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Biomedical subjects

J Hoch

Publications and source records attributed to J Hoch.

At least 19 recordsLinked to original sources
PubMed1992

Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement.

Kinetic constants for the interaction of NADH and NADPH with native rat dihydropteridine reductase (DHPR) and an Escherichia coli expressed mutant (D-37-I) have been determined. Comparison of kcat and Km values measured employing quinonoid 6,7-dimethyldihydropteridine (q-PtH2) as substrate indicate that the native enzyme has a considerable preference for NADH with an optimum kcat/Km of 12 microM-1 s-1 compared with a figure of 0.25 microM-1 s-1 for NADPH. Although the mutant enzyme still displays an apparent preference for NADH (kcat/Km = 1.2 microM-1 s-1) compared with NADPH (kcat/Km = 0.6 microM-1 s-1), kinetic analysis indicates that NADH and NADPH have comparable stickiness in the D-37-I mutant. The dihydropteridine site is less affected, since the Km for q-PtH2 and K(is) for aminopterin are unchanged and the 14-26-fold synergy seen for aminopterin binding to E.NAD(P)H versus free E is decreased by less than 2-fold in the D-37-I mutant. No significant changes in log kcat and log kcat/Km versus pH profiles for NADH and NADPH were seen for the D-37-I mutant enzyme. However, the mutant enzyme is less stable to proteolytic degradation, to elevated temperature, and to increasing concentrations of urea and salt than the wild type. NADPH provides maximal protection against inactivation in all cases for both the native and D-37-I mutant enzymes. Examination of the rat DHPR sequence shows a typical dinucleotide binding fold with Asp-37 located precisely in the position predicted for the acidic residue that participates in hydrogen bond formation with the 2'-hydroxyl moiety of all known NAD-dependent dehydrogenases. This assignment is consistent with x-ray crystallographic results that localize the aspartate 37 carboxyl within ideal hydrogen bonding distance of the 2'- and 3'-hydroxyl moieties of adenosine ribose in the binary E.NADH complex.

Amino Acid Sequence↗
PubMed1992

Heparin-induced thrombocytopenia in the newborn.

This pilot study was initiated to determine whether heparin-induced thrombocytopenia occurs in the newborn and whether thromboembolic complications in the newborn could be related to heparin-induced thrombocytopenia. Thirty-four infants in whom thrombocytopenia (less than 70,000/mm3) (n = 23), precipitous (30% to 50%) fall in platelet count (n = 5), or thromboses (n = 6) developed while they were receiving heparin were studied. Heparin-associated antiplatelet antibodies were demonstrated in 14 infants by platelet aggregation testing. The average gestational age (29 +/- 6 weeks); birth weight (1300 +/- 945 gm); and platelet count at birth (234,000/mm3 +/- 111,000/mm3) of these 14 infants did not differ statistically from the 20 infants without heparin-associated antiplatelet antibodies. An umbilical artery catheter was inserted in all infants except a single patient from each group. Aortic thrombosis was documented by abdominal ultrasonography in 11 of 13 (85%) infants with heparin-associated antiplatelet antibodies. One patient died with a midgut volvulus before the aorta could be examined. Five aortic thromboses were detected in the 20 infants without heparin-associated antiplatelet antibodies. Bleeding was not associated with the heparin-induced thrombocytopenia. One patient with previously demonstrated thrombocytopenia and heparin-associated antiplatelet antibodies had recurrent thrombocytopenia when reexposed to heparin; her platelet count recovered after heparin withdrawal. Thus heparin-induced thrombocytopenia does occur in preterm and term infants receiving heparin and is associated with arterial thromboses. Therefore infants receiving any form or amount of heparin must be carefully monitored for heparin-induced thrombocytopenia.1+

Autoantibodies↗
PubMed1992

The fatty acid synthase (FAS) gene and its promoter in Rattus norvegicus.

