey LCV major membrane glycoprotein and discovered that the binding epitope for the EBV receptor, CD21, was highly conserved. Stable infections of human B cells with recombinant amplicons packaged in rhesus monkey or baboon LCV envelopes were also consistent with a species-restricted block occurring after virus binding and penetration. Transient infections of human B cells with simian LCV resulted in latent LCV EBNA-2 gene expression and activation of cell CD23 gene expression. EBV-immortalized human B cells could be coinfected with baboon LCV, and the simian virus persisted and replicated in human B cells. Thus, several lines of evidence indicate that the species restriction for efficient LCV-induced B-cell immortalization occurs beyond virus binding and penetration. This has important implications for the study of LCV infection in Old World primate models and for human xenotransplantation where simian LCVs may be inadvertently introduced into humans.

Amino Acid Sequence↗

Effect of calcitonin on the activity of ANG II-responsive neurons in the rat subfornical organ.

In addition to the well-documented ability of calcitonin to lower blood calcium levels, blood-borne calcitonin may also affect neurons located outside the blood-brain barrier, e.g., in the subfornical organ (SFO), where numerous receptors for this peptide have been described. In an in vitro preparation of the rat SFO, calcitonin activated 61% of 36 neurons, only 1 neuron was inhibited, and the remainder were unresponsive. All but two of the neurons excited by 10(-7) M calcitonin were also stimulated by 10(-7) M ANG II. The threshold concentration for the excitatory effects of calcitonin was 10(-9) M and was thus similar to ANG II. Like ANG II, subcutaneous injection of calcitonin stimulated water intake, although to a lower extent. These results suggest that blood-borne calcitonin could stimulate drinking by its excitatory effect on neurons in the SFO. Calcitonin, which is released during food intake, might be involved in prandial drinking, which is presently considered an acquired behavior.

Angiotensin II↗

Pathology of the palatal aponeurosis in cleft palate.

OBJECTIVE: The palatal aponeurosis is a controversial structure, both in terms of its anatomy and its function. This article points out a pathologic finding in the cleft palate condition that has not been previously described. DESIGN AND METHOD: By means of surgical dissections, this study demonstrates in detail that the palatal aponeurosis exists even in cleft palates, but it is disrupted, malpositioned, and folded in two layers. PATIENTS: This dissection method has been performed on more than 150 patients with cleft of the hard and soft palate, with or without cleft of the lip and alveolus. At the time of operation, the children were between 6 and 8 months of age. RESULTS: It is possible to dissect the two layers of the palatal aponeurosis, to unfold the aponeurosis, and to form a tough tendinous plane. CONCLUSION: For a functional physiologic reconstruction of the cleft palate, it is necessary not only to reconstruct the levator veli palatini and palatopharyngeus muscle slings, but also to approximate and suture the fibers of the palatal aponeurosis to the corresponding fibers of the opposite side after unfolding them in a medio-dorso-cranial direction. In this manner, a continuous palatal aponeurosis can be created, which subsequently can serve as a transmitter of the muscle forces.

Cleft Palate↗

[Gunshot wounds in a historical light].

At the beginning of the Renaissance the advent of firearms really progressed. The injuries needed new methods of treatment. Due to the high incidence of infection and the theory of poisoning an increased interest to remove the bullets with probes and forceps was seen. However, improvement in the treatment did not occur until the middle of the 19th century, when anaesthesia and antiseptic were generally known. The Medical History Museum has the disposal of a representative selection of instruments to remove bullets from gunshot wounds. A description concerning their origin as well as function is given.

Denmark↗

The role of body composition measurements in wasting syndromes.

Wasting is a state of nonvolitional weight loss that frequently afflicts patients with cancer or those infected with the human immunodeficiency virus. Body composition measurements afford a more clinically relevant assessment of an individual's functional capacity, energy stores, and prognosis. Several techniques of body composition measurements exist, each with selected advantages and disadvantages. This review summarizes the methods and the utility of body composition analysis.

Anthropometry↗

Small intestine pathogens in AIDS: conventional and opportunistic.

The small intestine, coming in direct contact with ingested potential pathogens, depends on active mucosal immunity to withstand invasion and damage. In patients with AIDS and severe impairment of immunoregulatory lymphocytes, proliferation of protozoal, viral, bacterial, and fungal pathogens produces diarrhea and malabsorption. When noninvasive tests of stool and blood fail to identify responsible organisms, endoscopy can reveal mucosal lesions which are suggestive if not diagnostic. Cryptosporidium, cf2E. intestinalis, cf1CMV, MAC, and other infections can be identified by intestinal biopsy quicker and often at lower overall cost than they can be by culture.

AIDS-Related Opportunistic Infections↗

[Therapy of hypertension in the elderly: Fosinopril in Old Patients Study (FOPS)].

The necessity for a persistent antihypertensive treatment in elderly persons has not been proven until the beginning nineties. An adequate reduction of blood pressure is required also in high age for prevention of cardiovascular accidents. A study is presented which investigates efficacy and tolerance of the ACE-inhibitor fosinopril in an unselected cohort of hypertensive outpatients older than 60 years over 12 weeks. Diastolic hypertension (DBP > or = 96-110 mm Hg) and isolated systolic hypertension (SBP > or = 160-219 mm Hg, DBP 80-94 mm Hg) were analyzed separately. Blood pressure values in both groups were normalized in more than 80% of the patients. In the case of insufficient response an additional dose of 12.5 mg hydrochlorochiazide was somewhat more effective than doubling the dose of the ACE-inhibitor. Efficacy and side effects of the antihypertensive treatment with fosinopril in this study were not dependent on the degree of impaired renal function.

Aged↗

Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial.

BACKGROUND: Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency. OBJECTIVE: To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices. DESIGN: Randomized, controlled clinical trial. SETTING: Three teaching hospitals. PATIENTS: 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS. INTERVENTION: Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein. MEASUREMENTS: Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs. RESULTS: Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). CONCLUSIONS: In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant.

Adult↗