Screening of rat liver genomic libraries yielded 5 overlapping clones for rat fatty acid synthase (FAS). From these clones we determined the 18,170 bp sequence of the rat FAS together with 5,028 bp of the 5'-flanking region and 515 bp of the 3'-adjacent genomic sequence. The two FAS transcripts which differ only in the positions of their polyadenylation/termination sites consist of one untranslated and 42 translated exons. Surprisingly, the substrate binding site for enoyl reductase, one of the FAS component functions, is interrupted by an intron. The sizes and the boundaries of the individual domains could be mapped in relation to the exon/intron structure of the gene. These eight partial functions coincide with discrete units of exons. The acyl carrier protein with its prosthetic 4'-phosphopantetheine group is located within a single exon supporting the idea that rat FAS has evolved by gene fusion. Using primer extension the main transcription start site of the FAS mRNA in both hepatic and mammary gland tissues was located at 5,028 bp in the sequence determined. As expected of a gene which is pretranslationally regulated the 5'-flanking region contains, in addition to TATA and CAAT boxes, consensus sequences for several DNA binding proteins.

Amino Acid Sequence↗
PubMed1992

[Primary resection of the large intestine].

The authors evaluate their own group of 49 patients subjected in 1982-1990 to primary resection of the large intestine with an immediately established anastomosis. 32 patients (65.31) recovered per primam and were discharged on average after 14.9 days. A disorder of the anastomosis was recorded in 5 patients, i.e. on 10.2%. In the conclusion the authors express conditions essential for the safety of these operations.

Anastomosis, Surgical↗
PubMed1991

Role of aspartate-37 in determining cofactor specificity and binding in rat liver dihydropteridine reductase.

Full-length rat dihydropteridine reductase (DHPR) cDNAs have been combined with a prokaryotic expression vector and introduced into Escherichia coli. Transformed bacteria express dihydropteridine reductase immunoreactive proteins and demonstrate conversion of quinonoid dihydropteridines to their tetrahydro forms. Several recombinant enzymes have been purified to homogeneity and biochemical studies have been carried out comparing their properties with those exhibited by the rat liver enzyme. The optimal reaction conditions, kinetic constants, and stability are similar for the recombinant and naturally occurring enzyme. The results indicate that the nonmutant recombinant rat DHPR is an authentic replica of the natural protein and that the characteristics of DHPR activity are determined by a single gene product and do not require specific modification via the eukaryotic cell. In addition to the wild type, three specific mutagenic forms of the reductase, A-6-V, W-104-F, and D-37-I, and an additional abbreviated structure have also been formed. Each of the products exhibits reductase activity, although they show varied affinities for their cofactor, NADH, and less stability to chromatography, dialysis, and concentration than the wild-type enzyme. The N-terminal sequence contains a classic NADH binding region between amino acids 9 and 36, and Asp 37 is essential for binding the cofactor as is shown by the approximately 20-fold increase in dissociation constant for the D-37-I mutant and diminished kcat (approximately 43 s-1 compared to 156 s-1 for the wild-type enzyme). The results indicate that the DHPR cofactor binding site is similar to typical dinucleotide requiring dehydrogenases such as lactic acid and liver alcohol dehydrogenase.

Amino Acid Sequence↗
PubMed1990

[Our attitude to the so-called extended surgical procedures for colorectal carcinoma].

The authors present their experience with 29 extended operations performed on account of tumours of the sigmoid, rectosigmoid and rectum. These operations accounted for 13.4% of all operations on account of operable tumours of the colon and rectum in 1984-1988. In addition to the basic operation one organ was removed 11 times, two organs twice, three organs four times and four organs were removed en bloc twice. Complications occurred in 61% of the patients, the mortality rate was 6.9%. The authors submit an account of recent views published in the literature on the given subject with emphasis on en bloc resection, and conclude that when certain principles are respected, these extended operations are justified.

Adult↗
PubMed1990

[An unusual combination of hemobilia and hemoperitoneum].

Injuries of the gallbladder belong to rare causes of haemobilia. The author presents the case-history of an injured woman who after a fall from a height developed among others haemobilia and haemoperitoneum. The source of haemorrhage into the biliary pathways and abdominal cavity was the gallbladder partly ruptured from its bed. The author gives a brief account of diagnostic possibilities as regards haemobilia and haemoperitoneum.

Adult↗
PubMed1989

Endothelial cell interactions with native surfaces.

Since native vessels are presumably the ideal surface for endothelial cells, we have examined endothelial cell interactions with natural surfaces as a standard to determine the possibilities obtainable on a surface. We have examined three separate types of natural surfaces including human amnion, superficially-injured human arteries, and tanned bovine carotid arteries. When basement membrane collagen is a principal component of a surface, such as with amnion or a superficially denuded large vessel, very rapid cell attachment and spreading occurs. Intact confluent monolayers covering 100% of the amnion surface are present as early as one hour. Human arteries superficially injured to denude their endothelium also exhibit excellent affinity for EC adherence and spreading. Endothelial monolayers cover 80.8% (+/- 5.3) of this surface after one hour, with 91.4% (+/- 1.2) coverage after two hours. For tanned bovine carotid arteries, one and two hour endothelial cell incubation results in coverage of 59.2% (+/- 1.3) and 75.9% (+/- 4.1), respectively. This surface is composed of interstitial collagen of the arterial wall in medial and adventitial layers. Electron microscopy reveals excellent endothelial cell spreading with little or no exposed underlying basement membrane. This suggests that polymeric surfaces designed to mimic injured native surface could allow an endothelialized surface to develop within minutes to hours.

Amnion↗
PubMed1989

[Sexual disorders after colorectal operations].

After extensive colorectal operations there are sexual dysfunctions in the patients in 16-100%. In our cohort of 36 men the post-operation sexual disorders were reported in 21.3%. The authors present an anatomical survey of nerve supply of the organs influencing sexual activity emphasizing tactical and technical measures during the operations which could prevent the damage of important nervous structures.

Colon↗
PubMed1988

[Long-term results following reconstruction of the tendon of the extensor pollicis longus muscle by transposition of the tendon of the extensor indicis muscle].

Twenty-six patients with injury of the tendon of the extensor pollicis longus have been studied and the long term results of the transfer of the tendon of the extensor indicis are reported. Using Geldmacher's evaluation scheme for assessment of the results of extensor tendon reconstruction we found thirteen excellent, ten good, and three fair results. The prognosis is dependent upon the kind of injury and the time after injury of the transfer of the tendon of the extensor indicis.

Adolescent↗
PubMed1986

[Greater omentumplasty for covering the chest wall following removal of ulcerating breast cancer].

The palliative excision of ulcerous and metastatic breast cancer produces large defects of skin and tissue on the anterior chestwall. In comparison with other methods in plastic surgery for covering up large defects of the chestwall the greater omentum-transposition is, concerning the technique, very practicable. It does not endanger the patients in their distressing condition of cancer generalisation, has less complications and is easy to command in the postoperative phase. The transposition of a highly vascular tissue, which offers some resistance to infection and acts as a immunity barrier is able to cover up the local lesion during a short period of hospitalization, strengthen effectively the self respect of the patients and improve their lifestyle even with the limited lifespan.

Breast Neoplasms↗
PubMed1986

Determination of the chromosomal locations of four Bacillus subtilis genes which code for a family of small, acid-soluble spore proteins.

The chromosomal locations of four genes which code for small, acid-soluble spore proteins (SASP) in Bacillus subtilis have been determined. Although these four genes code for extremely homologous small, acid-soluble spore proteins (greater than 65% sequence identity), the genes are not clustered but are located at 70 degrees (adjacent to glyB [sspB gene]), 115 degrees (between metC and pyr cluster [sspD gene]), 180 degrees (between metB and kauA [sspC gene]), and 260 degrees (between ilvC and aroG [sspA gene]) on the B. subtilis genetic map.

Bacillus subtilis↗
PubMed1983

Assessment of health needs and willingness to utilize health care resources of adolescents in a suburban population.

We investigated whether adolescents living in a middle-class suburb believed that their health needs were being met, and the extent to which they were willing to utilize local health care resources for a range of problems. Self-administered, anonymous questionnaires were completed by 649 students in grades 9 through 12. The mean age of respondents was 15.4 years; 52% were female, and 95% white. They had ready access to medical care: 90% used a specific private physician. From a list of 15 health problems, 60% indicated that they had seen a health provider for at least one of them, most often for stomach pains (22%), headaches (18%), and coughing (16%). From an identical list, 48% indicated that there was at least one problem for which they had never seen a health provider but would like to, most often for a weight problem (14%), birth control (10%), and emotional upset (9%). Although 20% regularly used illegal drugs, 24% were sexually active, and 38% thought they had a weight problem, only 1%, 4%, and 10%, respectively, had sought care for these matters. A majority of students would not choose to go to a private physician for care related to sexuality, substance abuse, or emotional upset, and would not be willing to seek care for these problems with their parents' knowledge. Ready access to private primary care did not assure attention to important health needs among these suburban adolescents.

Adolescent↗